Antibiotics in ENT Surgery Magdy M. Amin RIAD Professor of Otolaryngology. Ain shames University Senior Lecturer in Otolaryngology University of Dundee Prophylactic antibiotics • Prophylaxis with antibiotics has decreased the high incidence of wound infection after head and neck operations that involve incisions through oral or pharyngeal mucosa. • Prophylactic administration of antibiotics can decrease postoperative morbidity, shorten hospitalization, and reduce overall costs attributable to infections. Prophylactic antibiotics • Many antibiotics require a single dose given within 30 minutes of skin incision to provide adequate tissue concentration throughout the operation. • Additional doses during the procedure are advisable if surgery is prolonged (i. e, >4 h), major blood loss occurs, or an antimicrobial with a short half-life is used The aim of prophylaxis • The aim of prophylaxis is to augment host defense mechanisms at the time of bacterial invasion,. • Prophylaxis is an attempt to attack organisms before they have a chance to induce infection. • Previous surgery (i. e, scarring) and radiation injury decrease host defenses. • Likewise, certain medical conditions, such as diabetes mellitus or HIV, predispose the patient to infection because of diminished host response. Choosing an antibiotic for prophylaxis • • • • Choosing an antibiotic for prophylaxis is multifactorial and should be based on the following: Type of operation Kinetics and toxicity of the drugs Microbiologic characteristics of the operative site Antibiotic sensitivities specific to the particular hospital environment Choosing an antibiotic for prophylaxis • If a number of drugs appear equally acceptable for prophylaxis, the agent least likely to be used for definitive therapy in postoperative wound infection should be chosen. • This strategy should minimize the selection of organisms resistant to valuable therapeutic agents. Choosing an antibiotic for prophylaxis • The regimen chosen should be compatible with findings from the hospital's infection control wound surveillance report. • This regimen is particularly important in hospitals with high incidence of infection with methicillinresistant organisms (eg, S aureus [MRSA], S epidermidis [MRSE]) or with newly vancomycinresistant organisms. CLASSIFICATION OF OPERATION Class Definition • Clean Operations in which no inflammation is encountered . The respiratory, alimentary or genitourinary tracts are not entered. There is no break in aseptic operating theatre technique. Non contaminated head and neck surgery • Non contaminated surgery refers to violation of prepared skin only and no mucosal exposure or incision (eg, neck dissection, parotidectomy, thyroidectomy). Non contaminated head and neck surgery • Clean surgical procedures are those in which no infection exists prior to surgery. • During surgery, sterility of the wound is maintained. • Following closure of the wound at completion of surgery, the wound is never again exposed to direct contact with bacteria. • The risk of postoperative wound infection under these circumstances is less than 5%. CLASSIFICATION OF OPERATION Class Definition Clean-contaminated Operations in which the respiratory, alimentary or genitourinary tracts are entered but without significant spillage. CLASSIFICATION OF OPERATION Class Definition Contaminated Operations where acute inflammation (without pus) is encountered. or where there is visible contamination of the wound. Examples include gross spillage from a hollow viscus during the operation or compound/open injuries operated on within four hours. CLASSIFICATION OF OPERATION Class Definition Dirty Operations: In the presence of pus. where there is a previously perforated hollow viscus, or compound/open injuries more than four hours old. PROBABILITY OF WOUND INFECTION BY TYPE OF WOUND AND RISK INDEX Clean Clean-contam. Contaminated 0 1.0% 2.1% 3.4% Risk Index 1 2 2.3% 5.4% 4.0% 9.5% 6.8% 13.2% ENT SURGERY • Head and neck surgery - A Antibiotic prophylaxis is recommended • Head and neck surgery - clean C Antibiotic prophylaxis is not recommended There is no evidence of effectiveness from RCTs • Ear surgery - clean A Antibiotic prophylaxis is not recommended There is no evidence of