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Addition of probenecid to oral β-lactam antibiotics: a systematic review and meta-analysis

OBJECTIVES: To explore the literature comparing the pharmacokinetic and clinical outcomes from adding probenecid to oral β-lactams. METHODS: Medline and EMBASE were searched from inception to December 2021 for all English language studies comparing the addition of probenecid (intervention) with an o...

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Autores principales: Wilson, Richard C, Arkell, Paul, Riezk, Alaa, Gilchrist, Mark, Wheeler, Graham, Hope, William, Holmes, Alison H, Rawson, Timothy M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9721384/
https://www.ncbi.nlm.nih.gov/pubmed/35726853
http://dx.doi.org/10.1093/jac/dkac200
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author Wilson, Richard C
Arkell, Paul
Riezk, Alaa
Gilchrist, Mark
Wheeler, Graham
Hope, William
Holmes, Alison H
Rawson, Timothy M
author_facet Wilson, Richard C
Arkell, Paul
Riezk, Alaa
Gilchrist, Mark
Wheeler, Graham
Hope, William
Holmes, Alison H
Rawson, Timothy M
author_sort Wilson, Richard C
collection PubMed
description OBJECTIVES: To explore the literature comparing the pharmacokinetic and clinical outcomes from adding probenecid to oral β-lactams. METHODS: Medline and EMBASE were searched from inception to December 2021 for all English language studies comparing the addition of probenecid (intervention) with an oral β-lactam [flucloxacillin, penicillin V, amoxicillin (± clavulanate), cefalexin, cefuroxime axetil] alone (comparator). ROBINS-I and ROB-2 tools were used. 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%) screened abstracts were included. Populations, methodology and outcome data were heterogeneous. Common populations included healthy volunteers (9/18; 50%) and those with gonococcal infection (6/18; 33%). Most studies were crossover trials (11/18; 61%) or parallel-arm randomized trials (4/18; 22%). Where pharmacokinetic analyses were performed, addition of probenecid to oral β-lactams increased total AUC (7/7; 100%), C(max) (5/8; 63%) and serum t(½) (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; I(2 )= 7%), favouring probenecid. CONCLUSIONS: Probenecid-boosted β-lactam therapy is associated with improved outcomes in gonococcal disease. Pharmacokinetic data suggest that probenecid-boosted oral β-lactam therapy may have a broader application, but appropriately powered mechanistic and efficacy studies are required.
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spelling pubmed-97213842022-12-06 Addition of probenecid to oral β-lactam antibiotics: a systematic review and meta-analysis Wilson, Richard C Arkell, Paul Riezk, Alaa Gilchrist, Mark Wheeler, Graham Hope, William Holmes, Alison H Rawson, Timothy M J Antimicrob Chemother Systematic Review OBJECTIVES: To explore the literature comparing the pharmacokinetic and clinical outcomes from adding probenecid to oral β-lactams. METHODS: Medline and EMBASE were searched from inception to December 2021 for all English language studies comparing the addition of probenecid (intervention) with an oral β-lactam [flucloxacillin, penicillin V, amoxicillin (± clavulanate), cefalexin, cefuroxime axetil] alone (comparator). ROBINS-I and ROB-2 tools were used. 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%) screened abstracts were included. Populations, methodology and outcome data were heterogeneous. Common populations included healthy volunteers (9/18; 50%) and those with gonococcal infection (6/18; 33%). Most studies were crossover trials (11/18; 61%) or parallel-arm randomized trials (4/18; 22%). Where pharmacokinetic analyses were performed, addition of probenecid to oral β-lactams increased total AUC (7/7; 100%), C(max) (5/8; 63%) and serum t(½) (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; I(2 )= 7%), favouring probenecid. CONCLUSIONS: Probenecid-boosted β-lactam therapy is associated with improved outcomes in gonococcal disease. Pharmacokinetic data suggest that probenecid-boosted oral β-lactam therapy may have a broader application, but appropriately powered mechanistic and efficacy studies are required. Oxford University Press 2022-06-21 /pmc/articles/PMC9721384/ /pubmed/35726853 http://dx.doi.org/10.1093/jac/dkac200 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Systematic Review
Wilson, Richard C
Arkell, Paul
Riezk, Alaa
Gilchrist, Mark
Wheeler, Graham
Hope, William
Holmes, Alison H
Rawson, Timothy M
Addition of probenecid to oral β-lactam antibiotics: a systematic review and meta-analysis
title Addition of probenecid to oral β-lactam antibiotics: a systematic review and meta-analysis
title_full Addition of probenecid to oral β-lactam antibiotics: a systematic review and meta-analysis
title_fullStr Addition of probenecid to oral β-lactam antibiotics: a systematic review and meta-analysis
title_full_unstemmed Addition of probenecid to oral β-lactam antibiotics: a systematic review and meta-analysis
title_short Addition of probenecid to oral β-lactam antibiotics: a systematic review and meta-analysis
title_sort addition of probenecid to oral β-lactam antibiotics: a systematic review and meta-analysis
topic Systematic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9721384/
https://www.ncbi.nlm.nih.gov/pubmed/35726853
http://dx.doi.org/10.1093/jac/dkac200
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