IV cefazolin plus probenecid vs oral cephalexin for the treatment of skin and soft tissue infections

It is traditionally thought that IV antibiotics are superior to those given orally. But IV administration comes with extra time, cost, resources, and possibly not necessary.

To answer the question, these authors designed an elegant bias-busting study. It was a prospective, multicentre, double-dummy blind, randomised non-inferiority trial conducted in two Canadian ED’s.

However, the authors soon learned valuable lessons in performing an RCT; feasibility and generalisability.

They had quite strict inclusion and exclusion criteria that hindered patient recruitment. In addition, this also made any conclusions rather difficult to generalise to a broader patient population.

They included adult patients who had what they thought was mild to moderate cellulitis (a bit subjective). They excluded very mild patients, those with renal disease, prior MRSA, prior antibiotic use in the preceding 7 days, infections requiring I&D or debridement, two or more signs of SIRS, bites, PVD, perioperative wounds, etc, etc.

They even excluded patients with BMI greater than 30. That’s most of Canada!

Arguably defeating the whole purpose of the study, participants were brought back to the ED every day for 7 days of treatment. This is hardly decreasing resources and simulating real conditions.

The primary outcome was failure rate at 72 hours. About 300 patients were thought needed to power the study to a 10% non-inferior margin.

Why 72 hours? A great pearl… 

“This end point is beyond the clinical extension of redness that may be seen in the first 24-48 hours of therapy which would not typically represent treatment failure.”

Results?

Over 4 years, they screened 2855 patients for eligibility but finally gave up after randomising 206 patients.

The proportion of patients failing therapy at 72 hours was not statistically different and about 5% in both groups. The authors conclude cephalexin is just as good as IV cefazolin for mild to moderate cellulitis.

It is probably true that we overdo IV antibiotics for many infectious disease processes. But it is disappointing to see such a well-designed study design ultimately unable to provide us with much useful information.

Covering:

Dalen D, Fry A, Campbell, S, et al. IV cefazolin plus probenecid vs oral cephalexin for the treatment of skin and soft tissue infections. Emerg Med J 2018;35:492-429 [link to article]