Addition of probenecid to oral ß-lactam antibiotics: a systematic review and meta-analysis.
J Antimicrob Chemother
; 77(9): 2364-2372, 2022 08 25.
Article
em En
| MEDLINE
| ID: mdl-35726853
ABSTRACT
OBJECTIVES:
To explore the literature comparing the pharmacokinetic and clinical outcomes from adding probenecid to oral ß-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 ß-lactam [flucloxacillin, penicillin V, amoxicillin (±âclavulanate), 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 ß-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; I2â=â7%), favouring probenecid.CONCLUSIONS:
Probenecid-boosted ß-lactam therapy is associated with improved outcomes in gonococcal disease. Pharmacokinetic data suggest that probenecid-boosted oral ß-lactam therapy may have a broader application, but appropriately powered mechanistic and efficacy studies are required.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Gonorreia
/
Probenecid
Tipo de estudo:
Clinical_trials
/
Etiology_studies
/
Systematic_reviews
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article