No Benefits Seen for Adjunctive Clindamycin in Cellulitis

In patients with limb cellulitis, the use of adjunctive clindamycin with flucloxacillin resulted in no benefits over flucloxacillin alone and a 2-fold greater likelihood of diarrhea, according to a study published in BMJ Open.

“The results of this clinical trial do not provide evidence that any feature of cellulitis was improved by the addition of clindamycin,” wrote the investigators. They also concluded that clindamycin was unlikely to be of benefit in invasive group A streptococci infections.

The double-blind randomized controlled trial (ClinicalTrials.gov identifier: NCT01876628), conducted in general practice patients, emergency department patients, and inpatients recruited from 20 hospitals in the United Kingdom, was the first to examine the effect of adjunctive clindamycin with β-lactam therapy for cellulitis. Clindamycin is commonly recommended in the treatment of cellulitis in UK hospital guidelines.

Patients selected for the trial received oral or intravenous flucloxacillin with the dose and route determined by their treating clinicians, and were randomly assigned to receive adjunctive clindamycin or placebo within 48 hours of initiation of flucloxacillin therapy.

The trial’s primary outcome was improvement at day 5, defined as the absence of fever and a reduction in either limb swelling or limb temperature.  In the clindamycin group, 87% (136/156) of patients improved at day 5 compared with 81% (140/172) in the placebo group, a statistically insignificant difference; OR 1.55 (95% CI 0.81 to 3.01), P =.17.

No differences between the clindamycin or placebo groups were found for secondary outcomes of resolution of systemic features, resolution of inflammatory markers, recovery of renal function, reduction in affected area, decrease in pain, or return to work or normal activities.

Diarrhea was the most frequently reported adverse event in patients receiving clindamycin. Of patients in the clindamycin group, 22% (34/158) experienced diarrhea compared with 9% (16/172) in the placebo group; odds ratio (OR) 2.7 (95% CI 1.41 to 5.07), P =.002

The research team noted that misunderstanding of the natural history of cellulitis frequently drives clindamycin use in the treatment of the condition. Local features of cellulitis often progress for several days following presentation, leading patients and physicians to believe that antibiotic treatment is failing despite improvement in systemic symptoms. “The addition of clindamycin or change to intravenous therapy is consequently and spuriously attributed as being responsible for the patient’s improvement,” they wrote.

In an email interview, lead investigator Richard Brindle BM, MSc, DM, MRCPath, FRCP, DTMH of Bristol Royal Infirmary, Bristol, United Kingdom told Infectious Disease Advisor that the key reason for doing the study was to determine whether there was any objective evidence for using clindamycin in group A streptococcal infections in general, such as in necrotizing fasciitis. “Nearly all guidelines recommend the use of additional clindamycin but can only find limited retrospective data to support its use. We think that these recommendations need to be validated by a prospective blinded trial, like the one we have done on cellulitis. Until they are validated doctors should not be recommending additional clindamycin.”

Reference

Brindle R, Williams OM, Davies P, et al. Adjunctive clindamycin for cellulitis: a clinical trial comparing flucloxacillin with or without clindamycin for the treatment of limb cellulitis. BMJ Open. 2017;7:e013260. doi:10.1136/bmjopen-2016-013260