Antibiotic Prophylaxis In Dermatology

Antimicrobial Prophylaxis in Dermatology J.V. Hirschmann Few circumstances in dermatology warrant antimicrobial prophylaxis. In cutaneous surgery postoperative infections are too infrequent and insufficiently severe to justify preventive antibiotics, except rarely. Petrolatum is as effective as, and cheaper than, topical antibiotic ointment to cover surgical wounds. In patients with numerous staphylococcal skin infections, oral clindamycin 150 mg every day for 3 months safely reduces further episodes. For recurrent cellulitis, oral penicillin or erythromycin 250 mg twice daily or monthly intramuscular benzathine penicillin decreases subsequent attacks. In patients with frequent episodes of genital or labial herpes simplex an antiviral agent such as valacyclovir 500 mg to I g every day is effective as a suppressant. Copyright 9 2000 by W.B. Saunders Company

from the resident flora, typically present on a nearby mucosal surface. Ahernativel); the antiinfective agent eradicates the target organism from the host's reservoir. An example is using antibiotics to prevent postoperative wound infections following dermatologic surgery. The infecting organisms are usually part of the resident flora of the skin or nearby mucous membranes. Another is using topical mupirocin to eliminate nasal carriage of Staphylococcus aureus in patients with repeated staphylococcal skin infections.

HE TERM "prophylaxis" has been applied to several different circumstances, depending on whether the organism is exogenous or part of the normal resident flora and whether the antimicrobial agent is given before or after the microbe has reached the target tissues. Four different situations existl:

The initial infection occurred previously, and the microbe remains alive, but inactive, in the asymptomatic host. The antimicrobial agent can either suppress or eradicate the organism. An example is using isoniazid to prevent clinical disease in an asymptomatic patient infected previously with Mycobacterium tuberculosis, which remains in the body but is currently dormant. Another is using an antiviral agent to avert recurrent episodes of symptomatic mucocutaneous lesions in a patient infected with herpes simplex.

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Prevention of Infection by an Exogenous Pathogen The target organisms are not present on the host and the antimicrobial agent, given before exposure, destroys the pathogens when they arrive. An example is penicillin to prevent streptococcal pharyngeal infections in patients with previous rheumatic fever.

Prevention of Infection of a Normally Sterile Site by the Host's Resident Flora The antimicrobial agent attains levels in the host's tissues or body fluids that prevent infection From Puget Sound VA Medical Center and University of Washington School of Medicine, Seattle, WA. Address reprint requests to J.V. Hirschmann, MD, Medical Service (III), Puget Sound VA Medical Center, 1660 S Columbian "~,hy,Seattle, WA 98108. Copyright 9 2000 by W.B. Saunders Company 1085-5629/00/1901-0002510.00/0 doi:lO.lO53/sd.2000.7372 2

Prevention of Disease by an Organism That Already Infects the Host But Is in a Dormant Stage

Prevention of Disease by Pathogens That Have Recently Infected the Host But Have Not Yet Caused Clinical Manifestations The organisms have already entered the host, and the purpose of the antimicrobial agent is to eradicate the microbes before they cause symptomatic disease. "Early therapy" is probably a more accurate term than prophylaxis. An example is giving an antimicrobial agent to someone who has suffered a tick bite to prevent kyme borreliosis. Antimicrobial prophylaxis is most likely to succeed when the duration of administration is brief or the susceptibility of the organism stable. Otherwise, because the agent used destroys sensitive bacteria, the surviving organisms are likely to

Seminars in Cutaneous Medicine and Surgew, Vo119, No I (March), 2000: pp 2-9

ANTIMICROBIALPROPHYLAXISIN DERMATOLOGY

be resistant to it. Streptococcus pyogenes is an example of a microbe with a stable susceptibility: it remains sensitive to penicillin, and this agent, even when given for years, continues to be effective in preventing streptococcal infections. Lengthy administration of antibiotics to patients with indwelling urinary catheters, on the other hand, does not decrease infections, because the target organisms are a wide variety of species that commonly become resistant to the medication being used. ANTIMICRGBIAL PROPHYLAXIS TO PREVENT WOUND INFECTIONS AFTER DERMATOLOGIC SURGERY

