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Prophylactic Use of Antimicrobial Agents in Adult Patients
Prophylactic Use of Antimicrobial Agents in Adult Patients
ROBERT E. VAN SCOY, M.D., CONRAD J. WILKOWSKE, M.D., Division ofInfectious Diseases and Internal Medicine
The prophylactic use of antimicrobial agents is recommended for prevention of numerous infections, including tuberculosis, endocarditis, rheumatic fever, recurrent cellulitis and lymphangitis in patients with lymphedema, meningococcal meningitis, and bite wounds. In addition, the prophylactic use of antimicrobial agents has proved effective in certain surgical procedures such as various abdominal operations, hysterectomy, and major operations that involve the head and neck. Except for oral bowel preparations, antimicrobial prophylaxis should be limited, in general, to the operative period. Prolonged perioperative prophylaxis has not been shown to enhance effectiveness and may result in increased toxicity, resistant superinfections, and inflated costs. The investigation of antimicrobial prophylaxis necessitates adequate evaluation of the potential advantages and disadvantages in a prospective, double-blind fashion.
GENERAL APPLICATIONS For years, the prophylactic use of antimicrobial agents has been a controversial subject. Although certain uses have been generally accepted (Table 1), not all are proven applications. Sexual partners of patients with chancroid, Chlamydia trachomatis infection, gonorrhea, lymphogranuloma venereum, nongonococcal urethritis, pediculosis pubis (lice), scabies, syphilis, or Trichomonas infection should be treated with an effective regimen for the exposure as well as investigated for other sexually transmitted diseases.' Women with recurrent cystitis can be treated in several ways (Table 1). Some women prefer to take antimicrobial agents after symptoms begin rather than prophylactically. For convenience, a prefilled prescription can be available. Those patients who take antimicrobial agents prophylactically only after sexual intercourse should be advised that no more than one dose a day is recommended regardless of the frequency of intercourse, advice particularly important for prostitutes." Recommendations for prevention of ophthalmia neonatorum have been reported.' Silver nitrate (1 %), erythromyIndividual reprints of this article are not available. The entire Symposium on Antimicrobial Agents will be available for purchase as a bound booklet from the Proceedings Circulation Office at a later date. Mayo Clin Proc 67:288-292, 1992
cin ointment (0.5%), and tetracycline ointment (1%) are used topically. The last two agents may be preferable when Chlamydia is predominantly suspected, and silver nitrate is preferred when resistant gonococcal organisms are prevalent in the area. Guidelines for malaria prophylaxis change frequently. Thus, current specific recommendations should be obtained from the Centers for Disease Control. For information about prevention of malaria in specific geographic areas to be visited, a telephone number (1-404-639-1610-2-1) and a publication ("Health Information for International Travel'") are available. An excellent review of measures for prevention of infection during international travel has been published by Ferenchick and Havlichek.' Although antimicrobial agents are seldom recommended for the prevention of traveler's diarrhea, in special circumstances one of the following daily regimens might be used: trimethoprim-sulfamethoxazole (160 + 800 mg), doxycycline (l00 mg), norfloxacin (400 mg), ciprofloxacin (500 mg), or ofloxacin (200 to 400 mg). Although a discussion of prophylaxis for bum wounds is beyond the scope of this article, a report by Monafo and West8 should be helpful. Endocarditis prophylaxis wallet cards, which are available from the American Heart Association and its various state chapters, are of considerable aid to patients, physi-
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Table I.-Generally Accepted Prophylactic Uses of Antimicrobial Agents Condition Tuberculosis Prophylaxis for rheumatic fever Recurrent cellulitis in conjunction with lymphedema Meningococcal meningitis Plague Bite wounds Influenza Recurrent cystitis Staphylococcus aureus colonization in patients on hemodialysis Pertussis (whooping cough)
Antimicrobial agent Isoniazid, 300 mg/day for I yr (monthly follow-up for toxicity) Penicillin G benzathine, 1.2 million U intramuscularly per month, or pencillin G, 200,000 U orally twice a day Bicillin (penicillin G benzathine plus penicillin G procaine) or penicillin G benzathine monthly or penicillin Y 1 wk of each month Rifampin, 600 mg twice a day for 2 days Tetracycline, 30 mg/kglday divided into 4 doses for 10 days, or streptomycin,* I g/day for I wk Penicillin Y, 400,000 U 3 times/day for 3-5 days Amantadine, 100 mg twice a day; decrease to 100 mg/day for elderly patients or those with renal insufficiency Trimethoprirn-sulfamethoxazole, 40 mg + 200 mg, or trimethoprim, 100 mg at bedtime (or 3 times/ wk or 1 time/day after sexual intercourse'[) Rifampin, 600 mg/day, mupirocin, twice a day intranasally for 5 days with or without pHisoHex bathing, or both drug regimens'< Erythromycin, 12.5 mg/kg 4 times/day not to exceed 1 g/day for 14 days for close contacts or carriers
*Currently unavailable. tSee text.
