NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 Disclaimer: The recommendations expressed in these guidelines reflect the existing available evidence from the current literature and are subject to change over time. The recommendations described here are general and may not apply to a specific patient. Application of these guidelines to a particular situation remains the professional responsibility of the caring physician and/or the prescriber. 1 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 Antimicrobial Subcommittee Dr. Amina Al Jardani, MD Dr. Amal Al Maani, MD Dr. Mubarak Al Yaqubi, MD Dr. Khalid Al Hinai, MD Dr. Nada Al Siyabi, MD Ph. Zaher Al Salmi, Msc Ph. Huda Al Harthi, Msc Dr. Khalid Al Harthi, MD Contributors Dr.Faryal Al Lawati, MD Dr. Seif Al Abri, MD Dr. Saleh Al Azri, MD Dr. Fatma Al Yaqubi, MD Dr. Azza Al Rashdi, MD Dr. Amal Al Tai, MD Dr. Hana Al-Areimi, MD Dr. Nashat Al Sukaiti Ph. Umkulthoum Al Barwani, MSc Ph. Wijdan Hashmani, MSc Ph. Fatma Al Raisi, MSc Ph. Mardheya Abdulla Al Kharusi Dr. Hanan Al Kindi, MD Dr.George Paul, MD Acknowledgments We thank all those who contributed to the review of this guideline: Departments of ENT & Ophthalmology at AlNahadhah Hospital Dr. Abraham Ooriapadickal ,MD(SQUH) Dr.Mohammed ALMukhaini,MD Dr. Issa Al Jahdhami ,MD(AFH) Dr.Fatma AlYaqoubi,MD Dr. Badria Al Adawi ,MD (SQUH) Dr. Said Abdul Rahman,MD Dr. Jalila Al-Lawatia,MD Dr. Nawal AlMaskri,MD Ms Zavila Shakeel Ms.Nazira Begum Abubakar 2 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 Table of Contents Preface Abbreviations Antimicrobials Prescribing Policy Table 1: Guidelines for Treatment of Respiratory Infections in Adults Table 2: Guidelines for Treatment of Ear, Nose and Throat Infections Table 3: Guidelines for Treatment of Eye Infection Table 4: Guidelines for Treatment of Infective Endocarditis and Related Infections Table 5-A: Prophylaxis of Infective Endocarditis Table 5-B: Antibiotic prophylactic regimens for dental procedures Table 6: Guidelines for Treatment of Central Nervous System Infections in Adults Table 7: Guidelines for Treatment of Bone and Joint Infections in Adults Table 8: Guidelines for Treatment of Abdominal Infections in Adults Table 9: Guidelines for Treatment of Skin and Soft Tissue Infections Table 10: Guidelines for Treatment of Urinary Tract Infections and Sexually Transmitted Diseases in Adults Table 11: Guidelines for Treatment of Systemic Infections Table 12: Guidelines for Treatment of Common Viral Infections Table 13-A: Guidelines for Emperical Treatment of Paediatric Infections Table 13-B: Paediatric antibiotics dosage guideline Table 14: Guidelines for Therapeutic Drug Monitoring Table 15: Guidelines for Surgical Antimicrobial Prophylaxis Table 16: Antimicrobial in Pregnancy and Lactation Penicillin Allergy Table 17: Suggested Duration of Antibiotic Therapy in Common Infections Guidelines for Antimicrobial Prophylaxis in Haematology/Oncology in Adults Table 18/A: Antibacterial prophylaxis for Haematology/Oncology patients Table 18/B: Primary Antifungal prophylaxis for Haematology/Oncology patients Table 18/C: Antiviral prophylaxis for Haematology/Oncology patients Table 18/D: Anti-PCP prophylaxis for Haematology/Oncology patients 3 4 5-6 7 - 20 21 - 25 26 - 29 30 - 33 34 - 40 41 42 43 - 47 48 - 50 51 – 56 57 – 62 63 – 65 66 – 70 71 – 72 73 – 87 88 – 93 94 – 97 98 - 104 105 - 110 111 - 114 115 - 116 117 118 – 119 119 – 120 121 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 Preface The emergence and the spread of antimicrobial resistance is a challenging epidemic with great impact on the global health economy. Antimicrobial resistance adversely affects patients’ outcomes with increasing mortality and morbidity. Inappropriate use of antibiotics in hospitals and the community is playing a major role in the increase of antimicrobial resistance. Many studies have shown that over 50% of antimicrobial use is inappropriate. Importance of prudent antimicrobial use (i.e. appropriate choice, dose and duration) has been shown to reduce the emergence of resistance and improves patient outcome. The aim of these national antimicrobial guidelines is to provide guidance for clinicians in the Ministry of Health and other healthcare settings for the empirical and targeted antimicrobial therapy of various infectious syndromes. Treatment guidelines for paediatric and adult patients are included. In addition, guidance on antibiotic prophylaxis is covered. The users of these guidelines should seek experts in antimicrobials such as infectious disease physicians, medical microbiologists and clinical pharmacists in order to optimize antimicrobial use in various healthcare settings. Empirical broad-spectrum antibiotic drugs are often prescribed. However, once culture and susceptibilities are known, therapy should be reviewed and adjusted accordingly. This guide does not address treatment of HIV, tuberculosis or malaria. Users are advised to consult the Ministry of Health’s specific guidelines for these conditions. This guideline is produced by the national antimicrobial subcommittee. While every attempt has been made to ensure the accuracy of the content, physicians and prescribers should ensure the correct drug and dose is prescribed as appropriate for each individual patient. The interpretation and implementation remains the responsibility of the treating physician. ___________________________ Dr.Ahmed Al Saidi Minister of Health 4 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 Abbreviations ABECB FEVI Forced expiratory volume in 1 second AHA ALL AM-CL AML Amoxi AMP AM-SB Azithro B. abortus B. cepacia Acute bacterial exacerbation of chronic bronchitis American Heart Association Acute lymphoblastic leukaemia Amoxicillin-clavulanate acute myelogenous leukaemia Amoxicillin Ampicillin Ampicillin-sulbactam Azithromycin Brucella abortus Burkholderia cepacia FQ g6PD GAS gent GI GP GU GVHD Hr HAART Fluoroquinolone Glucose-6-phosphate dehydrogenase Group A Streptococcus Gentamycin Gastrointestinal General practitioner Genitourinary Graft-versus-host disease Hour Highly active antiretroviral therapy B. henselae Bartonella henselae HACEK A group of Gram-negative bacteria that includes Haemophilus spp. B-Lactam B. melitensis B. quintana B. suis BID C. pneumoniae CA-MRSA H. influenzae HSCT HSV ICU IM INH IV Haemophilus influenzae Hematopoietic stem cell Herpes simplex virus Intensive care unit Intramuscular Isoniazid Intravenous Caz CAP CAPD Beta-lactam Brucella melitensis Bartonella quintana Brucella suis Twice a day Chlamydophila pneumoniae Community-associated methicillinresistant S. aureus Ceftazidime Community-acquired pneumonia Chronic Ambulatory Peritoneal Dialysis IVDU IVIG K. pneumoniae Intravenous drug user Intravenous immunoglobulin Klebsiella pneumonia CBC CBT Ceph Cip Complete blood count Cord blood test Cephalosporin Ciprofloxacin Levo M. catarrhalis M. pneumoniae MDR-GNB Levofloxacin Moraxella catarrhalis Mycoplasma pneumoniae Multidrug-resistant Gram-negative bacilli Clarith CML Clarithromycin Chronic myelogenous leukaemia MDR MDRSP CNS CoNS CRBSI CrCl Central nervous system Coagulase-negative staphylococci Catheter-related bloodstream infection Creatinine clearance MDS MIC Moxi MRI Multidrug-resistant multidrug-resistant Streptococcus pneumoniae Myelodysplastic syndrome Minimum inhibitory concentration Moxifloxacin CRE MRSA Methicillin-resistant S. aureus CSF Carbapenem-resistant Enterobacteriaceae Cerebrospinal fluid MSSA CT CVP line Computed tomography central venous pressure line N. farcinica NG Methicillin-sensitive S. aureus Nocardia farcinica Nasogastric CXR Dapto DM doxy DRSP DS E. faecium ENT ESBL ESR FAMCO FDA PO q1h Chest X-ray Daptomycin Diabetes mellitus Doxycycline Drug-resistant S. pneumoniae Double strength Enterococcus faecium Ear, nose and throat Extended spectrum beta-lactamases Erythrocyte sedimentation rate Family and community medicine Food and Drug Administration (USA) Per OS (by mouth) Every hour NTD OD P. aeruginosa PCP PCR PD Pen Pen-G Pen-V Pip q4h PJP Vanco VRE Neglected Tropical diseases Once daily Pseudomonas aeruginosa Pneumocystis pneumonia Polymerase chain reaction Peritoneal dialysis Penicillin Penicillin G Penicillin V Piperacillin Every 4 hours Pneumocystis jiroveci pneumonia Vancomycin Vancomycin-resistant Enterococci 5 Magnetic resonance imaging NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 q8h QID R R/O Every 8 hours Four times a day Resistant Rule out RFT Rif RR RT rt Rx S. aureus S. bovis S. milleri S. pneumoniae Renal function test Rifampicin Respiratory rate Radiation therapy Right Treatment Staphylococcus aureus Streptococcus bovis Streptococcus milleri Streptococcus pneumoniae SBP Staph Strept Taz TB TDM TID TMP-SMX Tobra Spontaneous bacterial peritonitis Staphylococcus Streptococcus Tazobactam Tuberculosis Therapeutic drug monitoring Three times a day Trimethoprim/sulfamethoxazole Tobramycin UTI Urinary tract infection VZV WBC β-lactam 6 Varicella zoster virus White blood cell beta-lactam NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 Antimicrobials Prescribing Policy 1. Introduction The emergence of antimicrobial resistance is becoming a major public health issue. Infections caused by multidrug-resistant (MDR) organisms are associated with increased morbidity, increased length of hospital stay and increased mortality. An effective strategy to limit the effect of multidrug resistance must be multifaceted and must include the education of patients and physicians about appropriate drug, dose and duration, establishment of national antimicrobial guidelines, use of effective infection control practices to prevent transmission from infected to uninfected patients, surveillance of antimicrobial resistance and antimicrobial use, and improved use of immunization. The combat of antimicrobial resistance is one of the important priorities of the Ministry of Health in Oman. Establishing a national antimicrobial policy and guidelines is one facet of many measures that will be undertaken to improve the prudent use of antibiotics and reduce antimicrobial resistance in the country. 2. Scope This policy applies to all healthcare settings in the Sultanate of Oman and to all employees who are involved in prescribing, administering and monitoring antimicrobials use. 3. Aim To ensure the appropriate use of antimicrobials to optimize the patient's outcome, minimize the risk of adverse reactions and reduce the emergence of antibiotic resistance. 4. Policy principles This guidance is based on the best available evidence; however, professional judgment based on patient clinical presentation should be used. Patients should be involved or informed on the decision of initiation of antibiotics. Antimicrobial prescriptions in all health care facilities in Oman are expected to adhere to the following principles: 1. Treat infections and not colonization. Prescribe antibiotics when there is evidence of a bacterial infection and there is likely to be a clear clinical benefit. In severe infections, initiate antibiotics as early as possible. 2. Specify clearly the indications, dose and duration in all the antibiotic prescription. 3. Always conduct appropriate microbiological investigations prior to antimicrobial therapy. Antimicrobial therapy should be reviewed in 24–48 hours upon the availability of microbiological investigations. De- 7 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 escalation of empirical therapy should be adjusted to target the causative organism based on patient’s susceptibility testing. (Fig.1). 4. When deciding on the most appropriate antibiotic to prescribe, the following factors should be considered: History of drug allergy and document the type of allergy: minor (rash only) or major (anaphylaxis, angioedema) Recent cultures (review previous culture, e.g. if the patient grew or colonized with multiple – resistant organisms Recent antibiotic therapy Potential drug interactions Potential adverse effects Some antibiotics are considered unsafe in pregnancy, infants or young children Dose adjustment may be required for renal or hepatic dysfunctions 5. Consider removal of any foreign body/indwelling devices, drainage of pus or any surgical interventions to control the infection source. 6. For advice on appropriate investigations and management of infections, consult your local infection specialists (infectious disease physician, medical microbiologists and/or clinical pharmacist). 7. The use of 2 agents with anaerobic activity to treat infections with potential anaerobic bacteria involvement. 7.1. Double anaerobic coverage is unnecessary and puts the patient at risk of drug toxicity. No data or guidelines support the use of double anaerobic coverage in clinical practice. Example: the use of piperacillin/tazobactam and metronidazole or meropenem and metronidazole is not recommended. 7.2. Two clinical exceptions: Addition of metronidazole to another agent with anaerobic activity to treat C. difficile Clindamycin added to another agent with anaerobic activity when treating necrotizing fasciitis 8. The use of “double coverage" for Gram-negative bacteria. 8.1. Double coverage of suspected Gram-negative infections serves the purpose of providing broadspectrum initial empiric coverage until susceptibility data are known. 8.2. No evidence exists to support the superiority of combination therapy over monotherapy for Gramnegative infections once susceptibilities are known. 8.3. Once culture identification and susceptibilities have been reported, de-escalation to a single agent is strongly recommended. 9. Avoid routine prescription of intravenous forms of highly bioavailable antimicrobials agents for patients who can reliably take and absorb oral medications. 8 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 Antibiotics such as fluoroquinolone, trimethoprim/sulfamethoxazole (TMP-SMX), clindamycin, linezolid, metronidazole and fluconazole have excellent bioavailability and only rarely need to be administered intravenously. Use of oral forms will reduce the need for IV access and their associated complications. FIG.1 4. Selected formulary antimicrobial and restriction status Group I Antibiotics for general use and primary health care This policy limits the general practitioner’s (GP) choice of antibiotics to a few drugs only. With these drugs, he/she should be able to treat most community-acquired infections successfully. Some antibiotics in this group are restricted to specialist in family and community medicine (FAMCO) or other physicians (e.g. dermatologist or, ear, nose and throat [ENT] specialist). However, some infections, such as pneumonia and otitis media caused by penicillin-resistant S. pneumoniae and M. catarrhalis and ampicillin (AMP)-resistant H. influenzae may not respond to treatment with any of the antibiotics available to the GP. Ideally, such infections are treated with ceftriaxone, co-amoxiclav or other ß-lactamase-resistant drugs. However, in order to rationalize antibiotic usage, it is not possible; to avail such drugs for general use. Nevertheless, doctors in general practice must be aware of the possibilities of infections by resistant organisms. They should, therefore refer all patients with pneumonia and children suffering from acute otitis media to the nearest specialist for further evaluation and management. 9 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 Table (a)-List of Group I Antimicrobials Antimicrobial Benzylpenicillin (penicillin G) Penicillin V Procaine penicillin Benzathine benzylpenicillin Amoxicillin Amoxicillin + Clavulanate Cloxacillin Cephalexin Cefuroxime Erythromycin Azithromycin Trimethoprim/sulfamethoxazole Doxycycline Ciprofloxacin Nalidixic acid Nitrofurantoin Metronidazole Acyclovir Valacyclovir Nystatin Ketoconazole Fluconazole Itraconazole Terbinafine Albendazole Comments Restricted Restricted Restricted Restricted Restricted Restricted Restricted Restricted Restricted Restricted Group II These antimicrobials are to be used by consultants (exceptions are prescribers in intensive care unit [ICU], ER, OR hematology oncology wards) in emergency and according to the prescribing criteria for a period not exceeding more than 3 days until microbiological investigations are through. All antimicrobials need review and approval after 72 hours in consultation with the infectious diseases unit, medical microbiologist or the antimicrobial stewardship team. Or In accordance with antibiotic susceptibility results, i.e. if the microorganism is sensitive only to the antibiotics in this group. 10 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 Or By the recommendation of the infectious disease physician, the medical microbiologist or the antimicrobial stewardship team in view of the prevalent antibiotic susceptibility pattern in the hospital concerned. Table (b)-List of Group II Antimicrobials Restricted Antibiotics Amikacin Meropenem imipenem Piperacillin/tazobactam Cefepime Ceftazidime Vancomycin Ertapenem Linezolid Tigecycline Colistin Fosfomycin Daptomycin Ambisome Anidulafungin Voriconazole Caspofungin Route IV IV IV IV IV IV IV IV IV & PO IV IV PO IV IV IV IV & PO IV Comments **Antibiotics not listed under group 1 or 2 should be prescribed or used for inpatients or outpatients with approval of specialist and above, and in accordance to the prescribing indications outlined in this guideline. 5. Prescribing criteria for restricted anti-infective agents Meropenem Suspected or proven polymicrobial infection when combination therapy with other antibiotics or piperacillin-tazobactam monotherapy is not desirable because: o The organism is documented or likely resistant to all alternatives, risk of toxicity with aminoglycosides or clinical failure. Infection with an organism proven or likely resistant to all alternatives. Vancomycin Serious infections due to beta (β)-lactam-resistant Gram-positive organisms. Infections due to Gram-positive organisms in patients with serious allergy to β-lactam antibiotics. 11 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 Empiric treatment pending susceptibility for S. aureus identified from a sterile site when there is a strong suspicion of methicillin-resistant S. aureus (MRSA), e.g. in hospitalized patients, patients with known MRSA colonization. Surgical prophylaxis in patients with life-threatening allergy to β-lactam antibiotics. Prophylaxis for endocarditis in patients with life-threatening β-lactam allergy. Empiric treatment of febrile neutropenic patients with suspected Gram-positive infections (e.g. inflamed IV site). C. difficile-associated colitis unresponsive to metronidazole. (Oral vancomycin). Piperacillin-tazobactam Suspected or proven polymicrobial infection when combination therapy with other antibiotics is not desirable because organisms are documented or likely to be resistant to narrower spectrum antibiotics or risk of toxicity with aminoglycosides. Empiric therapy of febrile neutropenia. Suspected or proven nosocomial pneumonia where the organisms are documented or likely resistant to narrower spectrum antibiotics. Moxifloxacin Moxifloxacin is a quinolone antibiotic. It has activity against Gram-positive cocci, Gram-negative cocci (except N. gonorrhoeae due to high prevalence of resistance), Gram-negative bacilli (including extended spectrum β-lactamases [ESBL] organisms, Legionella spp.), Chlamydophila and M. pneumoniae, and activity against anaerobes except C. difficle. Indications: Mild to moderate community-acquired pneumonia (CAP), including MDR S. pneumoniae. Acute bacterial exacerbation of chronic bronchitis. Acute bacterial sinusitis. Uncomplicated skin and soft tissue infections. Intra-abdominal infections. Bacterial conjunctivitis. Acceptable off-label use: Treatment of infections caused by Legionella spp. Unacceptable uses: Avoid in use in CAP if tuberculosis (TB) suspected. Linezolid Treatment of vancomycin-resistant E. faecium infections. 12 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 Proven glycopeptide intermediate S. aureus infection. One of the following infections that is vancomycin-resistant or methicillin-resistant when vancomycin (or other sensitive antimicrobial) is contraindicated, has failed or is not tolerated: i. Nosocomial pneumonia ii. Skin and skin structure infections including diabetic foot infections iii. Community-acquired necrotizing pneumonia Oral switch from IV glycopeptide where oral Rifampicin and trimethoprim are not appropriate. Poor IV access and glycopeptide is indicated. Tigecycline Complicated polymicrobial intra-abdominal infections. Complicated skin and soft tissue infections. If the patients cannot receive other combination or the organism is resistant to other first line treatment. Note: Not active against P. aeruginosa. Colistin Treatment of MDR Gram-negative bacteria such as A. baumannii, P. aeruginosa and no other treatment options are available. Ertapenem Ertapenem is a carbapenem antibiotic. It has in vitro activity against many Gram-negative organisms including those that produce ESBL, but it does not have activity against Pseudomonas spp. or Acinetobacter spp. Its anaerobic and Gram-positive activity is similar to that of other carbapenem, except it does not have activity against Enterococcus spp. Indications: Mild to moderate intra-abdominal infections (biliary tract infections, diverticulitis, secondary peritonitis/gastrointestinal-intestinal [GI] perforation). Moderate diabetic foot infections without osteomyelitis. Moderate surgical site infections following contaminated procedures. Pelvic Inflammatory disease. Urinary tract infections due to ESBL producing organisms (not severe infections). Note: Ertapenem is not recommended for severe infections in which Pseudomonas spp. are suspected. Daptomycin Daptomycin is a lipopeptide antibiotic. 