Antimicrobial administration to prevent postoperative wound infections is an example of brief prophylaxis. These infections usually arise from contamination by organisms present on the skin or adjacent mucous membranes. The goal is to use an antimicrobial agent that can kill most of these bacteria when they enter the surgical wound or reduce their numbers to a level that the local host defenses can handle without an infection occurring. Studies indicate that the anti-infective agent must be present in the tissues at the time of contamination or shortly afterwards to be effective. 2 Once the wound is closed, contamination ordinarily ceases. Therefore, for most procedures, a single preoperative dose of the antibiotic suffices. 3 More preoperative doses are likely to encourage the replacement of the resident flora with resistant organisms, rendering the prophylaxis unsuccessful; postoperative doses are unnecessary because contamination has ended, they are costly, and they are potentially hazardous in increasing the risks of adverse effects. For a procedure to justify the expense and possible adverse effects of systemic antimicrobial prophylaxis, however, postoperative infections should be very frequent or particularly severe or devastating, such as involvement of a prosthetic heart valve or vascular graft. Surgical procedures are typically stratified according to risk as4: Clean

No inflammation is encountered and no entry occurs into the respirator); alimentary, or genitourinary tracts. Without antimicrobial prophylaxis, the expected wound infection rate in these procedures, which account for about 75% of all

surger); is less than 5% and typically about 1% to 2%. Clean-Contaminated

The operation involves entry into the alimentar); respiratory, or genitourinary tract but no significant spillage occurs. The expected infection rate in these procedures, which constitute about 15% of all surgeD', is approximately 10%. The rate can be considerably higher in some operations, such as colorectal surgeD', when the incision crosses a mucosal surface that has a dense and diverse resident flora and contamination with a substantial number of organisms is common. Contaminated

These operations involve acute nonpurulent inflammation, gross spillage from the gastrointestinal tract, a major break in sterile technique, fresh trauma, or entry into infected biliary or urinary tracts. The anticipated infection rate is approximately 20%.

Dirty or Infected Wounds These include traumatic wounds with retained devitalized tissue, foreign bodies, fecal contamination, or already infected tissues. The expected postoperative wound infection rate is approximately 30% to 40%. The vast majority of dermatologic procedures are dean surgery, and the rate and severity of infections are too low to justify routine prophylaxis with systemic antimicrobials, although they may reduce the incidence still further2 Some have argued that patients undergoing laser resurfacing of the facial skin to remove wrinkles should receive prophylactic antibiotics but no compelling information shows either a need or a benefit in this setting. 6 A study intended to investigate this question was too poorly designed and executed to provide any useful information. 7 With clean-contaminated dermatologic surgery, such as resecting a deep basal cell carcinoma of the nose, infections are uncon]mon and typically mild. Even with contaminated or dirty dermatologic surgery, the risks and severity of infection are low. Wound infections, for example, are unusual after draining a cutaneous abscess, and antimicrobials appear both unnecessary and ineffective.8,9 Rarely, then, is systemic ar~timicrobial prophylaxis warranted to prevent postopera-

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tive wound infections. In situations in which its use seems justified, a single dose of an oral agent administered approximately 1 hour before the procedure will typically suffice. The antimicrobial should be active against the usual pathogens, primarily S aureus. Cephalexin, dicloxacillin, or clindamycin would be reasonable choices. An alternative approach is to apply systemic antimicrobials topically. One method is to place the powder of an agent ordinarily administered by intravenous or intramuscular routes, such as cefazolin, directly into the wound. 5 While the dose may be smaller than is given parenterally, absorption from the wound is substantial and the systemic adverse effects are not avoided. 4 Another tactic studied is to mix nafcillin with lidocaine to achieve a concentration of 0.5 mg of the antibiotic per milliliter of 1% buffered lidocaine with epinephrine 1:100,000 and inject the combination into the wound during preoperative local anesthesia. 1~When compared in a double-blind, placebocontrolled trial with lidocaine alone in 908 procedures, predominantly Mohs' surgery, the infection rate was reduced from 2.5% to 0.2%. The cost of the antibiotic was less than 1 cent per patient, and the antibiotic mixture retained its antibacterial effects after 11 days of refrigeration, 60 days of freezing, and 7 days at room temperature. However, it had lost its potency after 20 days at room temperature. This approach is an effective, inexpensive measure t h a t is unnecessary for most dermatologic surgery, because the baseline infection rate is so low already, but seems appropriate for those procedures in which a wound infection would leave a cosmetically significant defect. The prophylactic use of antimicrobial ointments formulated for topical use, such as bacitracin or mupirocin, has been to cover the postoperative wound. Since contamination of the wound rarely occurs after the incision has been sutured, this use is unlikely to decrease infection rates, which depend on the organisms present in the surgical site before closure. 1~ On the other hand, in patients with open wounds, such as those after a shave biopsy, infection is very uncommon and unlikely to be lowered substantially by a topical antibiotic. Although the prescription of such agents is common, no evidence supports their use. One double-blind, randomized study compared the use o f bacitracin to white petrolatum as the ointment used to cover the wounds in more

