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@article{Wilson:2022,
author = {Wilson, R and Arkell, P and Riezk, A and Wheeler, G and Gilchrist, M and Hope, W and Holmes, A and Rawson, TM},
journal = {Journal of Antimicrobial Chemotherapy},
pages = {2364--2372},
title = {Addition of probenecid to oral beta-lactam antibiotics: a systematic review and meta-analysis},
url = {https://academic.oup.com/jac/article/77/9/2364/6612118},
volume = {77},
year = {2022}
}

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TY  - JOUR
AB  - Objective: Explore literature comparing the pharmacokinetic and clinical outcomes from addition of probenecid to oral beta-lactams.Data sources: Medline and EMBASE were searched from inception to December 2021.Study eligibility criteria: All English language studies comparing the addition of probenecid (intervention) to an oral beta-lactam (flucloxacillin, penicillin-V, amoxicillin(+/-clavulanate), cephalexin, cefuroxime-axetil) alone (comparator).Risk of bias: Risk of Bias in Non-randomised studies of interventions (ROBINS-I) and Risk of Bias for Randomised studies 2 (ROB-2) tools were used.Methods of data synthesis: Data on antibiotic therapy, infection diagnosis, primary and secondary outcomes relating to pharmacokinetics and clinical outcomes plus adverse events were extracted and reported descriptively. For a subset of studies comparing treatment failure between probenecid and control groups, meta-analysis was performed. Results: Overall, 18/295 (6%) abstracts screened were included. Populations, methodology, and outcome data were heterogenous. Common populations included healthy volunteer (9/18;50%) and gonococcal infection (6/18;33%). Most studies were cross-over trials (11/18;61%) or parallel arm randomised trial (4/18;22%). Where pharmacokinetic analyses were performed, addition of probenecid to oral beta-lactams increased total AUC (7/7;100¬%), peak observed concentration (Cmax,5/8;63%), and serum half-life (t1/2,6/8;75%). Probenecid improved PTA (2/2;100%). Meta-analysis of 3105 (2258 intervention, 847 control) patients treated for gonococcal disease demonstrated a relative risk of treatment failure in the random effects model of 0.33 (95%CI:0.20-0.55; I2=7%), favouring probenecid. Conclusion: Probenecid boosted beta-lactam therapy is associated with improved outcomes in gonococcal disease. Pharmacokinetic data suggest that probenecid boosted oral beta-lactam therapy may have a broader application, but appropriately powered mechanistic and efficacy st
AU  - Wilson,R
AU  - Arkell,P
AU  - Riezk,A
AU  - Wheeler,G
AU  - Gilchrist,M
AU  - Hope,W
AU  - Holmes,A
AU  - Rawson,TM
EP  - 2372
PY  - 2022///
SN  - 0305-7453
SP  - 2364
TI  - Addition of probenecid to oral beta-lactam antibiotics: a systematic review and meta-analysis
T2  - Journal of Antimicrobial Chemotherapy
UR  - https://academic.oup.com/jac/article/77/9/2364/6612118
UR  - http://hdl.handle.net/10044/1/97562
VL  - 77
ER  -

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