Efficacy and safety of colistimethate sodium in critical patients: anin vitro study by using of Monte Carlo simulation / 中华危重病急救医学

ABSTRACT

Objective To evaluate the efficacy and safety of colistimethate sodium (CMS) for the treatment of critical patients infected by pan-drug resistantAcinetobacter baumannii (PDR-AB) or pan-drug resistant Pseudomonas aeruginosa (PDR-PA).Methods 321 isolates of PDR-AB and 204 isolates of PDR-PA from critical patients admitted to 35 intensive care units (ICUs) of grade two or above were collected from the Anhui Antimicrobial Resistance Investigation Net (AHARIN) program from September 2012 to September 2015, while the minimal inhibitory concentrations (MIC) of colistin were determined by the E-test. A series of Monte Carlo simulations was performed for CMS regimens (1 MU q8h, 2 MU q8h, and 3 MU q8h, and MU meant a million of unit), and the probability of achieving a 24-hour area under the drug concentration time curve (AUC24)/MIC ratio > 60 and risk of nephrotoxicity for each dosing regimen was calculated. Each simulation was run over three CLCr ranges 32.51%). Moreover, low value of PTA ( 89.24%) even in patients with CLCr ≥ 90-120 mL/min, and PTA was 33.68%).Conclusion Measurement of MIC, individualized CMS therapy and therapeutic drug-level monitoring should be considered to achieve the optimal drug exposure and ensure the safety of CMS.