cians, and dentists in remembering appropriate recommendations. Every patient with a cardiovascular condition that predisposes to endocarditis should carry such a card. These cards can also be a convenient reference source for physicians. The current recommendations for antimicrobial prophylaxis for bacterial endocarditis are shown in Tables 2 and 3.9 SURGICAL ANTIMICROBIAL PROPHYLAXIS The subject of antimicrobial prophylaxis for surgical procedures has been reviewed elsewhere.P:" A reliable study of the prophylactic use of antimicrobial agents intraoperatively is characterized by a prospective, randomized, double-blind evaluation in which the study regimen is compared with a currently acceptable regimen. The factors assessed should include wound infection, infection at sites other than the wound, toxicity (including allergic reactions), and cost. For detection of delayed infections, the period of follow-up should be prolonged-perhaps I month after dismissal from the hospital. A sufficient number of patients should be studied to ensure detection of a significant difference within reasonable limits. In adequate investigations of efficacy of prophylactic antimicrobial agents for surgical intervention, many variables are considered: age of the patient; type of surgical
procedure; underlying disease; type, dose, duration, and route of administration of the drug; hospital; and surgeon. Prolonged perioperative use of a prophylactic agent may result in a pattern of decreased susceptibility of the bacterial flora in the involved hospital. Although this factor is difficult to evaluate in a prospective patient study, it is important. In experimental animals, Burke!" demonstrated that prophylactic use of antimicrobial agents was effective only during the period of the surgical procedure. Antimicrobial agents administered several hours postoperatively were ineffective. Several clinical studies have supported this concept in prosthetic valve cardiac operations," gynecologic surgical procedures," and gastrointestinal operations,'? and DiPiro and associates" have reviewed the subject. Elective Colonic Operations.-General recommendations for antimicrobial prophylaxis in colonic operations are summarized in Table 4. In a double-blind prospective study, Washington and colleagues" demonstrated a substantial decrease in postoperative infections in patients who had received neomycin and tetracycline in comparison with those who were given a placebo or neomycin. The dosage schedule was 500 mg of neomycin and 250 mg of tetracycline four times a day for the 2 days before the operation. Other investigators have reported a decrease in infectious complications with use of erythromycin and neomycin.P'"
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Table 2.-Recommendations for Antimicrobial Prophylaxis for Bacterial Endocarditis for Dental, Oral, and Upper Respiratory Tract Procedures*
Table 3.-Recommendations for Antimicrobial Prophylaxis for Bacterial Endocarditis for Genitourinary and Gastrointestinal Procedures*
Standard regimenin patients at risk (includingthose with prostheticheart valves and other high-riskpatients): Amoxicillin, 3 g orally 1 h before procedureand 1.5 g 6 h after initial dose
Standard regimen: Ampicillin, 2 g intravenously or intramuscularly,plus gentamicin, 1.5 mg/kg intravenously or intramuscularly not to exceed 80 mg 30 min before procedure, followed by amoxicillin, 1.5 g orally 6 h after initial dose. Alternatively, the parenteral regimen may be repeated once 8 h after initial dose If allergic to amoxicillin, ampicillin, or penicillin: Vancomycin, 1 g intravenously administeredduring a l-h period, plus gentamicin, 1.5 mg/kg intravenously or intramuscularly not to exceed 80 mg 1 h before procedure. May be repeated once 8 h after initial dose Alternative oral regimen for low-risk patients: Amoxicillin, 3 g orally 1 h before procedure and then 1.5 g 6 h after initial dose
If allergic to amoxicillinor penicillin:
Erythromycin ethylsuccinate,800 mg, or erythromycin stearate, 1 g, orally 2 h before procedureand liz the dose 6 h after initial dose or Clindamycin, 300 mg orally 1 h before procedureand 150 mg 6 h after initial dose Alternativeprophylacticregimensfor patients at risk Standard: Ampicillin, 2 g intravenously or intramuscularly 30 min before procedure, followedby 1 g intravenously or intramuscularly, or amoxicillin, 1.5 g orally 6 h after initial dose If allergic to amoxicillinor penicillin: Clindamycin, 300 mg intravenously 30 min before procedure and 150 mg intravenously or orally 6 h after initial dose Alternativeregimen for high-riskpatients who are not candidates for the standard regimen: Ampicillin,2 g intravenously or intramuscularly, plus gentamicin, 1.5 mg/kg intravenously or intramuscularly not to exceed 80 mg 30 min before procedure,followed by amoxicillin, 1.5 g orally 6 h after initial dose, or repeat the parenteral regimen 8 h after initial dose For high-risk patients allergic to amoxicillin, ampicillin, or penicillin: Vancomycin, 1 g intravenously administeredduring a l-h period, beginning 1 h before procedure. No repeat dose is necessary *Doses for pediatric patients: Amoxicillin 50 mglkg 2 mg/kg Gentamicin Clindamycin 10 mglkg Vancomycin 20 mglkg Ampicillin 50 mg/kg Erythromycin ethylsuccinateor stearate 20 mg/kg
Other Abdominal Operations.-General recommendations for antimicrobial prophylaxis in gastrointestinal surgical procedures are outlined in Table 5. Patients who are at high risk for infection after gastroduodenal procedures are those who have gastric cancer, have bleeding gastric or duodenal ulcers, or undergo a gastric operation for obesity. Patients who undergo cholecystectomy are at high risk if they have jaundice, are older than'60 years of age, have acute symptoms, or have previously undergone a biliary operation. Those who have penetrating abdominal trauma or ruptured viscus need treatment, not just prophylaxis. Obstetric and Gynecologic Operations.-Prophylaxis for gynecologic surgical procedures has been studied exten-
*See Table 2 for doses for pediatric patients.