effectiveness from RCTs • Nose or sinus surgery C Antibiotic prophylaxis is not recommended There is evidence of no effectiveness from RCTs • Tonsillectomy C Antibiotic prophylaxis is not recommended There is no evidence of effectiveness of prophylaxis from RCTs. The cited trials are of treatment for seven days after tonsillectomy, not prophylaxis. ADMINISTRATION OF INTRAVENOUS PROPHYLACTIC ANTIBIOTICS Prophylaxis should be started preoperatively in most circumstances ideally within 30 minutes of the induction of anesthesia. ADMINISTRATION OF INTRAVENOUS PROPHYLACTIC ANTIBIOTICS Antibiotic prophylaxis should be administered immediately before or during a procedure. Prophylactic antibiotics should be administered intravenously. The single dose of antibiotic for prophylactic use is, in most circumstances, the same as would be used therapeutically. ADMINISTRATION OF INTRAVENOUS PROPHYLACTIC ANTIBIOTICS An additional dose of prophylactic agent is not indicated in adults, unless there is blood loss of up to 1500 ml during surgery or haemodilution of up to 15 ml/kg. Fluid replacement bags should not be primed with prophylactic antibiotics because of the potential risk of contamination and calculation errors. Duration of Perioperative Antibiotic Use 1. Prophylactic perioperative antibiotics should be started prior to skin incision for maximal benefit. Duration of Perioperative Antibiotic Use 2. There is no advantage to continuation of perioperative antibiotics beyond 24 to 48 hours postoperatively has ever been demonstrated. Duration of Perioperative Antibiotic Use The possible exception to this is metronidazole; • because metronidazole may enter abscess spaces better than other antibiotics. • its prolonged use has been associated with less severe postoperative infections in one study. Prophylactic Antibiotic Regimens for Major Clean-Contaminated 1. Clindamycin: 600 mg IV within 1 hour of surgery, 4 additional doses Q6H following surgery. The antibiotic may alternatively be given for a full 48 hours postoperatively. there is no compelling evidence that the additional 24 hours confers any additional benefit. Prophylactic Antibiotic Regimens for Major Clean-Contaminated 2. Augmentine: 1.5 grams IV within 1 hour of surgery . and 8 additional doses at 6-hour intervals following surgery. Prophylactic Antibiotic Regimens for Major Clean-Contaminated 3. Cefazolin: 2.0 grams IV within 1 hour of surgery. and 3 postoperative doses at 8-hour intervals. This regimen may be extended to a total of 48 hours postoperatively. Prophylactic Antibiotic Regimens for Major Clean-Contaminated 4. Cefazolin/metronidazole: cefazolin 1 gm IV 1 hour prior to surgery then 1 gram IV every 8 hours postoperatively for a total of 6 doses. and metronidazole 900 mg IV 1 hour prior to surgery then 900 mg IV every 8 hours postoperatively for a total of 6 doses. ENT SURGERY Antibiotic prophylaxis is recommended in: • A – Head and neck surgery (cleancontaminated/contaminated) • • • • • Antibiotic prophylaxis is not recommended in: A – Ear surgery (clean) C – Head and neck surgery (clean) C – Nose or sinus surgery C – Tonsillectomy Contaminated head and neck surgery • Contaminated surgery refers to transmucosal operations (eg, composite resection, glossectomy, maxillectomy). • Saliva contains 108 bacteria per milliliter, 90% of which are anaerobic. Ninety-six percent of wound infections in the head and neck are polymicrobial. Contaminated head and neck surgery • Organisms involving oropharyngeal flora included: • anaerobic organisms (Bacteroides, 76%) • gram-negative rods (eg, Escherichia coli and Klebsiella, Serratia, and Proteus species) • gram-positive organisms (ie, Staphylococcus, Streptococcus). Contaminated head and neck surgery • Clindamycin (600 mg PO/IV q8h for 4 doses) is the recommended antibiotic to prevent anaerobic wound contamination in extensive surgeries of the head and neck. • Appropriate antibiotic choices also include a combination of ampicillin and sulbactam (3 g IV followed by 1.5 g q8h for 3 doses) • combination Ancef and Flagyl. • As an oral mouth rinse, use of clindamycin (75-mg caps stirred in 8 oz of tap water) or chlorhexidine (Peridex) provides rapid and sustained reductions in the concentrations of