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.
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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.
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