13 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 It has activity against most strains of staphylococci and streptococci (including MRSA and Vancomycin-Resistant Enterococci [VRE]. Daptomycin does NOT have activity against Gram-negative organisms. Indications: All cases need to be discussed and approved by the infectious diseases and/or antimicrobial stewardship team Bacteraemia or endocarditis due to MRSA or coagulase-negative staphylococci (CoNS) in a patient with serious allergy to vancomycin. Bacteraemia or endocarditis due to MRSA in a patient failing vancomycin therapy as defined by: o Clinical decompensation after 3–4 days. o Failure to clear blood culture after 7 days despite maintaining vancomycin level at 15–20 mcg/ml. o Vancomycin minimum inhibitory concentration (MIC) is 2 mcg/ml. Treatment of VRE infections. Daptomycin is NOT indicated for: Pneumonia as it is inactivated by the pulmonary surfactant. Initial therapy of Gram-positive infections. VRE colonization of the urine, drains, wounds or sputum. Fosfomycin Fosfomycin is a synthetic, broad-spectrum, bactericidal antibiotic with in vitro activity against large number of Gram-negative and Gram-positive organisms including E. coli, Klebsiella spp., Proteus spp., Pseudomonas spp., and VRE. It does not have activity against Acinetobacter spp. Indications: Management of uncomplicated UTI in patients with history of antibiotic allergies and/or when no other oral therapy options are available. Uncomplicated UTI due to VRE. Salvage therapy of UTI due to MDR Gram-negative organisms. Susceptibility to fosfomycin should be confirmed prior to initiation of therapy Antifungals Liposomal amphotericin B Indications: 14 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 Cryptococcal meningitis in HIV-infected patients: treatment of cryptococcal meningitis in HIVinfected patients. Fungal infections, empiric therapy: empiric treatment in febrile neutropenic patients with presumed fungal infection. Fungal infections, systemic therapy: treatment of systemic infections caused by Aspergillus spp., Candida spp., and/or Cryptococcus spp. in patients refractory to conventional amphotericin B deoxycholate therapy or when renal impairment or unacceptable toxicity precludes the use of the deoxycholate formulation. Leishmaniasis (visceral): treatment of visceral leishmaniasis. Note: Lipid-based amphotericin formulations (AmBisome) may be confused with conventional formulations (desoxycholate [Amphocin, Fungizone]) or with other lipid-based amphotericin formulations (amphotericin B lipid complex [Abelcet], amph. Lipid-based and conventional formulations are not interchangeable and have different dosing recommendations. Overdoses have occurred when conventional formulations were dispensed inadvertently for lipid-based products. Usual (Adult) dosage range: IV: 3 to 6 mg/kg/day. Note: Premedication: For patients, who experience non-anaphylactic immediate infusion-related reactions, pre-medicate with the following drugs 30 to 60 minutes prior to drug administration: A nonsteroidal anti-inflammatory agent ± diphenhydramine; OR acetaminophen with diphenhydramine; OR hydrocortisone. Caspofungin Indications: Treatment of invasive Aspergillus infections in patients who are refractory or intolerant of other therapies. Treatment of Candidaemia and other Candida infections (intra-abdominal abscesses, peritonitis, pleural space). Empirical treatment for presumed fungal infections in febrile neutropenic patients. Voriconazole Oral voriconazole is approximately 96% bioavailable. For this reason, it is recommended that oral voriconazole be used whenever possible. 15 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 Indications: Primary treatment of pulmonary Aspergillus. Primary treatment of amphotericin B and fluconazole resistant fungal infections (including Fusarium spp. and Scedosporium apiospermum - asexual form of Pseudoallescheria boydii). Treatment of invasive fungal infections in patients who are intolerant of, or refractory to, other antifungal therapy. Posaconazole Restricted to ID consultant only. Indications: Prophylaxis of invasive Aspergillus and Candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised (e.g., hematopoietic stem cell transplant [HSCT] recipients with graft-versus-host disease [GVHD] or those with prolonged neutropenia secondary to chemotherapy for haematologic malignancies). Off-label indications: Treatment of invasive aspergillosis (refractory to or intolerant of conventional therapy). Mucormycosis. Refractory or relapsed invasive fungal infections (salvage therapy). 6. Intravenous (IV) to oral (PO) antibiotic conversion This describes the practice of converting intravenous antimicrobial therapies to effective alternative oral formulation. Several clinical trials have been conducted that demonstrate the efficacy and safety of IV to PO antimicrobial conversion, and several studies have also addressed the economic impact of this conversion. Cost savings are achieved through lowering direct acquisition costs, eliminating the need for ancillary supplies, reducing pharmacy and nursing time, and shortening the length of hospital stay. Intravenous to oral antimicrobials conversion also benefits the patient by eliminating adverse events associated with IV therapy, increasing patient comfort and mobility, and increasing the possibility of earlier discharge. Conversion to oral therapy also reduces the risk of adverse effects associated with intravascular lines like catheter‐related bloodstream infection (CRBSI) and thrombophlebitis. For examples of antimicrobials that can be included in IV to PO therapy conversion and bioavailability of selected antimicrobials available in both IV and PO formulations, please refer to Table (c). 16 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 Table : Bioavailability of selected antibiotics available in both IV and PO formulations 80% to 100% Ciprofloxacin Clindamycin Doxycycline Fluconazole Linezolid Metronidazole Moxifloxacin Sulfamethoxazole/trimethoprim Azithromycin (<50%: although azithromycin has a low bioavailability, it is well‐distributed into tissues) Table (c) Criteria used to determine patients for IV to PO therapy conversion: 1. Intact and functioning gastrointestinal (GI) tract as evidenced by: Patient is tolerating food, fluids or enteral feeds Patient is receiving other oral medications No nausea, emesis or diarrhoea in the past 24 hours 2. Criteria indicating absorption of oral medications may be compromised: Nil by mouth status (and no medications are being administered orally) Nasogastric (NG) tube with continuous suction Severe/persistent nausea or vomiting Gastrointestinal transit time too short for absorption such as malabsorption syndromes, partial or total removal of the stomach, short bowel syndrome Active upper gastrointestinal bleeding High doses of vasopressor medications (typically in persistent hypotension despite high dose of vasopressor) Difficulty swallowing or loss of consciousness and no NG access available Documented ileus or gastrointestinal obstruction Continuous tube feedings that cannot be interrupted and patient requires a medication known to bind to enteral nutrition formulas 3. Improving clinical status: The patient should be clinically stable and deterioration should not be expected Should be afebrile or have had a maximum temperature of less than 38°C in the previous 24 hours White blood cell (WBC) count should be trending downward. It is important to examine the patient’s medication therapy for other medications that can cause an increase or sustained high WBC count such as steroids It is also important to review the cultured pathogen (bacteria, fungus, etc.) and ensure that it is susceptible to the oral medication 17 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 4. Does not meet any of the following exclusion criteria: Endocarditis Central nervous system infections (e.g. meningitis, brain abscess, etc.) Orbital cellulitis Osteomyelitis Endophthalmitis Melioidosis (at least 10 to 14 days of IV therapy) Abscesses Patients who are neutropenic are typically excluded from IV to PO therapy conversion Table(d): Antimicrobials IV-PO conversion equivalent doses Antimicrobials Parenteral IV dose PO equivalent dose Comments Azithromycin 500 mg IV daily 500 mg daily With and without food for the tab suspension: take 1 hr before or 2 hrs after food Cefuroxime * 750–1500 mg IV Q8hrs 500 mg PO Q12 hrs Ciprofloxacin * 400 mg IV q8hrs 400 mg IV q12 hrs 400 mg IV q24 hrs 750 mg PO q12hrs 500 mg PO q12 hrs 500 mg PO q24 hrs Moxifloxacin 400 mg IV daily 400 mg PO daily Clindamycin 600 mg IV q8 hrs 300 mg PO q6 hrs OR 600 mg q8 hrs for severe skin infections Doxycycline 100 mg IV q12 hrs With or without 100 mg PO q 12 hrs 18 Give 2 hrs before calcium, iron or dairy products -Not for patients with continuous enteral feeding or jejunostomy tube -stop tube feeding 2 hrs before and 2 hrs after administration** With or without food Take 1 hour (hr) before or 2 hrs after meals NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 Linezolid 600 mg IV q12 hrs 600 mg PO q12 hrs Metronidazole* 500 mg IV q 8-12 hrs 500 mg PO q 8-12 hrs Fluconazole IV dose daily Same dose PO daily Avoid tyramine rich Foods e.g chocolate, cheese, yoghurt, shrimp * Not affected by food (1:1 conversion) (patients with Candidaemia or disseminated candidiasis, keep IV) Note: *Consider renal dosing for patients with renal impairment ** Patients with feeding tubes: tubes should be flushed with water both before and after Medication administration 7. Performance measures: The compliance with this guide and policy will be monitored by specific activities such as audit and feedback. Antimicrobials bundle of care audit tool: 1. Life-threatening conditions 1.1 Median time from first clinical contact to the first dose of antibiotics for patients with suspected bacterial meningitis or for patients with suspected sepsis. 2. Use of antimicrobial guidelines and clinical conditions 2.1 Proportion of antibiotic prescriptions that are in accordance with guidelines. 3. Documentation 3.1 Rate of documentation of clinical indications (reason) for prescribing antibiotics. 4. Use of broad-spectrum antibiotics 19 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 4.1 Proportion of patient prescriptions of broad-spectrum antibiotics for which a medical review is documented within 72 hours from first prescription. 5. Surgical prophylaxis 5.1 Proportion of patients for whom surgical prophylactic antibiotics were prescribed in accordance with guideline. 5.2 Proportion of patients who are administered indicated prophylactic antibiotics within 30–60 minutes prior to surgical procedure. 5.3 Proportion of patients whose prophylactic antibiotics were discontinued within 24 hours after surgery or 48 hours after cardiac surgery. 20 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 1: GUIDELINES FOR TREATMENT OF RESPIRATORY INFECTIONS IN ADULTS ANATOMIC SITE/ DIAGNOSIS ETIOLOGIES RESPIRATORY SYSTEM Acute Usually viral bronchitis M. pneumoniae 5%, C. pneumoniae 5% Pertussis B. pertussis, B. parapertussis SUGGESTED REGIMENS FIRST LINE COMMENTS SECOND LINE Supportive care No antibiotics are indicated If persistent fever and cough do chest x-ray (CXR) Azithromycin 500 mg day 1 then 250 mg q24 hr days 2-5 Erythromycin 500 mg 4 times a day (QID) x 14 days OR Clarithromycin twice a day (BID) X 7 days OR Prophylaxis of household or close contacts is indicated as per treatment regimens TMP-SMX (1 DS tab q12h for 14 days) is an alternative if macrolides resistance is expected (Persistent cough >14 days, afebrile 10–20% of adults will have pertussis) 21 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 1: GUIDELINES FOR TREATMENT OF RESPIRATORY INFECTIONS IN ADULTS ANATOMIC SITE/ DIAGNOSIS ETIOLOGIES SUGGESTED REGIMENS FIRST LINE RESPIRATORY SYSTEM Acute Bacterial Viruses causes 20– Exacerbation of 50%, Chronic Bronchitis C. pneumoniae , (ABECB) M. pneumonia, H. influenzae, S. pneumoniae, M. catarrhalis, Gram-negative enteric organisms Risk factors for Pseudomonas: Recent hospitalization (within 3 months), frequent administration of antibiotics (≥4 courses in past year), isolation of Pseudomonas in previous exacerbation, systemic steroids use, colonization with Pseudomonas during stable disease, FEV1<50%. SECOND LINE Role of antibiotics is debated. However recent evidence showed benefit in patients hospitalized with severe disease. -Mild disease: Amoxicillin 500 mg PO 3 times daily (TID) OR Cotrimoxazole 1 DS tab BID, OR Doxycycline100 mg BID, OR Cefuroxime 500 mg PO BID. - Moderate or severe disease And no risk of Pseudomonas amoxicillin-clavulanate plus azithromycin OR clarithromycin OR fluoroquinolone (FQ) with enhanced activity against pneumococci (moxifloxacin, levofloxacin [levo]) -if Risk for Pseudomonas : IV FQ (levo) OR tazocin. 22 COMMENTS Severe: increased dyspnea, sputum viscosity and volume, FEV1 <50%, >4 exacerbations in the last 12 months, Home O2, Coronary artery disease or heart failure, chronic steroid use, antibiotics in the last 3 months Consider: 1) CXR esp. if febrile or has low O2 sat 2) inhaled bronchodilators 3) corticosteroids taper over 2 weeks 4) stop smoking 5) non-invasive positive pressure ventilation NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 1: GUIDELINES FOR TREATMENT OF RESPIRATORY INFECTIONS IN ADULTS ANATOMIC SITE/ DIAGNOSIS Bronchiectasis ETIOLOGIES H. influenzae, P. aeruginosa, S. pneumoniae SUGGESTED REGIMENS FIRST LINE SECOND LINE COMMENTS Levo 500 q24h, OR moxifloxacin 400 mg q24h Prevention: consult respiratory/chest physician Community-acquired pneumonia prognosis prediction using CURB65 criteria(C=confusion, U=urea >7.5 mmol/L, R=RR ≥30,B=SBp <90 or DBp ≤60,Age ≥65.) Score: - 0–1 (mortality 1.5%) treat as outpatient. - 2 (mortality 9.2%) admit to medical ward. - 3 or more (mortality 22%) consider admission to ICU. NB: clinical judgment should be used for all patients. -Obtain appropriate cultures -Start empirical influenza treatment during flu season and look for S. aureus CAP, Outpatient Outpatient : Previously healthy and no use of antimicrobials within the S. pneumoniae, previous 3 months: M. pneumoniae, Amoxicillin 1 gm TID PLUS clarithromycin 500 mg BID PO H. influenzae, OR C. pneumoniae, respiratory FQ (levo OR moxifloxacin) Respiratory viruses OR Doxycycline 200 mg PO stat then 100 mg BID for 7 days. Presence of comorbidities such as chronic heart, lung, liver or renal disease; diabetes mellitus; alcoholism; malignancies; asplenia; immunosuppressing conditions or drugs; OR use of antimicrobials within the previous 3 months (in which case an alternative from a different class should be selected): Amoxicillin high dose (1 g q8h) (OR amoxicillinclavulanate) PLUS a macrolide (clarithromycin /azithromycin). OR a respiratory FQ (Moxifloxacin 400 mg q24h OR levo (750 mg) q24h. 23 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 1: GUIDELINES FOR TREATMENT OF RESPIRATORY INFECTIONS IN ADULTS ANATOMIC SITE/ DIAGNOSIS CAP, In-patient (nonICU): CAP In-patient (ICU): Aspiration pneumonia +/-lung abscess Empyema ETIOLOGIES S. pneumoniae, M. pneumoniae, C. pneumoniae, H. influenzae, Legionella spp., Respiratory viruses SUGGESTED REGIMENS COMMENTS FIRST LINE SECOND LINE IV AMP (OR amoxicillin-clavulanate) PLUS IV azithromycin OR clarithromycin OR Respiratory fluoroquinolone (levo 750 mg IV q24h OR moxifloxacin 400 mg IV q24h. S. pneumoniae, S. aureus, Legionella spp., Gram-negative bacilli H. influenzae Ceftriaxone plus either macrolide OR a respiratory fluoroquinolone (for penicillin [pen]-allergic patients, a respiratory fluoroquinolone is recommended). Special concerns -If pseudomonas is a consideration (see above): piperacillin-tazobactam OR cefepime plus levo (750 mg once daily ) -If community-associated methicillin-resistant S. aureus (CAMRSA) is a consideration, add vancomycin (vanco) OR linezolid Anaerobes 34%, Clindamycin 600 Ceftriaxone 1g IV Gram-positive mg IV q8h q24h plus metro cocci 26%, S. milleri 500 mg IV q6hOR 16%, K. Piperacillinpneumoniae 25%, Tazobactam 4.5 g Nocardia spp.3% IV q8h S. pneumoniae. Clindamycin 600 Ceftriaxone 1 g IV Diagnostic Group A Strept, mg IV q8h PLUS q24h plus metro thoracentesis and S. aureus, (Ceftriaxone 1 g IV 500 mg IV q6h OR chest tube for H. influenzae, q24h OR cefepime 1 g IV q12h drainage coliforms, IV 2 g q12h) anaerobes OR PIP-TAZ 4.5 g IV q8h 24 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 1: GUIDELINES FOR TREATMENT OF RESPIRATORY INFECTIONS IN ADULTS ANATOMIC SITE/ DIAGNOSIS ETIOLOGIES SUGGESTED REGIMENS Pneumonia with fever, night sweats and weight loss Cystic fibrosis, pulmonary exacerbation To rule out pulmonary TB Refer to national TB guidelines S. aureus and H. influenzae early in disease P. aeruginosa later in disease B. cepacia Non-tuberculous mycobacteria is emerging important pathogen Tobramycin + piperacillin/ tazobactam . for methicillinsensitive S. aureus (MSSA) use cloxacillin. For MRSA use vanco. For B. cepacia: TMP-SMX (Septrin) FIRST LINE COMMENTS SECOND LINE Tobramycin + Ceftazidime If P.aeruginosa resistant then Ciprofloxacin OR levo can be used if P.aeruginosa is susceptible. Consult ID/Chest Physician to streamline therapy. References: 1. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, et al. IDSA/ATS guidelines for CAP in adults. CID 2007;44(Suppl 2):S27–S72. 2. Rothberg MB, Pekow PS, Lahti M, Brody O, Skiest DJ, Lindenauer PK. Antibiotic therapy and treatment failure in patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease. JAMA 2010;303(20):2035– 42. 25 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 2: GUIDELINES FOR TREATMENT OF EAR, NOSE AND THROAT INFECTIONS The microbial flora of the external canal is similar to the flora of skin elsewhere. There is predominance of S. epidermidis, S. Aureus, Corynebacterium, and, to a lesser extent, anaerobic bacteria such as P. acnes. Pathogens responsible for infection of the middle ear (S. pneumoniae, H. influenzae, or M. catarrhalis) are uncommonly found in cultures of the external auditory canal when the tympanic membrane is intact). ANATOMIC SITE/DIAGNOSIS ETIOLOGIES SUGGESTED REGIMENS FIRST LINE COMMENTS SECOND LINE Chronic Otitis Externa Usually due to seborrhoea Eardrops (polymyxin B+ neomycin+ hydrocortisone QID) + selenium sulphide shampoo Otitis Externa Fungal Candida spp. Clotrimazole ear drops BID for 10–14 days then reassess Fluconazole 200 mg PO one dose & then 100 mg PO once daily for 3–5 days Oral therapy is given in refractory cases were no response to topical antifungals Otitis Externa Malignant P. aeruginosa >95% early in the disease: S. aureus Cip 750 mg PO q8–12 h Piperacillintazobactam 4.5 g IV q8h OR Meropenem 1 g IV q8h OR any other antipseudomonal ± aminoglycoside R/O osteomyelitis by computed tomography (CT) or MRI scans. If bone involved treat for 6– 8 weeksConsult ENT specialist 26 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 2: GUIDELINES FOR TREATMENT OF EAR, NOSE AND THROAT INFECTIONS ANATOMIC SITE/DIAGNOSIS Acute Otitis Media ETIOLOGIES Commonly caused by viral infection (70%) Bacterial: S. pneumoniae H. influenzae , M. Cattarhalis, rarely S. aureus, S. pyogenes Acute mastoiditis Require inpatient therapy Chronic mastoiditis First episode: S. pneumoniae, H. influenzae, M. cattarhalis Secondary to chronic otitis media: S. aureus, P. aeruginosa, S. pneumoniae Often polymicrobial (Gram-positive, enterobacteriaceae and Pseudomonas) SUGGESTED REGIMENS FIRST LINE SECOND LINE Mild to moderate disease : amoxicillin PO 500 mg every 12 hrs, OR 250 mg every 8 hrs Cefuroxime 500 mg q12 hrs OR clarithromycin 500 mg BID x 10 days Severe disease: amoxicillinclavulanate 875 mg every 12 hrs IV ceftriaxone 2 gm IV once daily Levo 750 mg IV once daily ENT consultation. Obtain cultures, treat for acute exacerbations or preoperatively 27 COMMENTS Duration of treatment: <2 yrs: 10 days >2 yrs: 5–7 days Antibiotics to be modified by availability of cultures and susceptibility CT or MRI for diagnosis. ENT consultation for surgical intervention and management of complications Diagnosis: CT or MRI NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 2: GUIDELINES FOR TREATMENT OF EAR, NOSE AND THROAT INFECTIONS Acute Sinusitis: It is generally not possible to distinguish acute viral from bacterial rhinosinusitis in first 10 days, based on history, examination or radiologic study. Since acute viral rhinosinusitis is expected to resolve within 10 days, and acute bacterial rhinosinusitis may also resolve spontaneously within the first 10 days, patients who present with fewer than 10 days of symptoms in general should be managed with supportive care. Exceptions would be patients who experience clinical worsening after initial improvement, patients with severe symptoms and clearly worsening clinical course, and immunocompromised patients. ANATOMIC SITE/DIAGNOSIS Acute Sinusitis ETIOLOGIES S. pneumonia, H. influenzae, Viral, M. catarrhalis, S. aureus, SUGGESTED REGIMENS FIRST LINE SECOND LINE Amoxicillin 1 g q8 hrs. Amoxicillinclavulanate (extended release) 1000/62.5 Mg BID Anaerobes: S. pyogenes OR Levo 750 mg PO q24h x 5 days 28 COMMENTS Pen allergy: Alternative first line therapy, narrow spectrum antibiotics include: trimethoprim/ sulfamethoxazole OR erythromycin OR azithromycin OR doxycycline. NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 2: GUIDELINES FOR TREATMENT OF EAR, NOSE AND THROAT INFECTIONS Chronic sinusitis: there is limited evidence that antibiotics, as a single therapy, are beneficial in the treatment of chronic sinusitis. Instead, a comprehensive approach to medical management, which includes antimicrobials combined with topical or systemic glucocorticoids, and sometimes other agents, is now encouraged. ANATOMIC SITE/DIAGNOSIS Chronic sinusitis Allergic Infective Dental ETIOLOGIES SUGGESTED REGIMENS FIRST LINE Anaerobes: Prevotella spp., Streptococcus spp., Fusobacterium spp. Aerobes: Streptococcus spp. ENT consultation, If antibiotics needed: amoxicillinclavulanate 875 mg PO BID COMMENTS SECOND LINE Clindamycin 300 mg QID Treatment should be continued for at least 3 weeks Clindamycin 300–450 mg PO q6–8h x 5days OR erythromycin 500 mg QID x 10 days If pen-allergic: clindamycin OR erythromycin Idiopathic H. influenzae, P. aeruginosa, Enterobacteriaceae: S. aureus, M. catarrhalis Pharyngitis / tonsillitis Avoid antibiotics as 90% resolve in 7 days without antibiotics Commonly viral EBV (Infectious mononucleosis) Pen V 500 mg PO BID OR 250 mg PO QID x 10 days Streptococcus spp. (group A,C,G) If compliance is unlikely give benzathine pen intramuscular (IM) x 1.2 million unit once only Other causes: Primary HIV C. diphtheria, A. hemolyticum, (rare)M.pneumoniae, F. Necrophorum. 