Two Popular Antibiotics Equally Effective in Skin Infections

Diedtra Henderson

March 19, 2015

Outpatients with uncomplicated skin infections who took clindamycin or a trimethoprim–sulfamethoxazole combination (TMP-SMX) experienced similar benefits and risks, leading the research team to conclude the antibiotic regimens were essentially equivalent, according to a randomized controlled trial.

Loren G. Miller, MD, MPH, from the Los Angeles Biomedical Research Institute and Division of Infectious Diseases, Harbor–University of California, Los Angeles, Medical Center, Torrance, and the David Geffen School of Medicine at the University of California, Los Angeles, and colleagues report the findings of their randomized clinical trial in an article published in the March 19 issue of the New England Journal of Medicine.

Methicillin-resistant Staphylococcus aureus is responsible for most of the skin infection lesions that send at least 14.2 million Americans to outpatient visits and hospitalize more than 850,000 annually, the authors note. Inexpensive, on-the-shelf products may hold promise for holding MSRA at bay, but few head-to-head studies have been performed to test the agents. In addition, the vast majority of cellulitis lesions cannot be properly cultured, raising questions about the causative agent.

Therefore, between May 2009 and August 2011, the researchers enrolled 524 children and adults with uncomplicated skin infections in the trial. In this group, 280 had cellulitis, 160 suffered abscesses larger than 5 cm, and 82 had both an abscess lesion and a cellulitis lesion. For two patients, lesions were uncharacterized, and the children's lesions were smaller. Some 264 people were assigned to receive two 150-mg tablets of clindamycin three times daily for 10 days, and 260 participants were assigned to take two tablets containing 160 mg TMP and 800 mg SMX twice daily for 10 days. Children enrolled in the study received liquid suspensions of doses titrated to their body weight.

The investigators tested cultures from 296 patients and found S aureus in 217 (73.3%). The cure rates with TMP-SMX and clindamycin did not differ significantly," Dr Miller and coauthors write. "The cure rate with TMP-SMX ranged from 5 percentage points higher to 7 to 10 percentage points lower than the cure rate with clindamycin, on the basis of the 95% confidence intervals for rate differences in the intention-to-treat population and the population that could be evaluated."

In an accompanying editorial, Michael R. Wessels, MD, from the Division of Infectious Diseases, Boston Children's Hospital, and the Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, notes that although the results indicate the two regimens are likely similar, the trial was designed as a superiority study and not a noninferiority study, which complicates the interpretation.

"[T]he design of the study obscures possible differences between the outcomes in the two major subgroups, differences that favor TMP-SMX for abscesses and clindamycin for cellulitis. There was a nonsignificant difference favoring TMP-SMX in patients who could be evaluated who had abscess only or abscess plus cellulitis, and there was a nonsignificant difference favoring clindamycin in those who had cellulitis without abscess," Dr Wessels writes.

He also notes that the study's exclusion criteria could have masked a higher failure rate for TMP-SMX for patients with cellulitis. "There remains a need for additional carefully designed clinical trials to define the most effective therapies for skin abscesses and cellulitis in more severely ill patients and patients with underlying chronic illness."

The authors point to the inclusion of children and adults and geographic as well as ethnic diversity of participants as being among the study's strengths.

"In summary, we found no significant differences between the efficacy of clindamycin and that of TMP-SMX for the treatment of uncomplicated skin infections in children and adults with few or no major coexisting conditions," the authors conclude.

Financial support for the study was provided by the National Institutes of Allergy and Infectious Diseases and the National Center for Research Resources. Various authors have disclosed receiving financial support from Cubist, Durata, Pfizer, EMMES, AstraZeneca, Theravance, Trius, Merck, and Cerexa. The remaining authors and the commentator have disclosed no relevant financial relationships.

N Engl J Med. 2015;372:1093-1103, 1164-1165. Article abstract, Editorial extract


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