SLR - June 2014 - Wendell Wallace

Penicillin to Prevent Recurrent Leg Cellulitis

Reference: Thomas KS, Crook AM, Nunn AJ, Foster KA, Mason JM, Chalmers JR, Nasr IS, Brindle RJ, English J, Meredith SK, Reynolds NJ, de Berker D, Mortimer PS, Williams HC. The New England Journal of Medicine 2013; 368:1695-703

Reviewed By: Wendell D. Wallace DPM, MS
Residency Program: Saint Vincent Hospital, Worcester, MA

Podiatric Relevance: Although podiatrists see patients that are not diabetic with cellulitis, a large segment of their patient population will be diabetic who have an increased risk for development of recurrent cellulitis. Recurrent cellulitis infections are usually due to an anatomic wound or to a secondary cause of immune suppression such as diabetes, Hep C, or HIV. Podiatrists will see these patients in the ER, clinic, and in-patient setting. The purpose of this trial was to further investigate the effectiveness of prophylatic low-dose penicillin.

Methods: The authors conducted a double-blind, randomized, and controlled trial which spanned five years. The participants were recruited and identified at 28 hospitals in the United Kingdom and Ireland between July 2006 and January 2010. Patients were considered to have had recurrent cellulitis if the last two episodes occurred within the previous three years. The authors screened 533 patients and 274 were eligible for inclusion. The penicillin group had 136 participants and the placebo group consisted of 138 participants. Participants were monitored for up to 36 months. The last follow-up contact was July 2011. The participants received low-dose oral penicillin (250 mg) or a placebo. The placebo consisted of calcium phosphate, starch, cellulose, and magnesium stearate. The penicillin and placebo doses were taken by participants twice daily for a total of 12 months after completing treatment for the index episode of cellulitis.

Results: In the penicillin group the median time to recurrence of cellulitis was 626 days, whereas in the placebo group it was 532 days. While in the prophylaxis phase, 30 of the 136 (22 percent) participants who received penicillin had a recurrence. In the placebo group, 51 of the 138 (37 percent) participants had a recurrence of cellulitis. During the prophylaxis phase patients in the penicillin group had a 45 percent reduction in the risk of a repeat episode of cellulitis as compared to those in the placebo group (hazard ratio, 0.55; 95 percent confidence interval [CI], 0.35 to 0.86; P=0.01). In the follow-up years two and three there was no difference between the groups of a first recurrence, with that value being 27percent. The participants in the penicillin group had fewer repeat episodes than those in the placebo group (119 vs. 164, P=0.02 for trend).

Conclusions: While being treated prophylactically, it was shown that penicillin was effective in preventing subsequent attacks of cellulitis in patients known to have had recurrent leg cellulitis. Low-dose penicillin given prophylactically for 12 months almost halved the risk of recurrence during the intervention period. There was some level of protection after the prophylactic period but that was lost by month 36. This suggests that there may be a longer time period for prophylaxis, but it is unknown for how long. There is also another consideration here, what effect will this have on organisms that are still susceptible to penicillin? Do we really want to run the risk of increasing the number of organisms that are resistant to penicillin? How cost effective would this prophylactic therapy be in the long run? These are questions which the medical community must consider when determining the risk and benefits. 

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