Addition of probenecid to beta-lactam antibiotics in the treatment of skin and soft tissue infections: a systematic review.

In 30 seconds

This systematic review assessed the effectiveness and safety of adding probenecid to beta-lactam antibiotics for skin and soft tissue infections (SSTIs). It included nine studies with over 1600 participants, most comparing once-daily intravenous cefazolin plus probenecid with ceftriaxone or more frequent cefazolin dosing. Treatment success, failure, relapse and hospital admission rates were similar between regimens. Evidence for oral beta-lactams combined with probenecid was more limited and did not suggest inferiority. Adverse events were generally mild, mainly gastrointestinal, but may have been more frequent with probenecid-containing regimens.

Key findings

• Across nine studies involving over 1600 participants, clinical outcomes were similar for probenecid-boosted cefazolin and comparator regimens.
• Most studies evaluated once-daily intravenous cefazolin plus probenecid against ceftriaxone or more frequent cefazolin dosing.
• Evidence for oral beta-lactams plus probenecid was limited but did not suggest inferiority.
• Reported adverse events were generally mild and predominantly gastrointestinal, with possibly higher rates in probenecid-containing regimens.

Why it matters

Probenecid may help maintain beta-lactam concentrations while enabling less frequent dosing. For SSTIs managed in ambulatory settings, once-daily cefazolin with probenecid could offer a narrower-spectrum alternative to ceftriaxone. The review also highlights uncertainty about oral regimens and adverse effects, so the apparent comparability of outcomes should be interpreted in light of the evidence base.

What to keep in mind

The review found limited evidence for oral regimens, adverse events were inconsistently reported, and a robust randomised controlled trial is needed to establish clinical non-inferiority and acceptability of adverse effects.