Policy Document Policy no. Neonatal department (003) Policy Owner: Farwaniya Section location: Hospital Neonatology Department. Applies to: All medical staff in Effective date: January 1, perinatal health care . 2014 Approved by: Dr. Hatem Abdelaziz Masoud – Senior Specialist Approved by: Dr. Rima Al-Sawan Head of the Department Approved by: Hospital Director Revision dates: Notes: Title: Antimicrobial Policy 1 Antimicrobial Policy Neonatal Department Farwaniya Hospital, MOH A) Neonatal Sepsis 1. Early Onset : Occurring within first 72 hours of life 1.1 Source : Maternal genital tract 1.2 Organisms. 1.2.a Common: Strep agalactiae (group – B) E.coli Klebsiella Enterobacter Proteus 1.2.b Occasional: Listeria monocytogenes, Haemophilus species, Anaerobes, Staph. Aureus 1.3 Investigation 1.3.a Predictive tests : to be done stat and to be repeated after 12 hours if indicated : Full blood count WBC I / T ratio quotient) Quantitative CRP : : : Abnormal shifts in WBC differentiation < 5.0 x 109 / l ≥ 0.2 (I / T Immature to total neutrophil : > 16 significant 1.3.b Collection of Specimens for Culture : (i) Neonate : Blood x2 seperate samples collected from different site. CSF. (To exclude concomitant meningitis) Urine x 2 (> 24 hours of age). Others nasopharyngeal, deep ear and umbilical swabs, gastric aspirate first hour/before feeding. 2 (ii) Maternal : Low vaginal / rectal swab for GBS. High vaginal swab (HVS) collected for all cases with suspected sepsis, GA ≤ 34 and /or admitted to NICU/SCBU. Copy of result to be sent to NICU/SCBU. Blood if mother have S/S of sepsis. Placental + swab culture (if possible). 1.4 Antibiotic Therapy 1.4.a A combination of Ampicillin and Gentamycin * are given empiricaly 1.4.b Dose : - Ampicillin dose 50 mg/kg/dose slow I.V. intervals as seen in table 1. - Gentamycin as in table 2. Table 1: Ampicillin dose intervals related to GA & PNA. Gestational Age GA (weeks) Postnatal Age PNA (days) Interval (Hours) ≤ 29 0 to 28 > 28 0 to 14 > 14 0 to 7 >7 All 12 8 12 8 12 8 6 30 to 36 37 to 44 ≥ 45 Table 2 : Gentamycin dose and intervals related to GA & PNA PMA (weeks) ≤29 30 to 34 ≥35 Postnatal (Days) 0 to 7 8 to 28 ≥29 0 to 7 ≥8 ALL 3 Dose (mg/Kg) Interval (Hours) 5 4 4 4.5 4 4 48 36 24 36 24 24 1.4.c After 48 hours: (i) In cases: Clinically well, no maternal risk factors. Culture negative. Predictive tests normal (3 values within 48 hours) , crp at day 1,2 negative : Consider withdrawing antibiotics (after discussion with consulltant). (ii) In cases: Culture positive. Ulter antibiotics according to microbial sensitivity. 1.4.d Duration of antibiotics depends on location of infection – Tab-3 Table – 3 – Duration of antibiotics of culture +ve cases. Culture +ve site Duration Blood Meningitis Urine Pneumonia 2 weeks ≥ 3 weeks 10 days 2 weeks Treatment of GBS infection : A. Bacteremia/sepsis: - Ampicillin 150 mg/kg/day plus Gentamycin 2.5 mg/kg/day for 10 days . B. Meningitis : - Ampicillin 300 mg/kg/day plus Gentamycin 2.5 mg/kg/day for 14 to 21 days . 4 2 Late Onset : Occurring after the first 72 hours of life 2.1 Source: Nursery environment The mother’s genital tract. 2.2 Organisms: 2.2.1 Common Coagulase negative Staphylococci Klebsiella pneumonia E.coli Pseudomonas aeuroginosa Enterobacter 2.2.2 UnCommon: Staph. Aureus, Enterococcus Faccalis / Facium (group – D), Strep. Pneumoniae, Haemophilus influenzae.,serratia. 2.2.3 Others: Organism considered in early onset sepsis (late presentation). 2.3 Collection of Specimens for Culture : Blood x 2, Urine clean catch/supra pubic bladder aspiration CSF, Endotracheal secretions (if ventilated)/ Nasopharengeal secretions, swabs from sites of infection e.g. inflamed umbilicus, Stool x 3 (if NEC suspected). 