Penicillin to prevent recurrent leg cellulitis.

BACKGROUND: Cellulitis of the leg is a common bacterial infection of the skin and underlying tissue. We compared prophylactic low-dose penicillin with placebo for the prevention of recurrent cellulitis. METHODS: We conducted a double-blind, randomized, controlled trial involving patients with two or more episodes of cellulitis of the leg who were recruited in 28 hospitals in the United Kingdom and Ireland. Randomization was performed according to a computer-generated code, and study medications (penicillin [250 mg twice a day] or placebo for 12 months) were dispensed by a central pharmacy. The primary outcome was the time to a first recurrence. Participants were followed for up to 3 years. Because the risk of recurrence was not constant over the 3-year period, the primary hypothesis was tested during prophylaxis only. RESULTS: A total of 274 patients were recruited. Baseline characteristics were similar in the two groups. The median time to a first recurrence of cellulitis 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%) (hazard ratio, 0.55; 95% confidence interval [CI], 0.35 to 0.86; P=0.01), yielding a number needed to treat to prevent one recurrent cellulitis episode of 5 (95% CI, 4 to 9). During the no-intervention follow-up period, there was no difference between groups in the rate of a first recurrence (27% in both groups). Overall, participants in the penicillin group had fewer repeat episodes than those in the placebo group (119 vs. 164, P=0.02 for trend). There was no significant between-group difference in the number of participants with adverse events (37 in the penicillin group and 48 in the placebo group, P=0.50). CONCLUSIONS: In patients with recurrent cellulitis of the leg, penicillin was effective in preventing subsequent attacks during prophylaxis, but the protective effect diminished progressively once drug therapy was stopped. (Funded by Action Medical Research; PATCH I Controlled-Trials.com number, ISRCTN34716921.).

Prophylactic antibiotics to prevent cellulitis of the leg: economic analysis of the PATCH I & II trials.

BACKGROUND: Cellulitis (erysipelas) is a recurring and debilitating bacterial infection of the skin and underlying tissue. We assessed the cost-effectiveness of prophylactic antibiotic treatment to prevent the recurrence of cellulitis using low dose penicillin V in patients following a first episode (6 months prophylaxis) and more recurrent cellulitis (12 months prophylaxis, or 6 months in those declining 12 months). METHODS: Within-trial cost-effectiveness analysis was conducted using the findings of two randomised placebo-controlled multicentre trials (PATCH I and PATCH II), in which patients recruited in the UK and Ireland were followed-up for up to 3 years. Incremental cost, reduction in recurrence, cost per recurrence prevented and cost/QALY were estimated. National unit and reference costs for England in 2010 were applied to resource use, exploring NHS and societal perspectives. A total of 397 patients from the two trials contributed to the analysis. RESULTS: There was a 29% reduction in the number of recurrences occurring within the trial (IRR: 0.71 95%CI: 0.53 to 0.90, p = 0.02), corresponding to an absolute reduction of recurrence of 0.31 recurrences/patient (95%CI: 0.05 to 0.59, p = 0.02). Incremental costs of prophylaxis suggested a small cost saving but were not statistically significant, comparing the two groups. If a decision-maker is willing to pay up to £25,000/QALY then there is a 66% probability of antibiotic prophylaxis being cost-effective from an NHS perspective, rising to 76% probability from a secondary, societal perspective. CONCLUSION: Following first episode or recurrent cellulitis of the leg, prophylactic low dose penicillin is a very low cost intervention which, on balance, is effective and cost-effective at preventing subsequent attacks. Antibiotic prophylaxis reduces cellulitis recurrence by nearly a third but is not associated with a significant increase in costs.