------------------------------------------------------------------------ TITLE: ANTIBIOTIC PROPHYLAXIS IN OTOLARYNGIC SURGERY SOURCE: Dept. of Otolaryngology, UTMB, Grand Rounds DATE: June 26, 1991 RESIDENT PHYSICIAN: R. Paul Fulmer, MD FACULTY: Byron J. Bailey, MD DATABASE ADMINISTRATOR: Melinda McCracken, M.S. ------------------------------------------------------------------------ "This material was prepared by resident physicians in partial fulfillment of educational requirements established for the Postgraduate Training Program of the UTMB Department of Otolaryngology/Head and Neck Surgery and was not intended for clinical use in its present form. It was prepared for the purpose of stimulating group discussion in a conference setting. No warranties, either express or implied, are made with respect to its accuracy, completeness, or timeliness. The material does not necessarily reflect the current or past opinions of members of the UTMB faculty and should not be used for purposes of diagnosis or treatment without consulting appropriate literature sources and informed professional opinion." I. INTRODUCTION: Furstenberg wrote in 1949 "The urge to administer appears to transcend therapeutic rationale and provokes use of antibiotics for purposes often obscure and irrelevant." The aim of prophylaxis is to augment host defenses mechanisms at the time of bacterial invasion, thereby decreasing the size of the inoculum. (Jackson, et. al). This is an attempt to attack organisms before they have a chance to induce infection. An effective prophylactic regimen should be directed against the most likely 'infecting' organism, but it need not include drugs active against every potential pathogen. II. ANTIBIOTICS: A. PENICILLINS 1. Natural penicillins are extracted from Penicillium chrypogenum. Synthetic PCN is prepared by incorporating precursors in mold culture and either modifying a natural PCN or adding side chains to 6-aminopenicillanic acid. (Common nucleus - Thiayolidine ring - Beta lactam ring) 2. Mechanism of action - PCNs exert their action on actively dividing cells by causing abnormal cell wall development. They inhibit the 3rd stage of cell wall synthesis. 3. Resistance a. alterations in PCN binding proteins b. inability to penetrate bacterial cell walls c. enzymatic hydrolysis of the PCN molecule. 4. PCN spectrum a. PCN G - (benzylpenicillin) - Gram + cocci: group A,B, and non Enterococcus D, Pneumococcus, few Staph. - Gram + bacilli: Bacillu antracis, C. Diphtheriae, Listeria monocytogenes. - Gram - cocci: Neisseria gonorrheae, N. meningitidis - Gram - bacilli: Pasteurella multiocida, Streptobacillium moniliformis, spirilium minor. - Anaerobes: Clostridium sp., Bacteroides sp.(except B. fragillis), Fisobascterium, peptostreptococcus. - Misc: Treponema pallidum, Leptospira. b. PCN V ( phenoxypenicillin) - same as PCN G c. Penicillinase-resistant PCNs: - active against most all Strep and Staph except MRSA - Methicillin, Nafcillin, Dicloxacillin, Oxacillin. d. Aminopenicillins: - similar spectrum to PCN G, but more active against Enterococcus and Listeria. - broken down by beta-lactamase. - Ampicillins, Amoxicillin e. Antipseudomonal PCNs: - active against P. aeruginosa and indole positive Proteus, Enterobacter and Acinetobacter. - Ticarcillin, Carbenicillin f. Extended Spectrum PCNs: - Mezlocillin - similar in activity to Ticarcillin, but more active against B. Fragilis and Enterococcus. - Piperacillin - identical spectrum to mezlocillin, but more active against Pseudomonas. g. Clavulanic Acid: - produced by fermentation of Streptomyces clavuligerus - a beta-lactam structurally related to PCNs that inactivated a wide variety of beta-lactamases by blocking active sites of these enzymes 5. Adverse Reactions: a. Hypersensitivity reactions (1-5%). b. Irritant properties effect the peripheral nervous system. c. Nephropathy - allergic rxn. manifested by interstitial nephritis. d. hypokalemia. B. CEPHALOSPORINS 1. Derived from Cephalosporium acremonium. ( Common nucleus - Beta lactum ring - dihydrothiazine ring, connected to a side chain). 