Population Pharmacokinetics and Pharmacodynamics Modeling To Optimize Dosage Regimens of Sulbactam in Critically Ill Patients with Severe Sepsis Caused by Acinetobacter baumannii

• Published in: Antimicrobial agents and chemotherapy Vol. 60; no. 12; pp. 7236 - 7244
• Main Authors: Jaruratanasirikul, Sutep, Wongpoowarak, Wibul, Wattanavijitkul, Thitima, Sukarnjanaset, Waroonrat, Samaeng, Maseetoh, Nawakitrangsan, Monchana, Ingviya, Natnicha
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.12.2016
• Subjects: Acinetobacter baumannii; Acinetobacter baumannii - drug effects; Acinetobacter Infections; Acinetobacter Infections - drug therapy; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Anti-Bacterial Agents - therapeutic use; Colistin - therapeutic use; Critical Illness - therapy; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pharmacology; Sepsis; Sepsis - drug therapy; Sepsis - microbiology; Sulbactam; Sulbactam - administration & dosage; Sulbactam - pharmacokinetics; Sulbactam - therapeutic use; Young Adult
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.01669-16

Sulbactam is being considered as an alternative concomitant medication with other effective antibiotics for the treatment of multidrug-resistant (MDR) Acinetobacter baumannii infections. Pathophysiological changes in critically ill patients with severe sepsis, resulting in altered pharmacokinetic (PK) patterns for antibiotics, are important factors in determining therapeutic success. The aims of this study were (i) to examine the population PK parameters and (ii) to assess the probability of target attainment (PTA) for sulbactam in patients with severe sepsis caused by A. baumannii PK studies were carried out following administration of 2 g of sulbactam every 12 h on the 4th day of drug administration in 27 patients, and a Monte Carlo simulation was performed to determine the PTA of achieving 40% exposure time during which the plasma drug concentration remained above the MIC (T ) and 60% T The central and peripheral volumes of distribution were 14.56 and 9.55 liters, respectively, and total clearances of sulbactam were 2.26 liters/h and 7.64 liters/h in patients aged >65 years and ≤65 years, respectively. The high PTAs (≥90%) for targets of 40% T and 60% T with a MIC of 4 μg/ml were observed when sulbactam was administered by a 4-h infusion of 1 g every 12 h and 1 g every 8 h, respectively. Sulbactam would be an alternative antibiotic option to coadminister with colistin for the treatment of infections caused by MDR A. baumannii However, for pathogens with MICs of >4 μg/ml, higher dosage regimens of sulbactam are required.