High-dose cephalexin for cellulitis: a pilot randomized controlled trial

BACKGROUND: Up to 3% of all Emergency Department (ED) visits are due to skin and soft tissue infections such as non-purulent cellulitis. The current treatment failure rate is approximately 20%. Evidence is lacking regarding the optimal outpatient management of cellulitis. OBJECTIVES: To evaluate the feasibility of a randomized trial comparing high-dose (1000 mg) to standard-dose (500 mg) cephalexin to treat ED patients with cellulitis. METHODS: A parallel arm double-blind randomized controlled pilot trial conducted at two EDs in Canada. Eligible participants were adults (age ≥ 18 years) presenting to the ED with non-purulent cellulitis and determined by the treating emergency physician to be eligible for outpatient management with oral antibiotics. Participants were randomized to high-dose or standard-dose cephalexin four times daily for 7 days. The primary feasibility outcome was participant recruitment rate (target ≥ 35%). The preliminary primary effectiveness outcome was oral antibiotic treatment failure. RESULTS: Of 134 eligible participants approached for trial participation, 69 (51.5%, 95% CI 43.1 to 59.8%) were recruited and randomized. After excluding three randomized participants due to an alternate diagnosis, 33 participants were included in each arm. Nineteen eligible cases (14.2%) were missed. Loss to follow-up was 6.1%. Treatment failure occurred in four patients (12.9%) in the standard-dose arm versus one patient (3.2%) in the high-dose arm. A greater proportion had minor adverse events in the high-dose arm. No patients had an unplanned hospitalization within 14 days. CONCLUSION: This pilot randomized controlled trial comparing high-dose to standard-dose cephalexin for ED patients with cellulitis demonstrated a high participant recruitment rate and that a full-scale trial is feasible. High-dose cephalexin had fewer treatment failures but with a higher proportion of minor adverse effects. The findings of this pilot will be used to inform the design of a future large trial. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT04471246). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43678-022-00433-7.