sively. Although theoretically one might expect a second- or third-generation cephalosporin to be superior to cefazolin (a first-generation drug), that result has not prevailed. Furthermore, a single dose of an antimicrobial agent at the onset of operation or after the umbilical cord has been clamped is adequate. Antimicrobial prophylaxis for radical hysterectomy in patients with a malignant tumor has been shown to be effective, but the most appropriate regimen has not yet been determined." Major Head and Neck Operations.-Tabet and Johnson" published an excellent review of antimicrobial prophylaxis in head and neck surgical procedures. Many studies have demonstrated no additional benefit from prolonged antimicrobial prophylaxis in comparison with a short-term regimen. Prophylaxis against anaerobes was effective and necessary in many studies in which the surgical procedure involved entry into the mucosa of the digestive or respiratory tract. Investigators have not demonstrated that prophylaxis against aerobic organisms is necessary. Therefore, the current recommendation is to administer either clindamycin (900 mg intravenously) or clindamycin (900 mg intravenously) plus gentamicin (1.7 mglkg) at the onset of the operation. A second dose may be indicated for prolonged surgical procedures-for example, those that last longer than 6 hours after administration of the initial antimicrobial prophylactic regimen. Orthopedic Operations.-Administration of 1 to 2 g of cefazolin intravenously at the onset of orthopedic surgical procedures may decrease the frequency of postoperative infections. In a study by Ritter and co-workers," only intraoperative use of antimicrobial agents was as effective as more prolonged antimicrobial prophylaxis. In another study, in-
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Table 4.-Recommendations for Antimicrobial Prophylaxis for ColonicSurgical Procedures Elective procedures Oral: Neomycin (500 mg) and tetracycline (250 mg)4 times/day for 2 days beforeoperation or Erythromycin (l g) and neomycin (l g) 3 times/day for I day beforeoperation or Metronidazole (500 mg)and neomycin (l g) 3 times/day for I day beforeoperation Nonelective procedures or if oral prophylaxis not possible Parenteral: Singleparenteral doseof an aerobic agentplus an anaerobic agent(as shown below), followed by a second doseif procedure lasts6 h beyond firstdose Aerobic agent Anaerobic agent Gentamicin 2 mglkg Clindamycin 900 mg Aztreonam Ig Metronidazole 500 mg Cefotaxime I g Ceftizoxime I g Ceftriaxone I g Alternatively: Singleparenteral dose of an agentwith aerobic and anaerobic coverage, followed by a second doseif procedure lasts6 h beyond firstdose Ampicillin-sulbactam 2 gil g lmipenem-cilastatin Ig Ticarcillin-clavulanate 3 g/lOO mg fection after amputation of a lower extremity was reduced by prophylactic use of antimicrobial agents." Whether cefoxitin is superior to cefazolin is unknown. Currently, we recommend administration of cefazolin or cefoxitin, 2 g intravenously, within an hour after the onset of the surgical procedure. Cardiovascular Operations.-Cefuroxime and cefamandole may be superior to cefazolin for prophylaxis in openheart surgical procedures." Because some hospitals may not have other reasons to include cefamandole on their formularies, cefuroxime is preferable. The optimal duration of antimicrobial prophylaxis for open-heart operations has not been determined. Cefuroxime in a dosage of 1 to 1.5 g intravenously every 6 to 8 hours for 48 hours may be indicated. Vancomycin in a single dose of 15 mg/kg or administered every 12 hours for 48 hours (with the dosage adjusted for impaired renal function) may be indicated in those patients who are allergic to cephalosporins. The benefits, however, must be carefully weighed against the side effects of this regimen.F:" Cefazolin has been shown to decrease infections in patients who have undergone operations that involve the abdominal aorta or blood vessels of the lower extremities. A single dose of 1 to 2 g of cefazolin will usually suffice. Because no infections occurred in 103 patients who un-
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derwent carotid or brachial artery operations, antimicrobial prophylaxis is not recommended for this subgroup of patients." Thoracic Operations.-Available data about the efficacy of antimicrobial prophylaxis for noncardiac thoracic surgical procedures are conflicting. Currently, a single dose of cefazolin (l to 2 g) at the onset of such an operation is recommended. Antimicrobial prophylaxis has not substantially decreased infections after closed-tube thoracostomy for chest trauma or spontaneous pneumothorax and is not recommended. Neurosurgical Procedures.-Haines 30 has reviewed antimicrobial prophylaxis in "clean" neurosurgical operations. Most published studies on the use of antimicrobial agents for prophylaxis in neurosurgical procedures have not fulfilled the requirements for adequate investigation. Cefazolin and gentamicin apparently reduce postoperative infections, as reported by Young and Lawner." Blomstedt and Kytta'" demonstrated decreased infections in patients who received a single dose of vancomycin in a randomized but nonblinded study. Again, these data support the single-dose concept of prophylaxis. Perhaps administration of 2 g of cefotaxime at the onset of a neurosurgical procedure and repeated at 6 hours should be studied because it penetrates the cerebrospinal fluid better than does cefazolin, is likely to be associated with fewer side effects than is vancomycin, and is relatively inexpensive. Data about antimicrobial prophylaxis in shunt operations are inconclusive. 33 Urologic Operations.-Hofer and Schaeffer" reported inconclusive findings in a review of prophylactic use of antimicrobial agents in transurethral resection of the prostate. For appropriate assessment, a large study should be conducted in which treatment of existing infections is separated from prophylaxis in previously uninfected patients. Certain data suggest that short-term antimicrobial prophylaxis with a first-generation cephalosporin may decrease the frequency of infection after open prostatectomy. Prolonged antimicrobial therapy during prophylaxis is contraindicated because this practice leads to resistant organisms.
