New RCT – High-Dose or Standard-Dose Cephalexin for Cellulitis?

February 7, 2023

Written by Amanda Mathews

Spoon Feed
Investigators compared high-dose cephalexin (1000mg QID) to standard dose (500mg QID) for the treatment of non-purulent cellulitis. High-dose cephalexin was associated with fewer instances of treatment failure but a higher proportion of adverse events.

Why does this matter?
Skin and soft tissue infections are a common presenting complaint in the ED, with many of these patients appropriate for outpatient antibiotic therapy. However, reported rates of oral antibiotic treatment failure range as a high as 20%, leading to repeat ED visits and hospitalization. This pilot study asked whether doubling the dose of oral cephalexin would lead to lower treatment failure.

A big flex for Keflex
This double-blind pilot randomized control trial occurred in two EDs in Canada, where cephalexin is the most prescribed antibiotic for the outpatient treatment of cellulitis. Eligible participants were ≥18 years old, presenting with non-purulent cellulitis and deemed appropriate for outpatient antibiotics by the treating physician. The intervention group took cephalexin 1000mg four times daily for 7 days while the control group received cephalexin 500mg four times daily.

The primary outcome was participant recruitment rate, and the preliminary primary effectiveness outcome was oral antibiotic treatment failure. 33 patients were allocated into each study arm, and approximately 75% of participants reported adherence to the treatment regimens. The study recruitment rate was 51%, above the designated threshold. Treatment failure occurred in four patients (12.9%) in the standard dose arm and one patient (3.2%) in the high dose arm. 38.7% of the high dose arm reported adverse events, primarily GI distress, versus 25.8% in the standard dose arm.

While this pilot study is not practice changing, the investigators demonstrate it is feasible to recruit for a larger study. Their clinical question is certainly interesting, as high dose cephalexin reaches serum concentrations comparable to IV cephalosporins, and could potentially prevent the need for patients to be admitted for IV antibiotics.

Source
High-dose cephalexin for cellulitis: a pilot randomized controlled trial. CJEM. 2023 Jan;25(1):22-30. doi: 10.1007/s43678-022-00433-7. Epub 2023 Jan 2.