29 OR cefuroxime 250 mg BID x 5 days NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 3: GUIDELINES FOR TREATMENT OF EYE INFECTION CONDITION External hordeolum/ Chalazion SUSPECTED ORGANISM Non (common) Staphylococcus (if associated preseptal cellulitis) TREATMENT Frequent hot compresses topical antibiotic/corticesteroid ointment combination (may benefit) ALTERNATIVE TREATMENT Referred to an ophthalmologist for incision and curettage OR direct glucocorticoid injection COMMENTS If there is concurrent preseptal cellulitis, oral antibiotics with Staphylococcal coverage are appropriate Blepharitis Aetiology unclear. Factors include Staphylococcus, seborrhoea, rosacea & dry eye. Lid margin care with baby shampoo & warm compresses q24h. Artificial tears if dry eye. Erythromycin ointment. Tetracycline ointment. Fucithalmic eye drops for 5–7 days If associated in chronic or refractory cases or rosacea, add doxycycline 100 mg PO bid for 2 weeks. Consult ophthalmologist Acute bacterial conjunctivitis S. epidermidis, S. aureus, S. pneumoniae, H. influenzae . Ofloxacin eye drops Gentamicin ointment for 5–7 days Eye washes with warm water (saline). Add systemic antibiotics. If extraocular involvement refer to ophthalmologist Viral conjunctivitis (pink eye) Adenovirus No treatment. If symptomatic, cold artificial tears may help. If membrane or pseudo membrane is present add mild steroid Viral keratoconjunctivitis herpes simplex TRifluridine virus (HSV), types ophthalmic solution, 1&2 one drop q2h up to 9 drops/day until reepithelialized, then 1 drop q4h up to 5 x days for total not to exceed 21 days Tetracycline ointment 30 Acyclovir ointment (30 mg) Five times a day at approximately 4 hourly intervals. Treatment should be continued for 14 days Highly contagious. Onset of ocular pain and photophobia in an adult suggests associated keratitis Consult ophthalmologist Topical Antibiotics to prevent infection can be considered. Alternate mild steroid & Artificial tears can be added NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 3: GUIDELINES FOR TREATMENT OF EYE INFECTION CONDITION SUSPECTED ORGANISM TREATMENT ALTERNATIVE TREATMENT COMMENTS Varicella zoster ophthalmicus VZV Valacyclovir 1 g PO q8h for 10 days Acyclovir 800 mg PO 5 x day for 10 days Inclusion Chlamydial conjunctivitis C. trachomatis Azithromycin 1 gm once Doxycycline once daily (OD) capsule 100 mg for 7 days Gonococcal conjunctivitis N. gonorrhoeae Ceftriaxone 1 g IM OR IV one dose AND azithromycin 1 gm once to cover for presumptive chlamydial coinfection. Trachoma C. trachomatis Azithromycin 1 g PO single dose Doxycycline caps 100 mg BID x 21 days. Tetracycline 250 mg PO QID for 14 days Topical therapy is of marginal benefit Fungal keratitis Aspergillus spp., fusarium spp., Candida spp. and others Amphotericin B 1 drop every 1–2 hrs for several days Consult ophthalmologist, obtain appropriate cultures, practice good hygiene and cleaning Bacterial keratitis S. aureus, S. pneumoniae, S. pyogenes, Haemophilus Natamycin 1 drop every 1–2 hrs for several days, then q3– 4h for several days -Voriconazole 1% eye solution hourly taper to 4 hourly for 4–6 weeks Moxifloxacin ophthalmic 0.5% 1 drop q1h for the first 48 hrs and then taper according to response. Fortified gentamicin / cefuroxime OR vanco eye drops hourly with tapering according to clinical response Consult Ophthalmologist, obtain appropriate cultures, practice good hygiene and cleaning Pseudomonas aeruginosa (contact lens wearer) Cip 0.3% ophthalmic drops 31 Consult ophthalmologist NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 3: GUIDELINES FOR TREATMENT OF EYE INFECTION CONDITION SUSPECTED ORGANISM TREATMENT ALTERNATIVE TREATMENT Orbital cellulitis S. pneumoniae, H. influenzae, M. catarrhalis, S. aureus, anaerobes, group A Strept, occasionally Gramnegative organisms. Ceftriaxone 2 g IV OD in adults q24h PLUS metronidazole adult 500 mg IV q6– 8h Topical erythromycin eye ointment. If allergic to pen: levo 750 mg IV OD and Metronidazole 500 mg IV q6–8h if MRSA DD vanco IV 1.5 mg/kg q12h Necrotizing herpetic retinopathy (ARN/PORN) Varicella zoster virus HSV type 2 Acyclovir IV 10–12 mg/kg q8h for 1–2 weeks then famciclovir 500 mg PO TID OR valacyclovir 1000 mg PO q8h OR acyclovir 800 Mg PO q8h ganciclovir/ valganciclovir Consult ophthalmologist and infectious disease physician intravitreal vanco 1 mg/0.1 ml and either, ceftazidime 2 mg/0.1 ml OR Amikacin 0.4 mg/0.1 ml Then topical third or fourth generation of fluoroquinolones PLUS oral cip 750 mg BID or IV injection Ceftriaxone 1 g BID Immediate ophthalmic consults Rarely CMV Postoperative endophthalmitis Most common: S. epidermidis, S. aureus, Streptococcal spp. less common Gram-negative bacteria: Pseudomonas, Haemophilus, Klebsiella, E. coli 32 COMMENTS NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 3: GUIDELINES FOR TREATMENT OF EYE INFECTION CONDITION Traumatic endophthalmitis Endogenous Bacterial Endophthalmitis SUSPECTED ORGANISM Bacillus spp. , S. epidermidis Gram-negative B. cereus (especially in IV drug abuse), streptococci, N. meningitidis, S. aureus, H. influenzae TREATMENT Topical fortified tobramycin q1h with fortified cefazolin OR fortified vanco. Systemic antibiotic cip 400 mg IV q12h and clindamycin 600 mg IV q8h. Intravitreal ceftazidime 2 mg/0.1 ml OR amikacin 0.4 mg/0.1 ml and vanco 1 mg/0.1 ml OR clindamycin 1 mg/0.1 may be repeated every 48–72 hrs Intravitreal amikacin 0.4 mg/0.1 ml OR Ceftriaxone 2 mg/0.1 ml and vanco 1 mg/0.1 ml OR Clindamycin 1 mg/0.1 ml 33 ALTERNATIVE TREATMENT Systemic antibiotic is recommended and should be given at least for 2 weeks depending on blood culture COMMENTS NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 4: GUIDELINES FOR TREATMENT OF INFECTIVE ENDOCARDITIS AND RELATED INFECTIONS ANATOMIC SITE/DIAGNOSIS Infective endocarditis: native valve-empirical Rx awaiting cultures-No IV illicit drugs, valvular or congenital heart disease but no modifying circumstances Infective endocarditis: Native valve- IV illicit drug use +/- evidence right-sided endocarditis-empirical therapy ETIOLOGIES Viridans streptococci 30– 40%, Other Strep. 15– 25%, enterococci 5– 18%, staphylococci 20– 35% including CoNS S. aureus (MSSA & MRSA). All others rare SUGGESTED REGIMENS FIRST LINE SECOND LINE Pen G 20 million Vanco 15-20 units IV divided mg/kg IV q12h, q4h OR AMP 12 not to exceed 2 gm IV /day g q24h unless divided q4h + serum level Fucloxacillin2 g monitored. Aim IV q4–6h (use for vanco target q4h regimen if trough level 15– weight >85 kg) + 20 mcg/ml + gentamicin 1 gentamicin 1 mg/kg IV q8h mg/kg IV q8h Vanco 15–20 mg/kg q 12 hrs IV divided in 2–3 doses to achieve target trough concentration of 15–20 mcg/ml, recommended for serious infections 34 Dapto 6 mg/kg IV q24h, approved for right-sided endocarditis COMMENTS If patient not acutely ill and not in heart failure, we prefer to wait for blood culture results. If initial 3 blood cultures negative after 24–48 hrs, obtain 2–3 more blood cultures before empiric therapy started. If acutely ill and high risk for MRSA, add vanco to first line till cultures are available or patient cannot tolerate pen -Consult ID NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 4: GUIDELINES FOR TREATMENT OF INFECTIVE ENDOCARDITIS AND RELATED INFECTIONS ANATOMIC SITE/DIAGNOSIS ETIOLOGIES Infective endocarditis: Native valve-culture positive viridians streptococci, S. bovis (S. gallolyticus) with pen G MIC <0.1 mcg/ml Viridans streptococci, S. bovis Infective endocarditis-Native valve-culture positive viridians streptococci, S. bovis (S. gallolyticus) with pen G MIC >0.1 to <0.5 mcg/ml SUGGESTED REGIMENS COMMENTS FIRST LINE Pen G 12–18 million units/day IV divided q4h x 2 weeks + gentamicin 1 mg/kg q8h IV x 2 weeks OR pen G12–18 million units/day IV divided q4h x 4 weeks SECOND LINE Ceftriaxone 2g IV q24h x 4 weeks. Viridians streptococci, S. bovis, nutritionally variant streptococci, (e.g. S. abiotrophia) tolerant streptococci. Pen G 18–24 million units/day IV divided q4h x 4 weeks) + (gentamicin 1 mg/kg IV q8h x 2 weeks) Note: low dose of gentamicin Vanco 15 mg/kg IV q12h to 2 g/day max unless serum levels measured x 4 weeks For viridians streptococci, S. bovis with pen G MIC >0.5 and enterococci susceptible to AMP/pen G, vanco, gentamicin Note: ID consultation suggested “Susceptible” enterococci, viridians streptococci, S. bovis, nutritionally variant streptococci Pen G 18–30 million units/24h IV, divided q4h x 4–6 weeks + gentamicin 1–1.5 mg/kg IV q8 hr IV x 4–6 weeks OR AMP 12g/day IV, divided q4h +gentamicin (as above)for 4–6 weeks Vanco 15 mg/kg IV q12h to 2 g/day max unless serum levels measured plus gentamicin 1–1.5 mg/kg q8h IV for 4–6 weeks Note: low dose of gentamicin Vanco for penallergic patients. Do not use cephalosporin. Enterococci: MIC streptomycin >2000 mcg/ml; MIC gentamicin >500– 2000 mcg/ml; no resistance to pen Enterococci, high-level aminoglycosi de resistance AMP 12g/day IV divided q4h PLUS ceftriaxone 2 g IV q12h for 8 weeks Prolonged pen G OR AMP for 8–12 weeks OR AMP plus dapto If prolonged Rx fails consider surgical removal of the valve 35 OR Ceftriaxone2 g IV q24h + gentamicin IV 1 mg/kg q8h IV x 2 weeks Always ensure that MICs are provided by the microbiology lab. Target gent levels peak 3 mcg/ml, trough gent level <1mcg/ml). If allergy with pen: use vanco 15 mg/kg IV q12h to 2 g/day max unless serum levels measured x 4 weeks NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 4: GUIDELINES FOR TREATMENT OF INFECTIVE ENDOCARDITIS AND RELATED INFECTIONS ANATOMIC SITE/DIAGNOSIS ETIOLOGIES SUGGESTED REGIMENS Enterococci: pen G MIC >16 mcg/ml; no gentamicin resistance Enterococci, intrinsic pen G /AMP resistance Vanco 15 mg/kg IV q12h (check levels if >2 g) PLUS gentamicin 1– 1.5 mg/kg q8h for 6 weeks. See comment. Desired vanco serum levels trough 10–15 mcg/ml. Gent used for synergy; peak levels need not exceed 4 mcg/ml. Enterococci: Pen/AMP resistance + high-level gent/Strept. resistance + vanco resistance, usually VRE ID consultation required Enterococci, vancoresistant, usually E. faecium No reliable effective therapy: linezolid 600 mg IV OR PO q12h OR dapto-see comment Quinupristin/dalfopristi n activity limited to E. faecium and is usually bacteriostatic, therefore expect high relapse rate. Dose: 7.5 mg/kg IV (via central line) q8h. Linezolid active against most enterococci, but bacteriostatic. Dose: 600 mg IV OR PO q12h. Linezolid failed in patients with E. faecalis endocarditis. Dapto is bactericidal in vitro; clinical experience in CID 41:1134, 2005. Native valve staphylococcal endocarditis MSSA S. aureus, methicillinsensitive Flucloxacillin 2 g IV q4–6h (Use q4h regimen if weight >85 kg) x 4–6 weeks FIRST LINE 36 COMMENTS SECOND LINE Teicoplanin active against a subset of vanco-resistant enterococci: 6 mg/kg (~400 mg) I.V. on the first day, followed by 6 mg/kg I.V. OD thereafter. For more severe infections: 6 mg/kg (~400 mg) I.V. given every 12 hrs for 3 doses, followed by 6 mg/kg/day; doses up to 12mg/kg/day may be used OR dapto: I.V.: 6 mg/kg OD for 2–6 weeks Cefazolin 2 g IV q8h x 4–6 weeks If pen allergy : vanco 15 mg/kg IV q12h. Check level if >2 g/day x 4–6 weeks. NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 4: GUIDELINES FOR TREATMENT OF INFECTIVE ENDOCARDITIS AND RELATED INFECTIONS ANATOMIC SITE/DIAGNOSIS ETIOLOGIES Native valve staphylococcal endocarditis MRSA, ID consultation required S. aureus, methicillinresistant Slow-growing fastidious Gramnegative bacilli in any valve A group of Gramnegative bacteria that includes Haemophilus spp. (HACEK) group (see comments). SUGGESTED REGIMENS FIRST LINE Vanco 30–60 mg/kg per day divided into 2–3 doses to achieve target trough concentration 15– 20 mcg/ml recommended for serious infections For 6 weeks SECOND LINE Dapto 6–10 mg/kg OD Ceftriaxone 2 g IV q24h x 4 weeks If penicillinasenegative, cip 1000 mg/24h PO OR 800 mg/24 h IV in 2 equally divided doses. Fluoroquinolone therapy recommended only for patients unable to tolerate cephalosporin and AMP therapy 37 COMMENTS Note: dapto is not Food and Drug Administration (FDA) approved for left sided endocarditis, can cause muscle toxicity. Need to monitor creatinine kinase regularly Penicillinase positive HACEK should be susceptible to AMSB plus gentamicin HACEK (acronym for H. parainfluenza, H. aphrophilus (Aggregatiba-cter, Actinobacillus), Cardiobact-erium, Eikenella, Kingella). AM-SB plus gentamicin. Patients with endocarditis involving prosthetic cardiac valve or other prosthetic cardiac material should be treated for 6 weeks NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 4: GUIDELINES FOR TREATMENT OF INFECTIVE ENDOCARDITIS AND RELATED INFECTIONS ANATOMIC SITE/DIAGNOSIS ETIOLOGIES SUGGESTED REGIMENS FIRST LINE COMMENTS SECOND LINE Bartonella species-any valve B. henselae, B. quintana Ceftriaxone 2 g IV q24h x 6 weeks + gentamicin 1 mg/kg q8h x 14 days + doxy 100 mg IV PO bid x 6 weeks Patients with Bartonella endocarditis should be treated in consultation with an ID specialist If gentamicin is not tolerated, Rifampicin (Rif) 300 mg IV PO bid for 14 days can be used. If doxy is not tolerated, azithromycin 250 mg PO OD can be used Infective endocarditis: Prosthetic valve empiric therapy (culture pending): -Early (<2 months postop) -Late (>2 months postop) S. aureus, S. epidermidis, Rarely, Enterobacteriaceae , diphtheroids, fungi S. epidermidis, viridians streptococci, enterococci, S. aureus. Vanco 15–20 mg/kg IV q12h + gentamicin 1 mg/kg IV q8h + Rif 600 mg IV/PO q24h Surgical and ID consultations 38 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 4: GUIDELINES FOR TREATMENT OF INFECTIVE ENDOCARDITIS AND RELATED INFECTIONS ANATOMIC SITE/DIAGNOSI S Infective endocarditis: Prosthetic valve-positive blood culture: ETIOLOGIES SUGGESTED REGIMENS FIRST LINE SECOND LINE S. epidermidis, Vanco 15–20 mg/kg IV q12h + Rif 300 mg PO q8h X 6 weeks + gentamicin 1 mg/kg IV q8h X 14 days. S. aureus, Methicillin-sensitive (flucloxacillin 2 g IV q4h + Rif 300 mg PO q8h X 6weeks + gentamicin 1 mg/kg IV q8h X 14 days. Methicillin-resistant (vanco 1g IV q12h+ Rif 300 mg PO q8h X 6weeks +gentamicin 1 mg/kg IV q8h X 14 days viridians streptococci, enterococci Enterobacteriacea e OR P. aeruginosa See infective endocarditis, native valve, and positive culture. Candida, aspergillus Aminoglycoside (tobramycin if P. aeruginosa) + β-lactam (e.g. Tazo or Cefeor Ceftazidime or Meropenem). Caspofungin 50–150 mg /day OR Anidulafungin 100–200 mg/day OR Lipidbase amphotericin B 3–5 mg/kg/day plus flucytosine 25 mg/kg QID Doxy 100 mg PO BID + hydroxychloroquine 600 mg/day for at least 18 months. Pregnancy: Need long term TMP-SMX Infective endocarditis-Q fever Coxiella burnetii Pacemaker/ defibrillator infections S. aureus (40%), S. epidermidis (40%), Gramnegative bacilli (5%), and fungi (5%) Device removal + vanco 15–20 mg/kg IV q8–12h + Rif 300 mg PO BID. Ventricular assist devicerelated infection S. aureus, S. epidermidis, Aerobic Gramnegative bacilli, candida spp. After culture of blood, wounds, drive line, device pocket & maybe pump: Empiric vanco 15–20 mg/kg IV q8–12h + (cip 400 mg IV q24h OR levo 750 IV q24h) + fluconazole 800 mg IV q24h. 39 COMMENTS Device removal + Dapto 6–10 mg/kg IV q24h + Rif 300 mg PO BID ID and surgical consultation required. Indications for surgery: severe heart failure, S. aureus infection, prosthetic dehiscence, resistant organism, emboli due to large vegetation. High mortality. Valve replacement plus antifungal therapy is recommended. ID consultation is required ID consultation is required Dapto is not FDA approved for this indication. ID consultation is required. Duration is 4–6 weeks after device removal ID consultation is required NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 4: GUIDELINES FOR TREATMENT OF INFECTIVE ENDOCARDITIS AND RELATED INFECTIONS ANATOMIC SITE/DIAGNOSI S Pericarditis, purulent Empirical therapy Rheumatic fever prophylaxis ETIOLOGIES S. aureus, S. pneumoniae, GAS , Gramnegative SUGGESTED REGIMENS FIRST LINE SECOND LINE COMMENTS Vanco + cip OR vanco + cefepime ID consultation is required Benzathine pen G 1.2 million units IM Q 3– 4 weeks OR pen V 250 mg PO BID Duration: for 5 years after acute rheumatic fever or until age 21, whichever is longer. If carditis present continue prophylaxis for 10 years 40 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 5-A: PROPHYLAXIS OF INFECTIVE ENDOCARDITIS ANTIMICROBIAL PROPHYLAXIS FOR THE PREVENTION OF BACTERIAL ENDOCARDITIS IN PATIENTS WITH UNDERLYING CARDIAC CONDITIONS Antibiotic prophylaxis for dental procedures is now directed at individuals who are likely to suffer the most devastating consequences should they develop endocarditis. Prophylaxis to prevent endocarditis is no longer specified for gastrointestinal or GU procedures. The following is adapted from and reflects the new American Heart Association (AHA) recommendations (2007). For patients with any of these highrisk cardiac conditions associated with endocarditis Prosthetic heart valves Previous infective endocarditis Congenital heart disease with any of the following: Completely Repaired cardiac defect using prosthetic material (only for first 6 months), partially corrected but with residual defect near prosthetic material, uncorrected cyanotic congenital heart disease, surgically constructed shunts and conduits, valvulopathy following heart transplant. SELECTION OF PATIENTS FOR ENDOCARDITIS PROPHYLAXIS Patients undergoing Patients Patients undergoing dental procedures undergoing invasive invasive procedures of involving… respiratory the GI or GU tracts procedures involving… Any manipulation of gingival tissue, dental periapical regions or perforating the oral mucosa. Prophylaxis recommended++ (See Table 5-B. Antibiotic Prophylactic Regimens for Dental Procedures). Prophylaxis is not recommended for routine anaesthetic injections (unless through infected area), dental x-rays, shedding of primary teeth, adjustment of orthodontic appliances or placement of orthodontic brackets or removable appliances. Incision of respiratory tract mucosa consider prophylaxis (See Table 5-B. Antibiotic Prophylactic Regimens for Dental Procedures) OR for treatment of established infection. Prophylaxis recommended (see Table 5-B. Antibiotic Prophylactic Regimens for Dental Procedures) for oral flora, but include anti-staphylococcal coverage when S. aureus is of concern). Prophylaxis is no longer recommended solely to prevent endocarditis, but the following approach is reasonable: for patients with enterococcal UTIs, treat before elective GU procedures. Include enterococcal* coverage in perioperative regimen for non-elective procedures + for patients with existing GU or GI infections or those who receive perioperative antibiotics to prevent surgical site infections or sepsis. It is reasonable to include agents with antienterococcal activity in perioperative coverage. Patients undergoing procedures involving infected skin and soft tissues Include coverage against staphylococci and Betahaemolytic staphylococci in treatment regimens. *Agents with anti-enterococcal activity include penicillin, amoxicillin, piperacillin, vancomycin and others. ++ 2008 AHA/ACC focused update of guidelines on valvular heart disease use term “is reasonable” to reflect level of evidence (Circulation 118:887, 2008). 41 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 5-B. ANTIBIOTIC PROPHYLACTIC REGIMENS FOR DENTAL PROCEDURES SITUATION AGENT Oral Unable to take oral medication Amoxicillin AMP OR 2g 2 g IM OR IV* Cefazolin OR ceftriaxone Cephalexin**† OR Clindamycin OR Azithromycin OR clarithromycin Cefazolin OR ceftriaxone † OR clindamycin 1 g IM OR IV Allergic to pen or AMP-oral regimen Allergic to pen or AMP and unable to take oral medication ** REGIMEN-SINGLE DOSE 30–60 MINUTES BEFORE PROCEDURE ADULTS CHILDREN 2g 50 mg/kg 50 mg/kg IM OR IV 50 mg/kg IM OR IV 50 mg/kg 600 mg 20 mg/kg 500 mg 1 g IM OR IV 15 mg/kg 50 mg/kg IM OR IV 20 mg/kg IM OR IV 600 mg IM OR IV Or other first or second generation oral cephalosporin in equivalent adult or paediatric dosage. †Cephalosporins should not be used in an individual with a history of anaphylaxis, angioedema or urticarial with penicillin or AMP. 42 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 6: GUIDELINES FOR TREATMENT OF CENTRAL NERVOUS SYSTEM INFECTIONS IN ADULTS ANATOMIC SITE/DIAGNOSIS Brain abscess (empirical treatment is guided by suspected source and underlying condition. While therapy should be adjusted based on culture results, anaerobic coverage should always continue even if none are grown Central nervous system (CNS) shunt infections ETIOLOGIES Primary (oral, otogenic, or sinus source) S. milleri, Bacteroides, Enterobacteriaceae S. aureus Rare: Nocardia, Listeria SUGGESTED REGIMENS PRIMARY ALTERNATIVE Ceftriaxone 2 g IV Cefotaxime 2 g q12h + IV q4h + metronidazole 7.5 metronidazole 7.5 mg/kg IV q8h mg/kg IV q8h Vanco (1 g IV q12h)to be used if MRSA is suspected COMMENTS Consult ID & neurosurgeon at the time of diagnosis. Obtain appropriate cultures. Duration should be guided by clinical response and radiological findings Post-surgery or post-traumatic Cloxacillin 2 g IV q4h + cefepime 2 g IV q8h Vanco 15–20 Adjust vanco mg/kg/day IV q12h + according to renal ceftazidime function and trough level If ESBL, Pseudomonas spp. or MDR organisms are suspected, consider using a carbapenem Nocardia (N.asteroids, N. farcinica, N. brasiliensis) TMP-SMX 15/75 mg/kg/day IV /PO divided into 2–4 doses + imipenem 500 mg IV q6h Linezolid 600 mg IV OR PO q12h + meropenem 2g IV q8h May add amikacin if multi-organ involvement after consulting with ID. CoNS , S. aureus, and other skin flora Vanco 15–20 mg/kg/dose IV q8h (not to exceed 2 g per dose) + cefepime OR ceftazidime 2 g IV q8h Vanco 15–20 mg/kg/dose IV q8h (not to exceed 2g per dose) + meropenem 2g IV q8h Successful management includes shunt removal and IV antibiotic therapy. Consult neurosurgeon and ID 43 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 6: GUIDELINES FOR TREATMENT OF CENTRAL NERVOUS SYSTEM INFECTIONS IN ADULTS ANATOMIC SITE/DIAGNOSIS ETIOLOGIES SUGGESTED REGIMENS PRIMARY ALTERNATIVE Acyclovir 10 mg/kg IV q8h COMMENTS Encephalitis Herpes simplex, VZV, arboviruses or flaviviruses Epidural abscess S. aureus and Gramnegative bacilli Cloxacillin 2 g IV q4h + ceftriaxone 2 g IV q12h + metronidazole 15 mg/kg IV q12h Vanco 15–20 mg/kg/dose IV q8h (not to exceed 2 g per dose) + cefepime 2 g IV q8h + Metronidazole 15 mg/kg IV q12h Consult ID & neurosurgeon for surgical drainage Meningitis, acute bacterial Age <1 month S. agalactiae, E. coli, L. monocytogenes, Klebsiella species AMP plus cefotaxime AMP plus an aminoglycoside See paediatric infection guide for dosage 44 Empiric therapy while awaiting for cerebrospinal fluid (CSF), herpes viruses, polymerase chain reaction (PCR), culture results, etc. Consult ID NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 6: GUIDELINES FOR TREATMENT OF CENTRAL NERVOUS SYSTEM INFECTIONS IN ADULTS ANATOMIC SITE/DIAGNOSIS ETIOLOGIES SUGGESTED REGIMENS PRIMARY ALTERNATIVE Meningitis, acute bacterial Age 1 month-50 years. Empirical therapy S. pneumoniae, N. meningitidis, and H. influenza (rare). Vanco 15–20 mg/kg/dose IV q8h (not to exceed 2 g per dose) + ceftriaxone 2 g IV q12h + dexamethasone 0.15 mg/kg IV q6h Vanco 15–20 mg/kg/dose IV q8h (not to exceed 2 g per dose) + Meropenem 2 g IV q8h + Dexamethasone Give dexamethasone before the first dose of antibiotic for 2–4 days. Discontinue if CSF Gram stain or culture is not suggestive of S. pneumoniae Meningitis, acute bacterial Age: >50 years or alcoholism or other debilitating associated illnesses or impaired immunity. Empirical therapy S. pneumoniae, N. meningitis, L.monocytogenes , aerobic Gramnegative bacilli AMP 2 g IV q4h + vanco 15–20 mg/kg dose IV q8h (not to exceed 2g per dose) + ceftriaxone 2 g IV q12h Vanco 15–20 mg/kg/dose IV q8h (not to exceed 2 g per dose) + Meropenem 2 g IV q8h Give dexamethasone before the first dose of antibiotic for 2–4 days. For patients with severe pen allergy, TMP-SMX + vanco can be used pending culture results Postneurosurgery or penetrating head trauma S. pneumoniae (if CSF leak), H. influenzae, staphylococci (MRSA, CoNS), Gram-negative Vanco 15–20 mg/kg/dose IV q8h (not to exceed 2 g per dose) PLUS ceftriaxone Vanco 15–20 mg/kg/dose IV q8h (not to exceed 2g per dose) PLUS meropenem 2 g IV q8h Give dexamethasone before the first dose of antibiotic for 2–4 days 45 COMMENTS NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 6: GUIDELINES FOR TREATMENT OF CENTRAL NERVOUS SYSTEM INFECTIONS IN ADULTS ANATOMIC SITE/DIAGNOSIS Acute bacterial meningitis Specific therapy: ETIOLOGIES S. pneumoniae SUGGESTED REGIMENS PRIMARY Check culture and sensitivity report. Pen G 4 million unit IV q4h COMMENTS ALTERNATIVE Ceftriaxone 2 g IV q12h Treat for 10–14 days. dexamethasone prior to first dose of antibiotics and continue for 4 days E. coli Ceftriaxone 2 g IV q12h OR cefotaxime ± gentamicin IV Cefepime 2 g IV q8h Meropenem 2 g IV q8h H. influenzae Ceftriaxone 2 g IV q12h OR cefotaxime Cefepime 2 g IV q8h Meropenem 2 g IV q8h N. meningitidis Ceftriaxone 2 g IV q12h OR cefotaxime Pen 4 million units IV q4h (24 million units per day OR AMP 2 g IV q4h Prophylaxis L. monocytogenes AMP 2 g IV q4h + gentamicin IV TMP/SMX meropenem 2 g IV q8h Addition of an aminoglycoside should be considered S. agalactiae Pen: 4 million units IV q4h (24 million units per day OR AMP: 2 g IV q4h plus IV gentamicin Ceftriaxone 2 g IV q12h OR cefotaxime Addition of an aminoglycoside should be considered 46 Consult ID. Treat for 21 days NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 6: GUIDELINES FOR TREATMENT OF CENTRAL NERVOUS SYSTEM INFECTIONS IN ADULTS ANATOMIC SITE/DIAGNOSIS ETIOLOGIES SUGGESTED REGIMENS PRIMARY ALTERNATIVE Isoniazid 300 mg OD + Rif 600 mg OD + Ethambutol 15–25 mg/kg/day + Pyrazinamide 15 to 30 mg/kg/day (maximum 2 g dose), x 2 months followed by isoniazid (INH) and Rif for 7–10 months. Meningitis, TB* Isoniazid 300 mg OD + Rif 600 mg OD + streptomycin 1g IM q24h + Pyrazinamide 15 to 30 mg/kg/day (maximum 2 g dose), x 2 months followed by INH and Rif for 7– 10 months Dexamethasone 0.3 to 0.4 mg/kg/day for 2 weeks, then 0.2 mg/kg/day week 3, then 0.1 mg/kg/day week 4, then 4 mg per day and taper 1 mg off the daily dose each week; total duration approximately 8 weeks. Consulting with ID is advisable especially if MRD-TB is suspected or confirmed Albendazole 400 mg PO BID + Dexamethasone 0.1 mg/kg/day + Antiseizure medications Viable cysts by MRI. Eye exam is needed for evidence of involvement. Duration of therapy depends on extent and severity of disease, please consult ID physician Plus steroids as adjucant thearapy.see comments for dose. Neurocysticercosis Taenia solium Albendazole 400 mg PO BID + Praziquantel 50 mg/kg/day Dexamethasone 0.1 mg/kg/day + antiseizure medications COMMENTS *REFRENCES: 1. American Thoracic Society, Center for Disease Control and Prevention, and Infectious Diseases Society of America. 2003. Treatment of tuberculosis. MMWR Recomm. Rep. 52:1–7. 2. NICE Guideline .2016.Tuberculosis.nice.org.uk/guidance/ng33 3. World Health organization. Treatment of tuberculosis Guidelines.Fourth edition. 47 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 7: GUIDELINES FOR TREATMENT OF BONE AND JOINT INFECTIONS IN ADULTS ANATOMIC SITE/DIAGNOSIS ETIOLOGIES SUGGESTED REGIMENS FIRST LINE COMMENTS SECOND LINE BONE: Osteomyelitis: Important: Essential to obtain specimens (blood, bone) before starting antibiotic treatment. Total duration of treatment differs from patient to patient but 4–6 weeks of antibiotic therapy is recommended as a minimum. Clinical, radiological and laboratory, erythrocyte sedimentation rate (ESR) should be used to monitor response to therapy. Other modalities of treatment such as surgical debridement of necrotic bone and removal of hardware are frequently needed. In selected cases, hyperbaric Oxygen therapy may be recommended. Team management including surgeons, microbiologist/ID physicians and pharmacists increases chance of successful treatment. Hematogenous (vertebral & non-vertebral) S. aureus (MSSA) Cloxacillin IV 2 g q4–6h OR Cefazolin 2 gm IV q8h. Vanco 1 g q12h MRSA Vanco 1 g q12h Teicoplanin IV 6– 12 mg/Kg q12h for 3–5 doses) then 6–12 mg/kg q24h OR linezolid 600 mg PO/IV q12h ± Rif 300 mg PO BID With SCD Enterobacteriaceae Cip PO 750 mg q12h Ceftriaxone 1–2 IV gm q24h Salmonella Cip 750 mg q12h orally OR IV 400 mg q12h Ceftriaxone 1–2 g q24h 48 OR levo 750 mg IV/PO q24h Empiric antibiotic treatment (after obtaining specimens) may include combination therapy to cover different potential pathogens Combination of quinolone and third generation cephalosporin can be considered if quinolone resistance is uncertain NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 7: GUIDELINES FOR TREATMENT OF BONE AND JOINT INFECTIONS IN ADULTS ANATOMIC SITE/DIAGNOSIS Intravenous drug user (IVDU) Contiguous without vasculopathy, e.g. trauma Contiguous without vasculopathy, e.g. trauma (targeted therapy) With orthopaedic implant ETIOLOGIES Pseudomonas SUGGESTED REGIMENS FIRST LINE SECOND LINE Piperacillin/tazob Cip IV 400 mg q12h actam 4.5g q8h Empiric therapy Pseudomonas (nail penetrating trauma to foot). Long bone post internal fixation: (MSSA, MRSA, Gramnegative or Pseudomonas) Cip 750 mg PO BID S. aureus Cloxacillin IV 2g q4–6h + Rif oral 900 mg daily Vanco 1 g q12h + Rif oral 900 mg daily Enterococcus AMP 1g IV q6h Vanco 1 g q12h Enterobacteriaceae Cip 750 mg PO BID OR IV 400 q12h Ceftriaxone 1–2 g q12h Pseudomonas Cip 750 mg PO BID OR IV 400 q12h Piperacillintazobactam 4.5 g q8h S. aureus Cloxacillin IV 2g q4–6h + Rif oral 600–900 mg daily Vanco 1g q12h + Rif oral 600–900 mg daily CoNS Vanco 1 gm q12h + Rif oral 600 mg daily Teicoplanin 400– 600 mg q12h + Rif oral 600 mg daily COMMENTS Oral Cip dose is 750 mg q12h Levo 750 mg PO once a day OR vanco plus cefepime OR Linezolid plus ceftazidime OR cefepime 49 Linezolid plus Rif is another alternative combination NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 7: GUIDELINES FOR TREATMENT OF BONE AND JOINT INFECTIONS IN ADULTS ANATOMIC SITE/DIAGNOSIS Contiguous with Vasculopathy e.g. DM ETIOLOGIES SUGGESTED REGIMENS FIRST LINE SECOND LINE Enterococci AMP 1 g IV q6h Vanco 1 g q12h Enterobacteriaceae Cip 750 mg PO BID OR 400 q12h Ceftriaxone 2 g q12h Pseudomonas Cip 750 mg PO BID OR IV 400 q12h PiperacillinTazobactam 4.5 g q8h S. aureus Cloxacillin IV 2 g q4–6h Vanco 1 g q12h Polymicrobial: Gramnegative bacilli, Anaerobic organisms Cip 750 mg PO q12h + Metronidazole 500 mg IV q8h Amoxicillinclavulanate, 875 mg and 125 mg, respectively, orally every 12 hrs Any MDR organisms According to identity and antibiotic susceptibility of the organism, please consult microbiologist /ID physician 50 COMMENTS Debridement of ulcers and obtain bone biopsy for culture and histology. Therapy should be guided by cultures NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 8: GUIDELINES FOR TREATMENT OF ABDOMINAL INFECTIONS IN ADULTS ANATOMIC SITE/ DIAGNOSIS ETIOLOGIES Esophagitis Candida albican, (mainly in HIV pts) HSV,CMV Duodenal/ Gastric Ulcer H.pylori Biliary infections (cholecystitis cholangitis, biliary sepsis, CBD obstruction) Enterobacteriacae Enterococci, anaerobes, Candida Diverticulitis Almost all infections are polymicrobial. (Most commonly Enterobacteriacae Bacteroides spp and enterococcus spp, Occasionally P. aeruginosa) SUGGESTED REGIMENS FIRST LINE Fluconazole 200400mg IV/PO q24h 14-21 days SECOND LINE Voriconazole 200 q12h 14-21 days Omeprazole 20 mg q12h + Amoxicillin 1g Q12H + Clarithromycin 500mg q12h Empiric treatment :Mild Ciprofloxacin or Moxifloxacin, plus Metronidazole Omeprazole 20mg q12h + Clarithromycin 500mg q12h + Metronidazole 500 mg PO TID Hospital or severe piperacillin/tazoba ctam 4.5 gm IV TID Cefepime 2 gm TID plus Metronidazole 500 mg IV TID Or Meropenem Mild to moderate Out- patient Rx AmoxicillinClavulanate 875/125 mg PO q12h Ciprofloxacin plus metronidazole OR TMP-SMX-SD plus metronidazole Moderate to Severe infection Piperacillin – Tazobactam ampicillin + aminoglycoside + metronidazole OR Meropenem OR Tigecycline 51 Ceftriaxone plus Metronidazole COMMENTS Amphotericin and echinocandins used for patient with fluconazole refractory infection Duration: 10-14 days In severely ill pts with cholangitis or complicated cholecystitis, adequate biliary drainage is crucial CT scan is important in assessing the need for drainage in severe disease. Duration: 7-10 days NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 8: GUIDELINES FOR TREATMENT OF ABDOMINAL INFECTIONS IN ADULTS Pancreatitis Acute alcoholic pancreatitis without necrosis does not require antibiotic therapy or prophylaxis as studies have shown no advantage. Observe for abscess formation or necrosis which will require therapy. ANATOMIC ETIOLOGIES SUGGESTED REGIMENS COMMENTS SITE/ DIAGNOSIS FIRST LINE SECOND LINE Pancreatitis, post necrotizing Infected pseudocyst, pancreatic abscess Enterobacteriaceae enterococci, S aureus, anaerobes, candida Piperacillintazobactam 4.5 gm q8h 52 Meropenem 1 gm IV q8h OR Cip OR levo,+ metronidazole Infected pancreatic necrosis is defined as one or both of the following : 1- CT scan with gas 2- Percutaneous aspirate or surgical specimen with organism evident on Gram stain or culture Pen and cephalosporin poorly penetrate into the pancreas, peak incidence of infection in the 3rd week NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 8: GUIDELINES FOR TREATMENT OF ABDOMINAL INFECTIONS IN ADULTS ANATOMIC SITE/ DIAGNOSIS Peritonitis Primary (spontaneous bacterial peritonitis (SBP) ETIOLOGIES FIRST LINE Enterobacteriaceae S. pneumoniae, Enterococci, anaerobes Primary: cefotaxime 2g IV TID If infection life threatening: piperacillin /tazobactam COMMENTS SECOND LINE Cip OR levo, + metronidazole Duration: Uncomplicated 5–7 days. Complicated or positive culture: 10 days, may be longer if patient is bacteremic Carbapenem Secondary Peritonitis secondary to GI perforation Prevention of SBP Chronic ambulatory peritoneal dialysis (CAPD) peritonitis SUGGESTED REGIMENS Mild to moderate: Cefepime PLUS Metronidazole Ciprofloxacin OR levo, PLUS metronidazole Severe (ICU): Piperacillin/ Tazobactam OR carbapenem AMP plus ciprofloxacin + metronidazole OR AMP + aminoglycoside + metronidazole Cip 500 mg PO once a week TMP-SMX DS 1 tab PO 5 days per week Most common: Gram-positive cocci: s. aureus, coagulase-negative, enterococci Less common: Gram-negative and yeast Mild to moderate: Intraperitoneal therapy is preferred Cefazolin and gentamicin Severe: Vanco + (ceftazidime OR meropenem OR cefepime OR gentamicin OR ciprofloxacin) (Intraperitoneal therapy unless bacteraemia for which IV therapy is used) Fluconazole to be added if yeast is seen in Gram stain. Duration: 10–14 days 53 Most infections caused by contamination of the catheter. Diagnosis of CAPD catheter infection if peritoneal dialysis fluid WBC >100/mm3 with >50% polymorphonuclear leukocytes + clinical signs and symptoms Empirical antifungal generally not indicated unless the patient has risk factors. Surgical source control is essential 1 year risk of SBP in patients with ascites and cirrhosis as high as 29%. TMP-SMX reduce SBP bacteraemia from 27% to 3% NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 8: GUIDELINES FOR TREATMENT OF ABDOMINAL INFECTIONS IN ADULTS ANATOMIC SITE/ DIAGNOSIS Infectious diarrhoea ETIOLOGIES SUGGESTED REGIMENS FIRST LINE COMMENTS SECOND LINE Campylobacter jejuni/coli (self-limited in normal host) Erythromycin 500 mg PO QID 5 days Cip 500 mg PO BID, azithromycin 500 PO OD x 3 days Duration: 3–5 days Campylobacter foetus gentamicin IV AMP OR imipenem IV Diarrhoea uncommon, more systemic disease in debilitated host Shiga toxinproducing E. coli Avoid antibiotics Salmonella spp. (non-typhi) Cip 500 mg/12 hrs for 7–10 days Azithromycin 500 mg q24H for 7 days (14 days if immunocompromised) Cipro 500 mg q12h for 3 days Azithromycin OR STM-SMZ No indicated treatment if asymptomatic or mild disease. Treat only if severe illness, ˂1 year, >50 yrs., prosthesis, vascular graft, valvular heart disease, severe atherosclerosis & immunocompro-mised patients. Treatment should be guided by antimicrobial sensitivity result Duration: 3 days. If severe infection, ceftriaxone 1–2 gm Q24H should be used. Longer (7–10 days) duration for immunocompromised Typhoid fever: refer to systemic infection guide Shigella 54 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 8: GUIDELINES FOR TREATMENT OF ABDOMINAL INFECTIONS IN ADULTS ANATOMIC SITE/ DIAGNOSIS ETIOLOGIES FIRST LINE Doxycycline 300 mg PO single dose. Y. enterocolitica Treatment recommended for: immunocompromised, bacteraemia, pseudoappendicitis syndrome Aeromonas/ plesiomonas E. histolytica Severe: doxycycline + gentamicin Giardia Metronidazole 250 mg PO TID for 5 days Albendazole 400 PO q24h with food for 5 days Cryptosporidium Nitazoxanide 500 mg PO q12h x 3days If AIDS: HAART and nitazoxanide for 14 days TMP-SMZ 1DS PO q12h for 7–10 days Initial episode, mild or moderate: Leucocytosis with a WBC count of 15,000 cells/ml or lower and no increase in serum creatinine Initial episode, severe: Leucocytosis with a WBC count of 15,000 cells/ml or higher or a serum creatinine level greater than or equal to 1.5 times the premorbid level Erythromycin 500 QID for 3 days OR Azithromycin 1 gm PO single dose TMP-SMX OR fluoroquinolone Cip 750 PO OD/BID Azithromycin 500 PO OD Metronidazole 500–750 MG Q8H for 10 days followed by intraluminal agent paromomycin 500 mg q8h for 7 days Metronidazole, 500 mg q8h by mouth for 10-14 days Vanco, 125 mg q6h by mouth for 10–14 days 55 COMMENTS SECOND LINE Vibrio cholera: Cyclospora C. difficile Infection (CDI) SUGGESTED REGIMENS Vanco 12 5 mg PO q6h for 10–14 days Duration: 3 days Discontinue offending antibiotics Consult ID & GI NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 8: GUIDELINES FOR TREATMENT OF ABDOMINAL INFECTIONS IN ADULTS ANATOMIC SITE/ DIAGNOSIS ETIOLOGIES SUGGESTED REGIMENS FIRST LINE COMMENTS SECOND LINE Initial episode, severe: Hypotension or shock, ileus, megacolon Vanco, 500 mg 4 times per day by mouth or by nasogastric tube, PLUS metronidazole, 500 mg every 8 hrs intravenously. If complete ileus, consider adding rectal instillation of vanco First recurrence second recurrence Same as for initial episode Vanco 125 mg PO q6 hs 10–14 days then start tapering. Tapered and/or pulsed Regimen. Consult ID and GI physicians Referral of severe cases to abdominal surgeon is recommended. Rectal installation of vanco into bowel, consult GI, ID team and clinical pharmacy References: 1. 2. 3. Guerrant, RL, Van Gilder T, Steiner TS, Thielman NM, Slutsker L, Tauxe RV, et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis 2001;32:331–50. Cheng AC, McDonald JR, Thielman NM. Infectious diarrhea in developed and developing countries. J Clin Gastroenterol 2005;39:757–773. Gilbert DN, Chambers HF, Eliopoulos GM, Saag MS, Black D, Freedman DO, et al. The Sanford Guide to Antimicrobial Therapy 2015. 45th ed. Sperryville,VA: Sanford; 2015. 56 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 9: GUIDELINES FOR TREATMENT OF SKIN AND SOFT TISSUE INFECTIONS DIAGNOSIS/ ETIOLOGIES SUGGESTED REGIMENS ANATOMIC (USUAL) PRIMARY SITE Bites : Remember tetanus prophylaxis Cat bite: complicated by infection in 80%. Patient should be cultured and treat empirically Pasteurella multocida, S. aureus SUGGESTED REGIMENS ALTERNATIVE COMMENTS Amoxicillinclavulanate 875/125 mg PO BID OR 500/125 mg PO TID Cefuroxime 500 mg PO BID OR doxy 100 mg PO BID P. multocida resistant to cloxacillin, cephalexin, clindamycin, many strains resistant to erythromycin. If the culture is positive for P. multocida, can switch to pen Dog bite: complicated by infection in 5%.Treat if bite is severe or with comorbidity (e.g. diabetes) Pasteurella canis, S. aureus, Bacteroides spp., Fusobacterium, Capnocytophaga Amoxicillinclavulanate 875/125 mg PO q12h OR 500/125 PO q8h Clindamycin 300 mg PO QID + fluoroquinolone (adults) OR clindamycin + TMPSMX (children) Consider anti-rabies prophylaxis (rabies immunoglobulin and vaccine) Human bite Viridians streptococci, S. epidermidis, S. aureus, Eikenella, Bacteroides, Peptostreptococcus Early (not infected) amoxicillinclavulanate 875/125 mg PO q12h for 5 days Later: signs of infection (usually in 3–24 h) PIP-TAZ 4.5 gm q8h If pen allergy: Clindamycin + (either cip OR TMP-SMX) Cleaning, irrigation and debridement most important for clenched fist injuries x-rays should be obtained. Bites inflicted by hospitalized patients, consider aerobic Gram-negative bacteria. Eikenella resistant to Clindamycin, nafcillin/oxacillin, metro, first gen cephalosporin, and erythromycin, susceptible to FQs, and TMP-SMX 57 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 9: GUIDELINES FOR TREATMENT OF SKIN AND SOFT TISSUE INFECTIONS DIAGNOSIS/ ANATOMIC SITE Snake bite Boils, furunculosis carbuncles afebrile Boils, subcutaneous abscesses, furunculosis, carbuncles (connecting abscesses) febrile Recurrent boils, subcutaneous abscesses, furunculosis ETIOLOGIES (USUAL) SUGGESTED REGIMENS PRIMARY Enterobacteriaceae, Pseudomonas, Staphylococcus, Clostridium spp. Primary therapy is antivenom, ceftriaxone AND tetanus prophylaxis S. aureus both MSSA & MRSA-increase incidence of communityassociated MRSA Incision & drainage is indicated. If abscess <5 cm in diameter: culture abscess, hot packs, NO drugs. If abscess >5 cm in diameter: TMP/SMX 1 DS tab q12h S. aureus both MSSA Incision & drainage is & MRSA-increase the mainstay of incidence of treatment communityassociated MRSA Outpatient: TMP/SMX 1 DS tab q12h for 5–10days MSSA, MRSA Consult ID if decolonization is considered. mupirocin 2% ointment to anterior nares twice a day for 7 days and daily chlorohexidine 2% bath for 7 days. Decontamination of personal items such as towels, linen, etc. 58 SUGGESTED REGIMENS ALTERNATIVE COMMENTS Antibiotic treatment indicated if signs of infections. Should be guided by culture report Clindamycin PO 300– 600 mg q6–8h for 5– 10 days Clindamycin PO 300– 600 mg q6–8h In-patient: vanco 15 mg/kg q12htill culture results are available Consult ID or microbiologist if oral antibiotics needed for decolonization Needle aspiration is inadequate. Consider imaging if not sure of extent or the diagnosis. Therapy should be given before incision and drainage in patients with prosthetic heart valves or other conditions placing them at high risk for endocarditis Adult patients should be evaluated for neutrophil disorder if recurrent abscesses started in early childhood NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 9: GUIDELINES FOR TREATMENT OF SKIN AND SOFT TISSUE INFECTIONS DIAGNOSIS/ ANATOMIC SITE Impetigo ETIOLOGIES (USUAL) Group A Strept (rare group B, C & G) S. aureus (MSSA, MRSA) Burns Non-infected Burns Wound sepsis Cellulitis, Erysipelas Extremities, non-diabetic S. pyogenes S. aureus, Enterobacterspp., P. aeruginosa, E. coli, Fungi, HSV (Rare) Strept spp. (group A,B,C,G) S. aureus SUGGESTED REGIMENS PRIMARY No oral antibiotics unless severe, extensive or bullous or in outbreak setting: cloxacillin 500 mg PO QID OR cephalexin 250 mg PO QID for 5–7 days based on clinical response SUGGESTED REGIMENS ALTERNATIVE For MRSA : doxycycline, TMP-SXT,OR clindamycin can be used Early excision, wound closure, skin graft. Role of topical antibiotic unclear Cefepime 2 gm q8–12h OR tazocin 4.5 gm q8h ± amikacin 10 mg/kg loading dose then 7.5 mg/kg IV q12h (therapeutic drug monitoring) Cefazolin IV 1 gm q8h OR cloxacillin 2 gm IV QID Silver sulfadiazine Anti-tetanus is indicated Meropenem PLUS vanco Consider adding vanco if patient is known or suspected MRSA. Monitor serum levels of vanco and amikacin as serum half-life of most antibiotics is decreased in burns patients. Candida usually colonizes wounds but rarely invades Always elevate the affected extremity. Cultures should be obtained for patients on chemotherapy, neutropenia, animal bites or immuno- compromised or immersion injuries. Pen G 1–2 million units IV q6h if streptococci When afebrile can step to oral therapy 59 Amoxicillinclavulanate OR clindamycin OR clarithromycin COMMENTS Reserve topical antibiotics for localized lesions : topical fusidic acid 2% TID for 5 days can be used Do not use mupirocin (Reserved for MRSA) NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 9: GUIDELINES FOR TREATMENT OF SKIN AND SOFT TISSUE INFECTIONS DIAGNOSIS/ ANATOMIC SITE ETIOLOGIES (USUAL) SUGGESTED REGIMENS PRIMARY Ceftriaxone 1 gm IV q 24 hrs SUGGESTED REGIMENS ALTERNATIVE Vanco 1 gm IV q12h if MRSA suspected Facial, adult (erysipelas) Strept (group A,B,C & G) S. aureus (MRSA), S. pneumoniae Erysipelas and Diabetes mellitus Strept (group A, B, C& G) S. aureus, Enterobacteriaceae Clostridia(rare) Early mild: TMP-SMX-DS 1–2 tabs PO q12h PLUS cephalexin PO 500 mg q6h Severe: Meropenem + (vanco OR linezolid) Diabetic foot Mild: presence of purulence & >1 sign of inflammation and cellulitis (if present) <2 cm around the ulcer limited to skin and superficial subcutaneous tissue S. aureus, Streptococci Group A,B Cephalexin PO 500 mg QID OR Clindamycin 600 mg PO TID Amoxicillin/ clavulanate 875 mg PO BID Diabetic foot: Moderate: same as mild PLUS >2 cm of cellulitis, lymphangitis streaking, spread beneath superficial fascia, deep tissue abscess, gangrene, involvement of muscle, tendon, joint or bone. As above + coliforms If IV needed : IV clindamycin 600 mg q8h OR IV cefazolin 1 gm q8h Ciprofloxacin 500 mg PO BID OR 400 mg IV BID plus either clindamycin 600 mg IV/PO TID OR metronidazole 500 mg IV/PO TID 60 Ertapenem 1 gm IV q24h OR piperacillintazobactam 4.5 gm q8h COMMENTS Obtain cultures Surgical