Emergence of KPC-2-Producing ST11-K64 Hypervirulent Klebsiella Pneumoniae for the Elderly in Intensive Care Unit: Antimicrobial Resistance, Molecular and Clinical Characteristics

Abstract

Background: In recent years, carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) has been increasingly reported and poses severe therapeutic challenge to global public health, but has not yet been systematically studied in elderly patients. This study aimed to investigate the clinical and molecular characteristics and risk factors of CR-hvKP infections in elderly patients. Methods: We retrospectively investigated elderly patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in intensive care unit (ICU),between January 2020 and December 2020, the clinical data being collected from medical records, and microbiological data including antimicrobial susceptibility testing, phenotype experiment, carbapenemases production, string test, virulence gene, capsular serotype-specific (cps) genes and multilocus sequence typing, of the CR-hvKP group defined by the presence of some combination of rmpA, rmpA2, iucA, iroB, and peg-344 was compared with those of carbapenem-resistant non-hypervirulent Klebsiella pneumoniae (CR-non-hvKP) strains.Results: Of 80 CRKP strains, 51(63.8%) met the definition of CR-hvKP and 7 of them had all five of the virulence genes tested. The main mechanism of resistance to carbapenems found in CR-hvKP strains was the presence of the blaKPC-2 gene. There was no statistical significance in the resistance rates of antimicrobial agents between the CR-hvKP and CR-non-hvKP subgroups (p ≥ 0.05). Compared with the minimum inhibitory concentration (MIC) 50 values of CR-non-hvKP group, those of antimicrobials, including ceftazidime, ceftazidime/avibactam, imipenem/avibactam, tigecycline, levofloxacin, cefoperazone-sulbactam, exhibited higher levels in the CR-hvKP group. Avibactam (4 µg/mL) significantly decreased the MIC90 values more than sixteen-fold than that of ceftazidime and imipenem alone against KPC-2-producing Klebsiella pneumoniae. K64 and ST11 were highly prevalent and strongly associated with CR-hvKP (P<0.05). 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.Conclusion: The CR-hvKP strains showed higher MIC50 values than CR-non-hvKP strains. KPC-2-producing ST11-K64 CR-hvKP is emerging, which might become new significant “superbugs” and a threat to elderly patients.