2.4 Antibiotic therapy: 2.4.1 Microbial surveillance showed high resistance to our standard second line antibiotics namely 3rd generation cephalosporine hence it was decided to replace it with tazocin for 2 years then reevaluate the results by surveillance study ( from 01/01/2013 to 31/12/2014 ). Doses and intervals of tazocin are seen in tab- 4. 5 Table – 4: Tazocin doses intervals related to GA & PNA. Gestational Age (GA) (weeks) Postnatal Age (Days) Interval (hours) ≤29 0 to 28 >28 0 to 14 >14 0 to 7 >7 All 12 8 12 8 12 8 8 30 to 36 37 to 44 >44 2.4.1 Standard second line antibiotics is a combination of Cefotaxime(Claforan) and Amikacin to be given empirically after doing septic work up including lumbar puncture and blood culture . 2.4.2 Doses as seen in table 5 and 6. Cefotaxime: 50 mg/kg/dose I.V over 30 minutes Table 5: Cefotaxime (Claforan) doses related to GA and PNA Postmenstrual Age (Weeks) Postnatal Age (days) Interval (hours) ≤ 29\* 0 to 28 > 28 0 to 14 >14 0 to 7 >7 All 12 8 12 8 12 8 6 30 to 36 37 to 44 > 44 6 Table 6: Doses intervals of Amikacin* related to GA in the first week of life PMA (Weeks) Postnatal (Days) Dose (mg/kg) Interval (hours) ≤ 29* 0 to 7 8 to 28 ≥ 29 0 to 7 ≥8 ALL 18 15 15 18 15 15 48 36 24 36 24 24 30 to 34 ≥35 2.4.3 After 72 hours: (I) (II) In cases: Cultures are negative but predictive tests, CRP, WBC count suggestive of infection or patient clinically believed to be infected and responding to antibiotic continues for 10 days. In cases: Cultures are negative , and no clinical evidence of infection withdraw antibiotic after 72 hours (after discussion with senior Dr.). 2.4.4 When aminoglycosides* are used, blood levels should be done 1 hour post dose and prior to medication (pre-dose) and dose adjusted accordingly (Table – 7). Table – 7: Drug levels of used amino glycosides* Drug Sampling time Target range Amikacin 1 hour post dose = Peak pre-dose = trough 15 – 20 microg/ml <4 microg/ml Gentamicin 1 hour post dose = Peak pre-dose = trough 6-10 microg/m <2 microg/ml If trough levels is too high = decrease frequency to 24 or even 36 hours. If peak level is high = decrease dose by 10 to 30 % 7 2.4.5 In cases of Fulminant Gram-negative sepsis: Imipenem (Tienam): is added and send another blood c/s before changing antibiotics Dose: 25mg/Kg/dose Q 12 hours I.V. over 30 minutes. Or Meropenem: Sepsis : 20 mg/kg per dose Q12 hours IV over 30 minutes. Meningitis and infections caused by pseudomonas species: 40 mg/kg per dose Q8 hours IV infusion over 30 minutes. 2.4.6 In cases suspected coagulase negative staph sepsis on clinically + surveillance culture: a combination of Vancomycin and Cefotaxime (Claforan) is used empirically. 2.4.7 In cases suspected to have pseudonmonas infection ( surveillance in the unit showed more than one case) 2nd line antibiotics should be : Ceftazideme ( fortum) + Amikacin. ( instead of cefotaxime , amikacin) Ceftazideme : 30 mg/kg/ dose IV infusion by syringe pump over 30 minutes. ( table 8) Table 8 ceftazideme ( fortum) doses related to GA and PNA Gestational Age GA (weeks) Postnatal Age PNA (days) Interval (Hours) ≤ 29 0 to 28 > 28 0 to 14 > 14 0 to 7 >7 All 12 8 12 8 12 8 8 30 to 36 37 to 44 ≥ 45 8 3 Fungal Sepsis 3.1 Common Organisms: 3.2 Collection of specimens for culture : Candida albicans. Blood x 2, CSF, suprapubic urine, endotracheal secretions (in ventilated patients), CSF serum for detection of Candida antigen ( subject to availability). 3.3 Antimicrobial therapy: 3.3.1 Amphotericin B : 0.5 to 1 mg/kg Q 24 hours IV infusion over 2 to 6 hours Dosage modification for renal dysfunction is only necessary if serum creatinine increase by > 35.4mmol/L during therapy – hold dose for 2 to 5 days. 3.3.2 Flucytosine: 100 mg/kg/day if patient did not respond to (a) or as a combination with (a). 