Table5.-Recommendations for Antimicrobial Prophylaxis for Gastrointestinal Surgical Procedures Procedure
Recommended prophylaxis
Gastroduodenal operation Cholecystectomy Appendectomy Smallbowel operation
Cefazolin, 2 g intravenously at onsetof operation (for high-risk patients only*) Sameas above* Sameas forcolonic surgical procedurest Sameas for colonic surgical procedurest
*Forexplanation of "high risk," see text. tSee Table 4.
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REFERENCES 1. Chow JW, Yu VL: Staphylococcus aureus nasal carriage in hemodialysis patients: its role in infection and approaches to prophylaxis. Arch Intern Med 149:1258-1262,1989 2. Reagan DR, Doebbeling BN, Pfaller MA, Sheetz CT, Houston AK, Hollis RJ, Wenzel RP: Elimination of coincident Staphylococcus aureus nasal and hand carriage with intranasal application of mupirocin calcium ointment. Ann Intern Med 114:101-106,1991 3. Zenilman JM (ed): 1989 Sexually transmitted diseases treatment guidelines. Rev Infect Dis 12 (Suppl 6):Sl-S690, 1990 4. Brumfitt W, Hamilton-Miller JMT: Prophylactic antibiotics for recurrent urinary tract infections. J Antimicrob Chemother 25:505-512,1990 5. Hammerschlag MR, Cummings C, Roblin PM, Williams TH, Deike I: Efficacy of neonatal ocular prophylaxis for the prevention of chlamydial and gonococcal conjunctivitis. N Engl J Med 320:769-772, 1989 6. Health Information for International Travel, 1990. Centers for Disease Control, Department of Health and Human Services, Publication No. CDC 90-8280. Washington, DC, US Government Printing Office, June 1990 7. Ferenchick GS, Havlichek DH: Primary prevention and international travel: infections, immunizations, and antimicrobial prophylaxis. J Gen Intern Med 4:247-258, 1989 8. Monafo WW, West MA: Current treatment recommendations for topical burn therapy. Drugs 40:364-373, 1990 9. Dajani AS, Bisno AL, Chung KJ, Durack DT, Freed M, Gerber MA, Karchmer AW, Millard HD, Rahimtoola S, Shulman ST, Watanakunakorn C, Taubert KA: Prevention of bacterial endocarditis: recommendations by the American Heart Association. JAMA 264:2919-2922, 1990 10. Antimicrobial prophylaxis in surgery. Med Lett Drugs Ther 31:105-108, 1989 II. Conte JE Jr: Antibiotic prophylaxis: non-abdominal surgery. Curr Clin Top Infect Dis 10:254-305, 1989 12. Nichols RL: Antibiotic prophylaxis in surgery. J Chemother I: 170-178, 1989 13. Hirschmann JV, Inui TS: Antimicrobial prophylaxis: a critique of recent trials. Rev Infect Dis 2:1-23, 1980 14. Burke JF: The effective period of preventive antibiotic action in experimental incisions and dermal lesions. Surgery 50:161-168,1961 15. Conte JE Jr, Cohen SN, Roe BB, Elashoff RM: Antibiotic prophylaxis and cardiac surgery: a prospective double-blind comparison of single-dose versus multiple-dose regimens. Ann Intern Med 76:943-949,1972 16. Ledger WJ, Gee C, Lewis WP: Guidelines for antibiotic prophylaxis in gynecology. Am J Obstet Gynecol 121:10381045, 1975 17. Griffiths DA, Shorey BA, Simpson RA, Speller DCE, Williams NB: Single-dose preoperative antibiotic prophylaxis in gastrointestinal surgery. Lancet 2:325-328,1976
18. 19.
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22. 23. 24.
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27. 28. 29. 30. 31. 32. 33. 34.
