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Addition of probenecid to oral β-lactam antibiotics: a systematic review and meta-analysis.
- Source :
- Journal of Antimicrobial Chemotherapy (JAC); Sep2022, Vol. 77 Issue 9, p2364-2372, 9p
- Publication Year :
- 2022
-
Abstract
- <bold>Objectives: </bold>To explore the literature comparing the pharmacokinetic and clinical outcomes from adding probenecid to oral β-lactams.<bold>Methods: </bold>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.<bold>Results: </bold>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%), Cmax (5/8; 63%) and serum t½ (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.<bold>Conclusions: </bold>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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03057453
- Volume :
- 77
- Issue :
- 9
- Database :
- Complementary Index
- Journal :
- Journal of Antimicrobial Chemotherapy (JAC)
- Publication Type :
- Academic Journal
- Accession number :
- 158725175
- Full Text :
- https://doi.org/10.1093/jac/dkac200