3.3.3 Liposomal amphotericin (ambisome or abelcet): subject to availability. 3.3.4 Fluconazole(Diflucan) : (CSF +ve) Meningitis suspected. Dose: 12 mg/kg/loading dose, then 6mg/kg per dose IV infusion by syringe pump over 30 minutes, or PO. Doses interval as seen in table – 9. Table – 9: Fluconazole doses interval in relation to GA and PNA Gestational Age GA (weeks) ≤ 29 30 to 36 37 to 44 ≥ 45 Postnatal Age (days) 0 to 14 >14 0 to 14 >14 0 to 7 >7 All 9 Interval (hours) 72 48 48 24 48 24 24 3.4 Patients at high risk of fungal infection should receive Prophylactic Therapy Local . 3.4.1 Prophylactic: Nystatin : 1 ml (=100 000 I.U) Q 8 hours Half orally and half by nasogastric. 3.4.2 Therapeutic: Nystatin : 1 ml (=100 000 I.U) Q 6 hours Half orally and half by nasogastric for 3 days after disappearance of signs and symptoms. 3.4.3 Nappy: Topical Nystatin (nappy rash) Q 6 hours continue 3 days after S/S subsided. Need also to give orally for 7 to 10 days to eradicate the candida from the gut 3.4.4 Eyes (Keratomycosis): Corneal baths of Amphotericin B : 1mg/ml 3.4.5 Cystitis: Bladder irrigation with Amphotesicim B : 5mcg/ml of distilled water, 3 times a day holding for 30 min X 5 days. 10 4. Neonatal Meningitis: It can present as focal infection usually in late onset sepsis or as part of multisystem septicaemia. 4.1 Organisms: Strep. Agalactiae (Group B) 40% E-coli, Klebsiella 40% Listeria 10%Others: Haemophilus, pneumococcus, Meningococcus 4.2 Antibiotic Therapy 4.2.1 Empirically: A combination of following is given. Inj. Ampicillin + Inj. Cefotaxime + Inj. Amikacin : 200mg/kg/day divided q 8 hourly IV : 100mg/kg/day divided q 12 hourly IV : 10mg/kg followed by 7.5 mg/kg q 12 hourly IV 4.2.2 In cases: Of fulminant gram-negative septicemia Ampicillin + Meropenem + Amikacin are given empirically instead of the above 4.2.3 Specify Therapy: Antibiotics need be modified according to the organism and its sensitivity. (table – 10). 4.2.4 Duration: At least 3 weeks . 11 Table – 10: Antibiotic for Neonatal Meningitis. Organism Antibiotic Total daily dose IV Number of doses per 24 hours 3 Group B Streptococcus or Pneumococcus Penicillin or Ampicillin + Gentamicin 150,000 units/kg 100mg /Kg Listeria Monocytogenes Ampicillin 150mg /Kg<1 days. 200 – 300mg/kg> 1 day old 2-3 7.5mg /kg 7.5 mg /kg 150 mg /kg 2-3 2-3 100mg /kg 20mg /kg 4 4 + gentamicin E-coli and other Gentamicin + coliforms Cefotaxime 7.5 mg /Kg/ day Staph aureus Flucloxacillin vancomycin Strept Faecalis Ampicillin and As above gentamicin Haemophilus Cefotaxime Pseudomonas Gentamicin As above Piperacillin or 300-400 mg /kg Ceftazidime 150 mg /kg Coagulase negative staph Vancomycin 1000 units 2-3 2 3 Intrathecal dose 1-2 mg 5mg 1-2 mg As above 20 mg /kg /day. 3-4 3 5mg 4 NB: gentamycin is preferred in CNS infection due to better penetration of BBB 12 6 Necrotizing Enterocolitis 6.1 Associated organism: E.coli Klebsiella pneumonia Staph epidermidis, Ps auroginosa C.perfringens 6.2 Empirical Therapy: 6.2.1 Combination of Tazocin ( Pipracillin- Tazobactam) + amikacin Dose of Tazocin 50 -100 mg/kg./dose as pipracillin component IV infusion by syringe pump over 30 minutes ( table 4) 6.2.2 Metronidazole (flagyl) is added to stage III NEC with or without Perforation. Loading: 15mg/Kg IV/over 60 minutes. Maintenance: 7.5mg/Kg. I.V over 60 minutes. Doses: interval related to GA & PNA (Table – 13). Table – 13: Metronidazol doses intervals related to GA & PNA. Gestational Age (GA) (weeks) Postnatal Age (Days) Interval (hours) ≤29 37 to 44 0 to 28 >28 0 to 14 >14 0 to 7>7 ≤45 All 48 24 24 12 24 12 8≤ 30 to 36 13 7 Urinary tract infection: UTI is confirmed by a positive culture 104 growth of single organism, usually with a raised WBC count. It may be associated with disseminated sepsis. 