DiPiro JT, Cheung RPF, Bowden TA Jr, Mansberger JA: Single dose systemic antibiotic prophylaxis of surgical wound infections. Am J Surg 152:552-559, 1986 Washington JA II, Dearing WH, Judd ES, Elveback LR: Effect of preoperative antibiotic regimen on development of infection after intestinal surgery: prospective, randomized, double-blind study. Ann Surg 180:567-571,1974 Nichols RL, Broido P, Condon RE, Gorbach SL, Nyhus LM: Effect of preoperative neomycin-erythromycin intestinal preparation on the incidence of infectious complications following colon surgery. Ann Surg 178:453-459, 1973 Clarke JS, Condon RE, Bartlett JG, Gorbach SL, Nichols RL' Ochi S: Preoperative oral antibiotics reduce septic complications of colon operations: results of prospective, randomized, double-blind clinical study. Ann Surg 186:251-258, 1977 Graham JE Jr: Infectious morbidity in gynecologic oncology. J Reprod Med 35:348-352, 1990 Tabet J-C, Johnson JT: Wound infection in head and neck surgery: prophylaxis, etiology and management. J Otolaryngol 19:197-200,1990 Ritter MA, Campbell E, Keating EM, Faris PM: Comparison of intraoperative versus 24 hour antibiotic prophylaxis in total joint replacement: a controlled prospective study. Orthop Rev 18:694-696, 1989 Sonne-Holm S, Boeckstyns M, Menck H, Sinding A, Leicht P, Dichmann 0, Prag lB, Baekgaard N, Ostri P, Getrik JK: Prophylactic antibiotics in amputation of the lower extremity for ischemia: a placebo-controlled, randomized trial of cefoxitin. J Bone Joint Surg [Am] 67:800-803, 1985 Slama TG, Sklar SJ, Misinski J, Fess SW: Randomized comparison of cefamandole, cefazolin, and cefuroxime prophylaxis in open-heart surgery. Antimicrob Agents Chemother 29:744-747, 1986 Southorn PA, Plevak DJ, Wright AJ, Wilson WR: Adverse effects of vancomycin administered in the perioperative period. Mayo Clin Proc 61:721-724,1986 Davis RL, Smith AL, Koup JR: The "red man's syndrome" and slow infusion of vancomycin (letter to the editor). Ann Intern Med 104:285-286, 1986 Kaiser AB, Clayson KR, Mulherin JL Jr, Roach AC, Allen TR, Edwards WH, Dale WA: Antibiotic prophylaxis in vascular surgery. Ann Surg 188:283-288, 1978 Haines SJ: Efficacy of antibiotic prophylaxis in clean neurosurgical operations. Neurosurgery 24:401-405, 1989 Young RF, Lawner PM: Perioperative antibiotic prophylaxis for prevention of postoperative neurosurgical infections: a randomized clinical trial. JNeurosurg 66:701-705,1987 Blomstedt GC, Kytta J: Results of a randomized trial of vancomycin prophylaxis in craniotomy. J Neurosurg 69:216-220,1988 Quigley MR, Reigel DH, Kortyna R: Cerebrospinal fluid shunt infections: report of 41 cases and a critical review of the literature. Pediatr Neurosci 15:111-120, 1989 Hofer DR, Schaeffer AJ: Use of antimicrobials for patients undergoing prostatectomy. Urol Clin North Am 17:595-600, August 1990
END OF SYMPOSIUM ON ANTIMICROBIAL AGENTS
ROBERT E. VAN SCOY, M.D., CONRAD J. WILKOWSKE, M.D., Division ofInfectious Diseases and Internal Medicine
The prophylactic use of antimicrobial agents is recommended for prevention of numerous infections, including tuberculosis, endocarditis, rheumatic fever, recurrent cellulitis and lymphangitis in patients with lymphedema, meningococcal meningitis, and bite wounds. In addition, the prophylactic use of antimicrobial agents has proved effective in certain surgical procedures such as various abdominal operations, hysterectomy, and major operations that involve the head and neck. Except for oral bowel preparations, antimicrobial prophylaxis should be limited, in general, to the operative period. Prolonged perioperative prophylaxis has not been shown to enhance effectiveness and may result in increased toxicity, resistant superinfections, and inflated costs. The investigation of antimicrobial prophylaxis necessitates adequate evaluation of the potential advantages and disadvantages in a prospective, double-blind fashion.
