Recurrent Cellulitis: Penicillin Effective for Prevention

Troy Brown

May 01, 2013

In patients with recurrent cellulitis, penicillin prevented subsequent attacks during prophylaxis, but the effect diminished progressively after the antibiotic was stopped, according to a double-blind, randomized controlled trial involving 274 patients in the United Kingdom and Ireland.

Kim S. Thomas, PhD, from the Centre of Evidence-Based Dermatology at the University of Nottingham in the United Kingdom, and colleagues present their findings in an article published in the May 2 issue of the New England Journal of Medicine.

The researchers randomly assigned participants to receive low-dose oral penicillin (250 mg; n = 136) or placebo (n = 138) twice daily after completing treatment for the index cellulitis episode.

The median time to first cellulitis recurrence was 626 days in the penicillin group and 532 days in the placebo group. "During the prophylaxis phase, 30 of 136 participants in the penicillin group (22%) had a recurrence, as compared with 51 of 138 participants in the placebo group (37%)," the authors write.

Also during prophylaxis, the risk for repeat cellulitis episode was reduced by almost half (45%) in the penicillin group compared with in the placebo group (hazard ratio, 0.55; 95% confidence interval [CI], 0.35 - 0.86; P = .01). This effect diminished progressively after prophylaxis stopped.

A total of 129 participants had 1 or more confirmed recurrences. Of those, 50 (39%) had 1 repeat episode, 38 (29%) had 2, 20 (16%) had 3, and 21 (16%) had 4 or more.

Those in the penicillin group had fewer recurrences overall than participants in the placebo group (119 vs 164; P = .02 for trend). During prophylaxis, 76 recurrences occurred in the penicillin group vs 122 in the placebo group (P = .03). During follow-up, 43 recurrences occurred in the penicillin group vs 42 in the placebo group (P = .88).

No significant between-group differences in the development of edema or ulceration were found during either prophylaxis (40% in the penicillin group and 48% in the placebo group; P = .46) or follow-up (40% and 45%, respectively; P = .60).

During prophylaxis, 85 participants had 1 or more adverse events (37 in the penicillin group and 48 in the placebo group; P = .50). Eleven participants died during the trial (8 in the penicillin group and 3 in the placebo group; P = .14), but none of the deaths were thought to be related to the study drugs.

In multivariable analyses of data from the prophylaxis period, the investigators found that a body mass index of 33 kg/m2 or higher, 3 or more previous cellulitis episodes, and the presence of edema (borderline significance) were significantly associated with a poor treatment response. They adjusted for all baseline characteristics including age, female sex, body mass index, venous insufficiency, and preexisting leg edema or ulceration associated with cellulitis.

"Physicians do want to prevent recurrent infections because each infection further damages lymphatics, causing further local immune compromise," said Robert T. Brodell, MD, a professor and chief of the division of dermatology at the University of Mississippi Medical Center in Jackson, in an email interview with Medscape Medical News. "Recurrent infections in the legs can lead to lymphangitis, sepsis, and even death.... Infections can be particularly severe in diabetics or individuals with immune deficiency of any kind."

Dr. Brodell, who was not involved in the study, noted that other strategies may help also. "There are other ways to prevent recurrent infections. It is not clear if these patients had interdigital tinea pedis. If they did, the mixed bacterial/dermatophyte fungus in the toe webs is a common source of recurrent bacterial infection in the legs. Treatment with topical antifungals such as ketoconazole cream is an inexpensive way to decrease recurrent infections in the legs," Dr. Brodell concluded.

Dr. Thomas and 10 other researchers have reported that their institution received grant funding and/or funding for travel to study-related meetings from Action Medical Research. Dr. Thomas's institution received funding from the National Institute for Health Research Comprehensive Local Research Network for writing assistance, medicines, equipment, or administrative support. One coauthor reported unrelated consultant fees to his institution from Reckitt-Beckiser and grant money to his institution from the National Institute for Health Research for studies unrelated to dermatology. Dr. Brodell has disclosed no relevant financial relationships.

N Engl J Med. 2013;368:1695-1703.