J.V. HIRSCHMANN

than 1,200 dermatologic procedures, including shave and punch biopsies, electrodesiccation and curettage, excision, Mohs' micrographic surgeD; and dermabrasion. 12 The overall infection rate was 1.5% and did not differ significantly between the 2 groups. Allergic contact dermatitis developed in nearly 1% of those receiving bacitracin but in none of those treated with petrolatum. The infections that occurred in the bacitracin group were caused by gram-negative bacilli, while those in the petrolatum recipients were primarily from S atu'eus. The costs of the bacitracin ointment and the systemic antibiotics used to treat the wound infections were nearly 4 times higher than those for the petrolatum group. ANTIBIOTICS TO PREVENT INFECTIVE ENDOCARDITIS AND PROSTHETIC INFECTIONS AFTER SURGERY

Although its efficacy remains unproved, antimicrobial prophylaxis has been widely endorsed and used to prevent endocarditis and infections of prostheses alter various procedures likely to cause bacteremia. A study of 50 patients undergoing dermatologic surgery showed no bacteremia in those whose lesions had an intact skin surface and 2.8% in eroded lesions, all of which grew bacteria before excision. ~3 This level is too low to justify routine preventive antibiotics, even in patients with abnormal cardiac valves, and the most recent guidelines of the American Heart Association specifically recommend that prophylaxis not be given for "incision or biopsy of surgically scrubbed skin. "14 Even with dental procedures, which have much higher rates of bacteremia than cutaneous surgery, endocarditis rarely develops, and enthusiasm for prophylaxis for them has markedly diminished) ~-17 Accordingly, antibiotics before dermatologic surgery are not routinely warranted in patients with valvular heart disease. Even in incising and draining clearly septic cutaneous loci, in which the incidence of bacteremia is relatively high, 18the effects of antibiotic therapy are uncertain and few, if any, cases of endocarditis have unequivocally arisen in these circumstances. A reasonable approach for surgery on clearly infected tissues, analogous to what one expert has suggested for dental procedures, 16is to provide antibiotics for patients at the highest risk: those with prosthetic valves or a history of previous endocarditis. Because staphy-

ANTIMICROBIAL PROPHYLAXIS IN DERMATOLOGY

lococci and streptococci are the likely pathogens a first-generation cephalosporin, an antistaphylococcal penicillin, or clindamycin is appropriate. The benefit of antimicrobial prophylaxis in patients with indwelling prosthetic joints or vascular grafts is also unproved. Most infections of these arise from contamination at the time of their insertion or from contiguous infection. 19,2~Few are clearly of hematogenous origin and most of these arise from distant sites of established suppuration. Infection developing from transient bacteremia associated with medical or surgical procedures, if it occurs at all, is very rare. Even with certain kinds of dental work that have high rates of bacteremia, antimicrobial prophylaxis is not recommended) 9,21 In the experimental animal studies of both vascular grafts and prosthetic joints, the intensity and duration of bacteremia necessary to cause an infection far exceed those associated with bacteremias caused by cutaneous procedures. 22-25 Accordingly, antimicrobial prophylaxis before routine dermatologic surgery is unnecessary in patients with orthopedic or vascular prostheses. ANTIMICROBIAL PROPHYLAXIS FOR RECURRENT STAPHYLOCOCCAL SKIN INFECTIONS S aureus is present in the anterior nares of approximately 20% to 40% of the normal population. 26 For most people, these organisms cause no problems, but some patients are plagued by recurrent staphylococcal skin infections, such as furuncles. In these patients, nasal carriage of S aureus represents a reservoir from which the organism can reinfect the skin and most systemic antibiotics, although successful in controlling the cutaneous infection, achieve inadequate levels in the nasal secretions to eradicate the staphylococci. One agent that does is oral clindamycin, and a double-blind, controlled trial compared a low dose (150 mg/d) of oral clindamycin versus a placebo given for 3 months in 22 patients who had 3 or more culture-proven staphylococcal skin infections in the preceding 6 monthsY Among the placebo recipients, staphylococcal infection developed in 7 of 11 patients compared to 2 of t l patients in the clindamycin group. Of the 9 patients free of infection after 3 months of clindamycin, 6 had no further infections in the 9 months after discontinuing therapy, indicating a

