Sutep Jaruratanasirikul1, Wajanarat Nitchot2, Wibul Wongpoowarak3, Maseetoh Samaeng2, Monchana Nawakitrangsan2. 1. Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla 90110, Thailand. Electronic address: jasutep@medicine.psu.ac.th. 2. Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla 90110, Thailand. 3. Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkla 90110, Thailand.
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 2 g of sulbactam every 12 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 ± 1.60 L and 6.76 ± 2.37 L/h, respectively. For pathogens with a MIC of 8 μg/mL, the high PTAs of achieving (≥90%) 60% T>MIC in patients with serum albumin 1.7-2.4 g/dL and CLCR 90-120 mL/min following administration of sulbactam as a 4-h infusion of 1 g every 6 h, 2 g every 12 h, and 2 g every 8 h were 98.65%, 78.07% and 98.23%, respectively. For pathogens with a MIC of 16 μg/mL, the high PTAs of achieving (≥90%) 60% T>MIC in patients with serum albumin 1.7-2.4 g/dL and CLCR 90-120 mL/min following administration of sulbactam as a 4-h infusion of 2 g every 6 h, and 3 g every 8 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.
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 illpatients. 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 2 g of sulbactam every 12 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 ± 1.60 L and 6.76 ± 2.37 L/h, respectively. For pathogens with a MIC of 8 μg/mL, the high PTAs of achieving (≥90%) 60% T>MIC in patients with serum albumin 1.7-2.4 g/dL and CLCR 90-120 mL/min following administration of sulbactam as a 4-h infusion of 1 g every 6 h, 2 g every 12 h, and 2 g every 8 h were 98.65%, 78.07% and 98.23%, respectively. For pathogens with a MIC of 16 μg/mL, the high PTAs of achieving (≥90%) 60% T>MIC in patients with serum albumin 1.7-2.4 g/dL and CLCR 90-120 mL/min following administration of sulbactam as a 4-h infusion of 2 g every 6 h, and 3 g every 8 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 illpatients with VAP.
Authors: Fabrício Rodrigues Torres de Carvalho; João Paulo Telles; Felipe Francisco Bodan Tuon; Roberto Rabello Filho; Pedro Caruso; Thiago Domingos Correa Journal: Antibiotics (Basel) Date: 2022-03-12