Background: Optimized antibiotic plasma predictor efficacy is essential in systemic infections. The uricosuric agent probenecid inhibits tubular excretion of antibiotics and may be used as β-lactam pharmacokinetic enhancer (BLPKE), even though few data are currently available for this purpose.
Methods: We conducted a monocentric and retrospective observational study including all patients who received probenecid in combination with parenteral β-lactam antibiotics for systemic infections from Jan 1, 2014 to Dec 31, 2019. Demographics, infection characteristics, treatment and ATC (antibiotics trough concentration) were investigated.
Results: All in all, 38 patients were included. Eight patients had a history of sickle cell disease. Hyperfiltration (defined as eGFR>130mL/min/1.73m2) was detected in twenty-one patients including six with sickle cell disease. Probenecid (500mg q6h orally) was added to antibiotics for a median (IQR) of 13 days (6.75-21.75), after a median (IQR) time lapse of 7 days (4-16) following the initiation of antibiotics. Probenecid was administered for low antibiotic trough concentration in 29 patients, for increased renal clearance in 5 patients and for persisting fever despite antibiotic therapy in 4 patients (including 1 infective relapse). A second plasma trough concentration, following probenecid administration, was available in 19 patients within a median (IQR) 3 days (2-5). Probenecid induced increased ATC in 18/19 patients (94.7%), with a median (IQR) change of +228.4% (IQR 38.7-633). No major adverse effects were reported.
Conclusion: Probenecid could be a BLPKE. Our data suggest this drug should be used more often to optimize β-lactam pharmacokinetics in clinical practice.
Keywords: Antibiotic; Pharmacokinetics; Probenecid; Renal hyperfiltration.
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