2. Mechanism of Action - also inhibits the third step of bacterial wall synthesis, binds to specific proteins on the cell membranes, alters their permeability, inhibits protein synthesis and releases autolysins 3. Resistance - decrease in the bacterial cell wall permeability to antibiotics. - production of bata-lactamase. 4. Spectrum: A. 1st Generation: (Ancef, Keflin, Kefzol) - greatest degree of activity against Gm + organisms (both staph and strep, not MRSA) - same coverage against Gm+, anaerobes, and aerobic bacilli as PCN G. B. 2nd Generation: (Ceclor, Zinacef, Mefoxin) - less active against Gm+ bacteria. - advantage against H. flue and some Gm- bacilli(Proteus and Enterobacter). C. 3rd Generation: (Ceftazadime, Cefotaxime, Cefoperazone) - greatest activity against Gm- aerobes, with variable activity against Pseudomonas. 5. Adverse Reactions: a. Hypersensitivity rxn - highest incidence in those allergic to PCN. b. Hematologic - neutropenia, leukopenia, thrombocytopenia. c. GI disturbances - nausea, vomiting, aneroxia, and diarrhea. d. Reversible renal impairment. C. ERYTHROMYCIN 1. Produced by Streptomyces erythreus 2. Mechanism of Action - inhibits bacterial protein synthesis by binding to the 50s ribosomal subunit. 3. Resistance a. Alteration in protein component of 50s ribosomal subunit. b. Plasmid mediated resistance. 4. Spectrum: a. similar to PCN G b. also effective against Mycoplasma, Legionella and Actinomyces. c. Pediazole - used in combination with Sulfisoxazole in pediatric population. d. effective against H. flue. 5. Adverse Reactions: a. GI disturbances - nausea, vomiting and diarrhea b. Hypersensitivity rxns c. Cholestatic Hepatitis D. CLINDAMYCIN 1. Semisynthetic derivative of Lincomycin. 2. Mecanism of Action - binds to 50s ribosomal subunit, thus inhibiting protein synthesis. 3. Resistance - simular the EES as above. 4. Spectrum - active against most Gm+ organisms, aerobic and anaerobic; and anaerobic Gm- organisms (some Staph have developed resistance). 5. Adverse Reactions: a. Pseudomembraneous Colitis - estimated to occur in < 1% in general population, to as much as 10% in the elderly. This can be fatal presenting with symptoms of crampy pain, watery and occ. bloody diarrhea. Plaque like lesions are seen in the colon that are composed of WBCs, epithelial debris and fibrin. - caused by entertoxigenic Clostridium difficille - Rx with po Vancomycin. b. mild nausea and diarrhea c. Hypersensitivity rxns d. leukopenia e. transient increase and rarely hepatotoxicity. E. METRONIDAZOLE (Flagyl) 1. A nitromidazole compound with in vitro activity against anaerobic protozoa and anaerobic bacteria. 2. Mechanism of action - is reduced intracellularly to its active metabolite, which is bactericidal. 3. May be administrated orally, intravenously, or rectally and is metabolized in the liver and excreted by the kidneys. 4. Adverse reactions - CNS toxicity(peripheral neuropathy, ataxia, vertigo, HA, and seizures); GI disturbances (nausea, vomiting, anorexia, and diarrhea); neutropenia, drug fever, synergistic alcohol effect, and prolonged PTT. Most adverse reactions are dose related and are not seen with regular short term use. III. SURGICAL SKIN PREPARATION: A. Study - Geelhoed GW, et.al 1. patients were randomized to receive either: a. traditional 5 min scrub with iodophor soap followed by painting of skin and cloth drapes, or b. traditional 5 min scrub with iodophor followed by a one min. alcohol cleansing of the skin and application of an antimicrobial film, or c. a one minute alcohol cleansing of the skin without iodophor followed by application of the antimicrobial film. 2. They found that the initial bacterial kill was greater with a one minute alcohol cleansing than a five minute traditional iodophor scrub. 3. This is also achieved in 20% of the time. IV. PROPHYLAXIS: A. OTOLOGY 1. 'Protective Umbrella' - modern otologist often perceives surgical antibiotic prophylaxis as enhancing surgical success and minimizing infection complications. Often prophylaxis is used for legal considerations. 