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long-term benefit. Although nasal cultures were not performed, a likely mechanism for the favorable effect was an eradication of nasal carriage of S aureus. The clindamycin was well-tolerated, with no patients having diarrhea or other gastrointestinal complaints. Among outpatients treated this way, the chance of having Clostridium difficile colitis, a concern among hospitalized patients receiving clindamycin, is very slight. This complication is almost exclusively a nosocomial infection, because this organism is present in the bowel flora of less than 5% of outpatients and is usually acquired in the hospital. 2s Furthermore, the dose of clindamycin may be too small to alter the colonic bacteri a enough to allow C difficile to emerge as a dominant microbe. An alternate approach in trying to prevent recurrent staphylococcal skin infections is to use intranasal topical antibiotics. Several topical agents, such as gentamicin, mupirocin, bacitracinneomycin, bacitracin alone, and neomycinchlorhexidine, can eliminate the nasal carriage rate in about 70% to 90% of patients compared to 0% to 27% disappearance either spontaneously or with placebo. LLIn most of the studies, the staphylococci returned shortly after the agent was discontinued. Mupirocin appeared to be the most effective antibiotic and the one with the longest duration of eradication. One trial examined the utility of neomycin-bacitracin-polyrnixin B ointment in 100 patients receiving oral isotretinoin, an agent known to increase nasal carriage of S aureus and skin infections caused by it. 29 After 5 months of treatment, nasal carriage increased from 8% to 64% in the placebo group and from 10% to 18% in the topical antibiotic group. Three months after isotretinoin therapy ended, the carriage rate was 52% in the placebo recipients compared to 12% in those treated ~vith the antibiotic. The clinical benefit was meager, however, although staphylococcal pyoderma occurred in none of the antibiotic recipients, it developed in only 2 patients in the control group (4%). Another trial examined the use of mupirocin ointment given twice a day for 5 days each month for i year compared to placebo in 34 patients who had developed 3 or more staphylococcal skin infections in the previous year. 3~ Staphylococci grew in 83 of the monthly nasal cultures in the 17 patients in the control group versus 22 in the mupirocin recipients, and 52 episodes of staphy-

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J.V. HIRSCHMANN

lococcal skin infections occurred in the former compared to 26 in the latter. Both of these differences were statistically significant. Mupirocin ointment was well tolerated, and only one patient developed mupirocin-resistant S aureus i n the nasal cultures during the year of therapy. In patients with recurrent staphylococcal skin infections, therefore, both oral clindamycin and topical mupirocin significantly decrease subsequent episodes. Although no trials have compared these 2 approaches directly, oral clindamycin appears more effective. Either tactic is reasonable, but it is important to show in both that the recurrent cutaneous problems are genuinely caused by S aureus by isolating this organism from cultures of the skin lesions. Many clinicians assume that most cutaneous abscesses, for example, are staphylococcal, but, in fact, the majority have a mixture of aerobic and anaerobic bacteria, with S aureus growing in only approximately 25%. 8,3t Even those with culture-proven staphylococcal skin infections, however, should not receive nasal mupirocin unless cultures show that S aureus is also present in the anterior nares. ANTIBIOTICS TO PREVENT RECURRENT CELLULITIS (ERYSIPELAS) AND IMPETIGO

