Population Pharmacokinetics and Pharmacodynamics Modeling To Optimize Dosage Regimens of Sulbactam in Critically Ill Patients with Severe Sepsis Caused by Acinetobacter baumannii.
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>MIC) and 60% T>MICThe 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>MICand 60% T>MICwith 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.
Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla, Thailand jasutep@medicine.psu.ac.th.
Sutep
S
Jaruratanasirikul
Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkla, Thailand.
Wibul
W
Wongpoowarak
Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Pathumwan, Bangkok, Thailand.
Thitima
T
Wattanavijitkul
Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Pathumwan, Bangkok, Thailand.
Waroonrat
W
Sukarnjanaset
Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla, Thailand.
Maseetoh
M
Samaeng
Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla, Thailand.
Monchana
M
Nawakitrangsan
Department of Pathology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla, Thailand.
Natnicha
N
Ingviya
D000151:Acinetobacter Infections / Q000188:drug therapy*; D040981:Acinetobacter baumannii / Q000187:drug effects*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003091:Colistin / Q000627:therapeutic use; D016638:Critical Illness / Q000628:therapy; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D013407:Sulbactam / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult
D000900:Anti-Bacterial Agents; D013407:Sulbactam; D003091:Colistin
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