2. The majority of otologic operations are 'clean' cases. Clean cases are most frequently complicated by Staph. species and other Gm+ organisms. Even in 'contaminated' cases, the mostly likely cause of a post op wound infection is GM+ organisms. (rarely are Pseudomonas species and Gm- organisms isolated). 3. Prolonged application of broad-spectrum antibiotics should be discouraged - superinfection can occur in approx. 2% of cases. 4. Studies: a). Eschelman, et.al: -330 patients; Ampicillin and PCN vs. placebo. - double-blinded, controlled randomized study - showed no statistical difference. b). Donaldson and Snyder: - reviewed prophylasis with Sulfa methoxazole in myringoplasty. - demonstrated no influence by abxs. c). Liu, et.al: - 103 otologic patients; IM PCN and Gentamicin - 67% graft take without abx., 92% take with abx. - endorsed prophylaxis d). Bagger-Sjobeck, et.al: - 100 consecutive middle ear cases; PCN V - no statistical significance between PCN V vs. placebo. e). Lindholdt, et.al: - perioperative ceftazadime in cases for COME - endorsed antibiotic prophylaxis. f). Jackson, CG: - 2,793 patients; Cefazolin 1gm IM q 6 hrs for 24 hrs. - all cases were prepared identically( Betadine 10% for 10 minutes; in neurootologic cases iodophor drapes covered the surgical field). - all cases were classified as clean(neuro cases); clean 'contaminated' (chronic ears which are dry), and discharging 'contaminated'. - Total infections = 6.0% for antibiotic group, = 5.7% for the no antibiotic group. - TM grafting success = 98.8% antibiotic; = 98.5% in no antibiotic. - NO Statistically Significant influence upon postoperative otologic infection rates was detectable as an effect of the administration of prophylactic antibiotics. This observation was over a wide range of surgical procedures. This was a consistent observation across all patients regardless of operation duration, patient age and preoperative condition. - Antibiotic prophylaxis appeared no more efficacious in the pediatric patient than it was in the adult. - Prophylaxis was not effective in altering the outcome of TM grafting in preop infected ears. - It is clear that aseptic technique and skillful tissue manipulation cannot be substituted for or augmented by antimicrobial prophylaxis. f). Carlin WV, et.al: -71 patients in multicenter study in myringoplasty - Ampicillin and Flucloxacillin IM preop and QID times 5 days. - prophylaxis did not eradicate even antibiotic-sensitive bacterial pathogens already present in the preoperative ears, nor did it prevent the development of such pathogens during the postoperative period. - the use of antibiotic and steroid ear drops effectively converted a wet postop ear to a dry, sterile ear.( 2 weeks) B. FACIAL FRACTURES 1). Chole RA and Yee J: - prospective study examining the effectiveness of cefazolin administrated during the perioperative period in preventing postoperative infections in a variety of facial fractures. - 101 patients - All facial fractures: 8.9% infected in antibiotic group; and 42.2% infected in the no antibiotic group. (p = 0.0001). - Mandible fractures alone: 13.2% infected in antibiotic group; and 43.9% infected in the no antibiotic group. (p=0.0025). Open fractures had an significant increase in infections in the no abx. group; where as there was no difference in the closed fracture group. - This study indicated that there was a significantly diminished incidence of postoperative infection in facial fractures in which antibiotic prophylaxis was used. - However, almost all of the infections that occurred in this study occurred in mandibular fractures and in those sites that produce compound fractures(either open into the mouth or have teeth in the fracture line). - There was no significant difference in those mandible fractures treated with either open or closed reduction as long as antibiotics were used in the perioperative period. - This study concluded that antibiotic prophylaxis significantly reduced the incidence of postoperative infections in facial fractures ( especially in mandible fractures of the body or parasymphyseal region). They did not find a significant difference in the infection rates in zygoma, Laforte fractures or mandibular subcondylar fractures. C. NASAL AND SINUS SURGERY 1). The use of prophylactic antibiotics in nasal surgery has increased despite the fact that there is little scientific justification for their use. 2). nasal bacterial flora consists of mainly diphtheroids, coagulase-negative cocci, and enterobacteria. Approx 50% of patients undergoing nasal surgery will have coagulase-positive Staph. residing in their nasal cavities. 