Some patients develop recurrent cellulitis (often called erysipelas, especially in the European literature), particularly of the legs. Predisposing factors include venous insufficiency, lymphedema, previous trauma, edema from several causes such as congestive heart failure or liver disease, prior episodes of cellulitis, and saphenous venectomy for coronary artery bypass surget): 32-3+ Cultures of skin aspirates, blood, and cutaneous biopsies are usually negative, with streptococci being, by far, the most frequent organism isolated. Direct immunofluorescent antigen detection in skin biopsies, combined with the data from cultures, implicates streptococci of various groups including A, B, C, and G in virtually all cases. 35 A site of entry for these organisms is often inapparent and they ordinarily do not colonize intact skin. In many circumstances, especially with patients who have had a previous venectom); the spaces between the toes of the ipsilateral foot shows cracking, maceration, scaling, or fissuring, usually from dermatophyte infection. In one study of 24 episodes of cellulitis

such abnormalities were present in 83% of the episodes. 36 Hemolytic streptococci grew from 85% of cultures of the interdigital toe spaces of these patients compared to 0% in a control group with the interdigital changes but no history of cellulitis. Apparently, this abnormal skin environment allows these bacteria to grow, and the toe webs, therefore, represent a reservoir from which these organisms can directly invade or can spread to adjacent skin where they can enter through areas of minor trauma or impaired local defenses. Treating tinea pedis in patients with recurrent leg cellulitis typically prevents further episodes. 32,34 If the toe spaces are normal, another area to culture is the distal anal canal, which grew Group G streptococci from 4 patients with recurrent leg cellulitis. 37 In those without a clear reservoir for streptococci or in whom cellulitis continues to occur despite treatment of the apparent source, prophylaxis with systemic antimicrobials may be helpful. One study, performed in the early 1960s, gave benzathine penicillin once a month or oral penicillin or erythromycin daily for I to 2 weeks each month to 21 patients with lymphedema and numerous episodes of recurrent cellulitis in the preceding months. 38 During a follow-up period of about 30 months, 18 patients were completely free of attacks and 3 had only minor episodes. In another study, 32 patients who had 2 or more episodes of cellulitis in the preceding year randomly received erythromycin 250 mg twice daily for 18 months or no therapy.39 None of the patients given erythromycin developed infections, compared to 8 of 16 in the control group. A third trial involved monthly injections of 1.2 million U of benzathine penicillin G in patients who had an episode of streptococcal leg cellulitis.4~ Patients who declined prophylaxis were the controls. Recurrence developed in 4 of 31 (12.9%) of those receiving penicillin versus 16 of 84 (19%) of the patients who refused it. The difference is not statistically significant. Because the criterion for entry was a single episode of cellulitis rather than a history of recurrences, the number of participants may have been too small to demonstrate a benefit for the subgroup of patients likely to have multiple episodes. For patients with recurrent attacks of leg cellulitis in which a reservoir is not found or in whom treatment of that reservoir does not terminate the

ANTIMICROBIALPROPHYLAXISIN DERMATOLOGY

recurrences, daily oral penicillin or erythromycin, both in doses of 250 mg twice dail); is a good prophylactic measure. In those with poor compliance for that regimen, monthly intramuscular benzathine penicillin 1.2 to 4.8 million U represents a reasonable alternative. One trial examined the effect of an antibiotic ointment containing bacitracin, polymixin, and neomycin compared to a placebo ointment in preventing impetigo in children 2 to 5 years old in Alabama from July to early October, the peak season for streptococcal pyoderma. 41 The ointment was applied thrice daily to insect bites and other breaks i n t h e skin. Streptococcal skin infections developed in 15 of 32 (47%) patients receiving the placebo versus 4 of 27 (15%) of the antibiotic group, a statistically significant difference. ANTIMICROBIAL PROPHYLAXIS TO PREVENT LYME BORRELIOSlS AFTER TICK BITES

The probability of contracting symptomatic infection with Borrelia burgdorferi after a tick bite in an endemic area is about 0.027 but with a range of 0.012 to 0.05. 42 Two studies have examined the benefit of prescribing antibiotics after tick bites to prevent this disease. In a trial conducted in an endemic location in Connecticut, 387 children and adults bitten by a deer tick within the previous 72 hours were randomized to receive 250 mg of amoxicillin or placebo 3 times a day for 10 days. 43 Of the 344 deer ticks submitted and analyzed for B bmgdorfeli, 15% were infected. The risk of Lyme disease was 1.2% in the placebo group versus 0% in the antibiotic recipients, an insignificant difference. In a similar study conducted in Westchester County, NY, another endemic area, children bitten within 72 hours by a deer tick received either a placebo or an antibiotic: either penicillin or tetracycline 250 mg 4 times daily for 10 days. 44 Erythema migrans developed in one of the placebo recipients. Both trials concluded that the risk of Lyme disease was too low in endemic areas to justify prophylaxis in patients who suffered tick bites. ANTIMICROBIAL PROPHYLAXIS FOR RECURRENT HERPES SIMPLEX INFECTIONS

