Addition of probenecid to beta-lactam antibiotics in the treatment of skin and soft tissue infections: a systematic 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.
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BibTeX
@article{hewitt2026addition,
title = {{Addition of probenecid to beta-lactam antibiotics in the treatment of skin and soft tissue infections: a systematic review}},
author = {Claudette Hewitt and Martin John Llewelyn and Elizabeth Cross},
journal = {Journal of Antimicrobial Chemotherapy},
year = {2026},
month = nov,
doi = {10.1093/jac/dkag376},
url = {https://doi.org/10.1093/jac/dkag376},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Addition of probenecid to beta-lactam antibiotics in the treatment of skin and soft tissue infections: a systematic review
AU - Claudette Hewitt
AU - Martin John Llewelyn
AU - Elizabeth Cross
PY - 2026
DA - 2026/11/04
JO - Journal of Antimicrobial Chemotherapy
DO - 10.1093/jac/dkag376
UR - https://doi.org/10.1093/jac/dkag376
AB - 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.
SN - 0305-7453
SN - 1460-2091
ER -