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多重耐药肺炎克雷伯菌:巴西一家三级教学医院中的遗传多样性、对多粘菌素的耐药机制及临床结局

Multidrug-resistant Klebsiella pneumoniae: genetic diversity, mechanisms of resistance to polymyxins and clinical outcomes in a tertiary teaching hospital in Brazil.

作者信息

Boszczowski Icaro, Salomão Matias Chiarastelli, Moura Maria Luísa, Freire Maristela Pinheiro, Guimarães Thais, Cury Ana Paula, Rossi Flávia, Rizek Camila Fonseca, Martins Roberta Cristina Ruedas, Costa Silvia Figueiredo

机构信息

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Subcomissão de Controle de Infecção Hospitalar, São Paulo, São Paulo, Brazil.

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Divisão de Laboratório Clínico, São Paulo, São Paulo, Brazil.

出版信息

Rev Inst Med Trop Sao Paulo. 2019 Jun 19;61:e29. doi: 10.1590/S1678-9946201961029.

DOI:10.1590/S1678-9946201961029
PMID:31241658
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6592011/
Abstract

Increased resistance to polymyxin in Klebsiella pneumoniae (ColRKP) has been observed. Molecular epidemiology, as well as the clinical impact of these difficult to treat pathogens need to be better characterized. We present the clinical outcomes of 28 patients infected by ColRKP in a tertiary hospital. Isolates with MIC >2 by Vitek 2 were confirmed by the microdilution broth test. Polymerase chain reaction (PCR) was performed for blaKPC, blaNDM, blaOXA-48 and blamcr-1 genes in the isolates, and Whole Genome Sequencing (WGS) was performed in six isolates. Seventeen (61%) patients were female and the mean age was 50 years old. In-hospital and 30-day mortality were 64% (18/28) and 53% (15/28), respectively. Central line-associated bloodstream infection in addition to bacteremia episodes due to other sources were the most frequent (61%). Mean APACHE and Charlson comorbidity index were 16 and 5, respectively. Twenty patients (71%) received at least one active drug and ten (35%) received two drugs: tigecycline 46% (13/28); amikacin 21% (6/28) and fosfomycin 3% (1 case). Twenty-six out of 28 tested cases were positive for blaKPC. Eight different clusters were identified. Four STs were detected (ST11, ST23, ST340, and ST437). Mutations on pmrA, arnB, udg, and yciM genes were present in all six isolates submitted to WGS; lpxMand mgrB mutations were also detected in all but one isolate. In conclusion, we observed resistance to polymyxin in severely ill patients mostly from intensive care units and/or immunosuppressed patients with high mortality rates in whom a diversity of ColRKP clusters was identified and might indicate selective pressure.

摘要

已观察到肺炎克雷伯菌对多粘菌素的耐药性增加(ColRKP)。这些难以治疗的病原体的分子流行病学以及临床影响需要得到更好的描述。我们展示了一家三级医院中28例感染ColRKP患者的临床结局。通过Vitek 2检测MIC>2的分离株通过微量肉汤稀释试验进行确认。对分离株中的blaKPC、blaNDM、blaOXA - 48和blamcr - 1基因进行聚合酶链反应(PCR),并对6株分离株进行全基因组测序(WGS)。17名(61%)患者为女性,平均年龄为50岁。住院死亡率和30天死亡率分别为64%(18/28)和53%(15/28)。除了其他来源引起的菌血症发作外,中心静脉导管相关血流感染最为常见(61%)。平均急性生理学与慢性健康状况评分系统(APACHE)和查尔森合并症指数分别为16和5。20名(71%)患者接受了至少一种活性药物治疗,10名(35%)患者接受了两种药物治疗:替加环素46%(13/28);阿米卡星21%(6/28),磷霉素3%(1例)。28例检测病例中有2​​6例blaKPC呈阳性。鉴定出8个不同的簇。检测到4种序列类型(ST11、ST23、ST340和ST437)。在所有6株进行WGS的分离株中均存在pmrA、arnB、udg和yciM基因的突变;除1株分离株外,在所有分离株中也检测到lpxM和mgrB突变。总之,我们在主要来自重症监护病房的重症患者和/或死亡率高的免疫抑制患者中观察到对多粘菌素的耐药性,其中鉴定出多种ColRKP簇,这可能表明存在选择性压力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6016/6592011/a409f1dc04a4/1678-9946-rimtsp-61-S1678-9946201961029-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6016/6592011/a409f1dc04a4/1678-9946-rimtsp-61-S1678-9946201961029-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6016/6592011/a409f1dc04a4/1678-9946-rimtsp-61-S1678-9946201961029-gf01.jpg

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