consultation to rollout necrotizing fasciitis and for debridement to obtain cultures. If septic consider x-rays to assess the presence of gas If MRSA risk or positive infection or colonization add vanco OR linezolid to regimens not containing clindamycin or microbiology reports indicates clindamycin resistance NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 9: GUIDELINES FOR TREATMENT OF SKIN AND SOFT TISSUE INFECTIONS DIAGNOSIS/ ANATOMIC SITE Diabetic foot Severe: same as above in addition to systemic toxicity or metabolic instability Necrotizing fasciitis ETIOLOGIES (USUAL) Streptococcal (A,C,G) All types require prompt surgical debridement. Pen G 2–4 million unit IV q4–6 h + clindamycin 600 mg IV q8h Polymicrobial Meropenem 1 gm IV TID, add vanco if MRSA suspected Pen G 2–4 million unit IV q4–6 h + clindamycin 600 mg IV q8h Clostridia spp. Staphylococcal scalded skin syndrome SUGGESTED REGIMENS PRIMARY piperacillintazobactam 4.5 gm q8h + vanco 15 mg/kg q12h Toxinproducing S. aureus MSSA: cloxacillin 2 gm IV q4h for 5–7 days MRSA: vanco 15 mg/kg q12h 61 SUGGESTED REGIMENS ALTERNATIVE COMMENTS Cip 400 mg IV q12h plus IV metronidazole 500 gm q8h plus IV vanco 15 mg/kg q12h OR Meropenem 1 gm q8h + vanco Toxin causes intraepidermal split and positive Nikolsky sign. Biopsy can differentiate drug cause such as toxin epidermal necrolysis NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 9: GUIDELINES FOR TREATMENT OF SKIN AND SOFT TISSUE INFECTIONS DIAGNOSIS/ ANATOMIC SITE Infected wound extremities posttrauma Infected wound Postoperative, not involving intestinal or genital surgeries Infected wound postoperative, involving intestinal or genital surgeries Scabies ETIOLOGIES (USUAL) Polymicrobial S. aureus, Streptococcus spp., Coliform, Clostridium spp., Water exposure: Pseudomonas spp., Aeromonas spp. S. aureus, Strept. A, B, C, G MSSA, MRSA Coliforms, Bacteroides, anaerobes SUGGESTED REGIMENS PRIMARY Mild: TMP/SMX DS PO 1 tab BID OR clindamycin Febrile with sepsis: piperacillin-tazobactam + vanco Mild: TMP/SMX 1 tab PO BID + cephalexin 500 mg q8h Severe: vanco 15 mg/kg q12h Mild: amoxicillinclavulanate 875/125 mg PO BID + TMP/SMX 1–2tab PO BID (if Gram-positives seen on Gram stain) Severe: piperacillin-tazobactam 4.5 gm q8h + vanco 15 mg/kg q12h OR meropenem + vanco 15 mg/kg q12h Permethrin 5% cream 62 SUGGESTED REGIMENS ALTERNATIVE Doxycycline PO 100 mg q12h OR amoxicillinclavulanate PO OR vanco + (cip OR levo) COMMENTS Debride the wound if necessary Culture and sensitivity is indicated Tetanus toxoid Mild: clindamycin 300–450 mg PO q8h Severe: Linezolid Drain wound and get cultures. Can substitute linezolid for vanco. Can substitute cip OR levo for betalactam antibiotics Treat all household and sexual contacts Check Gram stain of exudate NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 10: GUIDELINES FOR TREATMENT OF URINARY TRACT INFECTIONS AND SEXUALLY TRANSMITTED DISEASES IN ADULTS ANATOMIC ETIOLOGIES SUGGESTED REGIMENS COMMENTS SITE/DIAGNOSIS FIRST LINE SECOND LINE Urinary A complicated UTI, whether localized to the lower or upper tract, is associated with an underlying condition that increases the risk of failing therapy, including the following: Diabetes Pregnancy Symptoms for 7 or more days before seeking care Hospital-acquired infection Renal failure Urinary tract obstruction Presence of an indwelling urethral catheter, stent, nephrostomy tube or urinary diversion Recent urinary tract instrumentation Functional or anatomic abnormality of the urinary tract History of UTI in childhood Renal transplantation Immunosuppression Infection with an uropathogen with broad-spectrum antimicrobial resistance is also considered complicated although there are no data to suggest that such infections are more likely to fail if an antimicrobial to which the infecting pathogen is susceptible is used. Uncomplicated Cystitis E. coli, Klebsiella, Proteus, S. saprophyticus Nitrofurantoin 100 mg q12h x 5 days 63 Trimethoprim/ sulfamethoxazole 960 mg q12h x 3 days OR fosfomycin 3 gm PO single dose OR if G6PD deficient amoxicillinclavulanate 875/125 mg x 7–10 days Routine urine culture is not recommended. Obtaining a urine culture prior to initiation of therapy is warranted if symptoms are not characteristic of UTI, if symptoms persist, recurring within 3 months following prior antimicrobial therapy, or if a complicated infection is suspected NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 10: GUIDELINES FOR TREATMENT OF URINARY TRACT INFECTIONS AND SEXUALLY TRANSMITTED DISEASES IN ADULTS ANATOMIC SITE/DIAGNOSIS ETIOLOGIES UTI (pregnancy) Candiduria SUGGESTED REGIMENS FIRST LINE SECOND LINE Nitrofurantoin Amoxicillin100 mg q12h x 7 Clavulanate days 875/125 mg x 10– 14 days COMMENTS Contraindicated in pregnancy: cip, tetracycline. Avoid during 1st trimester: Trimethoprim, nitrofurantoin. Avoid near term: nitrofurantoin, sulphonamides. Avoid the day before delivery: Ceftriaxone. A follow up culture (test of cure) should be obtained a week after completion of therapy. Consult ID/micro if bacteriuria persists Candida species Asymptomatic, Candiduria No treatment required except if undergoing urologic procedure, in the setting of neutropenia or in low birth weight neonates Symptomatic cystitis (or asymptomatic but undergoing urologic procedure or high risk for disseminated infection) Fluconazole 200 mg (3 mg/kg) daily for 14 days 64 If possible, remove the urinary catheter or stent Amphotericin B 0.3–0.6 mg/kg daily (for fluconazole resistant organisms) for 1–7 days. Bladder irrigation with amphotericin B is NOT recommended for cystitis or pyelonephritis NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 10: GUIDELINES FOR TREATMENT OF URINARY TRACT INFECTIONS AND SEXUALLY TRANSMITTED DISEASES IN ADULTS ANATOMIC SITE/DIAGNOSIS Pyelonephritis, Candiduria ETIOLOGIES SUGGESTED REGIMENS FIRST LINE Fluconazole oral/IV 200– 400 mg (3–6 mg/kg) daily 14 days 65 COMMENTS SECOND LINE Amphotericin B 0.5–0.7 mg/kg daily (for fluconazole resistant organisms) for 1–7 days. Lipid formulations of amphotericin B should not be used to treat UTIs because they do not penetrate into the kidney or achieve adequate concentrations in the urine NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 11: GUIDELINES FOR TREATMENT OF SYSTEMIC INFECTIONS ANATOMIC SITE/DIAGNOSIS ETIOLOGIES SUGGESTED REGIMENS FIRST LINE SECOND LINE Important: Obtain careful epidemiologic history Brucellosis B. abortus (cattle), B. suis (swine), B. melitensis, (goats), B. canis (dogs) No focal disease: doxycycline 100 mg PO BID for 6 weeks + gentamicin 5 mg/kg OD for the first 7 days Doxycycline 100 mg PO BID PLUS Rif 600– 900 PO OD for 6 weeks Spondylitis, sacroiliitis: Cip 750 mg PO BID + gentamicin (7 days as Rif 600–900 PO OD for above) PLUS doxycycline a minimum of 3 and Rif for minimum of months 3 months Neuro-brucellosis: doxycycline and Rif (as above) + ceftriaxone 2 gm q12h until CSF parameters return to normal Endocarditis: Surgery + combination of (doxycycline + Rif + cotrimoxazole for 6 weeks-6months) PLUS gentamicin for 2–4weeks Pregnancy: Rif 900 mg PO OD for 6 weeks Leptospirosis Leptospira: urine of domestic livestock, dogs and small rodents Severe illness: pen G 1.5mU IV q6h OR ceftriaxone 1 gm q24h Duration: 7 days 66 Rif 600–900 mg PO OD + cotrimoxazole 5 mg/kg PO BID for 4 weeks. (Cotrimoxazole may cause kernicterus if given during the last week of pregnancy) Mild illness: doxycycline 100 mg IV/PO q12h OR AMP 0.5–1 gm IV q6h for 7 days COMMENTS NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 11: GUIDELINES FOR TREATMENT OF SYSTEMIC INFECTIONS ANATOMIC SITE/DIAGNOSIS Typhoid fever ETIOLOGIES Salmonella Typhi Salmonella Paratyphi A,B,C SUGGESTED REGIMENS FIRST LINE SECOND LINE Ceftriaxone 2g IV Cip 750 mg PO q24h x 10–14 bid OR 400 mg days IV q12h 7–10 days OR Azithromycin 1 g PO x one dose, then 500 mg OD x 5–7 days Salmonella bacteraemia (Non-typhoidal) Salmonella enteritidis or other serotypes from animal sources Ceftriaxone 2 g IV q24h for 2 weeks Q Fever, acute C. burnetii Doxycycline 100 mg q12h + Rif 600 mg OD 67 COMMENTS Susceptibility test results are essential to guide therapy as resistance to cip is increasing. Dexamethasone is used in severe infections, first dose should be prior to antibiotics 3 mg/kg IV, then 1 mg /kg IV q6h x 8 doses Cip 400 IV q12h Do not use quinolones until OR Levo 750 PO susceptibility determined. for 14 days Bacteraemia can infect any organ or tissue: look for endovascular infection, osteomyelitis in sickle cell disease patients. Treatment duration ranges from 14 days (immunocompetent) to ≥6 weeks (if mycotic aneurysm or endocarditis). Azithromycin 1 gm for the first days then, 500 mg PO OD for 5–7 days is another alternative treatment. Test for HIV status Cip 500 mg h/o animal contact q12h + Rif 600 mg OD Consult ID NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 11: GUIDELINES FOR TREATMENT OF SYSTEMIC INFECTIONS ANATOMIC SITE/DIAGNOSIS Sepsis (suggested empiric therapy assumes patient is bacteremic) Not neutropenic No clear source Life-threatening Refer to specific sections of this guide for the empiric recommendatio n therapy for specific source of infection Shock syndromes ETIOLOGIES Aerobic Gramnegative S. aureus, streptococci See specific syndromes Proven therapies: replete intravascular volume with IV saline, goal is CVP >8 cm within 6 hrs of admission Attempt to correct the source of bacteraemia. Obtain cultures then start appropriate antibiotics, time of first dose is crucial Appropriate pressors if still hypotensive and elevated lactate SUGGESTED REGIMENS FIRST LINE SECOND LINE Piperacillin/ Meropenem + tazobactam vanco 4.5 gm IV q6h OR cefepime + vanco plus vanco Piperacillin/ tazobactam 4.5 gm IV q6h + vanco 68 If high prevalence of MDR Gramnegative Gram (such as carbapenemresistant Enterobacteriac eae [CRE] or MDR-GNB) consider adding IV colistin Meropenem + vanco If high prevalence of MDR Gramnegative (such as CRE or MDRGNB), consider adding IV colistin COMMENTS Sepsis : (SIRS + a documented infection ) Severe sepsis: sepsis + organ dysfunction. Obtain appropriate cultures prior to antimicrobial therapy Check patient. old cultures and their antibiograms Could substitute linezolid for vanco, however linezolid is bacteriostatic against S. aureus. Stop vanco and colistin if no resistant organisms are isolated from cultures Hydrocortisone in stress dose 100 mg IV q8h if BP persistent after fluids and one pressor. Benefit in patients with severe sepsis (systolic pressure <90 mmHg) NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 11: GUIDELINES FOR TREATMENT OF SYSTEMIC INFECTIONS ANATOMIC SITE/DIAGNOSIS Toxic shock syndrome due to Clostridium sordellii present as shock, capillary leak, hemoconcentration, very high WBCs, afebrile ETIOLOGIES Clostridium sordellii (haemorrhagi c and lethal toxins) Staphylococcal toxic shock syndrome- S. aureus (toxic shocktoxin mediated) Streptococcal toxic shock syndrome associated with invasive disease like necrotizing fasciitis or chickenpox Febrile neutropenia Low risk (ANC >100, normal CXR, normal liver function tests and creatinine, no clinical IV site/tunnel infection, tem <39, no abdominal pain, no comorbidities. Neutropenia <7 days) Group A, B, C, G streptococci Aerobic Gramnegative bacilli, viridians streptococci SUGGESTED REGIMENS FIRST LINE SECOND LINE See above shock syndrome pen G 18–20 million units divided q4h + clindamycin 600 mg q6–8h surgical debridement is a key Cloxacillin 2 gm If MRSA vanco IV q4h plus 1 g IV q12h) + clindamycin 600 clindamycin 600 mg IV q6–8h + mg IV q6–8h + intravenous IVIG immunoglobulin (IVIG) (see comment for dose) Pen G 24 million Ceftriaxone 2 units per day in gm IV q24h + divided doses + clindamycin clindamycin 600– 600–900 mg IV 900 mg IV q8h q8h Low risk: cip 500–750 mg PO q12h daily + amoxicillinclavulanate 500 mg PO q8h 69 COMMENTS Occurs in variety of settings that produce anaerobic tissue, e.g. IVDU, post-partum, use of mifepristone & misoprostol for abortion IVIG dose 1 gm per kg on day 1 then 0.5 gm per kg days 2 & 3 IVIG associated with reduction in sepsis related organ failure IVIG dose 1 gm per kg on day 1 then 0.5 gm per kg days 2 & 3. Consider household contacts prophylaxis Fever defined as a single oral temperature of >38.3°C or a temperature of >38.0°C sustained for >1 hr. Neutropenia defined as ANC <500/mm3. Obtain appropriate cultures and radiological investigations to identify the focus of infection. Adjust antibiotics according to susceptibility profiles NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 11: GUIDELINES FOR TREATMENT OF SYSTEMIC INFECTIONS ANATOMIC SITE/DIAGNOSIS Febrile neutropenia High Risk: (anticipate >7 days, profound neutropenia & active comorbidities). Initial fever Persistent fever or new fever after 4–7 days in clinically stable patient without established bacterial infection Clinically unstable patient despite appropriate antibiotic and antifungal coverage ETIOLOGIES SUGGESTED REGIMENS FIRST LINE SECOND LINE Aerobic Monotherapy with: (Cefepime OR Grampiperacillin/tazobact piperacillin/tazo negative am 4.5 gm TID. -bactam) + bacilli, Consider vanco if aminoglycoside P. aeruginosa, indicated (see OR viridians comments) (cefepime + streptococci, cip). MRSA Consider vanco if indicated (see comments) Candida spp., Aspergillus, VRE Gramnegative bacilli Continue antibiotics as above and add antifungal coverage: -if receiving fluconazole or no fungal prophylaxis, start voriconazole or caspofungin -if receiving voriconazole or posaconazole as prophylaxis then start amphotericin B liposomal . Meropenem + vanco + an aminoglycoside 70 COMMENTS -Indications for vanco: history of MRSA infection OR colonization OR suspected CRBSI, skin and soft tissue infection or pneumonia or severe pharyngitis or mucositis or positive blood culture with Gram-positive organisms. -If suspected multidrug Gram-negative consider meropenem Prior to antifungal: obtain cultures, biopsy suspected skin lesions, CT chest/abdomen/sinuses, galactomannan assay, consult ID Obtain cultures and radiological workup. Consult ID NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 12: GUIDELINES FOR TREATMENT OF COMMON VIRAL INFECTIONS DISEASE Chickenpox DRUG Valacyclovir 1 g TID PO for 5–7 days ALTERNATIVE Oral acyclovir 800 mg 5 x a day for 7 days IV acyclovir 10 mg/kg every 8 hrs Shingles Valacyclovir 1 g TID for 7 days Acyclovir 800 mg 5 x a day 71 COMMENTS Clinical value of antiviral is minimal (especially if treatment started more than 24 hrs from onset of rash) Exceptions in the following situations: Case is immunocompromised Case is on steroid. Severe pain. Presence of secondary household case. If case is pregnant seek advice. Treatment can be given as outpatient basis. If admission is required, infection control team should be notified. Immediate hospitalization and IV treatment should be offered if the patient develops lifethreatening complications such as encephalitis, pneumonitis or CNS deterioration. Immunocompromised patients with severe chickenpox must always be given IV acyclovir If case is pregnant seek expert advice. Treatment should be offered in the following situation: case is presenting for the first time up to 72 hrs after onset of rash AND there are ophthalmic signs or age is more than 50 years (strong predictor predictors of postherpetic neuralgia). Severe pain or severe skin rash prolonged prodromal pain Case is immunosuppressed. Consider HIV testing NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 12: GUIDELINES FOR TREATMENT OF COMMON VIRAL INFECTIONS DISEASE Oral herpes simplex DRUG Acyclovir 5% topical cream 5 times a day for 5 days ALTERNATIVE Genital herpes simplex infection (first episode) Valacyclovir 1 g TID for 5 days or Oral acyclovir 200 mg 5 x a day for 5 days (review and continue for further 5 days if new lesions continue to appear) Valacyclovir 1 g TID for 5 days Oral acyclovir 200 mg 5 times a day for 5 days Oseltamivir 75 mg every 12 hrs orally for 5 days (for ICU admission, 75 to 150 mg 12 hourly) For children less than 13 years of age, dose should be adjusted accordingly IV acyclovir (5 mg/kg every 8 hrs) Recurrent genital herpes simplex infection Influenza COMMENTS Counsel patient that treatment needs to be initiated at the onset of symptoms before vesicles appear and that topical antivirals only affect the course of the current episode, they do not cure the individual or prevent further recurrence Treatment is effective if started within 5 days of onset of first lesion and while new lesions are appearing. In severe cases consult a specialist and consider IV treatment. If case is pregnant, consult ID Only supportive measures are required for the majority of cases. If greater than 6 episodes per year suppressive therapy should be considered and refer the patient to a specialist Please note that annual influenza vaccination is essential for all those at risk of influenza infection. Antiviral drugs are not in a substitute for vaccination, which remain the most effective way of preventing illness from influenza. This is particularly important in pregnant women 72 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 13-A: GUIDELINES FOR EMPERICAL TREATMENT OF PEDIATRIC INFECTIONS CENTRAL NERVOUS SYSTEM SYSTEM AGE GROUP Brain abscess Primary or contiguous source PostSurgical , Post traumatic Meningitis Neonate Meningitis 1-3 months SUSPECTED MICROBIAL AGENT INITIAL THERAPY ALTERNATIVE THERAPY OR COMMENTS Streptococcus spp. Bacteroides, Enterobacteriaceae, S. milleri, S. aureus, Rare: Nocardia, Listeria, Consider Toxoplasma gondii in HIV patient S. aureus, Enterobacteriaceae Group B Streptococcus, gram negative enteric bacilli (e.g E. Coli, Listeria) Ceftriaxone+ Vancomycin +Metronidazole Consult infectious diseases specialist Use initially Vancomycin to cover MRSA or beta lactam resistant S.pneumoniae then adjust according to culture results. Use Ceftazidime instead of Ceftriaxone if secondary to chronic otitis externa. Meropenem may be used in situation of antibiotic resistant(ESBL) S. aureus more likely if endocarditis +ve blood culture. Need neurosurgical consult for potential drainage Ampicillin + Cefotaxime Add Vancomycin if pneumococcus suspected on gram stain pending culture results. If patient diagnosed with meningitis after prolonged hospitalization and /or after neurosurgical procedure consider coverage for resistant gram negative, enterococci and candida Includes organisms usually seen in neonates or older children Ampicillin + Cefotaxime + Vancomycin listeria should be considered as a cause of meningitis in infants < 2months of age) Treatment durations (S. pneumonia 1014 days, N. Meningitides 5-7 days, H. influenza 10 days, Group B streptococci, Listeria 2-3 weeks, and E. coli ≥ 3weeks) 73 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 13-A: GUIDELINES FOR EMPERICAL TREATMENT OF PEDIATRIC INFECTIONS SUSPECTED MICROBIAL AGENT INITIAL THERAPY ALTERNATIVE THERAPY OR COMMENTS S. pneumonia, N. meningitides, H. Influenzae Ceftriaxone or Cefotaxime + Vancomycin Shunt infection Coagulase-negative, Staphylococcus, coliform bacilli Vancomycin+ Ceftriaxone Or Vancomycin + Meropenem Subdural empyema Most of the time its extension of sinusitis or otitis media Encephalitis/ Neonate meningo encephalitis Same as for primary brain abscess If allergic to cephalosporin: Consult ID .Consider Chloramphenicol to cover N.meningitidis, Co trimoxazole to cover Listeria in addition to the Vancomycin. Prophylaxis of close contact recommended for N. meningitidis and H. influenzae meningitis Use Ceftazidime if concerned about pseudomonas or Meropenem if ESBL suspected guided by institute antibiogram. Consult neurosurgery for shunt Taping and need for shunt removal Surgical emergency and must be drained. Herpes simplex IV: Acyclovir 20mg/kg/dose every 8 hrs and for 21 days Add Cefotaxime and Vancomycin to cover for meningitis till results of CSF culture and viral PCR available. Encephalitis Herpes simplex Others : Enteroviruses, Arboviruses, EBV Influenza, Varicella, Mycoplasma, Bartonella henselae, TB, Malaria and Listeria in immunocompromised IV Acyclovir 20mg/kg/dose every 8hrs for 21 days Ampicillin + Gentamicin if suspected Listerial rhomboencephalitis Herpes simplex is the most common and treatable cause. Add ceftriaxone and Vancomycin to cover for meningitis till results of CSF culture and viral PCR available. CSF should be sent for HSV PCR SYSTEM Meningitis AGE GROUP Older children Older children 74 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 13-A: GUIDELINES FOR EMPERICAL TREATMENT OF PEDIATRIC INFECTIONS SYSTEM SUSPECTED MICROBIAL AGENT ANTIMICROBIAL OF CHOICE ALTERNATIVE THERAPY OR COMMENTS RESPIRATORY SYSTEM Epiglottitis H. influenza, S. aureus, S. pyogenes, S. pneumoniae, Group A Streptococcus in immunized children (Ceftriaxone / cefotaxime ) + (clindamycin OR vanco) If suspected call paediatric ICU. Administer anaesthesia and ENT without distressing the child. Do not attempt IV for antibiotics or throat examination before securing airway. Keep in position of comfort (usually sitting) Peritonsillar cellulitis or retropharyngea l abscess Group A Streptococcus, S. aureus, Haemophilus spp., oral microflora / anaerobes Group A Streptococcus, group C and G streptococci, mycoplasma. Majority of cases (>70%) viral etiology and do not require antimicrobial therapy Clindamycin+ cefuroxime alternative amoxicillin/clavulanate Pen V OR Amoxicillin Urgent ENT consult and consider drainage. Close observation of airway as artificial airway may be required Dental abscess Oral aerobic & anaerobic flora Bacterial tracheitis S. aureus, S. Pneumonia, Group A streptococci, H. influenzae (Pen + metronidazole) OR clindamycin Cefuroxime OR clindamycin Alternative Amoxicillin Clavulanate Tooth extraction may be necessary Bacterial tracheitis can present as a croup but will have more rapid onset and higher temperature. In patient with tracheostomy, consider Pseudomonas or other Gram-negative organisms. If C-MRSA suspected use vanco until sensitivity available Oropharyngeal infection Pharyngitis 75 For patients with pen allergy clindamycin, erythromycin can be an alternative. For uncommon failure or frequent relapses amoxicillinclavulanate OR clindamycin will be more effective NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 13-A: GUIDELINES FOR EMPERICAL TREATMENT OF PEDIATRIC INFECTIONS SUSPECTED MICROBIAL AGENT SYSTEM Bacterial Neonate pneumonia Immunocompromised Aspiration Neonates pneumonia ANTIMICROBIAL OF CHOICE ALTERNATIVE THERAPY OR COMMENTS Group B