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

OBJECTIVES: 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: -15.0 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: -8.0 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.

Cellulitis: current insights into pathophysiology and clinical management.

Cellulitis is a bacterial skin and soft tissue infection which occurs when the physical skin barrier, the immune system and/or the circulatory system are impaired. Diabetes, obesity and old age are associated with defects in all of these areas and as a result are major predisposing factors for cellulitis. In this review, we summarise current insights into the pathophysiology of cellulitis and place the Dutch guidelines on the clinical management of cellulitis of the lower extremities in perspective. Recent evidence on diagnostic strategies is discussed, the importance of which is underscored by findings that venous insufficiency, eczema, deep vein thrombosis and gout are frequently mistaken for cellulitis. Empiric antibiotic choices are designed against the background of a low prevalence of multi-resistant Staphylococcus aureus. Novel antimicrobial agents registered for cellulitis are also discussed. Relapses occur frequently due to a high prevalence of risk factors associated with cellulitis in combination with the ccurrence of persistent post-inflammatory lymphatic damage. Lastly, we identify knowledge gaps which, if addressed, will advance our understanding of the pathophysiology of cellulitis and improve its clinical management.