Continuous Infusion of Piperacillin/Tazobactam and Meropenem in ICU Patients Without Renal Dysfunction: Are Patients at Risk of Underexposure?

• Published in: European journal of drug metabolism and pharmacokinetics 2021-07, Vol.46 (4), p.527-538
• Main Authors: Esteve-Pitarch, Erika, Gumucio-Sanguino, Víctor Daniel, Cobo-Sacristán, Sara, Shaw, Evelyn, Maisterra-Santos, Kristel, Sabater-Riera, Joan, Pérez-Fernandez, Xosé L., Rigo-Bonnin, Raül, Tubau-Quintano, Fe, Carratalà, Jordi, Colom-Codina, Helena, Padullés-Zamora, Ariadna
• Format: Article
• Language: English
• Subjects: Aged; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Anti-Bacterial Agents - pharmacology; Biomedical and Life Sciences; Biomedicine; Critical Illness; Dose-Response Relationship, Drug; Female; Human Physiology; Humans; Infusions, Intravenous; Intensive Care Units; Male; Medical Biochemistry; Meropenem - administration & dosage; Meropenem - pharmacokinetics; Meropenem - pharmacology; Microbial Sensitivity Tests; Middle Aged; Original Research Article; Pharmaceutical Sciences/Technology; Pharmacology/Toxicology; Pharmacy; Piperacillin, Tazobactam Drug Combination - administration & dosage; Piperacillin, Tazobactam Drug Combination - pharmacokinetics; Piperacillin, Tazobactam Drug Combination - pharmacology; Prospective Studies; Risk Factors; Sepsis - drug therapy; Sepsis - microbiology
• ISSN: 0378-7966; 2107-0180
• DOI: 10.1007/s13318-021-00694-0

Background and Objectives Morbidity and mortality from serious infections are common in intensive care units (ICUs). The appropriateness of the antibiotic treatment is essential to combat sepsis. We aimed to evaluate pharmacokinetic/pharmacodynamic target attainment of meropenem and piperacillin/tazobactam administered at standard total daily dose as continuous infusion in critically ill patients without renal dysfunction and to identify risk factors of non-pharmacokinetic/pharmacodynamic target attainment. Results We included 118 patients (149 concentrations), 47% had microorganism isolation. Minimum inhibitory concentration (MIC) [median (interquartile range, IQR) values in isolated pathogens were: meropenem: 0.05 (0.02–0.12) mg/l; piperacillin: 3 (1–4) mg/l]. Pharmacokinetic/pharmacodynamic target attainments (100% f C ss≥1xMIC , 100% f C ss≥4xMIC and 100% f C ss ≥ 8xMIC , respectively) were: 100%, 96.15%, 96.15% (meropenem) and 95.56%, 91.11%, 62.22% (piperacillin) for actual MIC; 98.11%, 71.70%, 47.17% (meropenem, MIC 2 mg/l), 95.83%, 44.79%, 6.25% (piperacillin, MIC 8 mg/l), 83.33%, 6.25%, 1.04% (piperacillin, MIC 16 mg/l) for EUCAST breakpoint of Enterobacteriaceae spp. and Pseudomonas spp. Multivariable linear analysis identified creatinine clearance (CrCL) as a predictive factor of free antibiotic concentrations ( f C ss ) of both therapies (meropenem [ β = − 0.01 (95% CI − 0.02 to − 0.0; p  = 0.043)] and piperacillin [ β  = − 0.01 (95% CI − 0.02 to 0.01, p  8 mg/l. CrCL was the most powerful factor predictive of f C ss in both therapies.