Colistin plus Sulbactam or Fosfomycin against Carbapenem-Resistant<i>Acinetobacter baumannii</i>: Improved Efficacy or Decreased Risk of Nephrotoxicity?
Weerayuth Saelim, Dhitiwat Changpradub, Sudaluck Thunyaharn, Piraporn Juntanawiwat, Parnrada Nulsopapon, Wichai Santimaleeworagun
Abstract
BACKGROUND: (CRAB). Thus, the small number of effective antibiotic options against CRAB represents a challenge to human health. This study examined the appropriate dosage regimens of colistin alone or in combination with sulbactam or fosfomycin using Monte Carlo simulation with the aims of improving efficacy and reducing the risk of nephrotoxicity. MATERIALS AND METHODS: Clinical CRAB isolates were obtained from patients admitted to Phramongkutklao Hospital in 2014 and 2015. The minimum inhibitory concentration (MIC) of colistin for each CRAB isolate was determined using the broth dilution method, whereas those of sulbactam and fosfomycin were determined using the agar dilution method. Each drug regimen was simulated using the Monte Carlo technique to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR). Nephrotoxicity based on RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria was indicated by colistin trough concentration exceeding ≥3.3 μg/mL. RESULTS: isolates. CONCLUSION: Colistin monotherapy at the maximum recommended dose might not cover some CRAB isolates. Colistin combination therapy appears appropriate for achieving the pharmacokinetic/pharmacodynamic targets of CRAB treatment.