Antibiotic treatment for 6 days versus 12 days in patients with severe cellulitis: a multicentre randomized, double-blind, placebo-controlled, non-inferiority trial

Abstract

a b s t r a c tObjectives: To investigate whether antibiotic treatment of 6 days' duration is non-inferior to treatment for 12 days in patients hospitalized for cellulitis. Methods: This multicentre, randomized, double-blind, placebo-controlled, non-inferiority trial enrolled adult patients hospitalized for severe cellulitis who were treated with intravenous flucloxacillin. At day 6 participants with symptom improvement who were afebrile were randomized between an additional 6 days of oral flucloxacillin or placebo in a 1:1 ratio, stratified for diabetes and hospital. The primary outcome was cure by day 14, without relapse by day 28. Secondary outcomes included a modified cure assessment and relapse rate by day 90. Results: Between August 2014 and June 2017, 151 of 248 included participants were randomized. The intention-to-treat population consisted of 76 and 73 participants allocated to 12 and 6 days of antibiotic therapy, respectively (mean age 62 years, 67% males, 24% diabetics); 38/76 (50.0%) and 36/73 (49.3%) were cured in the 12-and 6-day groups respectively (ARR 0.7 percentage points, 95%CI: e15.0 to 16.3). Cure rates were 56/76 (73.7%) and 49/73 (67.1%) with the modified cure assessment (ARR 6.6, 95%CI:e8.0 to 20.8). After initial cure without relapse, day 90 relapse rates were higher in the 6-day group (6% versus 24%, p < 0.05). Conclusions: Given the wide confidence intervals, we can neither confirm nor refute our hypothesis that 6 days of therapy is non-inferior to 12 days of therapy. However, a 6-day course resulted in significantly more frequent relapses by day 90. These findings require confirmation in future studies. D.R. Cranendonk, Clin Microbiol Infect 2020;26:606

‘Antibiotic treatment for 6 days versus 12 days in patients with severe cellulitis’ – Author's reply

“…We appreciate the comment and interests in our recent report [1]. Indeed, we agree with the authors that the optimal management of cellulitis can be challenging to investigate.…”

“…In line with this, we would like to argue against the suggestion that the observed low cure rates reflect wrong diagnoses in the DANCE trial [1]. Once again, most probably this is just a reflection of the severity of disease in the studied population.…”

Duration of antibiotic therapy for common infections

“…One randomized controlled study of patients with uncomplicated cellulitis (both outpatients and inpatients) concluded that despite some residual erythema, 5 days of therapy resulted in similar cure rates compared to 10 days. (81) In a study involving patients admitted to hospital with cellulitis, there appeared to be more readmissions in the shorter (6 days) duration group suggesting that some hospitalized patients may have more extensive disease requiring longer durations of therapy to prevent relapse. (82) In cases of recurrent cellulitis, consideration should be given to penicillin prophylaxis and other supportive measures.…”

Re: ‘Antibiotic treatment for 6 days versus 12 days in patients with severe cellulitis’ by Cranendonk et al.

“…We read with interest the results of the 'Duration of ANtibiotic therapy for CEllulitis (DANCE)' trial [1], a multicentre, doubleblind, non-inferiority trial comparing 6 versus 12 days of antibiotics in patients hospitalized with severe cellulitis. We applaud the authors for studying cellulitis, a disease that is both prevalent and confounding to study.…”