Nulsopapon Parnrada, Pongchaidecha Manat, Nasomsong Worapong, Polwichai Pitimon, Suphankong Sirilada, Sirichote Pantip, Chaisomboonpan Siriwan, Santimaleeworagun Wichai
Department of Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.
Pharmaceutical Initiative for Resistant Bacteria and Infectious Diseases Working Group [PIRBIG], Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.
Antibiotics (Basel). 2022 Mar 7;11(3):355. doi: 10.3390/antibiotics11030355.
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.
耐碳青霉烯类肠杆菌科细菌(CRE)的传播构成了全球健康负担。抗菌药物敏感性和碳青霉烯酶类型因地理区域而异。本研究旨在:(1)检测最低抑菌浓度(MIC)和抗生素耐药基因;(2)使用蒙特卡洛模拟研究针对CRE的抗生素给药方案。从泰国西部的多家医院收集临床耐碳青霉烯肺炎克雷伯菌(CRKP)、大肠埃希菌(CREC)和阴沟肠杆菌(CREclo)分离株。进行肉汤微量稀释,并使用聚合酶链反应(PCR)检测碳青霉烯酶和mcr-1基因的类型。使用蒙特卡洛模拟确定符合累积反应分数(CFR)>90%标准的最佳抗菌给药方案。共纳入来自12家医院的150株CRE分离株。CRKP的比例(76%)高于CREC(22%)和CREclo(2%)。地区医院报告的耐药率高于综合医院。大多数分离株对氨曲南和头孢他啶/阿维巴坦耐药,而对氨基糖苷类高度敏感。大多数碳青霉烯酶为NDM(47.33%)、OXA-48(43.33%)和NDM加OXA-48(6.67%);5株OXA-48阳性分离株携带mcr-1基因。目前,高剂量替加环素是针对CRE分离株的唯一最佳方案。应进一步开展关于抗生素协同作用或新抗生素的广泛研究。
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