Chaves Lucas, Tomich Lísia Moura, Salomão Matias, Leite Gleice Cristina, Ramos Jessica, Martins Roberta Ruedas, Rizek Camila, Neves Patricia, Batista Marjorie Vieira, Amigo Ulysses, Guimaraes Thais, Levin Anna Sara, Costa Silvia Figueiredo
Department of Infectious Diseases, School of Medicine, University of São Paulo, São Paulo, Brazil.
Laboratory of Bacteriology-LIM54, Hospital das Clínicas, Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil.
J Med Microbiol. 2017 Dec;66(12):1722-1729. doi: 10.1099/jmm.0.000631. Epub 2017 Nov 2.
Carbapenem resistance in P. aeruginosa is increasing worldwide. In Brazil, SPM-1 is the main P. aeruginosa carbapenemase identified. Little is known about the virulence factor in SPM-1 clones.Methodolgy. We describe a carbapenem-resistant P. aeruginosa bloodstream infection (CRPa-BSI) outbreak in a bone marrow transplant Unit (BMT). Twenty-nine CRPa-BSI cases were compared to 58 controls. Microbiological characteristics of isolates, such as sensitivity, carbapenemase gene PCR for P. aeruginosa, and PFGE are described, as well as the whole-genome sequence (WGS) of three strains.Results/Key findings. The cultures from environmental and healthcare workers were negative. Some isolates harboured KPC and SPM. The WGS showed that the 03 strains belonged to ST277, presented the same mutations in outer membrane protein, efflux pump, and virulence genes such as those involved in adhesion, biofilm, quorum-sensing and the type III secretion system, but differ regarding the carbapenemase profile. A predominant clone-producing SPM harbouring Tn 4371 was identified and showed cross-transmission; no common source was found. Overall mortality rate among cases was 79 %. The first multivariate analysis model showed that neutropenia (P=0.018), GVHD prophylaxis (P=0.016) and prior use of carbapenems (P=0.0089) were associated with CRPa-BSI. However, when MASCC>21 points and platelets were added in the final multivariate analysis, only prior use of carbapenems remained as an independent risk factor for CRPa-BSI (P=0.043).
The predominant clone belonging to ST277 showed high mortality. Carbapenem use was the only risk factor associated with CRPa-BSI. This finding is a wake-up call for the need to improve management in BMT units.
全球范围内，铜绿假单胞菌对碳青霉烯类抗生素的耐药性正在增加。在巴西，SPM-1是鉴定出的主要铜绿假单胞菌碳青霉烯酶。关于SPM-1克隆中的毒力因子知之甚少。方法。我们描述了在一家骨髓移植病房（BMT）发生的耐碳青霉烯类铜绿假单胞菌血流感染（CRPa-BSI）暴发。将29例CRPa-BSI病例与58例对照进行比较。描述了分离株的微生物学特征，如敏感性、铜绿假单胞菌碳青霉烯酶基因PCR和脉冲场凝胶电泳（PFGE），以及三株菌株的全基因组序列（WGS）。结果/主要发现。环境和医护人员的培养物均为阴性。一些分离株携带KPC和SPM。WGS显示，这三株菌株属于ST277，在外膜蛋白、外排泵以及毒力基因（如参与黏附、生物膜形成、群体感应和III型分泌系统的基因）中存在相同的突变，但在碳青霉烯酶谱方面存在差异。鉴定出一个携带Tn4371的产生SPM的优势克隆，并显示出交叉传播；未发现共同来源。病例的总体死亡率为79%。第一个多变量分析模型显示，中性粒细胞减少（P=0.018）、移植物抗宿主病预防（P=0.016）和先前使用碳青霉烯类抗生素（P=