Herpes simplex virus (HSV) infection is common in adults in the United States, who have a seropositivity of about 50% to 60% for HSV-1,

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which primarily affects the oral mucosa, and 20% for HSV-2, 4~ which usually involves the genital mucosa. Whether the primary infection causes clinical disease or is asymptomatic, which is common, 46 the virus enters the sensory nerves at the primary site and travels retrograde to the sensory neurons, where it remains for the duration of the host's lifespan. Periodicall); the infection becomes active, and painful vesicular lesions develop near the initial site of inoculation. Recurrent episodes are common, especially with genital involvement, in which the average duration of pain is about 6 days in women, 4 days in men. The lesions heal in approximately 9 to 10 days. Recurrences tend to be shorter and less severe with oral lesions, which are often precipitated by certain factors,such as trauma, ultraviolet light, menstruation, fever, and emotionalstress. The pain, typically mild, usually lasts less than 4 days, and the lesions commonly disappear within 7 days. When recurrences are common (6 or more episodes per year) or particularly severe, especially with genital lesions, oral antiviral agents, if taken on a daily basis, can diminish the frequency of episodes. Acyclovir 400 mg twice dail); famciclovir 250 mg twice dail); or valacyclovir--either 500 mg or 1 g every day--are all significantly better than placebo in preventing relapses of genital HSV infection. 47 Comparisons between these regimens are few4s but they seem approximately equivalent, and the least expensive approach is one of 2 valacyclovir doses, 47 the larger of which seems better for patients with more than 10 attacks annually. 48 These programs will render 50% to 75% of patients free of recurrences during a year of medication ingestion, 47 and in those who do have breakthrough attacks, the frequency of relapses is usually substantially less. Over time, many patients have a diminishing number of episodes, even if they do not receive prophylaxis; accordingl); it is worthwhile to discontinue the medication periodically (perhaps once a year) to determine if the incidence of recurrences has decreased sufficiently to render further prophylaxis unnecessary. 49 Such long-term suppression is less commonly used in oral herpes because the attacks are shorter, milder, and less frequent. With i~articularly numerous, severe, or protracted episodes

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a c y c l o v i r 400 m g t w i c e daily will r e d u c e the i n c i d e n c e by a p p r o x i m a t e l y 50%. 50 A n a l t e r n a t i v e a p p r o a c h in p a t i e n t s w i t h s u n - i n d u c e d attacks has b e e n to initiate a c y c l o v i r 400 to 800 m g t w i c e daily 12 h o u r s b e f o r e e x p o s u r e . T h e results of 2

studies w i t h this p r o g r a m are c o n t r a d i c t o r y ; h o w ever, o n e s h o w e d a r e d u c t i o n o f HSV i n f e c t i o n s f r o m 26% in the p l a c e b o g r o u p to 7% in t h e a c y c l o v i r recipients, 51 a n d the o t h e r s h o w e d n o a d v a n t a g e to acyclovir. 52