3). Reasons for Antibiotics: a. a postoperative infection is so devastating that if just one infection is prevented, it is worth if from a cost, medicolegal and outcome viewpoint. b. intranasal packing causes sinusitis that can be prevented with antibiotics. c. the nose is a contaminated field and prophylactic antibiotics should be used to prevent infection. d. the benefits far out weigh the problems. 4). Reasons against Antibiotics: a. it encourages laxity of good surgical technique. b. it is associated with allergic, toxic reactions and side effects. c. it promotes antibiotic resistance. d. in contributes to superinfection e. it is costly. 5). Recommendations: (Larrabee WF) a. Active infection - delay this elective surgery until the infection has cleared. b. When using nasal packing for longer than 24 hrs., it should be impregnated with antibiotic ointment to reduce the local bacterial population. The few studies done state that packing for less than 72 hrs. does not result in sinus infection. c. Hematoma - since an infected septal hematoma is such a serious complication, antibiotics seem indicated. d. Alloplastic implants are used - presoak in an antibiotic (ie. Gentamycin, PCN) and especially the porous alloplastic implants such as Proplast. e. Immunocompromised or immunosuppressed patient. *(This is the same list of recommendations that Tardy gave to us at the Rhinoplasty course!!)* 6). Studies: 1. Derkay CS, et.al: - Are IV abx. really necessary in Posterior Nasal Packing? - 22 patients; Ancef and placebo. Petroleum jelly coated nasal packing. - No infectious complications were noted in either group - However, 89% of patients who received NO abx. showed Heavy growth and a foul odor on the posterior nasal pack when removed @ 72 hrs. (Gm - rods = Proteus mirabilis and Enterobacter species). - In contrast, 90% of packs removed from the patients in the Antibiotic group demonstrated either sterility or a light to moderate growth of a single microorganism (ie. S. viridans, Staph. A.). - This study indicates that by giving IV Ancef there able to eliminate the offensive order that is commonly associated with posterior packs, and also change the bacterial flora that colonizes the foreign body from a heavily overgrown Gm- milieu to a lightly colonized Gm+ flora. b. Jacobson JA, et.al: - Investigated the effect of a single IV dose of Ancef on nasal carriage of Staph Aureus carries. - 30 pts.; 15 were carriers and 12 remained carriers after prophylaxis. - Most culture positive patients will not be carrying toxigenic strains of Staph aureus and among those who are, most will have antibody to the toxins and will probably not be susceptible to TSS. - They concluded that this regimen is unlikely to have a major effect on the incidence of toxic shock syndrome following nasal surgery. D. NON-CONTAMINATED HEAD & NECK SURGERY 1. 'Clean' surgical procedures are those in which no infection exists prior to surgery. During surgery the sterility of the wound is maintained, and following closure of the wound at the completion of the surgery, the wound is never again exposed to direct contact with bacteria. - the risk of postoperative wound infections under these circumstances is less than 5%. 