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慢性肺部感染中耐碳青霉烯类铜绿假单胞菌:囊性纤维化患者的当前耐药情况及高突变性

Carbapenem-Resistant Pseudomonas aeruginosa in Chronic Lung Infection: Current Resistance Profile and Hypermutability in Patients with Cystic Fibrosis.

作者信息

Almeida Mila M, Freitas Meyvianne T, Folescu Tania W, Firmida Monica C, Carvalho-Assef Ana Paula D'A, Marques Elizabeth A, Leão Robson S

机构信息

Departamento de Microbiologia, Imunologia e Parasitologia, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.

Instituto Nacional de Saúde da Mulher, Criança e do Adolescente Fernandes Figueira, Centro de Referência para Crianças e Adolescentes com Fibrose Cística - Ministério da Saúde, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.

出版信息

Curr Microbiol. 2021 Feb;78(2):696-704. doi: 10.1007/s00284-020-02337-0. Epub 2021 Jan 6.

Abstract

Pseudomonas aeruginosa is associated with chronic and progressive lung disease and is closely related to increased morbidity and mortality in cystic fibrosis (CF) patients. Hypermutable (HPM) P. aeruginosa isolates have been described in these patients and are usually associated with antibiotic resistance. This study aimed to investigate the occurrence of carbapenem resistance and hypermutable phenotype in 179 P. aeruginosa isolates from 8 chronically CF patients assisted at two reference centers in Rio de Janeiro, Brazil. Using disk diffusion test, non-susceptible (NS) rates higher than 40% were observed for imipenem, amikacin, and gentamicin. A total of 79 isolates (44.1%), 71 (39.6%), and 8 (4.4%) were classified as carbapenem-resistant (CR resistance to at least one carbapenem), multidrug-resistant (MDR), and extensively drug-resistant (XDR), respectively. Minimal inhibitory concentration was determined for 79 CR P. aeruginosa and showed the following variations: 4 and 128 μg/mL to imipenem, 4 and 64 µg/mL to meropenem, and 4 and ≥ 32 µg/mL to doripenem. We have found only four (2.23%) HPM isolates from 4 patients. Analyzing the genetic relationship among the HPM isolates, 3 pulsed-field gel electrophoresis/pulsotypes (D, M, and J) were observed. Only M pulsotype was recovered from two patients in different years. Polymerase chain reaction screening for bla, bla, bla, bla, bla, bla, and bla genes was performed for all CR isolates and none of them were positive. Our results demonstrate a high occurrence of CR and MDR P. aeruginosa of CF patients follow-up in both centers studied, while the presence of HPM is still unusual.

摘要

铜绿假单胞菌与慢性进行性肺部疾病相关,并且与囊性纤维化(CF)患者的发病率和死亡率增加密切相关。在这些患者中已发现高突变(HPM)铜绿假单胞菌分离株,通常与抗生素耐药性有关。本研究旨在调查从巴西里约热内卢两个参考中心接受治疗的8例慢性CF患者的179株铜绿假单胞菌分离株中碳青霉烯耐药性和高突变表型的发生情况。使用纸片扩散法检测,亚胺培南、阿米卡星和庆大霉素的非敏感(NS)率高于40%。共有79株(44.1%)、71株(39.6%)和8株(4.4%)分别被分类为耐碳青霉烯(CR,对至少一种碳青霉烯耐药)、多重耐药(MDR)和广泛耐药(XDR)。对79株CR铜绿假单胞菌测定了最低抑菌浓度,结果显示以下变化:亚胺培南为4至128μg/mL,美罗培南为4至64μg/mL,多利培南为4至≥32μg/mL。我们仅从4例患者中发现了4株(2.23%)HPM分离株。分析HPM分离株之间的遗传关系,观察到3种脉冲场凝胶电泳/脉冲型(D、M和J)。仅在不同年份的两名患者中发现了M脉冲型。对所有CR分离株进行了bla、bla、bla、bla、bla、bla和bla基因的聚合酶链反应筛查,结果均为阴性。我们的结果表明,在两个研究中心随访的CF患者中,CR和MDR铜绿假单胞菌的发生率很高,而HPM的存在仍然不常见。

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