GENERAL APPLICATIONS For years, the prophylactic use of antimicrobial agents has been a controversial subject. Although certain uses have been generally accepted (Table 1), not all are proven applications. Sexual partners of patients with chancroid, Chlamydia trachomatis infection, gonorrhea, lymphogranuloma venereum, nongonococcal urethritis, pediculosis pubis (lice), scabies, syphilis, or Trichomonas infection should be treated with an effective regimen for the exposure as well as investigated for other sexually transmitted diseases.' Women with recurrent cystitis can be treated in several ways (Table 1). Some women prefer to take antimicrobial agents after symptoms begin rather than prophylactically. For convenience, a prefilled prescription can be available. Those patients who take antimicrobial agents prophylactically only after sexual intercourse should be advised that no more than one dose a day is recommended regardless of the frequency of intercourse, advice particularly important for prostitutes." Recommendations for prevention of ophthalmia neonatorum have been reported.' Silver nitrate (1 %), erythromyIndividual reprints of this article are not available. The entire Symposium on Antimicrobial Agents will be available for purchase as a bound booklet from the Proceedings Circulation Office at a later date. Mayo Clin Proc 67:288-292, 1992
cin ointment (0.5%), and tetracycline ointment (1%) are used topically. The last two agents may be preferable when Chlamydia is predominantly suspected, and silver nitrate is preferred when resistant gonococcal organisms are prevalent in the area. Guidelines for malaria prophylaxis change frequently. Thus, current specific recommendations should be obtained from the Centers for Disease Control. For information about prevention of malaria in specific geographic areas to be visited, a telephone number (1-404-639-1610-2-1) and a publication ("Health Information for International Travel'") are available. An excellent review of measures for prevention of infection during international travel has been published by Ferenchick and Havlichek.' Although antimicrobial agents are seldom recommended for the prevention of traveler's diarrhea, in special circumstances one of the following daily regimens might be used: trimethoprim-sulfamethoxazole (160 + 800 mg), doxycycline (l00 mg), norfloxacin (400 mg), ciprofloxacin (500 mg), or ofloxacin (200 to 400 mg). Although a discussion of prophylaxis for bum wounds is beyond the scope of this article, a report by Monafo and West8 should be helpful. Endocarditis prophylaxis wallet cards, which are available from the American Heart Association and its various state chapters, are of considerable aid to patients, physi-
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Table I.-Generally Accepted Prophylactic Uses of Antimicrobial Agents Condition Tuberculosis Prophylaxis for rheumatic fever Recurrent cellulitis in conjunction with lymphedema Meningococcal meningitis Plague Bite wounds Influenza Recurrent cystitis Staphylococcus aureus colonization in patients on hemodialysis Pertussis (whooping cough)
Antimicrobial agent Isoniazid, 300 mg/day for I yr (monthly follow-up for toxicity) Penicillin G benzathine, 1.2 million U intramuscularly per month, or pencillin G, 200,000 U orally twice a day Bicillin (penicillin G benzathine plus penicillin G procaine) or penicillin G benzathine monthly or penicillin Y 1 wk of each month Rifampin, 600 mg twice a day for 2 days Tetracycline, 30 mg/kglday divided into 4 doses for 10 days, or streptomycin,* I g/day for I wk Penicillin Y, 400,000 U 3 times/day for 3-5 days Amantadine, 100 mg twice a day; decrease to 100 mg/day for elderly patients or those with renal insufficiency Trimethoprirn-sulfamethoxazole, 40 mg + 200 mg, or trimethoprim, 100 mg at bedtime (or 3 times/ wk or 1 time/day after sexual intercourse'[) Rifampin, 600 mg/day, mupirocin, twice a day intranasally for 5 days with or without pHisoHex bathing, or both drug regimens'< Erythromycin, 12.5 mg/kg 4 times/day not to exceed 1 g/day for 14 days for close contacts or carriers
*Currently unavailable. tSee text.
cians, and dentists in remembering appropriate recommendations. Every patient with a cardiovascular condition that predisposes to endocarditis should carry such a card. These cards can also be a convenient reference source for physicians. The current recommendations for antimicrobial prophylaxis for bacterial endocarditis are shown in Tables 2 and 3.9 SURGICAL ANTIMICROBIAL PROPHYLAXIS The subject of antimicrobial prophylaxis for surgical procedures has been reviewed elsewhere.P:" A reliable study of the prophylactic use of antimicrobial agents intraoperatively is characterized by a prospective, randomized, double-blind evaluation in which the study regimen is compared with a currently acceptable regimen. The factors assessed should include wound infection, infection at sites other than the wound, toxicity (including allergic reactions), and cost. For detection of delayed infections, the period of follow-up should be prolonged-perhaps I month after dismissal from the hospital. A sufficient number of patients should be studied to ensure detection of a significant difference within reasonable limits. In adequate investigations of efficacy of prophylactic antimicrobial agents for surgical intervention, many variables are considered: age of the patient; type of surgical
