The purpose was to explore the optimal dosage regimen of colistin using Monte Carlo\nsimulations, for the treatment of carbapenem-resistant Klebsiella pneumoniae and carbapenem-resistant\nEscherichia coli based on PK/PD targets in critically ill patients. A total of 116 carbapenem-resistant\nK. pneumoniae and E. coli were obtained from various clinical specimens at Siriraj Hospital in\nBangkok, Thailand. Minimum inhibitory concentrations (MICs) of colistin were determined by\nbroth microdilution method. Monte Carlo simulation was used to calculate the cumulative fraction\nof response (CFR) for European Medicine Agency (EMA), US-Food and Drug Administration\n(FDA), Nation et al., Siriraj Hospital and our study regimens. The targeted CFR was 90%.\nFor colistin-susceptible K. pneumoniae, all of the dosage regimens achieved greater than equal to90% CFR in patients with\ncreatinine clearance <80 mL/min except the FDA-approved regimens for patients with creatinine\nclearance 51-79 and 11-29mL/min, respectively. While, patients with creatinine clearance greater than equal to80mL/min,\nCFR greater than equal to90% was observed in Siriraj Hospital and our study regimen. For colistin-susceptible E. coli,\nall of the dosage regimens achieved greater than equal to90% CFR regardless of renal function. In contrast, the currently\napproved regimens achieved CFR target in only 10-50% for colistin-resistant isolates subgroup. These\nresults suggest that currently approved regimens still recommended for colistin-susceptible CRE.\nFor colistin-resistant CRE, alternative approaches such as high dose or combination therapy should\nbe considered.
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