Prophylactic administration of penicillin reduces the number of leg cellulitis recurrences without an increase in adverse events in patients who have a history of recurrences, according to a study published in the May 2 issue of the New England Journal of Medicine.
"Low-dose prophylactic penicillin given for a period of 12 months almost halved the risk of recurrence during the intervention period, and patients who received prophylaxis had significantly fewer recurrent episodes over the 3-year period than those who received placebo," reported Dr. Kim S. Thomas of the University of Nottingham, England, and her associates (N. Engl. J. Med. 2013 [doi: 10.1056/NEJMoa1206300]).
A total of 274 patients with recurrent cellulitis of the leg (two episodes within the past 3 years) who had experienced an episode within the previous 24 weeks, confirmed by a dermatologist or by medical records, were enrolled in the study between July 2006 and January 2010 from 28 hospitals in the United Kingdom and Ireland.
Patients were only included if they had "local warmth, tenderness or acute pain," unilateral or bilateral erythema, and unilateral edema. They were excluded if they had taken antibiotics for cellulitis within the previous 6 months, were allergic to penicillin, or had a "previous leg ulceration, surgery or penetrating trauma," the investigators wrote.
In the double-blind, randomized controlled trial, the placebo group included 138 subjects and the intervention group included 136 participants who received 250 mg of penicillin twice daily for a year, beginning after the index episode of cellulitis had been treated. At least 90% of the participants underwent a minimum of 18 months’ follow-up – 5% withdrew or were lost to follow-up and 4% died.
During the 12 months of prophylaxis, 76 recurrences of cellulitis occurred in the penicillin group and 122 occurred in the placebo group (P = .03). The 45% risk reduction for a recurrence of cellulitis among the patients taking the penicillin, however, did not persist after the year of prophylaxis, with 43 recurrences in the penicillin group and 42 in the placebo group (P = .88) during postprophylaxis follow-up, Dr. Thomas and her associates reported.
During all of the follow-up (median, 25 months), 119 repeat episodes occurred in the penicillin group, with a median 626 days to first recurrence, and 164 occurred among the placebo patients, with a median 532 days to first recurrence (P = .02 for repeat episodes). Overall, 129 participants experienced 281 recurrences, including 50 patients (39%) who had one repeat episode, 38 patients (29%) who had two, 20 patients (16%) who had three, and 21 patients (16%) who had at least four. A total of 58 repeat episodes (30 in the penicillin group and 28 in the placebo group) resulted in admission to the hospital.
None of the 11 deaths (8 penicillin, 3 placebo) that occurred were attributed to the study drugs, and adverse event rates were similar in both groups, with 37 among the penicillin patients and 48 in the placebo group (P = .05).
Participants who responded poorly to penicillin treatment were more likely to have a body mass index of 33 or higher (P = .01), to have a history of at least three previous cellulitis episodes (P < .001), or to have an edema (P = .06, or borderline statistical significance). "The poor treatment response in participants with a high BMI may mean that a higher dose of penicillin is required in these patients," Dr. Thomas and her associates suggested.
Because the effect of the prophylaxis was gone by the third year of follow-up, the authors noted that it is unclear how long the penicillin should be given and may depend "on whether any predisposing factors, such as broken skin or lymphedema, can be adequately treated."
The study was funded by a grant from Action Medical Research. Dr. James Mason reported non–cellulitis-related consultancy for Reckitt Beckiser and receiving non–cellulitis-related grant funding from the U.K.’s National Institute for Health Research (NIHR). Dr. Kim Thomas reported that NIHR Comprehensive Local Research Network has provided funding to her institution for her work on this study. No other disclosures were reported beyond travel funds from the Action Medical Research study grant.