streptococci, Listeria, Coliforms, S. aureus, P. aeruginosa Others: C. trachomatis, syphilis AMP + gentamicin OR cefotaxime + gentamicin Add erythromycin if Chlamydia suspected in late onset pneumonia. If baby behaves septic, obtain blood culture and send CSF for culture Any organisms but particularly pneumocystis, P. aeruginosa, Gram-negative enteric bacilli (e.g. E. coli), S. aureus Piperacillin/ tazobactam + gentamicin ± cotrimoxazole (for Pneumocystis pneumonia [PCP]) ± clindamycin OR vanco (for MRSA) Meropenem + gentamicin +/cotrimoxazole is an alternative. An early bronco alveolar lavage may be needed to prove or exclude PCP and look for other rare aetiologies (e.g. Aspergillus) Please consult infectious disease unit and pulmonologist Oral anaerobes, Streptococcus spp., S. aureus Gram-negative enteric bacilli Empiric antibiotic not recommended Mild-moderate: none Moderately severe: amoxicillin clavulanate Hospital-acquired infection: amoxicillinclavulanate + gentamicin If infection suspected, start AMP + gentamicin. Use Clindamycin + gentamicin if severe case OR if AMP therapy within last 5 days. Use clindamycin OR piperacillin + tazobactam if pen-resistant organisms suspected Older children 76 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 13-A: GUIDELINES FOR EMPERICAL TREATMENT OF PEDIATRIC INFECTIONS EMPIRIC TREATMENT OF COMMUNITY- ACQUIRED BACTERIAL PNEUMONIA IN CHILDREN# AGE GROUPS 1–3 months ORGANISMS S. pneumoniae, C. trachomatis, B. pertusis, S. aureus, H. influenzae AGENTS OF CHOICE Cefuroxime (IV) +/clarithromycin (if PO) For ICU patients: cefotaxime + erythromycin /clarithromycin ± cloxacillin* ALTERNATIVE AGENTS AMP (IV) +/- erythromycin or clarithromycin cefotaxime +/ - vanco ** 3 months – 5 years S. pneumoniae, S. aureus (MSSA/MRSA), H. influenzae, M. pneumoniae,GAS AMP (IV) amoxcillin OR amoxicillin-clavulanate if PO ± clarithromycin For ICU patients: Cefuroxime + either Erythromycin OR Clarithromycin Cefuroxime OR amoxicillinclavulanate ± clarithromycin AMP (IV), Amoxicillin if PO + either erythromycin OR clarithromycin For ICU patients: cefuroxime + either erythromycin OR clarithromycin Cefuroxime OR amoxicillinclavulanate + either erythromycin OR clarithromycin >5 years S. pneumoniae, S. aureus, H. influenzae, M. pneumoniae Ceftriaxone +vanco** Cefotaxime OR ceftriaxone + vanco** # Consider viral etiologies in differential diagnosis and start empirically oseltamivir until influenza diagnosis is excluded *Use Cloxacillin if one suspected S. aureus pneumonia/sepsis in critically ill infants ** use vancomycin if resistant S. pneumoniae or CA-MRSA suspected Beta-lactam allergic patients: For patients with significant β-lactam allergy, macrolides or clindamycin are alternatives to the β-lactams 77 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 13-A: GUIDELINES FOR EMPERICAL TREATMENT OF PEDIATRIC INFECTIONS SYSTEM Hospitalacquired pneumonia SUSPECTED MICROBIAL AGENT ANTIMICROBIAL OF CHOICE ALTERNATIVE THERAPY OR COMMENTS P. aeruginosa, S. aureus, Gram-negative enteric bacilli (Enterobacter, Klebsiella, Serratia, E. coli) Stenotrophomonas and Gram-positive organisms – enterococci including VRE, MRSA Piperacillin/tazobactam OR meropenem, OR cefepime with or without gentamicin and vanco Empirical therapy based on prior colonization and hospital epidemiology Add vanco if MRSA suspected Meconium aspiration syndrome, neonates AMP + gentamicin recommended if there is a septic set-up and/or a clinical suspicion of sepsis Pertussis B. pertussis Pneumonia in Sickle cell disease S. pneumoniae, M. pneumoniae, H. influenzae Acute pulmonary exacerbations of cystic fibrosis Lung Empyema 1 month - 5 years P. aeruginosa, S. aureus, B. cepacia, H. influenzae >5 years S. pneumoniae, group A streptococci S. aureus, S. pneumoniae H. influenzae, K. pneumoniae Erythromycin IV OR PO X 14 days OR clarithromycin X 7 days OR azithromycin X 5 days Ceftriaxone/cefotaxime ± erythromycin/ clarithromycin (PO) ± vanco Piperacillin + tazobactam + gentamicin. Where possible base antibiotic selection on patients most recent culture & sensitivity reports Ceftriaxone OR cefotaxime + vanco 78 Isolate for first 5 days of therapy. Report the case to communicable diseases. Family prophylaxis In presence of significant Blactam allergy: use clindamycin. Add erythromycin OR clarithromycin if required for coverage against chlamydia, mycoplasma Ceftazidime + gentamicin. Consider vanco if MRSA suspected. Consult respiratory medicine Clindamycin is an option for sensitive CA-MRSA and in patients with beta-lactam allergy. Consult pulmonologist and infectious diseases regarding drainage and further management. NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 13-A: GUIDELINES FOR EMPERICAL TREATMENT OF PEDIATRIC INFECTIONS SYSTEM SUSPECTED MICROBIAL AGENT ANTIMICROBIAL OF CHOICE ALTERNATIVE THERAPY OR COMMENTS Heart Infection Infective endocarditis Native valve (including congenital heart disease): viridians streptococci, Enterococcus, staphylococci including CoNS, Pneumococcus Empirical therapy: Penicillin + gentamicin OR ceftriaxone + gentamicin Group A streptococci Prosthetic valve: including above and gGramnegative bacilli, diphtheroids Vancomycin+ Gentamicin+ Rifampin 79 If patient not acutely ill or in heart failure, wait for blood culture results. If initial 3 blood cultures negative after 24–48 hrs incubation obtain another 2–3 more blood cultures before starting empiric therapy. If MRSA suspected Add Vancomycin. Gentamicin is synergistic dosage for gram positive organisms. Definitive therapy should be guided by results of blood culture NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 13-A: GUIDELINES FOR EMPERICAL TREATMENT OF PEDIATRIC INFECTIONS SYSTEM SUSPECTED MICROBIAL AGENT ANTIMICROBIAL OF CHOICE Gr B streptococci, Gramnegative enteric bacilli (e.g. E. coli, Enterococcus, listeria). AMP + aminoglycosides Includes organisms usually seen in neonates or older children Cloxacillin + cefotaxime ± AMP OR vanco + cefotaxime ALTERNATIVE THERAPY OR COMENTS SEPSIS New admission neonate 1–3 months AMP + cefotaxime Consider AMP if listeria suspected >3 months S. pneumoniae, meningococcus,S. aureus, H. influenzae Ceftriaxone/cefotaxime + vanco Sickle cell disease with fever S. pneumonia, H. influenza, Salmonella species Ceftriaxone/cefotaxime ± vanco Piperacillin + tazobactam CVL-tunnel infection Coagulase-negative Staphylococcus, S. aureus, less likely Gram-negative organisms and Candida spp. Vanco Consider removing the central lines. Modify therapy with culture reports. S. typhi, S. paratyphi Cefotaxime/ceftriaxone Narrow therapy once sensitivity available Enteric fever 80 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 13-A: GUIDELINES FOR EMPERICAL TREATMENT OF PEDIATRIC INFECTIONS SUSPECTED MICROBIAL AGENT SYSTEM ANTIMICROBIAL OF CHOICE ALTERNATIVE THERAPY OR COMMENTS SKIN AND SOFT TISSUE Cellulitis neonates Gram-negative enteric bacilli, S. aureus IV cloxacillin + aminoglycoside Infants & children S. aureus, group A streptococci Cephalexin oral OR IV cephazolin OR Cloxacillin Impetigo S. aureus, group A streptococci Mild: mupirocin (topical) Moderate-severe: Cloxacillin OR cephazolin Clindamycin (oral) OR cephalexin (oral) Necrotizing fasciitis** ** For suspected cases consult ID and surgeons Group A streptococci, S. aureus IV clindamycin+ cloxacillin OR IV cephazolin + clindamycin. Use vanco if MRSA suspected Invasive group A streptococci disease. Suspected (chickenpox, immunocompromised, trauma). Consider also IVIG Myositis, supportive (tropical myositis, pyomyositis) Cervical adenitis S. aureus Cloxacillin Vanco for CA-MRSA, clindamycin OR linezolid. Surgical drainage/excision when needed S. aureus, group A streptococci S. pneumoniae, Group A streptococci, S.aureus, H. influenzae, M. catarrhalis, anaerobes Cloxacillin PO/IV Clindamycin , cephalexin or cefazolin IV cloxacillin + ceftriaxone/cefotaxime ± metronidazole Ceftriaxone /cefotaxime + clindamycin Orbital cellulitis 81 Drain any abscess first. If Late onset group B streptococci suspected add IV AMP. If Invasive group A streptococci suspected (chickenpox, immunocompromised, trauma) IV pen +clindamycin to be started. Use vanco if MRSA suspected. NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 13-A: GUIDELINES FOR EMPERICAL TREATMENT OF PEDIATRIC INFECTIONS SYSTEM Periorbital cellulitis Traumatic Non-traumatic Dog bite/cat bite Human bite Soil contamination injuries SUSPECTED MICROBIAL AGENT S. aureus, group A streptococci ANTIMICROBIAL OF CHOICE ALTERNATIVE THERAPY OR COMMENTS IV cloxacillin Vanco OR clindamycin S. pneumoniae, group A streptococci, S. aureus, H. influenzae, M. catarrhalis IV cefotaxime OR ceftriaxone + Cloxacillin OR vanco if MRSA suspected If no associated bacteraemia and mild disease step down to oral therapy is appropriate with cefuroxime OR amoxicillin-clavulanate P. multocida, Streptococcus spp., S. aureus, anaerobes and many other organisms Streptococcus spp., S. aureus, anaerobes Oral: amoxicillinclavulanate OR (if severe) IV amoxicillinclavulanate Pen-allergic patients: >8 yrs: doxycycline + clindamycin ≤8 yrs: cotrimoxazole + clindamycin OR cotrimoxazole + metronidazole. Assess need for tetanus, rabies prophylaxis Oral: Amoxicillin/ clavulanate OR (if severe) IV: amoxicillinclavulanate Pen-allergic patients: >8 yrs: doxycycline + clindamycin ≤8 yrs: cotrimoxazole + clindamycin OR cotrimoxazole + metronidazole. Assess need for tetanus, rabies prophylaxis Mixed flora, including Clostridium, S. aureus, Gramnegative enteric bacilli IV: Amoxicillinclavulanate + gentamicin Assess need for tetanus vaccine ± immune globulin 82 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 13-A: GUIDELINES FOR EMPERICAL TREATMENT OF PEDIATRIC INFECTIONS SYSTEM SUSPECTED MICROBIAL AGENT SKELETAL INFECTIONS Septic arthritis Neonates Group B streptococci, S. aureus, Gramnegative enteric bacilli (e.g., E. coli). Infants 1–3 months H. influenzae, Streptococcus spp., Staphylococcus spp. Also pathogens as of neonates. Children Group A streptococci, S. aureus, S.pneumoniae, K. kingae, H. influenzae Osteomyelitis (acute) Neonate S. aureus, Group B streptococci, Gramnegative enteric bacilli (e.g., E. coli) Infants 1–3 H. influenzae, months Streptococcus spp., Staphylococcus spp. Also pathogens as of neonates Children S. aureus, S.pneumoniae Group A Streptococci, rarely Kingella Sickle cell disease S. aureus, Salmonella with spp., S. pneumoniae osteomyelitis/ septic arthritis Puncture wound P. aeruginosa of foot Sneakers No sneakers S. aureus ANTIMICROBIAL OF CHOICE Cloxacillin + cefotaxime OR gentamicin Cefotaxime + cloxacillin ALTERNATIVE THERAPY OR COMMENTS Drain any abscess first, consider late onset group B streptococci If MRSA suspected OR cultured use vanco OR clindamycin as per sensitivity report. Can step down to oral option once patient afebrile, mobilizing joint and inflammatory markers coming down Cefazolin OR cloxacillin Vanco + cefotaxime. Cloxacillin + cefotaxime Cefotaxime + cloxacillin Cefazolin Cefotaxime/ceftriaxone + cloxacillin Drain any abscess first consider late onset Group B streptococci If MRSA suspected or cultured use vanco OR clindamycin as per sensitivity report Can step down to oral option once patient afebrile, mobilizing joint and inflammatory markers coming down Vanco + ceftriaxone/cefotaxime Cloxacillin + cip Significant B-lactam allergy; Cip + gentamicin Oral/IV: cloxacillin Culture and sensitivity desirable 83 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 13-A: GUIDELINES FOR EMPERICAL TREATMENT OF PEDIATRIC INFECTIONS SYSTEM SUSPECTED MICROBIAL AGENT ANTIMICROBIAL OF CHOICE ALTERNATIVE THERAPY OR COMMENTS Add metronidazole for perforation, peritonitis and rapidly advancing sepsis. Add antifungal if infection suggested by Gram stain or culture Gastrointestinal Infections Necrotizing enterocolitis neonate Enteric Gram-negative bacilli, Enterococcus, anaerobes, Pseudomonas in hospitalized patient AMP + aminoglycoside ± metronidazole OR piperacillintazobactam Colitis –antibiotic associated C. difficile Stop implicated antibiotics, start metronidazole OR, if failed, oral vanco Cholera V. cholerae Doxycycline for age >8 yrs. Azithromycin OR cip as alternative to doxycycline Gastritis, peptic ulcer disease H. pylori Triple therapy : (clarithromycin amoxicillin, omeprazole) Most data are from adult. Treat for 10 days Perforated appendix Enteric Gram-negative bacilli, Enterococcus, anaerobes AMP + gentamicin + Metronidazole Piperacillin + tazobactam Bloody diarrhoea Salmonella spp., Shigella spp., C. jejuni, verotoxin-producing E. coli (including 0157:H7), Y. enterocolitica, toxin-producing C. difficile, E. histolytica Empiric therapy is generally not indicated, except for certain pathogens and selected situations where the child is very sick or toxic. Use empirically cip and adjust according to pathogen isolated Based on culture results . Antibiotic is indicated for: all Shigella and E. histolytica infections; Salmonella in severe infections or at-risk patients including immunocompromised or <3months old; Yersinia infections in presence of terminal ileitis or mesenteric adenitis; toxinproducing C. difficile; enteric infection with sepsis. Antibiotics NOT indicated for: Verotoxin-producing E. coli infections, uncomplicated Yersinia, Salmonella, Campylobacter infection 84 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 13-A: GUIDELINES FOR EMPERICAL TREATMENT OF PEDIATRIC INFECTIONS SYSTEM Peritonitis Primary Secondary to bowel perforation Secondary to peritoneal dialysis SUSPECTED MICROBIAL AGENT Pneumococcus, S. aureus, enteric Gram-negative organism, Streptococcus spp. Enteric Gram-negative bacilli Bacteroides, Enterococcus, Pseudomonas in hospitalized patient Coagulase-negative staph., S. aureus, Gram-negative organism, candida 85 ANTIMICROBIAL OF CHOICE Ceftriaxone If pen susceptible, pen AMP +gentamycin + metronidazole Ceftriaxone+ vanco. Antibiotic added to the dialysate in concentration approximating those attained in serum for systemic disease. ALTERNATIVE THERAPY OR COMMENTS Other antibiotics according to culture and sensitivity Piperacillin-tazobactam Surgical management is essential Selection of antibiotics based on organism isolated from peritoneal fluid. Systemic antibiotics if there is bacteraemia. Catheter removal especially with fungal infection and in recurrent episodes of bacterial infection. NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 13-A: GUIDELINES FOR EMPERICAL TREATMENT OF PEDIATRIC INFECTIONS SYSTEM SUSPECTED MICROBIAL AGENT EYE, EAR AND SINUS INFECTIONS Conjunctivitis N. gonorrhoeae, neonates C. trachomatis, herpes simplex, Pseudomonas aeruginosa, Older infants & children Mastoiditis (acute) Sinusitis (acute & subacute) Non-typeable H. influenzae, S. pneumoniae, N. gonorrhoea S. pneumoniae, S. aureus, H. influenzae, M. catarrhalis, Group A streptococci S. pneumoniae, H.influenzae, M. catarrhalis, Group A streptococci ANTIMICROBIAL OF CHOICE Cefotaxime erythromycin PO. Acyclovir topical and IV piperacillin + gentamicin gentamicin ophthalmic solution Topical ofloxacin. Consult ophthalmologist. IV ceftriaxone IV: ceftriaxone/cefotaxime + cloxacillin OR vanco if MRSA suspected Amoxicillin (high dose) ALTERNATIVE THERAPY OR COMMENTS Consider switch to oral therapy when clinically improved. Definitive therapy depends on cultures result and sensitivity Amoxicillin-clavulanate May need 14–21 days 86 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 ANTIBIOTICS TREATMENT OF OTITIS MEDIA S. pneumoniae, M. catarrhalis, H. influenzae non-type B ANTIBIOTICS IN MONTH PRIOR TO DIAGNOSIS NO YES Initial Usual dose of amoxicillin High dose amoxicillin OR high dose amoxicillin-clavulanate OR cefuroxime Failure day 3 High dose amoxicillin-clavulanate OR cefuroxime OR ceftriaxone/IM given OD x 3 days Tympanocentesis and culture should be considered. Antibiotic therapy is same as day 3 Ceftriaxone IM/IV given OD x 3 days and/or culture-guided therapy Failure day 10–28 Tympanocentesis and culture should be considered. High dose amoxicillin-clavulanate or ceftriaxone IM/IV given OD x 3 days TABLE 13-A: GUIDELINES FOR EMPERICAL TREATMENT OF PEDIATRIC INFECTIONS SYSTEM SUSPECTED MICROBIAL AGENT ANTIMICROBIAL OF CHOICE ALTERNATIVE THERAPY OR COMMENTS GENITOURINARY UTI: Neonate Infants & children E. coli, P. mirabilis, klebsiella, Enterococcus spp., P. aeruginosa IV: AMP + gentamicin Cath or suprapubic urine sample for culture and adjust antibiotics according to sensitivity. E. coli, P. mirabilis, klebsiella, Enterococcus spp, p. aeruginosa,group B Streptococcus Oral: amoxicillinclavulanate Consider step down to oral sequential therapy when clinically improved. IV: AMP + gentamicin 87 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 13-B: PAEDIATRIC ANTIBIOTICS DOSAGE GUIDELINE ANTIMICROBIAL RECOMMENDED DOSAGE PENICILLIN Amoxicillin 50 mg/kg/day PO divided every 8 or 12 hrs 80–90 mg/kg/day PO divided every 8 or 12 hrs (high dose) Amoxicillin-clavulanate 45–50 mg/kg/day PO (amoxicillin) divided every 8 hrs (4:1) formulation 80–90 mg/kg/day PO (amoxicillin) divided every 12 hrs (7:1) formulation (high dose) Ampicillin 100–200 mg/kg/day IV divided every 6 hrs 300–400 mg/kg/day IV divided every 6 hrs for severe infection Penicillin V 25–50 mg/kg/day PO divided every 6 hrs or every 12 hrs Penicillin G 100,000–250,000 units/kg/day IV divided every 4–6 hrs 250,000–400,000 units/kg/d IV day IV divided every 4–6 hrs for severe infections Cloxacillin 50–100 mg/kg/day PO/IV/IM divided every 6 hrs for mild to moderate infections 150–200 mg/kg/day IV/IM divided every 6 hrs for severe infections Piperacillin-Tazobactam 240–300 mg piperacillin/kg/day IV divided every 6–8 hrs All doses based on piperacillin component: Infant <6 mos.: 150- 300 mg/kg/d IV div q6–8h Infant >6 mos.: 300- 400 mg/kg/d IV div q6–8h Cystic fibrosis: 350–600 mg/kg/d IV div q4–6h 88 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 13-B: PAEDIATRIC ANTIBIOTICS DOSAGE GUIDELINE ANTIMICROBIAL RECOMMENDED DOSAGE Imipenem CARBAPENEMS 60–100 mg/kg/day IV div q6h Meropenem 60–120 mg/kg/day IV div q8h CEPHALOSPORINS Cephalexin 25-50 mg/kg/d PO div q6–8h 50–100 mg/kg/d PO div q6–8h in severe infections Cefazolin 25–50 mg/kg/d IV div q6-8h 100–150 mg/kg/d IV div q6-8h in severe infections Cefuroxime axetil 20–30 mg/kg/d PO div q12h 75-150 mg/kg/day IV div Q8H for severe infections. Cefixime 8 mg/kg/d PO div q12–24h Cefotaxime 100–200 mg/kg/d IV div q6–8h 200–225 mg/kg/d IV div q4–6h in severe infections; up to 300 mg/kg/d div q6h has been used for meningitis, pneumococcal meningitis Ceftriaxone 50–100 mg/kg/d IV div q12–24h Ceftazidime 100–150 mg/kg/d IV div q8h 200–300 mg/kg/d IV div q8h in severe infections 100–150 mg/kg/d IV div q8h Cefepime Amikacin AMINOGLYCOSIDES 15–30 mg/kg/day IV/IM div q8h 20 mg/kg/dose IV q24h for febrile neutropenia 30 mg/kg/dose IV q24h in cystic fibrosis 89 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 13-B: PAEDIATRIC ANTIBIOTICS DOSAGE GUIDELINE ANTIMICROBIAL Gentamicin RECOMMENDED DOSAGE 7.5 mg/kg/day IV/IM div q8h Febrile neutropenia patients: 1 month- <9 yrs. initial dose 10 mg/kg/dose IV/IM q24h 9–12 yrs. initial dose 8 mg/kg/dose IV/IM q24h >12 yrs. initial dose 6 mg/kg/dose IV/IM q24h Synergy with β-lactams for Gram-positive infections : 3 mg/kg/day IV/IM div q8h For cystic fibrosis: 7.5- 10.5 mg/kg/d IV div q8h Tobramycin 7.5 mg/kg/d IV div q8h 10–12 mg/kg/dose q24q in cystic fibrosis. MACROLIDES Erythromycin 20-50 mg/kg/d PO/IV div q6h Azithromycin Serious infection: 10 mg/kg IV OD Cystic fibrosis: 18–35.9 kg: 250 mg PO 3 times weekly ≥36 kg: 500 mg 3 times weekly Other infections oral therapy: 5-day regimen: 10 mg/kg once on day 1 followed by 5 mg/kg OD on days 2–5 3-day regimen: 10 mg/kg OD for 3 days 1-day regimen: 30 mg/kg as a single dose Clarithromycin 15-30 mg/kg/day PO div q12h OTHERS Clindamycin Mild to moderate infections : 20–30 mg/kg/d PO/IV div q6–8h Severe infections: 30–40 mg/kg/day IV div q6–8h 90 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 13-B: PAEDIATRIC ANTIBIOTICS DOSAGE GUIDELINE ANTIMICROBIAL RECOMMENDED DOSAGE Metronidazole 15–30 mg/kg/d PO div q8-12h 30 mg/kg/d IV div q6–8h Cotrimoxazole 6–12 mg TMP/kg/d PO div BID 15–20 mg TMP/kg/d IV div q6–8h for severe infections 20 mg TMP/Kg/d IV/PO div q6h for treatment of Pneumocystis jiroveci pneumonia 5mg TMP/kg/d PO OR IV div q12h in pneumocystis prophylaxis 2–4 mg TMP/kg/d PO q6h in UTI prophylaxis Trimethoprim 4–6 mg/kg/d PO div q12h For UTI prophylaxis: 2–3 mg/kg/day PO qhs Doxycycline For children >8 yrs. of age: 2–4 mg/kg/d PO div q12–24h Nitrofurantoin For treatment: 5–7 mg/kg/d PO div QID UTI prophylaxis: 1–2 mg/kg/day PO qhs Vancomycin 40–60 mg/kg/d IV div q6–8h Linezolid <12 yrs. old: 30 mg/kg/d IV/PO div q8h ≥12 yrs. old: 600 mg IV/PO q12h ANTIVIRAL Acyclovir HSV: 40–60 mg/kg/d PO div q6–12h HSV encephalitis : 60 mg/kg/d IV div q8h for 21 days VZV: 80 mg/kg/d PO div q8h VZV immunocompromised: 30 mg/kg/d IV div q8h 91 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 13-B: PAEDIATRIC ANTIBIOTICS DOSAGE GUIDELINE ANTIMICROBIAL Amantadine Oseltamivir RECOMMENDED DOSAGE Treatment & prophylaxis of influenza A ONLY 1–9 yrs. and/or <40 kg: 5 mg/kg/d PO div q12h (max 150 mg/day) ≥ 10 yrs. & ≥40 kg: 100 mg PO q12h Treatment of Influenza A & B 1–3 mos.: 2.5 mg/kg PO q12h x 5 days 3 mos-1 yr.: 3 mg/kg PO q12h x 5 days >1 yr.: 10–15 kg: 30 mg PO q12h x 5 days 15–23 kg: 45 mg PO q12h x 5 days 23–40 kg: 60 mg PO q12h x 5 days >40 kg: 75 mg PO q12h x 5 days 13 yrs.: 75 mg PO BID Prophylaxis Of Influenza A&B >1 yr.: 10–15 kg : 30 mg PO daily x10 days 15–23 kg: 45 mg PO daily x 10 days 23–40 kg: 60 mg PO daily x 10 days 40 kg: 75 mg PO daily x 10 days ANTIFUNGAL Amphotericin B 0.25–1.5 mg/kg/d IV daily Amphotericin B Lipid Complexed (Abelcet) 5 mg/kg/IV OD Amphotericin B Liposomal (AmBisome) 3–5 mg/kg IV OD Caspofungin ketoconazole For age ≥3 mos. : 70 mg/m²/day IV (max 70 mg) day 1, then 50 mg/m²/day IV (Max50 mg in patients <12 yrs., max 70 mg in patients ≥12 yrs.) 5–10 mg/kg/d PO div q12–24h fluconazole 3–12 mg/kg/d IV/PO div q24h Itraconazole 5–10 mg/kg/d PO div q12–24h 2.5- 5 mg/kg/d PO div q8–12h for prophylaxis OR oropharyngeal candidiasis treatment 92 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 13-B: PAEDIATRIC ANTIBIOTICS DOSAGE GUIDELINE ANTIMICROBIAL RECOMMENDED DOSAGE Nystatin 400,000–2,400,000 units/day PO div q6–8h Voriconazole PO 18mg/kg/day PO div q12h Voriconazole IV 2-12y: 18mg/kg/day div q12h x 2doses, then 16mg/kg/day div q12h. >12 years: 12 mg/kg/d IV div q12h x 2 doses, then 8 mg/kg/d IV div q12h, may be increased to 5 mg/kg/dose q12h if needed or reducedto 3 mg/kg/dose q12h if patient is unable to tolerate. mg/kg/d=milligram per kilogram per day. Usual doses for paediatric patients with normal renal and hepatic function. Paediatric dose should not exceed recommended adult dose (except for cefuroxime where maximum is 1.5g IV q8h). 