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在接受抗假单胞菌治疗的医院获得性肺炎重症监护病房患者下呼吸道分离的铜绿假单胞菌菌株中,抗菌药物耐药性的体内发展。

In vivo development of antimicrobial resistance in Pseudomonas aeruginosa strains isolated from the lower respiratory tract of Intensive Care Unit patients with nosocomial pneumonia and receiving antipseudomonal therapy.

机构信息

Unité de Pharmacologie Cellulaire et Moléculaire & Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.

出版信息

Int J Antimicrob Agents. 2010 Dec;36(6):513-22. doi: 10.1016/j.ijantimicag.2010.08.005.

DOI:10.1016/j.ijantimicag.2010.08.005
PMID:20926262
Abstract

Pseudomonas aeruginosa causes severe nosocomial pneumonia in Intensive Care Unit (ICU) patients, with an increased prevalence of multiresistant strains. We examined the impact of the use of antipseudomonal antibiotic(s) on the susceptibility of P. aeruginosa isolated from ICU patients with clinically suspected hospital-acquired pneumonia collected in five teaching hospitals (110 non-duplicate initial isolates; 62 clonal pairs of initial and last isolates during treatment). Minimum inhibitory concentrations (MICs) were determined for amikacin, ciprofloxacin, meropenem, piperacillin/tazobactam (TZP), cefepime and ceftazidime (used in therapy) as well as five reporter antibiotics (aztreonam, colistin, gentamicin, piperacillin and ticarcillin) using Clinical and Laboratory Standards Institute (CLSI) methodology. Susceptibility was assessed according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) and CLSI breakpoints. Resistance rates prior to treatment exceeded 25% for cefepime, ceftazidime, piperacillin, ticarcillin and aztreonam (EUCAST and CLSI) and for gentamicin, TZP and colistin (EUCAST only). The highest rates of cross-resistance were noted for ceftazidime and cefepime and the lowest rate for amikacin. Mean MIC values were systematically higher in isolates from patients previously exposed (1 month) to the corresponding antibiotic. For clonal pairs, a systematic increase in MIC between initial and last isolates (significant for amikacin, cefepime, meropenem and TZP) was noted. There was a significant correlation between the use of antibiotics (adjusted for respective proportional use of each drug) and loss of susceptibility at the population level when using EUCAST breakpoints. The high level of resistance of P. aeruginosa in ICU patients with nosocomial pneumonia as well as its further increase during treatment severely narrows the already limited therapeutic options. Further observational studies and the development of early diagnosis for resistant isolates are warranted.

摘要

铜绿假单胞菌会引起重症监护病房(ICU)患者严重的医院获得性肺炎,而且多耐药菌株的流行率增加。我们研究了使用抗假单胞菌抗生素对在五所教学医院收集的临床疑似医院获得性肺炎的 ICU 患者分离的铜绿假单胞菌的敏感性的影响(110 例非重复初始分离株;62 例治疗期间初始和最后分离株的克隆对)。使用临床和实验室标准协会(CLSI)方法测定阿米卡星、环丙沙星、美罗培南、哌拉西林/他唑巴坦(TZP)、头孢吡肟和头孢他啶(用于治疗)以及 5 种报告抗生素(氨曲南、多粘菌素、庆大霉素、哌拉西林和替卡西林)的最小抑菌浓度(MIC)。根据欧洲抗菌药物敏感性试验委员会(EUCAST)和 CLSI 折点评估敏感性。治疗前,头孢吡肟、头孢他啶、哌拉西林、替卡西林和氨曲南(EUCAST 和 CLSI)以及庆大霉素、TZP 和多粘菌素(仅 EUCAST)的耐药率超过 25%。头孢他啶和头孢吡肟的交叉耐药率最高,阿米卡星的耐药率最低。先前(1 个月)暴露于相应抗生素的患者分离株的平均 MIC 值系统升高。对于克隆对,在初始和最后分离株之间观察到 MIC 系统增加(阿米卡星、头孢吡肟、美罗培南和 TZP 有统计学意义)。使用 EUCAST 折点时,抗生素的使用(按每种药物的相应比例调整)与群体水平的敏感性丧失之间存在显著相关性。ICU 医院获得性肺炎患者的铜绿假单胞菌耐药率较高,且在治疗过程中进一步增加,严重限制了本已有限的治疗选择。需要进一步的观察性研究和耐药分离株的早期诊断。

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