procedure; underlying disease; type, dose, duration, and route of administration of the drug; hospital; and surgeon. Prolonged perioperative use of a prophylactic agent may result in a pattern of decreased susceptibility of the bacterial flora in the involved hospital. Although this factor is difficult to evaluate in a prospective patient study, it is important. In experimental animals, Burke!" demonstrated that prophylactic use of antimicrobial agents was effective only during the period of the surgical procedure. Antimicrobial agents administered several hours postoperatively were ineffective. Several clinical studies have supported this concept in prosthetic valve cardiac operations," gynecologic surgical procedures," and gastrointestinal operations,'? and DiPiro and associates" have reviewed the subject. Elective Colonic Operations.-General recommendations for antimicrobial prophylaxis in colonic operations are summarized in Table 4. In a double-blind prospective study, Washington and colleagues" demonstrated a substantial decrease in postoperative infections in patients who had received neomycin and tetracycline in comparison with those who were given a placebo or neomycin. The dosage schedule was 500 mg of neomycin and 250 mg of tetracycline four times a day for the 2 days before the operation. Other investigators have reported a decrease in infectious complications with use of erythromycin and neomycin.P'"
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Table 2.-Recommendations for Antimicrobial Prophylaxis for Bacterial Endocarditis for Dental, Oral, and Upper Respiratory Tract Procedures*
Table 3.-Recommendations for Antimicrobial Prophylaxis for Bacterial Endocarditis for Genitourinary and Gastrointestinal Procedures*
Standard regimenin patients at risk (includingthose with prostheticheart valves and other high-riskpatients): Amoxicillin, 3 g orally 1 h before procedureand 1.5 g 6 h after initial dose
Standard regimen: Ampicillin, 2 g intravenously or intramuscularly,plus gentamicin, 1.5 mg/kg intravenously or intramuscularly not to exceed 80 mg 30 min before procedure, followed by amoxicillin, 1.5 g orally 6 h after initial dose. Alternatively, the parenteral regimen may be repeated once 8 h after initial dose If allergic to amoxicillin, ampicillin, or penicillin: Vancomycin, 1 g intravenously administeredduring a l-h period, plus gentamicin, 1.5 mg/kg intravenously or intramuscularly not to exceed 80 mg 1 h before procedure. May be repeated once 8 h after initial dose Alternative oral regimen for low-risk patients: Amoxicillin, 3 g orally 1 h before procedure and then 1.5 g 6 h after initial dose
If allergic to amoxicillinor penicillin:
Erythromycin ethylsuccinate,800 mg, or erythromycin stearate, 1 g, orally 2 h before procedureand liz the dose 6 h after initial dose or Clindamycin, 300 mg orally 1 h before procedureand 150 mg 6 h after initial dose Alternativeprophylacticregimensfor patients at risk Standard: Ampicillin, 2 g intravenously or intramuscularly 30 min before procedure, followedby 1 g intravenously or intramuscularly, or amoxicillin, 1.5 g orally 6 h after initial dose If allergic to amoxicillinor penicillin: Clindamycin, 300 mg intravenously 30 min before procedure and 150 mg intravenously or orally 6 h after initial dose Alternativeregimen for high-riskpatients who are not candidates for the standard regimen: Ampicillin,2 g intravenously or intramuscularly, plus gentamicin, 1.5 mg/kg intravenously or intramuscularly not to exceed 80 mg 30 min before procedure,followed by amoxicillin, 1.5 g orally 6 h after initial dose, or repeat the parenteral regimen 8 h after initial dose For high-risk patients allergic to amoxicillin, ampicillin, or penicillin: Vancomycin, 1 g intravenously administeredduring a l-h period, beginning 1 h before procedure. No repeat dose is necessary *Doses for pediatric patients: Amoxicillin 50 mglkg 2 mg/kg Gentamicin Clindamycin 10 mglkg Vancomycin 20 mglkg Ampicillin 50 mg/kg Erythromycin ethylsuccinateor stearate 20 mg/kg
Other Abdominal Operations.-General recommendations for antimicrobial prophylaxis in gastrointestinal surgical procedures are outlined in Table 5. Patients who are at high risk for infection after gastroduodenal procedures are those who have gastric cancer, have bleeding gastric or duodenal ulcers, or undergo a gastric operation for obesity. Patients who undergo cholecystectomy are at high risk if they have jaundice, are older than'60 years of age, have acute symptoms, or have previously undergone a biliary operation. Those who have penetrating abdominal trauma or ruptured viscus need treatment, not just prophylaxis. Obstetric and Gynecologic Operations.-Prophylaxis for gynecologic surgical procedures has been studied exten-
*See Table 2 for doses for pediatric patients.
