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欧洲重症监护病房中肺炎克雷伯菌属的抗生素耐药性及超广谱β-内酰胺酶的产生

Antibiotic resistance and production of extended-spectrum beta-lactamases amongst Klebsiella spp. from intensive care units in Europe.

作者信息

Livermore D M, Yuan M

机构信息

Department of Medical Microbiology, London Hospital Medical College, UK.

出版信息

J Antimicrob Chemother. 1996 Sep;38(3):409-24. doi: 10.1093/jac/38.3.409.

Abstract

Consecutive klebsiellae were collected from ICU patients at 35 centres in Western and Southern Europe. Of 966 isolates obtained, 716 were Klebsiella pneumoniae, 248 were Klebsiella oxytoca and two were Klebsiella ozaenae. Most were from Belgium, France, Germany, Holland, Italy, Portugal, Spain, Turkey and a few from Greece and the UK. Production of extended-spectrum beta-lactamases (ESBLs) was inferred in 220 isolates on the basis of synergy between ceftazidime and clavulanate. Putative ESBL producers were received from 23 centres, including 20 of the 27 that contributed more than 10 klebsiellae. Over 88% of putative ESBL producers were resistant to ceftazidime 2 mg/L, ceftriaxone 1 mg/L and aztreonam 1 mg/L, whereas, amongst ESBL-negative isolates, more than 98% of K. pneumoniae and 87% of K. oxytoca were susceptible to these concentrations. Putative ESBL producers wre also more resistant to cefuroxime and cefoxitin than non-producers, but not to biapenem. MIC distributions of ciprofloxacin, piperacillin/tazobactam and aminoglycosides were bimodal for ESBL producers, with some isolates highly sensitive and others very resistant. For example, 70% of putative ESBL producers were susceptible to piperacillin/tazobactam 16 + 4 mg/L, but 30% were resistant, some highly so. Resistance to this combination, and to ciprofloxacin, was clustered in certain centres. Two other groups of cephalosporin-resistant isolates were identified besides ESBL producers, viz. (i) nine isolates, from three centres, with AmpC beta-lactamases and (ii) 20 K. oxytoca, from 15 centres, that hyperproduced K1 enzyme. Examination of the hospitals' own susceptibility data indicated that up to 33% of putative ESBL producers had been reported susceptible to third-generation cephalosporins or monobactams. This is disturbing, since ESBLs have been associated with clinical failure even when only low-level resistance was apparent in vitro.

摘要

在西欧和南欧的35个中心,从重症监护病房(ICU)患者中收集了一系列克雷伯菌。在获得的966株分离菌中,716株为肺炎克雷伯菌,248株为产酸克雷伯菌,2株为鼻硬结克雷伯菌。大多数分离菌来自比利时、法国、德国、荷兰、意大利、葡萄牙、西班牙、土耳其,少数来自希腊和英国。根据头孢他啶和克拉维酸之间的协同作用,推断220株分离菌产生超广谱β-内酰胺酶(ESBLs)。推测的ESBL产生菌来自23个中心,包括提供了10株以上克雷伯菌的27个中心中的20个。超过88%的推测ESBL产生菌对2mg/L的头孢他啶、1mg/L的头孢曲松和1mg/L的氨曲南耐药,而在ESBL阴性分离菌中,超过98%的肺炎克雷伯菌和87%的产酸克雷伯菌对这些浓度敏感。推测的ESBL产生菌对头孢呋辛和头孢西丁的耐药性也高于非产生菌,但对比阿培南不耐药。对于ESBL产生菌,环丙沙星、哌拉西林/他唑巴坦和氨基糖苷类的最低抑菌浓度(MIC)分布呈双峰,一些分离菌高度敏感,另一些则耐药性很强。例如,70%的推测ESBL产生菌对16+4mg/L的哌拉西林/他唑巴坦敏感,但30%耐药,有些耐药性很强。对这种联合用药以及环丙沙星的耐药性在某些中心聚集。除了ESBL产生菌外,还鉴定出另外两组耐头孢菌素的分离菌,即:(i)来自三个中心的9株携带AmpCβ-内酰胺酶的分离菌,以及(ii)来自15个中心的20株产酸克雷伯菌,这些菌株过量产生K1酶。对医院自身药敏数据的检查表明,高达33%的推测ESBL产生菌曾被报告对第三代头孢菌素或单环β-内酰胺类药物敏感。这令人不安,因为即使在体外仅表现出低水平耐药时,ESBLs也与临床治疗失败有关。

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