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Molecular characterization of carbapenem-resistant Enterobacteriaceae and emergence of tigecycline non-susceptible strains in the Henan province in China: a multicentrer study.

ABSTRACT: Introduction. Carbapenem-resistant Enterobacteriaceae (CRE) have been responsible for nosocomial outbreaks worldwide and have become endemic in several countries.Hypothesis/Gap Statement. To better understand the epidemiological trends and characteristics of CRE in the Henan province.Aim. We assessed the molecular epidemiological characteristics of 305 CRE strains isolated from patients in 19 secondary or tertiary hospitals in ten areas of the Henan province in China.Methodology. A total of 305 CRE isolates were subjected to multiple tests, including in vitro antimicrobial susceptibility testing, PCR for carbapenemase genes bla _KPC, bla _NDM, bla _IMP, bla _VIM, bla _OXA-_48-like. Tigecycline-resistant genes ramR, oqxR, acrR, tetA, rpsJ, tetX, tetM, tetL were analysed in five tigecycline non-susceptible carbapenem-resistant Klebsiella pneumoniae isolates (TNSCRKP). Additionally, multilocus sequence typing (MLST) was performed for carbapenem-resistant K. pneumoniae (CRKP).Results. The most common CRE species were K. pneumoniae (234, 77 %), Escherichia coli (36, 12 %) and Enterobacter cloacae (13, 4 %). All strains exhibited multi-drug resistance. Overall, 97 % (295/305) and 97 % (297/305) of the isolates were susceptible to polymyxin B and tigecycline, respectively. A total of 89 % (271/305) of the CRE isolates were carbapenemase gene-positive, including 70 % bla _KPC, 13 % bla _NDM, 6 % bla _IMP, and 1 % combined bla _KPC/bla _NDM genes. K. pneumoniae carbapenemase (KPC) was the predominant carbapenemase in K. pneumoniae (87 %), whereas NDM and IMP were frequent in E. coli (53 %) and E. cloacae (69 %), respectively. Mutations in the ramR, tetA, and rpsJ genes were detected in five TNSCRKP. Moreover, 15 unique sequence types were detected, with ST11 (74 %), ST15 (9 %) and ST2237 (5 %) being dominant among K. pneumoniae strains.Conclusion. A high proportion of CRE strains were carbapenemase-positive, and five carbapenem-resistant K. pneumonia isolates were tigecycline non-susceptible, indicating a need for the ongoing surveillance of CRE and effective measures for the prevention of CRE infections.

SUBMITTER: Yan WJ

PROVIDER: S-EPMC8346725 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Carbapenem-resistant Klebsiella pneumoniae (CRKP) has disseminated globally and is difficult to treat, causing increased morbidity and mortality rates in critically ill patients. We conducted a multicenter cross-sectional study of intensive care unit (ICU) inpatients in 78 hospitals to investigate the prevalence and molecular characteristics of CRKP in Henan Province, China, a hyperepidemic region. A total of 327 isolates were collected and downsampled to 189 for whole-genome sequencing. Molecular typing revealed that sequence type 11 (ST11) of clonal group 258 (CG258) was predominant (88.9%, n = 168), followed by ST2237 (5.8%, n = 11) and ST15 (2.6%, n = 5). We used core genome multilocus sequence typing (cgMLST) to further classified the population into 13 subtypes. Capsule polysaccharide (K-antigen) and lipopolysaccharide (LPS; O-antigen) typing revealed that K64 (48.1%, n = 91) and O2a (49.2%, n = 93) were the most common. We studied isolates collected from both the airway and the gut of the same patients and showed that intestinal carriage was associated with respiratory colonization (odds ratio = 10.80, P < 0.0001). Most isolates (95.2%, n = 180) showed multiple drug resistance (MDR), while 59.8% (n = 113) exhibited extensive drug resistance (XDR), and all isolates harbored either blaKPC-2 (98.9%, n = 187) or blaCTX-M and blaSHV extended-spectrum beta-lactamases (ESBLs) (75.7%, n = 143). However, most were susceptible to ceftazidime-avibactam (CZA) (94.7%, n = 179) and colistin (97.9%, n = 185). We found mgrB truncations in isolates conferring resistance to colistin and mutations in blaSHV and OmpK35 and OmpK36 osmoporins in CZA-resistant isolates. Using a regularized regression model, we found that the aerobactin sequence type and the salmochelin sequence type, among others, were predictors of the hypermucoviscosity phenotype. IMPORTANCE In this study, we address the ongoing epidemic of carbapenem-resistant Klebsiella pneumoniae, a critical threat to public health. The alarming genotypic and phenotypic convergence of multidrug resistance and virulence highlights the increasingly aggravated threat posed by K. pneumoniae. This calls for a combined effort of physicians and scientists to study the potential mechanisms and establish guidelines for antimicrobial therapies and interventions. To this end, we have conducted a genomic epidemiology and characterization study using isolates collected in a coordinated effort of multiple hospitals. Innovative biological discoveries of clinical importance are made and brought to the attention of clinical researchers and practitioners. This study presents an important advance in the application of genomics and statistics to recognize, understand, and control an infectious disease of concern.

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Molecular characterization of carbapenem-resistant Enterobacteriaceae and emergence of tigecycline non-susceptible strains in the Henan province in China: a multicentrer study.

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