7.1 Specimens for culture and other investigation 7.1.1 Clean urine catch ,or by catheter or by suprapubic aspiration.( Urine bag samples are invalid ). 7.1.2 Blood culture, others as indicated CBC - WBC count. 7.2 Antibiotic Therapy 7.2.1 Specific therapy starts only on the basis of culture and sensitivity. 7.2.2 If accompanied by suspected sepsis, empiric therapy is initiated (after specimen collection) as in sepsis depending on age of onset ≤48 hours, or ≥ 48 hours. 8 Osteomyelitis: 8.1 Common Organisms Staph. Aureus Strep group B and A Antibiotic therapy 8.2 Inj. Flucloxacillin + Inj. Cefotaxime : 50-100mg/kg/day, divided q/12 hourly, IV : 50mg/kg, q, 8 or 12 hourly, IV – Table – 5 Treatment continued at least 21 days upto 4-6 weeks. Antibiotic may be modified according to culture and sensitivity whenever available. 14 9. Umbilical sepsis: 9.1 Sticky umbilicus 9.1.1 Investigations: Send a swab for culture (in case infection develops). 9.1.2 Treatment: No antibiotic, Spirit swabbing of the area, Daily cleaning/bath locally with Hibiscrub 9.2 Periumbilical infection : Indicated by purulent discharge ± foul smelling with surrounding erythema 9.2.1 Sepcimens for culture : Blood culture x 2 and local Swab 9.2.2 Treatment Inj. Flucloxacillin + Inj. Gentamycin 10. : 25-50 mg/kg, q 6 hourly, IV : Table 2. Prophylactic Antibiotics 10.1 If baby given a course of corticosteroids to help extubation or for any other reason this must be covered with antibiotics till the end of steroid course. 10.2 Babies with insertion of catheters or central lines must be done under complete aseptic technique and covered with prophylactic antibiotics . 15 11. Conjunctivitis See table 14 Table – 14 – Management of Neonatal Conjunctivitis Organism Diagnosis Treatment. Maternal history Profuse conjunctival discharge. Urgent Gram Stain on pus shows Gramnegative intracellular diplococci. Culture of swab sent in transport medium I.V penicillin 75,000 units/Kg/24 hours given in two divided for a week. Also penicillin eye drops hourly for 24 hours. Then 4 hourly for a week notifiable disease. Remember to organize treatment for mother and contact tracing. No distinguishing clinical features. May be maternal history. Conventional cultures can be sterile. Antigen detected in eye swab by immunofluorescence. 3 – 5 days peak but may Culture of Swab be at any time including day 1 Systemic erythromycin (45mg/Kg/24 hours in three divided doses) for at least 2 weeks to prevent pneumonia. Well absorbed orally. Age at Presentation Gonococcus 1 day (some recognized in 1st week) Chlamydia Trachomatis 5 days or more Others; commonest are Staph aureus. E-coli, Haemophilus, Strep Pneumoniae 16 Use 0.5% chloramphenicol eye drops and eye ointment BD x 3 days after S/S disappear. References & Further Readings References & Further Readings 1. John P, Cloherty , Ann R.. Manual of Neonatal Care. 2012 lippincott Raven, Philadelphia. 2. Gomella T, Douglas C . Gomella neonatology . 3. National Health Service ( NHS ) in UK 2013-2015 . 4. Thomas E, young, Barry M . Neofax 9th ed , 2012. Acron pub. North Carolina. 5. Richard E, Robert M, Hal B. Nelson Textbook of pediatrics 18th ed 2012. WB saunders . 6. Rennie JM, Roberton NRC: Infection PP 223-265 In: Rennie, Roberton eds. Amanual of Neonatal Intensive Care (4 Med.). Great Britain, Arnold 2002. 7. Hughes J.M: Guide lines for the prevention of intravascular Catheter – Related infections Vol. 51/RR-10 2002 Aug: 1-29. Important Web Sites: 1. http://www.pediatrics.org/cgi/content/full/101/3/e13 2. http://www.nd.edul~kkolberg/DesignStandards.htm 3. http://www.cdc.gov/ncidod/hip/2bactpn.htm 4. http://www.cac.gov/mmwr/preview/mmwrntm/rrp11va3.htm 5. http://www.cac.gov/neidod/hip/pneumonia/2bactpn.htm 17