2. Study by Johnson JT, et.al: a. 438 patients: parotidectomies, thyroidectomies and submandibular gland excision. (Retrospective review) b. 20% received Antibiotics; 80% No antibiotics. c. Cephlasporins most commonly used and PCN 2nd most common. d. Only 3 (0.7%) infections in the entire study. (2 -no abx. and 1 in abx. group). e. This study clearly demonstrates the nonefficacy of antibiotics administrated to patients undergoing 'clean' operations of the head and neck. E. CONTAMINATED HEAD & NECK SURGERY 1). Organisms involved: (Johnson JT, et.al) - Oropharyngeal flora includes anaerobic organisms (most commonly Bacteroides - 76%), Gm- rods (ie. E. coli, Klebsiella, Serratia, Proteus, etc.) and Gm+ organisms (ie. Staphlococcus and Streptococcus). - Saliva contains 10 to the 8th bacteria/cc and 90% are anaerobic. - 96% of wound infections in H & N procedures are polymicrobial. - Aerobic Gm- bacilli commonly colonize the oropharynx of hospitalized patients within days of admission. - All the fungi in this study were Candida species and all the postoperative wound infections resolved without any antifungal chemotherapy. Therefore this strongly suggests that fungi in the wound represent colonization rather than infection. - They also feel that isolation of aerobic Gm- bacilli and fungi from postoperative wounds after Head & Neck surgery are generally representative of colonization. Therefore antimicrobial prophylaxis for these microorganisms is usually unnecessary. - They recommend Clindamycin 600mg q 8 hrs. for total of 4 doses to prophylaxis for anaerobic contamination of the wound in big head and neck surgery. b. Becker, Gary D.: - Tried to predict which patients would be high risk for postop wound infections after contaminated head and neck procedures, by culturing the drainage from the hemovacs postoperatively. - The cultures were NOT predictive of those patients who would be at high risk. 2). Antibiotic Prophylaxis Studies: a. Topical: (i). Kirchner, JC, et.al: - pilot, placebo-controlled, double-blind - 6 healthy males topical Clindamycin and its effect on oral flora was recorded. - Aerobic organisms at one hour dropped to 10% of their initial density, compared to 53% after use of the placebo. At 4 hrs. the figures are 14% and 67% respectively. - Anaerobic = 18% @ 1 hr vs 65% for placebo. At 4 hrs the figures are 11% and 95% respectively. - this study purposes that the use of clindamycin (75mg capsule stirred into 8 ounces of tap water) mouthwash provides rapid and sustained reductions in the concentrations of both aerobic and anaerobic oral flora. (ii). Jones, TR, et.al: - 12 patients in prospective, double blind - Showed large reduction in bacterial counts with an antibiotic mouthwash preop(Neomycin 500mg and EES 500mg in 30 mls solution). - None of the patients who received the mouthwash had postoperative complications, vs. 2 of 5 in placebo group. b. Systemic: (i). Duration of Treatment - (Johnson JT, et.al) - found no beneficial effect from administration of antibiotics for longer than 24 hrs ,when compared to 5 days, postoperatively in patients undergoing myocutaneous flap reconstruction. (Cefoperazone sodium 2 gm q 12 hrs). - (Sawyer R, et.al) - Conversely, in this study, a statistically significant reduction in the total number of wound infectious complications if treated with metronidazole and cefazolin for 7 days instead of 2 days. They found a 13-fold greater likelihood of a major wound complication in the 2-day course of antibiotic treatment. (ii). Choice of Antibiotic - (Robbins KT,et.al) - found that with the addition of Metronidazole to Ancef perioperatively(total of 6 doses); the postoperative wound infections were significantly reduced. This is felt to be due to the high amount of anaerobic contamination causing these postoperative wound infections. - (Johnson JT, et.al) - looked at the efficacy of prophylaxis against Gm- organisms in H & N surgery. He found no advantage in clindamycin and gentamycin over clindamycin alone. Reiterating that aerobic Gm- rods are most likely due to colonization. 3). Etiologic factors involved in wound infections: a. Increased Incidence: (i). Stage IV tumors have an increased rate of wound infections vs. lesser staged tumors. (ii). Reconstruction with a myocutaneous flap vs. primary or STSG closure. (iii). Probable errors in surgical technique associated with high percentage of wound infections. b. No Increased Incidence: (i). Weight loss, diabetes mellitus (ii). prior radiation or prior tracheostomy. 