Pharmacokinetic and pharmacodynamic analysis of cefoperazone/sulbactam for the treatment of pediatric sepsis by Monte Carlo simulation

Analytical Methods Pub Date: 2022-02-07 DOI: 10.1039/D1AY01385H

Abstract

Pediatric sepsis syndrome is one of the most common reasons for pediatric intensive care unit hospitalization (PICU). Cefoperazone/sulbactam is a time-dependent beta-lactamase inhibitor combination which has been widely used in the treatment of sepsis. But the pharmacokinetic (PK) and pharmacodynamic (PD) data of cefoperazone/sulbactam are unknown in children with sepsis. The present work aimed to determine whether the usual dosing regimens of cefoperazone/sulbactam (1 hour infusion, 50 mg kg?1, every 12 hours) were suitable for these patients in PICU. A total of fourteen patients were enrolled and the PK parameters were estimated by non-compartmental analysis using WinNonlin software. The t1/2 and AUC0–12 of cefoperazone and sulbactam were 3.60 and 1.77 h, and 900.97 and 67.68 h μg mL?1, respectively. The Vd and CL of cefoperazone and sulbactam were 1.65 L and 5.16 L, and 17.41 mL min?1 and 122.62 mL min?1, respectively. The probability of target attainments (PTAs) of cefoperazone at different minimum inhibitory concentrations (MICs) based on the percentage time that concentrations exceed the minimum inhibitory concentration (% T > MIC) value were performed by Monte Carlo simulation and PTA was >90% at MICs ≤16 μg mL?1. The PK/PD profile of dosing regimens tested will assist in selecting the appropriate cefoperazone/sulbactam regimens for these patients. At a target of 80% T > MIC, the usual dosing regimens can provide good coverage for pathogens with MICs of ≤32 μg mL?1. The ratio between cefoperazone and sulbactam at 1?:?1 may be more suitable in pediatric sepsis. Individual dose and therapeutic drug monitoring in clinical practice will help achieve the best therapeutic effect while minimizing toxicity.

Graphical abstract: Pharmacokinetic and pharmacodynamic analysis of cefoperazone/sulbactam for the treatment of pediatric sepsis by Monte Carlo simulation
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