Carbapenem-resistant hypermucoviscous Klebsiella pneumoniae clinical isolates from a tertiary hospital in China: Antimicrobial susceptibility, resistance phenotype, epidemiological characteristics, microbial virulence, and risk factors

Abstract

Hypervirulent and multidrug-resistant <i>Klebsiella pneumoniae</i> poses a significant threat to public health. We aimed to determine the common carbapenemase genotypes and the carriage patterns, main antibiotic resistance mechanisms, and <i>in vitro</i> susceptibility of clinical isolates of carbapenem-resistant <i>K. pneumoniae</i> (CRKP) to ceftazidime/avibactam (CZA) for the reasonable selection of antimicrobial agents and determine whether hypermucoviscous (HMV) phenotype and virulence-associated genes are key factors for CRKP colonization and persistence. Antibiotics susceptibility of clinical CRKP isolates and carbapenemase types were detected. CRKP isolates were identified as hypermucoviscous <i>K. pneumoniae</i> (HMKP) using the string test, and detection of virulence gene was performed using capsular serotyping. The <i>bla</i> _KPC-2, <i>bla</i> _NDM, <i>bla</i> _IMP, and/or <i>bla</i> _OXA-48-like were detected in 96.4% (402/417) of the isolates, and the <i>bla</i> _KPC-2 (64.7%, 260/402) was significantly higher (<i>P</i><0.05) than those of <i>bla</i> _NDM (25.1%), <i>bla</i> _OXA-48-like (10.4%), and <i>bla</i> _IMP (4.2%). Carriage of a single carbapenemase gene was observed in 96.3% of the isolates, making it the dominant antibiotic resistance genotype carriage pattern (<i>P</i> < 0.05). Approximately 3.7% of the isolates carried two or more carbapenemase genotypes, with <i>bla</i> _KPC-2 + <i>bla</i> _NDM and <i>bla</i> _NDM + <i>bla</i> _IMP being the dominant multiple antibiotic resistance genotype. In addition, 43 CRKP isolates were identified as HMKP, with a prevalence of 10.3% and 2.7% among CRKP and all <i>K. pneumoniae</i> isolates, respectively. Most clinical CRKP isolates were isolated from elderly patients, and carbapenemase production was the main mechanism of drug resistance. Tigecycline and polymyxin B exhibited exceptional antimicrobial activity against CRKP isolates <i>in vitro</i>. Furthermore, <i>bla</i> _KPC-2, <i>bla</i> _NDM, and <i>bla</i> _OXA-48-like were the main carbapenemase genes carried by the CRKP isolates. CZA demonstrated excellent antimicrobial activity against isolates carrying the single <i>bla</i> _KPC-2 or <i>bla</i> _OXA-48-like genotype. Capsular serotype K2 was the main capsular serotype of the carbapenem-resistant HMKP isolates. Survival rates of <i>Galleria mellonella</i> injected with <i>K. pneumoniae</i> 1-7 were 20.0, 16.7, 6.7, 23.3, 16.7, 3.3, and 13.3, respectively. Therefore, worldwide surveillance of these novel CRKP isolates and carbapenem-resistant HMKP isolates as well as the implementation of stricter control measures are needed to prevent further dissemination in hospital settings.