1. These doses do not apply to neonates, except where noted. 2. For completion of therapy of bone and joint infections. 3. For meningitis and other CNS infections, higher end of the dosage listed should be used 93 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 14: GUIDELINES FOR THERAPEUTIC DRUG MONITORING (TDM): CLINICAL GUIDE FOR ADULTS Therapeutic drug monitoring is required for patients on aminoglycoside (e.g. gentamicin, amikacin) and glycopeptides (e.g. vancomycin). Serum concentration monitoring aims to avoid both excessive and sub-therapeutic concentration thereby preventing toxicity and ensuring efficacy. DRUG Gentamicin TROUGH AND PEAK RANGE (mg/l) Trough: <2 mg/l (<1 mg/l for Endocarditis) Peak: 5–10 mg/l (3–5 mg/l for endocarditis) SAMPLING TIME REMARKS Multiple daily regimen: initial trough sampling: take sample just before 3rd or 4th dose. Trough: should be taken 8–12 hrs after the previous dose for TID and BID regimen respectively Peak: 30 min after 30 minutes infusion Once daily regimen: Obtain a single serum level after 1st dose, 8 hrs after start of infusion. Evaluate on the nomogram (SEE THE FORM ATTACHED). If the level falls in area q24h, q36h or q48h, the interval should be every 24, 36 or 48 hrs respectively. If the point is on a slanting line, choose longer interval. If the point is above the nomoGram, stop schedule treatment. Do serial levels to determine time of next dose (2 mg/l). Fresh sample must be used if pen group is also prescribed. Aminoglycoside adverse drug reactions (ADRs): nephrotoxicity, autotoxicity (especially when combined with other aminoglycoside/diuretics). Subsequent levels should be measured every 2–3 days until the dose is stabilized, then weekly. More frequent monitoring may be required if renal impairment is present, or if other nephrotoxic drugs are being administered concomitantly. Interpretation: If trough concentration is >2 mg/l, withhold until it falls >2 mg/l (check serum level daily if necessary) and seek pharmacist advice 94 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 14: GUIDELINES FOR THERAPEUTIC DRUG MONITORING (TDM): TROUGH AND PEAK RANGE (mg/l) SAMPLING TIME REMARKS Amikacin Trough: <10 mg/l Peak: 20–30 mg/l (25–30 for CNS, pulmonary, bone, serious infections, and patients with febrile neutropenia) Initial trough sampling: take sample 15 hrs after the start of the first dose infusion Trough: within 30 minutes of next due dose Peak: 30 minutes after end of infusion. 1 hr following IM injection Vancomycin Trough: once or twice daily regimen: 10–15 mg/l (15–20 mg/l for serious infections due to MRSA including bacteraemia, infective endocarditis, osteomyelitis, meningitis) pneumonia and severe SSTI) Initial trough sampling: take sample just before the fourth dose. Trough: For once or twice daily regimen collect within 30 minutes of next due dose Peak: not required Fresh sample must be used if pen group is also prescribed. Subsequent levels should be measured every 2–3 days until the dose is stabilized, then weekly. More frequent monitoring may be required if renal impairment is present, or if other nephrotoxic drugs are being administered concomitantly If trough concentration is higher than target level, withhold until it falls (check serum level daily if necessary) and seek advice Subsequent levels should be measured every 2–3 days until the dose is stabilized, then weekly. Nephrotoxicity: 2–3 consecutive documented increase by 50% in serum creatinine from baseline. More frequent monitoring may be required if patient haemodynamically unstable or renal impairment is present, or if other nephrotoxic drugs are being administered concomitantly. If trough level is higher than 25 mg/l, withhold until it falls (check serum level daily if necessary) and seek pharmacist advice DRUG 95 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 Please consider the following : - These are guidelines only; if you need more advice on the appropriateness of the sampling time, and the interpretation of the levels, contact the clinical pharmacist. TDM results must be interpreted in conjunction with the clinical status of the patient. Always use actual body weight for dose calculations. Recording the sampling time (e.g. sample was taken at 6.30 am) is a MUST in order to interpret the results and modify the dose accordingly. Tips assist in interpreting TDM results - Was the sample taken at steady state? - Was the sample taken at the right time? - Was the drug administered at the right time? - Was the sample taken is peak or trough? - Are there any interacting drugs/foods? - Drug compliance? - Is the result what you would expect? - If any of the following clinical conditions is present: Ascites, burns, CHF, Gram-negative sepsis, hepatic/renal failure, neonate. References: 1. Surrey and Sussex Healthcare NHS trust. Therapeutic Drug Monitoring (TDM). Gentamicin prescribing guidelines –updated 27th Mar 2014, AL. 2. BNF, 2010. 3. Rybak M, Lomaestro B, Rotschafer JC, Moellering R Jr, Craig W, Billeter M, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of HealthSystem Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm 2009;66:82–98. 4. Pharmacy Bulletin. SQUH. Vol.4, No 1. 5. Therapeutics: A Handbook for prescribers. NHS Greater Glasgow and Clyde, UK. August 2010. 96 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 HARTFORD HOSPITAL ONCE DAILY GENTAMICIN NOMOGRAM FIG 2 97 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 GUIDELINES FOR SURGICAL ANTIMICROBIAL PROPHYLAXIS Rationale Antibiotics are administered prior to surgical procedures to prevent surgical site infections. Aims 1. To provide antimicrobial recommendations for surgical prophylaxis in adult and children undergoing surgical procedures taking into consideration the type of surgery, most common organisms involved, international guidelines, expert opinion and cost. 2. To optimize antimicrobial use and patient outcome in prevention of surgical site infections in a rational way to prevent the emergence of resistance among bacteria. Antimicrobial surgical prophylaxis is generally indicated for the following type of surgery: 1. Clean wounds are uninfected operative wounds in which no inflammation is encountered and the wound is closed primarily. By definition, a viscus (respiratory, alimentary, genital or urinary tract) is not entered during a clean procedure. 2. Clean-contaminated wounds are operative wounds in which a viscus is entered under controlled conditions and without unusual contamination. Antimicrobial prophylaxis is not indicated for an operation classified as dirty or contaminated as treatment is required. General considerations When prescribing an antimicrobial surgical prophylaxis, the following points should be considered: 1. Selection of an appropriate agent for specific patients should take into account not only comparative efficacy but also adverse-effect profiles and patient drug allergies. 2. For most procedures, cefazolin 1 g or cefuroxime should be the agent of choice because of their relatively long duration of action, their effectiveness against the organisms most commonly encountered in surgery and their relatively low cost. 3. Clindamycin or vancomycin should be used in penicillin-allergic patients. 4. Clindamycin may be preferable for patients not at risk for infections due to resistant Gram-positive organisms secondary to its narrower spectrum and a more rapid infusion time. 5. Routine vancomycin use is discouraged. 6. Modification of a surgical prophylaxis regimen may be necessary in patients with pre-existing infections prior to surgery, significant length of hospital stay prior to surgery and previous positive cultures/colonization. Consult infectious diseases unit for specific recommendations. 7. The recommendations in this guideline are provided for adult and paediatric (1–12 years) patients. They do not specifically address infants. 8. Decolonization therapy for MRSA is recommended prior to surgery and antibiotic prophylaxis should include cover for MRSA. Please refer to infection prevention protocol for decolonization. 9. Hospital-based guidelines should be developed in accordance to surgical site surveillance, the most frequently isolated pathogens implicated and their local antibiogram. 98 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 Timing 1. Administration of antibiotics for surgical prophylaxis should be as near to the incision time as possible. Infusion of antibiotics for surgical prophylaxis should begin within 1 hour prior to skin incision (i.e. at induction of anaesthesia in case of general anaesthesia). 2. Vancomycin may begin within 2 hours prior to incision due to the longer infusion time and to ensure adequate tissue levels at the time of incision. 3. All antibiotic infusions should be completed prior to incision. Duration 1. The optimal duration of perioperative prophylaxis is unknown. It is unlikely that further benefit is attained by the administration of additional doses beyond wound closure and postoperative prophylaxis is not recommended. 2. Single prophylactic doses +/- additional intraoperative doses in prolonged procedures are strongly recommended. If prophylaxis is extended beyond the operative period, antibiotics should be discontinued within 24 hours unless otherwise specified. 3. Additional intraoperative doses are strongly recommended in prolonged procedures at intervals approximately 2 times the half-life of the drug. This roughly corresponds with redosing antimicrobials at a frequency of one interval shorter than usual (see Table 1). Additional intraoperative doses may not be warranted in patients for whom the half-life of the antimicrobial is prolonged, such as those patients with renal insufficiency. 4. The continuation of prophylaxis until all catheters and drains have been removed is not appropriate and not recommended. Responsibility for application The attending surgeon should ensure that the appropriate dose, timing and duration are followed. References: 1. Bratzler DW, Dellinger EF, Olsen KM, Perl TM, Auwaerter PG, Bolon MK, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J health Syst Pharm 2013;70:195–283 2. Gulf Cooperation Council. Infection prevention and control manual. 2nd edition. Riyadh, KSA: National Guard Health Affairs; 2013. 3. Garey KW, Dao T, Chen H, Amrutkar P, Kumar N, Reiter M, et al. Timing of vancomycin prophylaxis for cardiac surgery patients and the risk of surgical site infections. J Antimicrobial Chemotherapy 2006;58:645–650. 4. Weber WP, Marti WR, Zwahlen, Misteli H, Rosenthal R, Reck S, et al. Annals of Surgery 2008;247: 918– 926. 5. Stuart Wolf, Jr., Chairman; Carol J. Bennett; Roger R. Dmochowski,; Brent K. Hollenbeck; Margaret S. Pearle,; Anthony J. Schaeffer, American Urological Association Best Practice Policy on Antibiotic prophylaxis for Urological Procedures (2008). 99 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 Recommended redosing intervals at which a supplemental dose is required if surgery is prolonged. ANTIBIOTICS ADULT DOSE PAEDIATRIC DOSE HALF-LIFE (H) 2 g, 3 g for patients weighing >120 kg 30 mg/kg 1.2–2.2 RECOMMENDED REDOSING INTERVAL (FROM INITIATION OF THE FIRST PREOPERATIVE DOSE) (H) 4 Cefuroxime 1.5 gm 50 mg/kg 1–2 4 Clindamycin 900 mg 10 mg /kg IV 2–4 6 Vancomycin 15 mg/kg 15 mg/kg/dose IV 6.0 6–12 Gentamicin 1.5 mg/kg 2.5 mg/kg 2.0 NA 500 mg 15 mg/kg 8.0 8 Cefazolin Metronidazole 100 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 15: SURGICAL PROCEDURES AND THE RECOMMENDED DRUGS SURGICAL PROCEDURE Cardiac: -Median sternotomy -pacemaker & implant -prosthetic valve -coronary artery bypass LIKELY PATHOGEN Coagulasenegative Staphylococcus, S. aureus, enteric Gramnegative bacilli RECOMMENDED DRUG AND DOSAGE Adult: cefazolin 2 gm IV pre-op dose (then q8h x 24 hrs postop) Paediatric: cefazolin 30 mg/kg/dose IV pre-op and q8h x 24 hrs post-op. (Consider use of intranasal mupirocin evening before, day of surgery & bid for 5 days, post-op in patients who are colonized with MRSA preoperatively) Adult: cefazolin 2 g pre-op Paediatric: cefazolin 30 mg/kg/dose IV pre-op -Thoracic non-cardiac -lung resections -Thoracoscopy -Thoracotomy S. aureus, coagulasenegative Staphylococcus, Enteric Gramnegative bacilli Vascular: -Arterial surgery abdominal aorta -Any vascular procedure that inserts prosthesis, or foreign body -Procedures on the leg that involve a groin incision -Lower extremity amputation for ischemia S. aureus, Coagulasenegative Staphylococcus, Enteric Gramnegative bacilli Adult: cefazolin 2 g IV pre-op and q8h x 1 days Paediatric: cefazolin 30 mg/kg/dose IV q8h x 1 days (Intranasal mupirocin as per cardiac surgery) S. aureus, Coagulasenegative Staphylococcus Adult: cefazolin 2 g IV pre-op Paediatrics: Cefazolin 30 mg/kg pre-op ALTERNATE DRUG AND DOSAGE Adult: cefuroxime 1.5 g pre-op Paediatric: cefuroxime 50 mg/kg pre-op Adult: vanco 1 g pre-op and continued q12h x 1 days Paediatric: vanco 15 mg/kg/dose IV pre-op and continued q12h 1 days Adult: vanco 1 g IV pre-op OR clindamycin 900 mg IV pre-op Paediatric: vanco 15 mg/kg/dose IV pre-op OR clindamycin 10 mg/kg IV pre-op Adult: vanco 1 IV g q12h x 1 d OR Clindamycin 900 mg IV pre-op Paediatric: vanco 15 mg/kg/dose IV continued q12h x1d OR clindamycin 10 mg /kg IV pre-op Prophylaxis is not indicated for carotid endarterectomy or brachial artery repair without prosthetic material Neurosurgery: -Craniotomy -Skull fracture -CSF leak -Penetrating trauma -Spine -CSF shunt 101 Adult: vanco 1 g IV pre-op Paediatrics: vanco 15 mg/kg pre-op NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 15: SURGICAL PROCEDURES AND THE RECOMMENDED DRUGS SURGICAL PROCEDURE -Orthopaedic -Hip arthroplasty -Hip fracture repair -Implantation of internal fixation devices (e.g. nails, screws, plates, wires) -Total joints replacement -Spinal fusion -Spinal procedures with and without instrumentation -Open fractures (considered contaminated, treatment is indicated rather than prophylaxis) Ophthalmic Head/neck: -Incision through oral, sinus or pharyngeal mucosa -Major neck dissection -Parotid surgery Note that prophylaxis is not recommended for tonsillectomy or functional endoscopic sinus procedure or tympanostomy tube insertion Gastrointestinal oesophageal, gastroduodenal (high risk only: morbid obesity, oesophageal obstruction, decreased gastric acidity or motility LIKELY PATHOGEN S. aureus, Coagulasenegative Staphylococcus RECOMMENDED DRUG AND DOSAGE Adult: cefazolin 2 gm IV pre-op (for 24 hrs post-op ) Paediatric: cefazolin 30 mg/kg/IV pre-op plus q8h for 2 doses post-op S. aureus, Staphylococcus epIdemidis. Streptococci, Enteric, Gramnegative bacilli, Pseudomonas spp. S. aureus, Streptococci, oral anaerobes, enteric Gramnegative bacilli Topical : gentamicin, OR tobramycin OR cip, ofloxacin OR Gramicidinpolymyxin GramB ophthalmic multiple drops topically over 2–24 hrs Adult: cefazolin 2 g IV plus metronidazole 500 mg IV pre-op Paediatric : cefazolin 30 mg/kg/dose IV pre-op IV single dose plus IV metronidazole 15 mg/kg pre-op Addition of cefazolin 100 mg by subconjunctival injection OR intracameral cefazolin 1–2.5 mg OR cefuroxime 1 mg at the end of the procedure is optional Enteric Gramnegative bacilli, Gram-positive cocci Adult: cefazolin 1–2 g IV pre-op Paediatric: cefazolin 30 mg/kg/dose IV pre-op single dose Adult: gentamicin 1.5 mg/Kg/ IV plus clindamycin 900 mg IV pre-op Paediatric: gentamicin 2.5 mg/kg/dose plus clindamycin 10 mg/kg/dose IV pre-op TABLE 15: SURGICAL PROCEDURES AND THE RECOMMENDED DRUGS 102 ALTERNATE DRUG AND DOSAGE Adult: vanco 1 g IV q12h for 1 day Paediatric: vanco 15 mg/kg pre-op plus q12h x 2 doses post-op Adult : clindamycin 600 mg IV preop Paediatric: clindamycin 10 mg/kg/dose IV *addition of gentamicin to clindamycin is recommended if Gram-negative contamination of procedure is likely NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 SURGICAL PROCEDURE Biliary tract: In high-risk patients: -Age over 70 yrs -Common duct stones -Obstructive jaundice -Acute cholecystitis -Non-functioning gall bladder -ERCP Inguinal hernia complicated or recurrent, mesh placement LIKELY PATHOGEN Enteric Gramnegative bacilli, Clostridia, Enterococcus RECOMMENDED DRUG AND DOSAGE Adult: cefazolin 1–2 g IV pre-op x 1 dose Paediatric: cefazolin 30 mg/kg/dose IV pre-op single dose Gram-positive cocci, Gramnegative bacilli Adult: cefazolin 2g IV pre-op x 1 dose Paediatric: cefazolin 30 mg/kg pre-op x 1 dose Appendectomy, Non-perforated Enteric Gramnegative bacilli, anaerobes, enterococci Adult: cefazolin 2 g IV plus metronidazole 500 mg IV pre-op single dose Enteric Gramnegative bacilli, anaerobes, enterococci Paediatric: cefazolin 30 mg/kg pre-op plus metronidazole 15 mg/kg/dose IV pre-op single dose Adult: cefazolin 2 g IV plus metronidazole 500 mg IV pre-op single dose Mastectomy S. aureus, Paediatric: cefazolin 30 mg/kg/IV pre-op plus metronidazole 15 mg/kg/dose IV pre-op single dose Adult: cefazolin, Involving placement of prosthetic materials, saline implant, tissue expander Coagulasenegative Staph. Colorectal: -Whipple procedure -Pancreatectomy -Small bowel 2 g IV Pre-op x 1 dose ALTERNATE DRUG AND DOSAGE Adult: gentamicin 1.5 mg/kg IV plus clindamycin 900 mg IV pre-op x 1 dose Paediatric: gentamicin 2.5 mg/kg/dose plus clindamycin 10 mg/kg/dose IV pre-op Adult: gentamicin 1.5 mg/kg/IV plus clindamycin 900 mg IV pre-op x 1 dose Paediatric: gentamicin 2.5 mg/kg/dose IV plus clindamycin 10 mg/kg dose IV pre-op Adult: gentamicin 1.5 mg/kg IV plus clindamycin 900 mg IV pre-op Paediatric: gentamicin 2.5 mg/kg/dose IV plus clindamycin 10 mg/kg/dose/IV pre-op Adult: gentamycin 1.5 mg/kg/IV plus clindamycin 900 mg IV Pre-op Paediatric: gentamicin 2.5 mg/kg/dose IV plus clindamycin 10 mg/kg dose IV pre-op Adult: vanco 1 g IV pre-op x 1 dose OR clindamycin 900 mg IV pre-op 103 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 15: SURGICAL PROCEDURES AND THE RECOMMENDED DRUGS SURGICAL PROCEDURE Gynaecologic vaginal, abdominal or laparoscopic hysterectomy Caesarean Section Urology: -Genitourinary preoperative catheter -Transrectal prostaticbiopsy -Placement of prosthetic material (Patients with preoperative bacteria should be treated to sterilize the urine before surgery or receive antibiotic active against the bacteria pre-op and continued until catheter removal or for 10 days) TURP, TURBT -Ureteroscopy -Rigid cystoscopy -Visual Internal urethrotomy -Lithotripsy -Nephrectomy -Pyeloplasty -Adrenalectomy Ileal conduit Renal transplantation LIKELY PATHOGEN Enteric Gram-negative anaerobes, group B Strept., Enterococcus RECOMMENDED DRUG AND DOSAGE Adult: cefazolin 2 g pre-op ALTERNATE DRUG AND DOSAGE Adult: gentamicin 1.5 mg/kg IV plus clindamycin 600 mg IV pre-op Enteric Gram-negative anaerobes, group B Strept., Enterococcus Enteric Gram-negative bacilli, enterococci Adult: cefazolin 2 g IV pre-op Enteric Gram-negative bacilli, enterococci Cefazolin 2 g pre-op Cip 500 mg PO OR 400 mg IV Preop OR gentamicin 1.5 mg/kg IV preop Enterobacteriaceae, anaerobes Adult : cefazolin 2 g IV pre-op PLUS metronidazole 500 mg IV pre-op Adult: cefazolin 2 g Iv pre-op Paediatric: cefazolin 30 mg/kg IV pre-op Adult: clindamycin 900 mg IV preop PLUS gentamicin 1.5 mg/kg IV pre-op Adult : clindamycin 900 mg IV pre-op plus cip 400 mg IV pre-op Paediatrics: clindamycin 10 mg/kg IV plus gentamicin 2 mg/kg IV pre-op S. aureus, coagulase-negative Staph, Streptococci, Enterobacteriaceae Adult : cip 500 mg PO 2 hrs pre-op OR 400 mg IV pre-op 1–2 hrs pre-op Paediatric : trimethoprim/sulfamethoxazole 6 mg/kg 2 hrs pre-op PO OR cefazolin 30 mg/kg IV pre-op OR, gentamicin 1.5 mg kg x 1 dose 104 Adult: gentamicin 1.5mg/kg IV plus clindamycin 600 mg IV both as pre-op Gentamicin 1.5 mg/kg IV pre-op +/- clindamycin 600 mg IV pre-op NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 16: ANTIMICROBIAL IN PREGNANCY AND LACTATION: Safe use of anti-infective agents Antibacterial agents NAME OF THE AGENT Amikacin Gentamycin PREGNANCY BREASTFEEDING AMINOGLYCOSIDES Avoid unless potential benefit outweighs risk. Risk of auditory or vestibular nerve damage in the infant when used in the second and third trimesters of pregnancy Safe during breastfeeding FDA PREGNANCY CATEGORY Category D PENICILLIN AMP Cloxacillin Pen G Amoxicillin-clavulanic acid Piperacillin/tazobacta m Safe during pregnancy Safe during amoxicillin-clavulanic acid breastfeeding should be avoided in women at risk of preterm delivery due to increased risk of neonatal necrotizing enterocolitis. Risk-pen allergy categories. CEPHALOSPORINS Category B Cefazolin Ceftazidime Ceftriaxone Cefuroxime Cephalexin Cefepime Safe during pregnancy Category B Ertapenem Meropenem Azithromycin Clarithromycin Erythromycin Safe during breastfeeding CARBAPENEMS Use only if potential benefit Not safe during outweighs risk breastfeeding MACROLIDES Safe during pregnancy Safe during breastfeeding 105 Category B Category B Category C Category B NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 16: ANTIMICROBIAL IN PREGNANCY AND LACTATION: Safe use of anti-infective agents Antibacterial agents NAME OF THE AGENT PREGNANCY BREASTFEEDING FDA PREGNANCY CATEGORY QUINOLONES Ciprofloxacin Levofloxacin Moxifloxacin Use only if potential benefit outweighs risk. Avoid G6PD deficiency cases. Safe during breastfeeding. Avoid breastfeeding an infant with G6PD deficiency. Select other than moxifloxacin during breastfeeding. Category C SULFONAMIDES Cotrimoxazole— TMP-SMX Case studies: Avoid during 1st trimester may cauase neural tube defects (NTDs), cardiovascular & malformation. Add folic acid 4.5 mg/day to minimize the risk of NTDs. Sulfamethoxazole should be avoided near term due to potential toxicity to the newborn haemolytic anaemia and kernicterus. Avoid G6PD deficiency cases. Avoid sulfonamides allergy Safe during breastfeeding for healthy and full term infants. Sulfamethoxazole used with caution while breastfeeding to premature infants or neonates with hyperbilirubinemia. Sulfamethoxazole should be avoided while breastfeeding an infants with G6PD deficiency Category D TETRACYCLINES Doxycycline Minocycline Tetracycline Should be avoided after 15 week of gestation due to reports of possible discoloration of the deciduous teeth Short term therapy during breastfeeding is