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Antibacterial Treatment for Uncomplicated Skin Infections To the Editor: Miller et al. (March 19 issue)1 found that clindamycin and trimethoprim–sulfamethoxazole (TMP-SMX) were similar in terms of efficacy when treating patients with uncomplicated skin infections. One assumption that was made is that all 524 patients needed antibiotics for their infection, but approximately 30% of the patients in each group had an uncomplicated skin abscess alone. Prospective, randomized studies have shown that in patients with uncomplicated skin abscesses, incision and drainage without administration of antibiotics seems to be sufficient when treating such infections.2,3 Given that approximately one third of the patients in each group would probably have been cured without antibiotics, the study could have been underpowered, which would have led to a type II error. It is also important to note that TMP-SMX has been shown to be less active than clindamycin in patients with community-associated methicillin-resistant Staphylococcus aureus (MRSA) infections.4,5 These points should be considered when applying these data in the treatment of patients with uncomplicated skin infections. Jihoon Baang, M.D.

resistant Staphylococcus aureus disease in three communities. N Engl J Med 2005;352:1436-44. 5. Naimi TS, LeDell KH, Como-Sabetti K, et al. Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection. JAMA 2003;290:2976-84. DOI: 10.1056/NEJMc1504843

To the Editor: Miller et al. found similar rates of cure for cellulitis alone and for mixed cellulitis with abscess and found marginally lower rates for abscess alone. This finding contradicts prior evidence. Because there are limited data on the use of incision and drainage alone for the treatment of simple abscesses and boils, guidelines from the Infectious Diseases Society of America1 state that such treatment may be inadequate. The randomized, double-blind trial by Rajendran et al.2 in which cephalexin was compared with placebo after incision and drainage of uncomplicated skin and soft-tissue abscesses showed cure rates of 84.1% and 90.5%, respectively. Since cephalexin is not effective against MRSA, the differences in cure rates were probably due to chance. this week’s letters 2459 Antibacterial Treatment for Uncomplicated Skin Infections

Temple University School of Medicine Philadelphia, PA [email protected] No potential conflict of interest relevant to this letter was reported. 1. Miller LG, Daum RS, Creech CB, et al. Clindamycin versus

trimethoprim–sulfamethoxazole for uncomplicated skin infections. N Engl J Med 2015;372:1093-103. 2. Schmitz GR, Bruner D, Pitotti R, et al. Randomized controlled trial of trimethoprim-sulfamethoxazole for uncomplicated skin abscesses in patients at risk for community-associated methicillin-resistant Staphylococcus aureus infection. Ann Emerg Med 2010;56:283-7. 3. Rajendran PM, Young D, Maurer T, et al. Randomized, doubleblind, placebo-controlled trial of cephalexin for treatment of uncomplicated skin abscesses in a population at risk for community-acquired methicillin-resistant Staphylococcus aureus infection. Antimicrob Agents Chemother 2007;51:4044-8. 4. Fridkin SK, Hageman JC, Morrison M, et al. Methicillin-

2461 Mongersen, an Oral SMAD7 Antisense ­Oligonucleotide, and Crohn’s Disease 2462 Valganciclovir for Congenital Cytomegalovirus 2464 Putting On and Removing Personal Protective Equipment 2465 A Man with Multiple Myeloma, Skin Tightness, Arthralgias, and Edema 2467 Shedding of Ebola Virus in an Asymptomatic Pregnant Woman

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This trial did include patients with diabetes and infection with hepatitis B or C virus and intravenous drug users, and approximately one third of the patients were homeless. Furthermore, 87.8% of cultures were positive for MRSA. However, the trial recruited patients with abscesses measuring more than 2 cm in diameter; for patients with smaller abscesses, incision and drainage alone are probably adequate. The addition of a placebo group to the study by Miller et al. would have provided some clarification. Sukhchain Singh, M.D. Ingalls Memorial Hospital Harvey, IL [email protected] No potential conflict of interest relevant to this letter was reported. 1. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guide-

lines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect Dis 2011; 52:285-92. 2. Rajendran PM, Young D, Maurer T, et al. Randomized, doubleblind, placebo-controlled trial of cephalexin for treatment of uncomplicated skin abscesses in a population at risk for community-acquired methicillin-resistant Staphylococcus aureus infection. Antimicrob Agents Chemother 2007;51:4044-8. DOI: 10.1056/NEJMc1504843

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abscess and cellulitis, they would have been detected, given the nature of our trial design. We did find differences in the susceptibility of S. aureus isolates to clindamycin and TMP-SMX, as noted by Baang. Although the study was not powered to detect differences in outcome based on antimicrobial susceptibility, a trend toward lower cure rates with clindamycin in the treatment of infections caused by clindamycin-resistant S. aureus as compared with susceptible S. aureus suggests that clindamycin may be a less favorable empirical choice for the treatment of uncomplicated skin infections if clindamycinresistant S. aureus is prevalent. Studies that are adequately powered to examine such differences would be informative and important. Singh argues that patients with small abscesses were excluded from our study and the study by Rajendran et al. and comments that patients with small abscesses that are treated with incision and drainage may not require antibiotics. The median abscess size in the study by Talan et al. was 2.5×2.0×1.5 cm3, which suggests that smaller abscesses would benefit from adjunctive antibiotic therapy. Moreover, we recently completed enrollment for a companion trial involving more than 700 participants with abscesses measuring 5 cm or less in diameter who underwent incision and drainage and then were randomly assigned to receive an antibiotic or placebo. The findings from this trial should clarify the role of antibiotics in the treatment of uncomplicated skin infections, a problem that remains common2 and understudied. Loren G. Miller, M.D., M.P.H.

The Authors Reply: Baang argues that incision and drainage of abscesses might be curative without antibiotic treatment. We did not study incision and drainage alone, so we cannot know its comparative efficacy. In the trials cited by Baang, the study by Schmidtz et al. had limited power to detect differences between groups, having evalu- LA BioMed at Harbor–UCLA Medical Center ated only 190 participants, and shown a nonsig- Torrance, CA nificant trend favoring TMP-SMX over placebo [email protected] (with an incidence of treatment failure of 17% vs. Robert S. Daum, M.D., C.M. 26%). Rajendran et al. compared cephalexin with University of Chicago placebo in a study population in which 88% of Chicago, IL S. aureus isolates were resistant to a β-lactam. Henry F. Chambers, M.D. Thus, the recipients of antibiotics received inef- University of California, San Francisco fective therapy, and the study cannot answer the San Francisco, CA Since publication of their article, the authors report no furquestion of whether effective antibiotic therapy is ther potential conflict of interest. beneficial after incision and drainage of abscesses. In a recent randomized, controlled trial, Talan 1. Talan D, Mower W, Krishnadasan A, et al. A randomized, double-blind placebo-controlled trial of trimethoprim-sulfaet al.1 found that among 1247 participants with methoxazole vs. placeo for patients with an excised and drained skin abscess treated with incision and drainage, cutaneous abscess. Presented at ID Week 2014, Philadelphia, the rate of treatment failure was significantly October 8–12, 2014. abstract. Ray GT, Suaya JA, Baxter R. Incidence, microbiology, and lower among those receiving TMP-SMX than 2. patient characteristics of skin and soft-tissue infections in a U.S. among those receiving placebo (7.1% vs. 14.3%). population: a retrospective population-based study. BMC Infect If there had been differences in the efficacy of Dis 2013;13:252. TMP-SMX and clindamycin for the treatment of DOI: 10.1056/NEJMc1504843 2460

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Antibacterial Treatment for Uncomplicated Skin Infections.

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