aerobic and anaerobic oral flora. Facial fractures • Open fractures have an increased incidence of infection in the absence of antibiotic prophylaxis when compared to closed or open fractures treated with prophylactic antibiotics. Facial fractures • Antibiotic prophylaxis significantly reduce the incidence of postoperative infections in facial fractures, especially mandible fractures of the body. • The infection rates in zygoma fractures, LeFort fractures, and mandibular subcondylar fractures are similar. Disadvantages of antibiotics • It promotes antibiotic resistance and contributes to super infection. • Antibiotic use is also costly and associated with allergic reactions, toxic reactions, and adverse effects • The use of antibiotics may encourage laxity of good surgical technique. Oral, Dental, Respiratory Tract, or Esophageal Procedures Situations Agent Adult Regimens Standards general prophylaxis Amoxicillin 2 gm PO one hour before procedure Clindamycin or 600 mg PO one hour before procedure Cephalexin or Cefadroxil or 2 gm PO one hour before procedure Azithromycin or Clarithromycin 500 mg PO one hour before procedure Ampicillin 2 gm IV/IM 30 minutes before procedure Clindamycin or 600 mg IV 30 minutes before procedure Cefazolin 1 gm IV/IM 30 minutes before procedure Allergic to Penicillin If unable to take oral medications Allergic to penicillin and unable to take oral medications Oral, Dental, Respiratory Tract, or Esophageal Procedures Situations Agent Pediatric Regimen* Standards general prophylaxis Amoxicillin 50 mg/kg PO one hour before procedure Clindamycin or 20 mg/kg PO one hour before procedure Cephalexin or Cefadroxil or 50 mg/kg one hour before procedure Azithromycin or Clarithromycin 15 mg/kg PO one hour before procedure Ampicillin 50 mg/kg IM/IV 30 minutes before procedure Clindamycin or 20 mg/kg IV 30 minutes before procedure Cefazolin 25 mg/kg IM/IV 30 minutes before procedure Allergic to Penicillin If unable to take oral medications Allergic to penicillin and unable to take oral medications Penicillin • Mechanism of action – Exerts action on actively dividing cells by causing abnormal cell wall development – Inhibits third stage of cell wall synthesis • Resistance – Alterations in penicillin-binding proteins – Inability to penetrate bacterial cell walls – Enzymatic hydrolysis of penicillin molecule Penicillin • Spectrum – – – – – Gram-positive cocci - Group A and group B Streptococcus Gram-positive bacilli - Corynebacterium diphtheriae Gram-negative cocci - Neisseria meningitidis Gram-negative bacilli - Streptobacillus moniliformis Anaerobes - Clostridium, Bacteroides, Fusobacterium, and Peptostreptococcus species – Miscellaneous - Treponema pallidum and Leptospira, Enterobacter, and Acinetobacter species Penicillin • Adverse reactions – Hypersensitivity (1-5%) – Irritant properties that affect the peripheral nervous system – Nephropathy - Allergic reaction manifested by interstitial nephritis and hypokalemia Cephalosporin • Mechanism of action – – – – – Inhibits third step of bacterial wall synthesis Binds to specific proteins on cell membranes Alters cell permeability Inhibits protein synthesis Releases autolysins • Resistance - Decrease in bacterial cell wall permeability to antibiotics and production of betalactamase Cephalosporin • Spectrum – First generation (eg, Ancef, Keflin, Kefzol) - Have the greatest degree of activity against gram-positive organisms, such as Staphylococcus and Streptococcus (not MRSA); have the same coverage against gram-positive, anaerobic, and aerobic bacilli as penicillin – Second generation (eg, Ceclor, Zinacef, Mefoxin) - Less active against gram-positive bacteria, but have an advantage against Haemophilus influenzae organisms and some gram-negative bacilli, including Proteus and Enterobacter species – Third generation (eg, Ceftazidime, Cefotaxime, Cefoperazone) Have the greatest activity against gram-negative aerobes, with variable activity against Pseudomonas organisms Cephalosporin • Adverse reactions – Hypersensitivity - Highest incidence in those allergic to penicillin – Hematologic - Neutropenia, leukopenia, and thrombopenia – GI disturbances - Nausea, vomiting, anorexia, and diarrhea – Reversible renal impairment Erythromycin • Mechanism of action - Inhibits bacterial protein synthesis • Resistance – Alteration in protein component of 50s ribosomal subunit – Plasmid-mediated resistance Erythromycin • Spectrum – Similar to that of penicillin G – Effective against Mycoplasma, Legionella, and Actinomyces species – Combined with sulfisoxazole to make Pediazole, which is used in the pediatric population – Effective against H influenzae organisms • Adverse reactions – GI disturbances – Hypersensitivity – Cholestatic hepatitis Clindamycin • Mechanism of action: Binds to 50s ribosomal subunit, thereby inhibiting protein synthesis • Resistance: Similar to that of erythromycin Clindamycin • Spectrum – Active against most aerobic and anaerobic grampositive organisms – Anaerobic gram-negative organisms – although some staphylococcal organisms have developed resistance Clindamycin • Adverse reactions – – – – Pseudomembranous colitis Mild nausea and diarrhea Hypersensitivity Leukopenia Transient increase • Hepatotoxicity (rare) Metronidazole (Flagyl) • Mechanism of action – Reduced intracellularly to its active metabolite that is bactericidal – May be administered orally, intravenously, or rectally – Metabolized in the liver and excreted by the kidneys Metronidazole (Flagyl) • Adverse reactions (most of which are dose related and are not seen with regular short-term use) – – – – – – CNS toxicity GI disturbance Neutropenia Drug fever Synergistic alcohol effect Prolonged activated partial thromboplastin time (aPTT) Drug Name Adult Dose Pediatric Dose Contraindic ations Ceftazidime (Ceptaz, Fortaz, Tazicef, Tazidime) -Third-generation cephalosporin with broadspectrum gram-negative activity, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin binding proteins. 2 g IV q8h Not established Documented hypersensitivity Interactions Nephrotoxicity may increase with aminoglycosides, furosemide, and ethacrynic acid; probenecid may increase ceftazidime levels Pregnancy Precautions B - Usually safe but benefits must outweigh the risks. Adjust dose in renal impairment Drug Name Nafcillin (Nafcil, Unipen) -- Initial therapy for suspected penicillin G–resistant streptococcal or staphylococcal infections. Use parenteral therapy initially in severe infections. Change to oral therapy as condition warrants. Due to thrombophlebitis, particularly in elderly patients, administer parenterally only for short term (1-2 d); change to oral route as clinically indicated. Adult Dose 2 g IV q4h Pediatric Dose Not established Contraindications Documented hypersensitivity Drug Name Levofloxacin (Levaquin) -- For infections due to multidrug-resistant gram-negative organisms. Adult Dose Pediatric Dose 500 mg IV q24h Not established Contraindica tions Documented hypersensitivity Interactions Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; levofloxacin reduces therapeutic effects of phenytoin; probenecid may increase levofloxacin serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT) Pregnancy C - Safety for use during pregnancy has not been established. Precautions In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy Drug Name Clindamycin (Cleocin) -- Lincosamide for treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes causing RNA-dependent protein synthesis to arrest. Adult Dose 600 mg IV q8h Pediatric Dose Not established Contraindicatio ns Documented hypersensitivity; regional enteritis; ulcerative colitis; hepatic impairment; antibiotic-associated colitis Interactions Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects of clindamycin; antidiarrheals may delay absorption of clindamycin Pregnancy B - Usually safe but benefits must outweigh the risks. Precautions Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis Drug Name Ampicillin (Marcillin, Omnipen, Polycillin) -- Bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take medication orally. Adult Dose 2 g IV q4h Pediatric Dose Not established Contraindicatio ns Documented hypersensitivity Interactions Probenecid and disulfiram elevate ampicillin levels; allopurinol decreases ampicillin effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives Pregnancy B - Usually safe but benefits must outweigh the risks. Precautions Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction Drug Name Gentamicin (Garamycin, Gentacidin) -- Aminoglycoside antibiotic for gram-negative coverage. Used in combination with an agent against gram-positive organisms and one that covers anaerobes. Not the DOC. Consider if penicillins or other less toxic drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms. Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of distribution. May be administered IV/IM. Adult Dose 2 mg/kg when using multiple daily dosing 5-7 mg/kg/d when once daily dosing used Pediatric Dose Not established Contraindications Documented hypersensitivity; non–dialysis-dependent renal insufficiency Interactions Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents, thus prolonged respiratory depression may occur; coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly) Pregnancy C - Safety for use during pregnancy has not been established. Precautions Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment Drug Name Tobramycin (Nebcin) -- Indicated in the treatment of staphylococcal infections when penicillin or potentially less toxic drugs are contraindicated and when bacterial susceptibility and clinical judgment justifies its use. Adult Dose 2 mg/kg bid/qid or 5-7 mg/kg IV/IM qd; subsequent dosing is individualized based on renal function Pediatric Dose Not established Contraindicatio ns Documented hypersensitivity Interactions Increases effects of neuromuscular blockers and potentiates effect of extended-spectrum penicillins; concurrent administration with amphotericin B, cephalosporins, and loop diuretics increases risk of nephrotoxicity Pregnancy B - Usually safe but benefits must outweigh the risks. Precautions Avoid use in renal impairment, preexisting auditory or vestibular impairment, and in patients with neuromuscular disorders; aminoglycosides are associated with nephrotoxicity and ototoxicity Drug Name Amikacin (Amikin) -- Irreversibly binds to 30S subunit of bacterial ribosomes; blocks recognition step in protein synthesis; causes growth inhibition. Use the patient's IBW for dosage calculation. Adult Dose 7.5 mg/kg bid/qid or 15 mg/kg/d qd; individualize subsequent dosing based on renal function Pediatric Dose Not established Contraindicatio ns Documented hypersensitivity Interactions Coadministration with other aminoglycosides, penicillins, cephalosporins, and amphotericin B increases nephrotoxicity; enhances effects of neuromuscular blocking agents; causes respiratory depression; irreversible hearing loss may occur with coadministration of loop diuretics Pregnancy C - Safety for use during pregnancy has not been established. Precautions Not intended for long-term therapy; caution in patients with renal failure (not on dialysis), hypocalcemia, myasthenia gravis, and conditions that depress neuromuscular transmission Drug Name Erythromycin (Erythrocin, Eryc, E-Mycin) -- Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes causing RNA-dependent protein synthesis to arrest. For treatment of staphylococcal and streptococcal infections. In children, age, weight, and severity of infection determine proper dosage. When bid dosing is desired, half-total daily dose may be taken q12h. For more severe infections, double the dose. Adult Dose 15 mg/kg IV q6h, up to 4 g/d Pediatric Dose Not established Contraindications Documented hypersensitivity; hepatic impairment Interactions Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis Pregnancy B - Usually safe but benefits must outweigh the risks. Precautions Caution in liver disease; estolate formulation may cause cholestatic jaundice; GI adverse effects are common (administer doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur Drug Name Azithromycin (Zithromax) -- Treats mild-to-moderate microbial infections Adult Dose 500 mg IV qd Pediatric Dose Not established Contraindicatio ns Documented hypersensitivity; hepatic impairment; do not administer with pimozide Interactions May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine Pregnancy B - Usually safe but benefits must outweigh the risks. Precautions Site reactions can occur with IV route; bacterial or fungal overgrowth may result with prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, geriatric, or debilitated patients