Comparing short to standard duration of antibiotic therapy for patients hospitalized with cellulitis (DANCE): study protocol for a randomized controlled trial

Abstract

BackgroundRecommended therapy duration for patients hospitalized with cellulitis is 10–14 days. Unnecessary use of antibiotics is one of the key factors driving resistance. Recent studies have shown that antibiotic therapy for cellulitis in outpatients can safely be shortened, despite residual inflammation. This study will compare in hospitalized patients the safety and effectiveness of shortening antibiotic therapy for cellulitis from 12 to 6 days.Methods/designIn a multicenter, randomized, double-blind, non-inferiority trial, adult patients admitted with cellulitis will be included. Cellulitis is defined as warmth, erythema, and induration of the skin and/or subcutaneous tissue, with or without pain (including erysipelas). All patients will initially be treated with intravenous flucloxacillin, and will be evaluated after 5–6 days. Those who have improved substantially (defined as being afebrile, and having a lower cellulitis severity score) will be randomized at day 6 between additional 6 days of oral flucloxacillin (n = 198) or placebo (n = 198). Treatment success is defined as resolution of cellulitis on day 14 (disappearance of warmth and tenderness, improvement of erythema and edema), without the need of additional antibiotics for cellulitis by day 28. Secondary endpoints are relapse rate (up to day 90), speed of recovery (using a cellulitis severity score until day 28, and VAS scores on pain and swelling until day 90), quality of life (using the SF-36 and EQ-5D questionnaires) and costs (associated with total antibiotic use and health-care resource utilization up to day 90).DiscussionInclusion is planned to start in Q2 2014.Trial registrationClinicalTrials.gov (NCT02032654) and the Netherlands Trial Register (NTR4360).

Optimizing design of research to evaluate antibiotic stewardship interventions: consensus recommendations of a multinational working group

“…Whereas demonstrating superiority only requires the confidence interval for the effect estimate to exclude zero, regardless of its width, determining non-inferiority requires the entire confidence interval to lie below the non-inferiority margin [24]. As a result, much larger participant numbers are usually required to demonstrate non-inferiority within clinically relevant margins which may be very small and difficult to define for outcomes such as mortality [25]. This difference lies in that superiority trials tend to be powered on an expected effect, which is often larger than what would be deemed a clinically relevant effect, whereas non-inferiority trials need to be powered on a clinically relevant effect.…”

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

“…Local institutional review boards approved the study for local execution. The study protocol and amendments are available online [12,13] (See Supplementary Material Table S1 for protocol amendments.). The trial is registered at clinicaltrials.gov (NCT02032654) and the Dutch trial register (NTR4360).…”

The Clinical Utility of Maceration Dressings in the Treatment of Inpatient Hand Infections: An Evaluation of Treatment Outcomes Compared to Standard Care

“…Infections of the hand require prompt and effective treatment to avoid the spread of infection as well as long-term local sequelae. A detailed history and physical exam 14-23 will lead to a diagnosis of these conditions and allow for timely and effective treatment. Treatment for oral antibiotic resistant infection includes splinting for comfort, elevation, hydration, and intravenous antibiotics.…”

“…14-18 Along with elevation and sufficient hydration of the affected area, 3 antibiotic therapy should be started and properly dosed based on the offending pathogen, purulence, and the weight of the patient. 19-22 Superficial abscesses might need a bedside incision and drainage versus a formal operative debridement to evacuate any purulent fluid collection in addition to appropriate intravenous antibiotic treatment, with deeper infections generally warranting a formal irrigation and debridement in the operating room if a trial of intravenous antibiotics does not help fully treat the infection. Physicians should be extremely wary of clinical signs that have been documented as markers of a more complicated clinical course, including objective fever when presenting to the emergency department, an elevated lactate level, or hemodynamic instability.…”