Abstract

The spread of carbapenem-resistant Enterobacterales (CRE) constitutes a global health burden. Antimicrobial susceptibility and types of carbapenemase differ by geographic region. This study aimed to (1) examine the minimum inhibitory concentrations (MICs) and antibiotic resistance genes and (2) investigate antibiotic dosing regimens against CRE using Monte Carlo simulation. Clinical carbapenem-resistant Klebsiella pneumoniae (CRKP), Escherichia coli (CREC), and Enterobacter cloacae (CREclo) isolates were collected from various hospitals in western Thailand. Broth microdilution was performed, and the types of carbapenemase and mcr-1 genes were detected using polymerase chain reaction (PCR). Monte Carlo simulation was used to establish optimal antimicrobial dosing regimens meeting the criterion of a cumulative fraction of response (CFR) >90%. A total of 150 CRE isolates from 12 hospitals were included. The proportion of CRKP (76%) was greater than that of CREC (22%) and CREclo (2%). Regional hospitals reported higher rates of resistance than general hospitals. Most isolates were resistant to aztreonam and ceftazidime/avibactam, whereas they were highly susceptible to aminoglycosides. Most carbapenemases were NDM (47.33%), OXA-48 (43.33%) and NDM plus OXA-48 (6.67%); five OXA-48 positive isolates carried mcr-1 genes. Currently, high-dose tigecycline is the only optimal regimen against CRE isolates. Further extensive research on antibiotic synergism or new antibiotics should be conducted.

Highlights

  • Introduction published maps and institutional affilThe development of antibiotic resistance is rapidly changing and represents a serious global health challenge

  • Bartsch et al estimated the economic burden from Carbapenem-resistant Enterobacterales (CRE) epidemiology and reported an increase in incidence from 2.93 to 15 per 100,000, and medical costs increased from USD 275 to 1406 million [4]

  • A total of 150 nonduplicated clinical CRE isolates from various specimens were collected from 12 hospitals: 4 regional hospitals and 8 general hospitals (5 hospitals at level S and 3 hospitals at level M1)

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Summary

Introduction

The development of antibiotic resistance is rapidly changing and represents a serious global health challenge. Carbapenem-resistant Enterobacterales (CRE), especially carbapenemresistant Klebsiella pneumoniae (CRKP), Escherichia coli (CREC) and Enterobacter cloacae (CREclo), represent critical Gram-negative bacteria with resistance to carbapenems and multiple antibiotics. Invasive CRE infections have been associated with mortality rates of 40 to. The risk of death among patients infected with CRE is 3 fold higher than among patients infected with carbapenem-susceptible Enterobacterales [3]. Bartsch et al estimated the economic burden from CRE epidemiology and reported an increase in incidence from 2.93 to 15 per 100,000, and medical costs increased from USD 275 to 1406 million [4]. In Thailand, an increase has been observed in the burden of CRE. The prevalence of CRE identified from clinical isolates of Enterobacterales rose from 1.1 to 13.2% from 2010 to 2020 [5].

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