safe. Prolonged treatment courses during nursing should be avoided. Black discoloration of breast milk has been reported with minocycline 106 Category D NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 16: ANTIMICROBIAL IN PREGNANCY AND LACTATION: Safe use of anti-infective agents NAME OF THE AGENT Clindamycin Daptomycin Linezolid Nitrofurantoin Rifampin Tigecycline Vancomycin Amphotericin B PREGNANCY BREASTFEEDING MISCELLANEOUS ANTIBACTERIAL AGENTS Safe during pregnancy To be monitored during breastfeeding to infants. Chance of diarrhoea, candidiasis (oral thrush) and for blood in the stool, antibiotic-associated colitis st Avoid during 1 trimester. Safe during breastfeeding Use only if potential benefit outweighs risk Use only if potential benefit Not safe during breastfeeding outweighs risk. An alternate agent would be preferred Safe during pregnancy. Not safe infant under 1 Avoid- g6PD deficiency cases. month and those with G6PD An alternate agent should be deficiency used after 37 weeks of Safe infants above 1 month gestation Prenatal exposure to Rif has Safe during breastfeeding been connected to haemorrhagic disease of the newborn. Prophylactic administration of vitamin K is recommended to prevent this complication Should be avoided after 15 Not safe during weeks of gestation. breastfeeding. Use an alternative agent with Use an alternative agent with known safety profile is known safety profile is recommended recommended during breastfeeding. Avoid unless potential Safe during breastfeeding benefit outweighs risk. ANTIFUNGAL AGENTS Not safe during pregnancy. Not safe during breastfeeding Should be used only when benefit outweighs unknown risk to the foetus 107 FDA PREGNANCY CATEGORY Category B Category B Category C Category B Category C Category D Category B Category B NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 16: ANTIMICROBIAL IN PREGNANCY AND LACTATION: Safe use of anti-infective agents NAME OF THE AGENT Caspofungin Fluconazole Itraconazole Pentamidine Posaconazole Voriconazole Acyclovir/valacy clovir Famciclovir Foscarnet PREGNANCY BREASTFEEDING FDA PREGNANCY CATEGORY Category C Not safe during pregnancy. Should be used only when benefit outweighs unknown risk to the foetus. Should be avoided in 1st trimester whenever possible Not safe during breastfeeding Not safe during pregnancy. Should be used (in low dose, 150 mg) only when benefit outweighs unknown risk to the foetus. for vaginal candidiasis Not safe during pregnancy. Should be used only when benefit outweighs unknown risk to the foetus. Ensure effective contraception during treatment and until the next menstrual period following end the treatment Not safe during pregnancy Safe during breastfeeding Category C Safe during breastfeeding Category C Not safe during breastfeeding Not safe during pregnancy. Should Not safe during be used only when benefit outweighs breastfeeding unknown risk to the foetus Not safe during pregnancy Not safe during Should be avoided during pregnancy breastfeeding at least for the 1 trimester unless other treatments have failed and the benefit outweighs the unknown risk to the foetus ANTIVIRAL AGENTS Safe during pregnancy Safe during breastfeeding Avoid unless potential benefit Not safe during outweighs risk breastfeeding Avoid unless potential benefit Not safe during outweighs risk (in 2nd and 3nd breastfeeding trimester) 108 Category C Category D Category B Category B Category C NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 16: ANTIMICROBIAL IN PREGNANCY AND LACTATION: Safe use of anti-infective agents NAME OF THE PREGNANCY AGENT Ganciclovir/ Avoid unless potential benefit valganciclovir outweighs risk-teratogenic risk, ensure effective contraception during and barrier contraception for men during and for at least 90days after treatment Oseltamivir Chloroquine Avoid unless potential benefit outweighs risk (during a pandemic) BREASTFEEDING Not safe during breastfeeding Safe during breastfeeding ANTIMALARIAL AGENTS Benefit of prophylaxis and treatment Safe during in malaria outweighs risk breastfeeding FDA PREGNANCY CATEGORY Category C Category C Category C Primaquine Risk of neonatal haemolysis and methemoglobinemia in 3rd trimester Not safe during breastfeeding Category X Quinine High doses are teratogenic in first trimester, but in malaria, benefit of treatment outweighs risk safe during breastfeeding Category C Artemether with lumefantrine Avoid unless potential benefit outweighs risk Avoid breastfeeding for at least 1 week after last dose Category C Appendix A - Dose adjustment in pregnancy: general considerations. Some of the physiological changes occurring in pregnancy may affect the pharmacokinetics of drugs taken during the gestational period and post-partum. Depending on the clinical significance of these changes, adjustment of the doses and/or dosing interval may warrant consideration. Below are some examples of altered drug distribution and elimination in pregnancy. Increased maternal plasma volume may increase the volume of distribution of the same drug, which may require a dose increase. Decreased plasma protein concentration, specifically albumin, may increase the free fraction of highly protein-bound drugs, which may require a dose reduction. Increased renal blood flow and glomerular filtration rate may increase the elimination of drugs that are excreted primarily in the urine. This may require use of an increased dose and/or a shorter dosing interval. 109 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 Alteration in the activity of hepatic drug metabolizing enzymes may require dosage adjustment as follows: o Decreased activity (e.g., CYP1A2 and CYP2C19). For drugs that are dependent on these enzymes for elimination, a dose reduction may be required. For drugs that require these enzymes for conversion to their active form, a dose increase may be appropriate. o Increased activity (e.g., CYP3A, CYP2D6 and CYP2CP). For drugs that are dependent on these enzymes for elimination, a dose increase may be required. For drug that requires these enzymes for conversion to their active form, a dose reduction may be required. Appendix B - Pregnancy category chart Pregnancy category A Pregnancy category B Pregnancy category C Pregnancy category D Pregnancy category X Adequate research has been done with the conclusion that drugs in this category are not likely to cause any harm to the foetus in the first trimester as well as later in pregnancy. Studies carried out on animals have shown no adverse effects on the foetus; however, there is a lack of controlled studies on human pregnancy. Animal studies have shown evidence of harmful effects on the foetus; however, no controlled study has been done on a human pregnancy. The medicines may be prescribed in cases where the potential benefits outweigh the possible adverse effects. Studies done on human pregnancy have shown positive risks to the foetus. However, doctors might prescribe them in certain cases where the potential benefits outweigh the risks. Both human and animal studies have shown positive risks to the foetus, with the adverse effects extending to serious birth defects, miscarriage and foetal death. The possible risks of using these medicines outweigh any potential benefits. 110 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 PENICILLIN ALLERGY Adverse drug reactions are defined as any noxious, unintended, undesired effect of a drug that occurs at doses used for prevention, diagnosis or treatment. Type of ADR Type of ADR A Predictable A Predictable Side Effect B Unpredictable Idiosyncratic Reaction Overdose Drug Allergy FIG-3 Drug Allergy is immunologically mediated reactions either antibody mediated or cell mediated. Penicillin: Belongs to ß-lactam antibiotics. Generally effective at eradicating common bacterial infections such as skin, ear, sinus and upper respiratory tract infections. Allergy to penicillin is the most commonly-reported medication allergy but true penicillin allergy is rare. Estimated frequency of anaphylaxis 1–5 per 10,000 cases of penicillin therapy. Allergic reactions to penicillin categorized based on time of onset of symptoms: Immediate reactions: o Begin within an hour of the first administered dose. o Reactions are usually type I (IgE-mediated) reactions. o May escalate to life-threatening anaphylaxis. Anaphylaxis symptoms and signs include: pruritus, flushing, urticaria, angioedema, and wheezing, laryngeal enema, abdominal distress with emesis or diarrhoea, and hypotension. The diagnosis of immediate allergic reactions to penicillin is based on clinical history, skin testing when available, and sometimes graded challenge 111 NATIONAL ANTIMICROBIAL GUIDELINES Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 Delayed reactions: o Begin after multiple doses, typically after days or weeks of treatment. o Maculopapular exanthemas and less commonly urticarial eruptions are the most common form. Usually mild and often related to a concomitant viral infection, especially in children. o o Rare delayed systemic reactions also exist and can be severe. Patients with past delayed systemic reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, hypersensitivity syndrome, or other exfoliating dermatoses should not receive penicillin again under any circumstances. Risk of recurrent reactions depends on the time elapsed since the patient’s last reaction. ~ 50% lost sensitivity after 5 years. ~ 80% lost sensitivity after 10 years. Thorough history is an essential component in the evaluation of patients with suspected drug allergy: Why was the medication prescribed? How long ago did the reaction occur? Which systems (e.g. cutaneous, respiratory, GI) were involved in the reaction and what were the characteristics? Characterization of the cutaneous lesions important in determining the cause, further diagnostic tests and management decisions When during the course did the reaction occur? Was the patient taking concurrent medications at the time of the reaction? What was the therapeutic management required secondary to the reaction? Had the patient taken the same or cross reacting medication before the reaction? Has the patient been exposed to the same or similar medication since the reaction? Does the patient have an underlying condition that favours reactions to certain medications? Cross reactivity among B-lactams i.e. “penicillin, cephalosporins, carbapenems and monobactams”. Cephalosporins: cross reactivity occurs because of the B-lactams ring and also the R chain side group. o Cross reactivity can be as high as 10%. o Avoid only drugs with similar R side chain. Carbapenems: o >99% of penicillin-allergic patients tolerate carbapenems e.g. meropenem. 112 NATIONAL ANTIMICROBIAL GUIDELINES Index NO: Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 Monobactams: o No immune cross reactivity, therefore penicillin-allergic patients may receive aztreonam normally. Diagnostic tests in drug allergy: o Testing for immediate reactions: Markers of anaphylaxis: tryptase, histamine. Skin testing for drug-specific IgE. In vitro tests. o Drug Provocative graded challenge: Purpose: VeRify that the patient will not experience an immediate adverse reaction to a given drug. Administration of progressively increasing doses of a medication until a full dose is reached. Medication is introduced in a controlled manner to a patient who has a low likelihood of reacting to it. Drug desensitization: o Procedure that modifies a patient’s immune response to a drug allowing him/her to take the drug temporarily in a safe manner. o Done only in case of: IgE-mediated drug allergy. When no other alternative exists. 113 NATIONAL ANTIMICROBIAL GUIDELINES Index NO: Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 APPROACHING THE PATIENT WITH PENICILLIN ALLERGY Clinical History Late or less common allergic reaction Immediate Reaction 1-discontinue penicillin drug 2-Use alternative eg erythromicin, clindamycin,azithromax..etc Refer to an allergist for assessment, testing and possible graded challenge If skin test is positive consider desensitization if no other alternative Mild reaction eg maculopapular rash Serious reaction or other systematic reactions eg SJS,TEN,DRESS Discontinue penicillin and use alternative antibiotic Strictly avoid penicillin ,use alternative antibiotic If skin test is negative can use penicillin after a trial of a test dose Refer to an allergist for assessment Refer to an allergist for assessment FIG 4 References: 1. Khan DA, Solensky R. Drug allergy. J Allergy Clin Immunol 2010; 125(2 Suppl 2):S126–137. 2. Daulat S, Solensky R, Earl HS, Casey W, Gruchalla RS. Safety of cephalosporin administration to patients with histories of penicillin allergy. J Allergy Clin Immunol 2004;113:1220–1222. 3. Kula B, Djordjevic G, Robinson JL. A systematic review: can one prescribe Carbapenems to patients with IgE-mediated allergy to penicillins or cephalosporins? Clin Infect Dis 2014;59:1113–1122. 4. Caubet JC, Eigenmann PA. Managing possible antibiotic allergy in children. Curr Opin Infect Dis 2012;25:279–285. 5. Blanca M, Romano A, Torres MJ, Férnandez J, Mayorga C, Rodriguez J, et al. Update on the evaluation of hypersensitivity reactions to betalactams. Allergy 2009;64:183–193. 114 NATIONAL ANTIMICROBIAL GUIDELINES Index NO: Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 17: SUGGESTED DURATION OF ANTIBIOTIC THERAPY IN COMMON INFECTIONS Early change from IV to oral regimens is cost effective in many infections. The recommended duration is a minimum or average time and should not be considered as absolute. CLINICAL DIAGNOSIS DURATION OF THERAPY (DAYS) COMMENTS Bacteraemia with removable focus (no 10–14 (1) endocarditis) Osteomyelitis Adult; acute 42 Adult; chronic Until ESR normal (often >3 months) Child; acute; Staph. and 21 Duration to be guided by Enterobacteriaceae clinical response and normalization of Child; acute; Strept. 14 inflammatory markers meningococci, Haemophilus Infective Enterococci 28 or 42 endocarditis, S. aureus 14 (R-sided only) or 28 native valve Viridians streptococci 14 or 28 Bacillary dysentery (Shigellosis)/traveller’s 3 diarrhoea Typhoid fever Ceftriaxone 10–14 (Typhi): Cip 7–10 Azithro Chloramphenicol 5- 7 (children/ adolescents) 14 H. pylori 10–14. For triple-drug regimes Pseudomembranous enterocolitis (C. difficile) 10 Genital disease Non-gonococcal urethritis or mucopurulent cervicitis Pelvic inflammatory disease Adult Infant/child 7 days doxy or single dose Azithromycin 14 14–28 Rx as osteomyelitis above. Cotrimoxazole Nitrofurantoin Pneumonia, pneumococcal 3 5 14 (7 days if cip used, 5 days if levo 750 mg) Until afebrile, minimum 5 days CAP Minimum 5 days & afebrile for 2–3 days. Septic arthritis (nongonococcal) Cystitis (bladder Bacteriuria) Pyelonephritis 115 Duration to be guided by clinical response and normalization of inflammatory markers NATIONAL ANTIMICROBIAL GUIDELINES Index NO: Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE 17: SUGGESTED DURATION OF ANTIBIOTIC THERAPY IN COMMON INFECTIONS CLINICAL DIAGNOSIS Pneumonia, Enterobacteriaceae or pseudomonal Pneumonia, staphylococcal DURATION OF THERAPY (DAYS) 21, often up to 42 21–28 Legionella, mycoplasma, chlamydia 7–14 Lung abscess Usually 28–42 Meningitis N. meningitidis H. influenzae S. pneumoniae 7 7 10–14 Listeria 21(longer in immunocompromised) 21(longer in immunocompromised) 10 (azithromycin effective at 5 days) meningoencephalitis, group B Strept, coliform Group A Strept. pharyngitis Also see pharyngitis Acute sinusitis 5–7 (mild to moderate) 14 or longer therapy if βlactam or for severe infection Cellulitis Until 3 days after acute inflammation disappears References: 1.(CID 14:75,1992) 2. J.D Nelson, APID 6:59, 1991 3. Ln351:197,1998 4. CID 44:S55,2007:AJM 120:783,2007 116 COMMENTS NATIONAL ANTIMICROBIAL GUIDELINES Index NO: Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 GUIDELINES FOR ANTIMICROBIAL PROPHYLAXIS IN HAEMATOLOGY/ONCOLOGY IN ADULTS ANTI-INFECTIVE PROPHYLAXIS FOR ADULT HAEMATOLOGY/ONCOLOGY PATIENTS TABLE (18/A): ANTIBACTERIAL PROPHYLAXIS FOR HAEMATOLOGY/ONCOLOGY PATIENTS (ADULT) ANATOMIC SITE/DIAGNOSIS ETIOLOGIES SUGGESTED REGIMENS FIRST LINE COMMENTS SECOND LINE Autologous HSCT: Myeloma patients receiving melphalan Allogeneic HSCT Cip: start at time of stem cell infusion until resolution of neutropenia OR initiation antibacterial therapy for febrile neutropenia. Prophylactic dose: 500 mg PO q12h Prophylaxis may increase risk of bacterial resistance and super infection, Separate administration from antacids, multivitamins, and other products containing aluminium, magnesium, iron, or zinc by 2 hrs. Renal dose adjustment required Chronic GVHD Pen VK: 500 mg PO q12h Until discontinuation of Immunosuppression renal adjustment required 117 NATIONAL ANTIMICROBIAL GUIDELINES Index NO: Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE (18/B): PRIMARY ANTIFUNGAL PROPHYLAXIS FOR HAEMATOLOGY/ONCOLOGY PATIENTS(ADULT) ANATOMIC ETIOLOGIES SITE/DIAGNOSIS ALL CML lymphoid blast crisis -Acute myelogenous leukaemia (AML) -Myelodysplastic syndrome (MDS) -CML myeloid blast crisis Autologous HSCT Allogeneic HSCT SUGGESTED REGIMENS FIRST LINE SECOND LINE Initial prophylaxis for most patients: fluconazole during neutropenia with induction and intensification/ consolidation chemotherapy cycles Fluconazole OR posaconazole (if high rate of zygomycetes): -Initial prophylaxis for most patients during chemotherapy induction -Fluconazole for consolidation chemotherapy Voriconazole OR posaconazole (if high rate of zygomycetes): To be used when >1 chemotherapy treatment course to achieve complete remission OR chemotherapy for relapsed or refractory disease. Micafungin:alternative to voriconazole/posaconazole AND any one of the following: Chemotherapy treatment with CYP3A4 substrate Inability to tolerate PO Ongoing diarrhoea precluding oral therapy Intolerability to voriconazole/posaconazole -No prophylaxis in low probability of developing mucositis -High probability of developing mucositis -Fluconazole in high probability of developing mucositis Fluconazole: initial prophylaxis for most patients COMMENTS Start 24 hrs after last anthracycline dose or on first day of chemotherapy inpatients not receiving anthracycline-based treatment. Until resolution of neutropenia AND achievement of complete remission. Re-start with each consolidation chemotherapy treatment and continue until resolution of neutropenia Until resolution of neutropenia Start fluconazole with conditioning regimen and continue until day 75 post-transplant Posaconazole: CBT ORT-cell depleted HLAStart posaconazole on haploidentical transplant OR unrelated donor with day of transplant and bone marrow stem cell source continue until Micafungin: alternative to posaconazole and any one discontinuation of of the following immunosuppression Inability to tolerate PO Intolerability to posaconazole 118 NATIONAL ANTIMICROBIAL GUIDELINES Index NO: ANATOMIC SITE/DIAGNOSIS Severe GVHD requiring treatment Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 ETIOLOGIES SUGGESTED REGIMENS FIRST LINE SECOND LINE Posaconazole : Initial prophylaxis for most patients Micafungin for intestinal GVHD OR diarrhoea COMMENTS Severe GVHD requiring treatment TABLE (18/C): ANTIVIRAL PROPHYLAXIS FOR HAEMATOLOGY/ONCOLOGY PATIENTS (ADULT) ANATOMIC SITE/DIAGNOSIS ETIOLOGIES SUGGESTED REGIMENS FIRST LINE SECOND LINE None unless prior HSV episode (during neutropenia) Standard chemotherapy regimens for solid tumours Autologous HSCT Lymphoma Purine analogue therapy (i.e., fludarabine, clofarabine, nelarabine, cladribine) HSV HSV VZV Acyclovir: 800 mg PO q12h OR Valacyclovir: 500 mg PO q12h OR Famciclovir: 250 mg PO q12h Renal dose adjustment required ALL AML MDS CML blast crisis Bortezomib (multiple myeloma patients only) Alemtuzumab HSV VZV During neutropenia: Acyclovir: 800 mg PO q12h OR Valacyclovir : 500 mg PO q12h OR Famciclovir: 250 mg PO q12h Until discontinuation of bortezomib: Acyclovir: 800 mg PO q12h OR Valacyclovir: 500 mg PO q12h OR Famciclovir: 250 mg PO q12H Acyclovir OR valacyclovir OR famciclovir VZV HSV VZV Allogeneic HSCT 119 COMMENTS Until 30 days after autologous HSCT During neutropenia with aggressive lymphoma regimens (e.g., hyperCVAD, CODOXM/ IVAC) Until 3 months after discontinuation of purine analogue therapy Renal dose adjustment required Renal dose adjustment required Until at least 2 months after discontinuation of alemtuzumab AND CD4 ≥200 cells/mm3 Start with conditioning regimen for allogeneic HSCT AND continue for 1 year NATIONAL ANTIMICROBIAL GUIDELINES Index NO: Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE (18/C): ANTIVIRAL PROPHYLAXIS FOR HAEMATOLOGY/ONCOLOGY PATIENTS (ADULT) ANATOMIC SITE/DIAGNOSIS Severe GVHD requiring treatment ETIOLOGIES CMV SUGGESTED REGIMENS FIRST LINE SECOND LINE No prophylaxis 120 COMMENTS Until resolution of severe GVHD AND presumed recovery of immune status. Monitor CMV PCR weekly. Perform surveillance until the respective time points listed above with HSV/VZV NATIONAL ANTIMICROBIAL GUIDELINES Index NO: Issued by: National Antimicrobial Sub Committee Applies to: All Healthcare Facilities in Oman Effective Date:09/05/2016 TABLE (18/D): ANTI-PCP PROPHYLAXIS FOR HAEMATOLOGY/ONCOLOGY PATIENTS (ADULT) ANATOMIC SITE/DIAGNOSIS ALL CML lymphoid blast crisis Allogeneic HSCT +/- GVHD Alemtuzumab ETIOLOGIES SUGGESTED REGIMENS FIRST LINE SECOND LINE Trimethoprim/s Dapsone1st-line ulfamethoxalternative to TMP-SMX: azole: 100 mg PO q24h. 1 DS tablet Atovaquone 2nd line (160/800 mg) alternative: PO 1500 mg PO q24h q24h(CrCl>50 ml/min) OR 1 SS tablet (80/400 mg) PO q24h(CrCl30–50 ml/min) OR 1 DS tablet (160/800 mg) PO TIW (CrCl<30 ml/min) Trimethoprim Dapsone 1st-line sulfamethoxalternative to azole trimethoprim sulfamethox-azole Atovaquone 2nd line alternative to trimethoprim sulfamethox-azole Initial Dapsone 1st line prophylaxis for alternative to TMP-SMX most patients: Atovaquone 2nd line TMP-SMX alternative to TMP-SMX Purine analogue therapy (i.e., fludarabine, clofarabine, nelarabine, cladribine) Temozolomide + RT COMMENTS Initial prophylaxis for most patients Until completion of antileukemic therapy G6PD required prior to initiating Dapsone therapy Administer atovaquone with meals to reduce diarrhoea and GI adverse effects Initial prophylaxis for most patients. Start with engraftment until discontinuation of immunosuppression with allogeneic HSCT Until at least 2 months after discontinuation of alemtuzumab AND CD4 ≥200 cells/mm3 Until 3–6 months after discontinuation of purine analogue therapy Until recovery of lymphopenia after temozolomide + R 121