4). Recommendations and Observations: a. Identify high risk patients for wound infection. b. Wound infections are polymicrobial. c. Preoperative systemic antibiotics significantly decreases postop wound infections. To be effective, it must be given within 3 hours of wound contamination. d. Optimum duration of prophylaxis has not been determined - probably btwn. 2-7 days. e. A single antibiotic with excellent anaerobic coverage (ie. Clindamycin) is probably as effective as multiple or broad spectrum antibiotics covering both aerobes and anaerobes. ------------------------------------------------------------------------------- BIBLIOGRAPHY: 1. Becker, GD. "Ineffectiveness of Closed Suction Drainage Cultures in the Prediction of Bacteriologic Findings in Wound Infections in Patients Undergoing Contaminated Head and Neck Cancer Surgery." Otolaryngology-Head & Neck Surgery. December 1985;93:743-747. 2. Becker, GD. "Identification and Management of the Patient at High RISK for Wound Infection." Head & Neck Surgery. Jan/Feb 1986:205-210. 3. Brown, BM., et.al. "Etiologic Factors in Head and Neck Wound Infections." Laryngoscope. May, 1987;97:587-590. 4. Carlin, WV,et.al. "Systemic Antibiotic Prophylaxis and Reconstructive Ear Surgery." Clinical Otolaryngology. 1987;12:441-446. 5. Chole, RA and Yee, J. "Antibiotic Prophylaxis for Facial Fractures." Arch Otolaryngol Head Neck Surg. Oct. 1987;113:1055-1057. 6. Derkay, CS, et.al. "Posterior Nasal Packing." Arch Otolaryngol Head Neck Surg. April 1989; 115:439-441. 7. Geelhoed, GW, et.al. "A Comparative Study of Surgical Skin Preparation Methods." Surgery, Gynecology & Obstetrics. September 1983; 157:265-268. 8. Jackson, CG. "Antimicrobial Prophylaxis in Ear Surgery." Laryngoscope. October 1988; 98:1116-1123. 9. Jacobson, JA, et.al. "Evaluation of Single-Dose Cefazolin Prophylaxix for Toxic Shock Syndrome." Arch Otolaryngol Head Neck Surg. March 1988; 114:326-327. 10. Johnson, JT and Yu, VL. "Role of Aerobic Gram-Negative Rods, Anaerobes, and Fungi in Wound Infection after Head and Neck Surgery: Implications for Antibiotic Prophylaxis." Head & Neck. Jan/Feb 1989:27-29. 11. Johnson, JT, et.al. "An Assessment of the Need for Gran-Negative Bacterial Coverage in Antibiotic Prophylaxis for Oncological Head and Neck Surgery." The Journal of Infectious Diseases. 1987; 155:331-333. 12. Johnson, JT and Wagner, RL. "Infection Following Uncontaminated Head and Neck Surgery." Arch Otolaryngology Head Neck Surg. April 1987; 113:368-369. 13. Johnson, JT, et.al. "Antibiotic Prophylaxis in High Risk Head and Neck Surgery: One-day vs. Five-day Therapy." Otolaryngology-Head & Neck Surgery. December 1986; 95:554-557. 14. Jones, TR, et.al. "Efficacy of an Antibiotic Mouthwash in Contaminated Head and Neck Surgery." The American Journal of Surgery. October 1989; 158:324-327. 15. Kirchner, JC, et.al. "The Use of Topical Oral Antibiotics in Head and Neck Prophylaxis: is it Justified?" Laryngoscope. January 1988; 98:26-29. 16. Larrabee, WF. "Prophylactic Antibiotics in Nasal Surgery." Arch Otolaryngol Head Neck Surg. October 1990; 116:1125-1126. 17. Morton, Ronald G. "Antimicrobials in Otolaryngology." Grand Rounds. May 3, 1989. 18. Pollack, AV. "Surgical Prophylaxis-The Emerging Picture." The Lancet. January 1988; pp. 225-230. 19. Robbins, KT, et.al. "Wound Prophylaxis with Metronidazole in Head and Neck Surgical Oncology." Laryngoscope. August 1988; 98:803-806. 20. Saginur, R, et.al. "Antibiotic Prophylaxis in Head and Neck Cancer Surgery." The Journal of Otolaryngology. 1988; 17:78-80. 21. Sawyer, R, et.al. "Metronidazole in Head and Neck Surgery-The Effect of Lengthened Prophylaxis." Otolaryngology-Head & Neck Surgery. December 1990; 103:1009-1011. 22. Sawyer, R. "Clinical Implications of Metronidazole Antianaerobic Prophylaxis in Major Head and Neck Surgical Procedures." Ear, Nose and Throat Journal. September 1988; 67:655-662. ---------------------------------END------------------------------------------