Work

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

Year: 2026

Type: review

Abstract: BACKGROUND AND OBJECTIVES: Among patients presenting to hospital with skin and soft tissue infection (SSTI), up to 50% have already failed oral antibiotic treatment and 90% receive intravenous (IV) antibiotics.Probenecid prolongs serum concentrations of beta-lactam antibiotics. Probenecid-boosted oral treatment may be an alternative to IV. Alternatively, probenecid could allow less frequent dosing of narrow-spectrum IV agents (e.g. cefazolin), reducing dependence on ceftriaxone in ambulatory settings. This systematic review evaluated the effectiveness and safety of probenecid combined with beta-lactam antibiotics for SSTI treatment. METHODS: MEDLINE and EMBASE were searched through February 2026. Eligible studies assessed the addition of probenecid to beta-lactam therapy in human participants with SSTIs and reported clinical outcomes or adverse effects. RESULTS: Nine studies (over 1600 participants) were included, most evaluating once-daily IV cefazolin plus probenecid versus ceftriaxone or more frequent cefazolin dosing. Treatment success, failure, relapse and hospital admission rates were similar between groups, indicating that probenecid-boosted cefazolin performs comparably to standard regimens while offering a narrower-spectrum alternative to ceftriaxone. Evidence for oral beta-lactams plus probenecid was more limited but did not suggest inferiority. Adverse events, inconsistently reported, were generally mild and predominantly gastrointestinal, with possibly higher rates in the probenecid-containing regimens. CONCLUSIONS: Current evidence suggests probenecid may enable once-daily IV cefazolin as an alternative to ceftriaxone for SSTI, supporting narrower-spectrum antibiotics in ambulatory care. Evidence for using oral beta-lactams plus probenecid remains limited. A robust RCT is needed to determine clinical non-inferiority and acceptability of adverse effects. If effective, this approach could reduce IV complications, healthcare attendance and costs.

Source: Journal of Antimicrobial Chemotherapy

DOI: 10.1093/jac/dkag376

Authors: Claudette Hewitt, Martin John Llewelyn, Elizabeth Cross

Institutions: Brighton and Sussex Medical School, University of Sussex, Royal Sussex County Hospital, University Hospitals Sussex NHS Foundation Trust, University of Brighton

Language: English

Topic: Antibiotics Pharmacokinetics and Efficacy

Subfield: Pharmacology (medical)

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,784