ABSTRACT
BACKGROUND: Ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) Acinetobacter baumannii remains one of the leading causes of the high mortality rate in critically ill patients. Sulbactam has been considered as an alternative concomitant medication with other effective antimicrobial agents for the treatment of these MDR microorganisms. The aims of this study were (i) to characterize the population pharmacokinetics (PK) and (ii) to assess the efficacy of various dosage regimens of sulbactam in terms of probability of target attainment (PTA). METHODS: The PK studies were carried out following administration of 2â¯g of sulbactam every 12â¯h on the 7th dose of drug administration in 16 patients with VAP, and a Monte Carlo simulation was performed to determine the PTA of achieving 40% and 60% the exposure time during which the total plasma drug concentration remained above the MIC (T>MIC). RESULTS: The volume of distribution and total clearance of sulbactam were 22.17⯱â¯1.60â¯L and 6.76⯱â¯2.37â¯L/h, respectively. For pathogens with a MIC of 8⯵g/mL, the high PTAs of achieving (≥90%) 60% T>MIC in patients with serum albumin 1.7-2.4â¯g/dL and CLCR 90-120â¯mL/min following administration of sulbactam as a 4-h infusion of 1â¯g every 6â¯h, 2â¯g every 12â¯h, and 2â¯g every 8â¯h were 98.65%, 78.07% and 98.23%, respectively. For pathogens with a MIC of 16⯵g/mL, the high PTAs of achieving (≥90%) 60% T>MIC in patients with serum albumin 1.7-2.4â¯g/dL and CLCR 90-120â¯mL/min following administration of sulbactam as a 4-h infusion of 2â¯g every 6â¯h, and 3â¯g every 8â¯h were 98.83% and 95.59%, respectively. CONCLUSION: These findings indicate that high dosage combination regimens are required for the treatment of life-threatening infections in critically ill patients with VAP.