REFERENCES 1. HirschmannJV: Antimicrobial prophylaxis for nonsurgical infections, in Gorbach SL, Bartlett JG, Blacklow NR (eds): Infectious Diseases (ed 2). Philadelphia, Saunders, 1998, pp 481-487 2. Burke JF: The effective period of preventive antibiotic action in experimental incisions and dermal lesions. Surgery 50:161-168, 1961 3. DiPiroJT, Cheung RPF,Bowden TA: Single dose systemic antibiotic prophylaxis of surgical wound infections. AmJ Surg 152:552-559, 1986 4. Hirschmann JV, Inui TS: Antimicrobial prophylaxis: A critique of recent trials. Rev Infect Dis 2:1-23, 1980 5. Beucini PL, Galimberti M, Signorini M, et al: Antibiotic prophylaxis of wound infections in skin surgery. Arch Dermatol 127:1357-1360, 1991 6. Sriprachya-Anunt S, Fitzpatrick RE, Goldman MP, et al: Infections complicating pulsed carbon dioxide laser resurfacing for photoaged facial skin. Dermatol Surg 23:527-536, 1997 7. Manuskiaatti W, Fitzpatrick RE, Goldman MP, et al: Prophylactic antibiotics in patients undergoing laser resurfacing of the skin. J Am Acad Dermato140:77-84, 1999 8. Meislin HW, Lerner SA, Graves MH, ct al: Cutaneous abscesses. Anaerobic and aerobic bacteriology and outpatient management. Ann Intern Med 87:145-149, 1977 9. Macfie J, Harvey J: The treatment of acute superficial abscesses: A prospective clinical trial. Br J Surg 64:264-266, 1977 10. Griego RD, Zitelli JA: lntra-incisional prophylactic antibiotics for dermatologic surgery. Arch Dermatol 134:688692, 1998 11. Hirschmann JV: Topical antibiotics in dermatology. Arch Dermato1124:1691-1700, 1988 12. Smack DP, Harrington AC, Dunn C, et al: Infection and allergy incidence in ambulatory surgery patients using white petrolatum vs bacitracin ointment. A randomized controlled trial.JAMA 276:972-977, 1996 13. Sabetta JB, Zitelli JA: The incidence of bacteremia during skin surgery. Arch Dermatol 123:213-215, 1987 14. Dajani AS, Taubert KA, Wilson W, et al: Prevention of bacterial endocarditis. Recommendations by the American Heart Association. Circulation 96:358-366, 1997 15. Strom BL, Abrutyn E, Berlin JA, et al: Dental and cardiac risk factors for infective endocarditis. A populationbased, case-control study. Ann Intern Meal 129:761-769, 1998 16. Durack DT: Antibiotics for prevention of endocarditis during dentistry: Time to scale back? Ann Intern Med 129:829-831, 1998 17. Van der Meer JTM, van Wijk W, Thompson J, et al: Efficacy of antibiotic prophylaxis for prevention of nativevalve endocarditis. Lancet 339:135-139, 1992 18. Everett ED, Hirschmann JV: Transient bacteremia and endocarditis prophylaxis: A review. Medicine 56:61-77, 1977

19. Wahl MJ: Myths of dental-induced prosthetic joint infections. Clin Infect Dis 20:1420-1425, 1995 20. O'Brien T, Collin J: Prosthetic vascular graft infection. BrJ Surg 79:1262-1267, 1992 21. Sandhu SS, Lo~a'y JC, Morton ME, et al: Antibiotic prophylaxis, dental treatment and arthroplasty: Time to explode a myth. J BoneJoint Surg 79-B:521-522, 1997 22. Blomgren G: Hematogenous infection of total joint replacement. An experimental study in the rabbit. Acta Orthop Scan 52:1-64, 1981 (suppl 187) 23. McDougal EG, Burnham SJ, Johnson G: Rifampin protection against experimental graft sepsis. J Vasc Surg 4:5-7, 1986 24. Moore WS, Malone JM, Keown K: Prosthetic arterial graft material. Influence neointimal healing and bacteremic infectibility. Arch Surg 115:1379-1383, 1980 25. Cavallaro A, Sciacca V, Cisternino S, et al: Bacteremic infectability of vascular grafts: An experimental study. Vasc Surg 25:89-99, 1991 26. Noble WC: Staphylococci on the skin, in Noble WC: The Skin Microflora and Microbial Skin Disease. Cambridge, UK, Cambridge University, 1992, pp 135-152 27. Klempner MS, Styrt B: Prevention of recurrent staphylococcal skin infections with low-dose oral clindamycin therapy. JAMA 260:2682-2685, 1988 28. Fekety R, Shah AB: Diagnosis and treatment of Clostridium difficile colitis. JAMA 269:71-75, 1993 29. Leyden JJ, James WD: Staphylococcus aureus infection as a complication of isotretinoin therapy: Arch Derrnatol 123:606-608, 1987 30. Raz R, Miron D, Colodner R, et al: A 1-year trial of nasal mupirocin in the prevention of recurrent staphylococcal nasal colonization and skin infection9 Arch Intern Med 156:11091112, 1996 31. Brook I, Frazier EH: Aerobic and anaerobic bacteriology of wound and cutaneous abscesses. Arch Surg 125:14451451, 1990 32. Greenberg J, DeSanctis RW, Mills RM: Vein-donor-leg cellulitis after coronary artery bypass surgeD: Ann Intern Med 97:555-556, 1982 33. Dan M, Heller K, Shapira I, et al: Incidence of erysipelas following venectomy for coronary artery bypass surgery Infection 15:107-108, 1987 34. Baddour LM, Bisno AL: Recurrent cellulitis after coronary bypass surgery. Association with superficial fungal infection in saphenous venectomy limbs. JAMA 251:1049-1052, 1984 35. Bernard P, Bedane C, Mounier M, et al: Streptococcal cause of erysipelas and cellulitis in adults. A microbiologic study using a direct immunofluorescent technique. Arch Dermatol 125:779-782, 1989 36. Semel JD, Goldin H: Association of athlete's foot with cellulitis of the lower extremities: Diagnostic value of bacterial