sively. Although theoretically one might expect a second- or third-generation cephalosporin to be superior to cefazolin (a first-generation drug), that result has not prevailed. Furthermore, a single dose of an antimicrobial agent at the onset of operation or after the umbilical cord has been clamped is adequate. Antimicrobial prophylaxis for radical hysterectomy in patients with a malignant tumor has been shown to be effective, but the most appropriate regimen has not yet been determined." Major Head and Neck Operations.-Tabet and Johnson" published an excellent review of antimicrobial prophylaxis in head and neck surgical procedures. Many studies have demonstrated no additional benefit from prolonged antimicrobial prophylaxis in comparison with a short-term regimen. Prophylaxis against anaerobes was effective and necessary in many studies in which the surgical procedure involved entry into the mucosa of the digestive or respiratory tract. Investigators have not demonstrated that prophylaxis against aerobic organisms is necessary. Therefore, the current recommendation is to administer either clindamycin (900 mg intravenously) or clindamycin (900 mg intravenously) plus gentamicin (1.7 mglkg) at the onset of the operation. A second dose may be indicated for prolonged surgical procedures-for example, those that last longer than 6 hours after administration of the initial antimicrobial prophylactic regimen. Orthopedic Operations.-Administration of 1 to 2 g of cefazolin intravenously at the onset of orthopedic surgical procedures may decrease the frequency of postoperative infections. In a study by Ritter and co-workers," only intraoperative use of antimicrobial agents was as effective as more prolonged antimicrobial prophylaxis. In another study, in-
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Table 4.-Recommendations for Antimicrobial Prophylaxis for ColonicSurgical Procedures Elective procedures Oral: Neomycin (500 mg) and tetracycline (250 mg)4 times/day for 2 days beforeoperation or Erythromycin (l g) and neomycin (l g) 3 times/day for I day beforeoperation or Metronidazole (500 mg)and neomycin (l g) 3 times/day for I day beforeoperation Nonelective procedures or if oral prophylaxis not possible Parenteral: Singleparenteral doseof an aerobic agentplus an anaerobic agent(as shown below), followed by a second doseif procedure lasts6 h beyond firstdose Aerobic agent Anaerobic agent Gentamicin 2 mglkg Clindamycin 900 mg Aztreonam Ig Metronidazole 500 mg Cefotaxime I g Ceftizoxime I g Ceftriaxone I g Alternatively: Singleparenteral dose of an agentwith aerobic and anaerobic coverage, followed by a second doseif procedure lasts6 h beyond firstdose Ampicillin-sulbactam 2 gil g lmipenem-cilastatin Ig Ticarcillin-clavulanate 3 g/lOO mg fection after amputation of a lower extremity was reduced by prophylactic use of antimicrobial agents." Whether cefoxitin is superior to cefazolin is unknown. Currently, we recommend administration of cefazolin or cefoxitin, 2 g intravenously, within an hour after the onset of the surgical procedure. Cardiovascular Operations.-Cefuroxime and cefamandole may be superior to cefazolin for prophylaxis in openheart surgical procedures." Because some hospitals may not have other reasons to include cefamandole on their formularies, cefuroxime is preferable. The optimal duration of antimicrobial prophylaxis for open-heart operations has not been determined. Cefuroxime in a dosage of 1 to 1.5 g intravenously every 6 to 8 hours for 48 hours may be indicated. Vancomycin in a single dose of 15 mg/kg or administered every 12 hours for 48 hours (with the dosage adjusted for impaired renal function) may be indicated in those patients who are allergic to cephalosporins. The benefits, however, must be carefully weighed against the side effects of this regimen.F:" Cefazolin has been shown to decrease infections in patients who have undergone operations that involve the abdominal aorta or blood vessels of the lower extremities. A single dose of 1 to 2 g of cefazolin will usually suffice. Because no infections occurred in 103 patients who un-
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derwent carotid or brachial artery operations, antimicrobial prophylaxis is not recommended for this subgroup of patients." Thoracic Operations.-Available data about the efficacy of antimicrobial prophylaxis for noncardiac thoracic surgical procedures are conflicting. Currently, a single dose of cefazolin (l to 2 g) at the onset of such an operation is recommended. Antimicrobial prophylaxis has not substantially decreased infections after closed-tube thoracostomy for chest trauma or spontaneous pneumothorax and is not recommended. Neurosurgical Procedures.-Haines 30 has reviewed antimicrobial prophylaxis in "clean" neurosurgical operations. Most published studies on the use of antimicrobial agents for prophylaxis in neurosurgical procedures have not fulfilled the requirements for adequate investigation. Cefazolin and gentamicin apparently reduce postoperative infections, as reported by Young and Lawner." Blomstedt and Kytta'" demonstrated decreased infections in patients who received a single dose of vancomycin in a randomized but nonblinded study. Again, these data support the single-dose concept of prophylaxis. Perhaps administration of 2 g of cefotaxime at the onset of a neurosurgical procedure and repeated at 6 hours should be studied because it penetrates the cerebrospinal fluid better than does cefazolin, is likely to be associated with fewer side effects than is vancomycin, and is relatively inexpensive. Data about antimicrobial prophylaxis in shunt operations are inconclusive. 33 Urologic Operations.-Hofer and Schaeffer" reported inconclusive findings in a review of prophylactic use of antimicrobial agents in transurethral resection of the prostate. For appropriate assessment, a large study should be conducted in which treatment of existing infections is separated from prophylaxis in previously uninfected patients. Certain data suggest that short-term antimicrobial prophylaxis with a first-generation cephalosporin may decrease the frequency of infection after open prostatectomy. Prolonged antimicrobial therapy during prophylaxis is contraindicated because this practice leads to resistant organisms.
Table5.-Recommendations for Antimicrobial Prophylaxis for Gastrointestinal Surgical Procedures Procedure
Recommended prophylaxis
Gastroduodenal operation Cholecystectomy Appendectomy Smallbowel operation
Cefazolin, 2 g intravenously at onsetof operation (for high-risk patients only*) Sameas above* Sameas forcolonic surgical procedurest Sameas for colonic surgical procedurest
*Forexplanation of "high risk," see text. tSee Table 4.
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