Abstract
The carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) poses a severe therapeutic challenge to global public health, and research on CR-hvKP in older patients remain limited. In this study, we aimed to investigate the clinical and molecular characteristics and risk factors of CR-hvKP infections in older patients. We retrospectively investigated older patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in the intensive care unit (ICU) between January 2020 and December 2020. The clinical data, and microbiological data including antimicrobial susceptibility testing, phenotype experiment and detection of carbapenemases, string test, virulence genes, capsular serotype-specific (cps) genes, and multilocus sequence typing, of the CR-hvKP group defined by the presence of any one of the virulence genes, including rmpA, rmpA2, iucA, iroN, and peg-344 were compared with those of CR-non-hvKP strains. Of the 80 CRKP strains, 51 (63.8%) met the definition of CR-hvKP. The main mechanism of resistance to carbapenems was the presence of the blaKPC−2 gene. Sequence type (ST)11 (81.3%, 65/80) and ST15 (16.3%, 13/80) were the most common STs in CRKP strains. The minimum inhibitory concentration (MIC)50 values of the CR-hvKP group against the six tested antibiotics (ceftazidime, ceftazidime-avibactam, imipenem-avibactam, tigecycline, levofloxacin, and Cefoperazone-Sulbactam) exhibited elevated levels than the CR-non-hvKP group. Ceftazidime and imipenem by combining avibactam (4 μg/mL) significantly decreased the MIC90 values more than 16-fold than ceftazidime and imipenem alone against Klebsiella pneumoniae carbapenemase (KPC)-2-producing K. pneumoniae. Cardiovascular disease [odds ratio (OR) = 11.956] and ST11-K64 (OR = 8.385) appeared to be independent variables associated with CR-hvKP infection by multivariate analysis. In conclusion, higher MICs of the last line antibiotic agents (ceftazidime-avibactam, tigecycline) might be a critical consideration in the clinical management of older patients where the concentration of these toxic antibiotics matters because of underlying comorbidities. Caution regarding KPC-2-producing ST11-K64 CR-hvKP as being new significant “superbugs” is required as they are widespread, and infection control measures should be strengthened to curb further dissemination in nosocomial settings in China.
Highlights
Klebsiella pneumoniae (K. pneumoniae), an important community-acquired and nosocomial pathogen, especially in the intensive care unit (ICU), causes widespread infections including pneumonia, bacteremia, urinary tract infection, endophthalmitis, liver abscesses, and sometimes even lifethreatening septic shock
The detection of the presence of virulence genes showed that 63.8% (51/ 80) strains were positive, suggesting to be carrying virulence plasmids, which were designated as carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hypervirulent K. pneumoniae (hvKP)) group, while the remaining 29 strains were designated as CR-non-hvKP group with negative results for virulence genes by Polymerase Chain Reaction (PCR) analysis
All strains were resistant to imipenem and meropenem, except one CR-hvKP strain that is susceptible to meropenem and that showed high resistance to cephalosporins, monobactam, β-lactams-βlactamase inhibitor combinations, and fluoroquinolones but less resistance to ceftazidimeavibactam, imipenem-avibactam, polymyxin B, and tigecycline
Summary
Klebsiella pneumoniae (K. pneumoniae), an important community-acquired and nosocomial pathogen, especially in the intensive care unit (ICU), causes widespread infections including pneumonia, bacteremia, urinary tract infection, endophthalmitis, liver abscesses, and sometimes even lifethreatening septic shock. Hypervirulent K. pneumoniae (hvKP) and carbapenem-resistant K. pneumoniae (CRKP), often cause fatal infections [1]. The majority of hvKP identified to date are susceptible to most antimicrobials. The CR-hvKP strains are widely found, because the virulence genes and antibiotic resistance genes are transmitted by mobile genetic elements [2–4]. In China, the prevalence of CR-hvKP infections is 0∼25.8%, with large numbers of infections found in Henan and Shandong [5]. The emergence of CR-hvKP could lead to the clinical crisis, which has attracted worldwide attention [2]
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