ANTIMICROBIAL PROPHYLAXIS IN DERMATOLOGY cultures of ipsilateral interdigital space samples. Clin Infect Dis 23:1162-1164, 1996 37. Eriksson BKG: Anal colonization of Group G [3-hemolytic streptococci in relapsing erysipelas of the lower extremity. Clin Infect Dis 29:119-120, 1999 38. Babb RR, Spittell JA, Martin WJ, et al: Prophylaxis of recurrent l)anphangitis complicating lymphedema.JAMA 195: 871-873, 1966 39. Kremer M, Zuckerman R, Avraham Z, et al: Long-term antimicrobial therapy in the prevention of recurrent softtissue infections. J Infect 22:37-40, 1991 40. x,Vang JH, Liu YC, Cheng DL, et al: Role of benzathine penicillin G in prophylaxis for recurrent streptococcal cellulitis of the lower legs. Clin Infect Dis 25:685-689, 1997 41. MaddoxJS, Ware JC, Dillon HC: The natural history of streptococcal skin infection: Prevention with topical antibiotics.J Am Acad Dermatol 13:207-212, 1985 42. Magrid D, Schwartz B, Craft J, et al: Prevention of L)ane disease after tick bites. A cost-effectiveness analysis. N Engl J Med 327:534-541, 1992 43. Shapiro ED, Gerber MA, Holabird NB, et al: A controlled trial of antimicrobial prophylaxis for Lyme disease after deer-tick bites. N EnglJ Med 327:1769-1773, 1992 44. Agre F, Schwartz R: The value of early treatment of deer tick bites for the prevention of Lyme disease. AJDC 147:945947, 1993

45. Fleming DT, McQuillan GM,Johnson RE, et al: Herpes simplex virus tk-pe 2 in the United States, 1976 to 1994. N EnglJ Med 337:105-111, 1997 46. Langenberg AGM, Corey L, Ashley RL, et al: A prospective study of new infections with herpes simplex virus type 1 and type 2. N EngIJ Med 341:1432-1438, 1999 47. Engel JF: Long-term suppression of genital herpes. JAMA 280:928-929, 1998 48. Reitano M, T}wing S, Lang W, et al: Valaciclovir for the suppression of recurrent genital herpes simplex virus infection: A large-scale dose range-finding study. J Infect Dis 178:603-610, 1998 49. Benedetti JK, Zeh J, Corey L: Clinical reactivation of genital herpes simplex virus infection decreases in frequency over time. Ann Intern Med 131:14-20, 1999 50. Rooney JF, Straus SE, Mannix ML, et al: Oral acyclo~ir to suppress frequently recurrent herpes labialis. A doubleblind, placebo-controlled trial. Ann Intern Med 118:268-272, 1993 51. Spruance SL, Hamill ML, Hoge WS, et al: Acyclovir prevents reactivation of herpes simplex labialis in skiers. JAMA 260:1597-1599, 1988 52. Raborn GW, Martel AY, Grace MGA, et al: Oral acyclovir in prevention of herpes labialis. A randomized, doubleblind, multi-centered trial Oral Surg Oral Med Oral Pathol Oral Radiol Endod 85:55-59, 1998