Emergence of Hypervirulent ST11-K64 Klebsiella pneumoniae Poses a Serious Clinical Threat in Older Patients.

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.

Wei T ，Zou C ，Qin J ，Tao J ，Yan L ，Wang J ，Du H ，Shen F ，Zhao Y ，Wang H ... -  《Frontiers in Public Health》

[Analysis of molecular and clinical characteristics of carbapenem-resistant hypervirulent Klebsiella pneumoniae in the intensive care unit].

Lei J ，Zhou WX ，Lei K ，Chen D ，Zhang PQ ，Xue L ，Geng Y ... -  《-》

Emergence of Tigecycline Nonsusceptible and IMP-4 Carbapenemase-Producing K2-ST65 Hypervirulent Klebsiella pneumoniae in China.

Zhang Y ，Wang X ，Wang Q ，Chen H ，Li H ，Wang S ，Wang R ，Wang H ... -  《Microbiology Spectrum》

Infection with Carbapenem-resistant Hypervirulent Klebsiella Pneumoniae: clinical, virulence and molecular epidemiological characteristics.

Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) is gradually becoming the dominant nosocomial pathogens in the healthcare setting. A retrospective study was conducted on patients with CR-KP from July 2021 to May 2022 in a teaching hospital. We identified bacterial isolates, collected the clinical data, and performed antimicrobial susceptibility testing, hypermucoviscosity string test, antimicrobial and virulence-associated genotype, as well as multi-locus sequence typing. CR-hvKP was defined as the presence of some combination of rmpA and/or rmpA2 with iucA, iroB, or peg-344. SPSS was used for data analysis. Univariate logistic regression analyses were used for risk factor and all statistically significant variables were included in the multivariate model. Statistical significance was taken to be P < 0.05. A total of 69 non-duplicated CR-KP isolates were collected, 27 of which were CR-hvKP. Out of the 69 CR-KP strains under investigation, they were distributed across 14 distinct sequence types (STs), wherein ST11 exhibited the highest prevalence, constituting 65.2% (45/69) of the overall isolates. The principal carbapenemase genes identified encompassed blakpc-2, blaNDM-1, and blaOXA-48, with blakpc-2 prevailing as the predominant type, accounting for 73.9% (51/69). A total of 69 CR-KP strains showed high resistance to common clinical antibiotics, with the exception of ceftazidime/avibactam. The ST11 (P = 0.040), ST65 (P = 0.030) and blakpc-2 ST11 clones (P = 0.010) were found to be highly related to hvKp. Regarding the host, tracheal intubation (P = 0.008), intracranial infection (P = 0.020) and neutrophil count (P = 0.049) were significantly higher in the patients with CR-hvKP. Multivariate analysis showed tracheal intubation to be an independent risk factor for CR-hvKP infection (P = 0.030, OR = 4.131). According to the clinical data we collected, tracheal intubation was performed mainly in the elderly with severe underlying diseases, which implied that CR-hvKP has become prevalent among elderly patients with comorbidities. The prevalence of CR-hvKP may be higher than expected in the healthcare setting. CR-hvKP is gradually becoming the dominant nosocomial pathogen, and its prevalence and treatment will be a major challenge. It is essential to enhance clinical awareness and management of CR-hvKP infection.

Li L ，Li S ，Wei X ，Lu Z ，Qin X ，Li M ... -  《-》

Detection of carbapenem-resistant hypervirulent Klebsiella pneumoniae ST11-K64 co-producing NDM-1 and KPC-2 in a tertiary hospital in Wuhan.

Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) poses serious challenges to public health. Only a few sporadic reports of strains co-producing NDM-1 and KPC-2 (NDM-1-KPC-2-CR-hvKP strains) are available to date. This retrospective study investigated the clinical features, prevalence and antibiotic resistance of hvKP in a tertiary hospital in central China, and characterized an NDM-1-KPC-2-CR-hvKP strain (KP169). Clinical data were collected. Antimicrobial and virulence-associated phenotyping and genotyping, capsular serotype gene analysis and multi-locus sequence typing of hvKP isolates were performed. Whole-genome sequencing (WGS) was performed on strain KP169. Forty-five of 109 K. pneumoniae clinical isolates were hvKP. Of these, 37 originated from nosocomial infections and 24 expressed carbapenemases. Eight NDM-1-KPC-2-CR-hvKP strains were identified, and enterobacterial repetitive intergenic consensus polymerase chain reaction showed that they were clonally related. WGS revealed that strain KP169, which belongs to ST11-K64, had a single 5.5-Mb chromosome and six plasmids of 5.5-221.6 kb. The blaNDM-1 gene was located on plasmid pKP169-P3, and blaKPC-2, blaSHV-12 and blaTEM-1 were located on IncFII/IncR pKP169-P2. IncHI 1/IncFIB virulence plasmid pKP169-P1 was similar to pKPC-CR-hvKP-C789 plasmid reported previously. Plasmid stability testing showed that blaKPC-2- and blaNDM-1-harbouring plasmids were maintained stably in the host. To the best of the authors' knowledge, this study identified the largest cohort, to date, of eight NDM-1-KPC-2-CR-hvKP strains, and suggests that antimicrobial stewardship and protocols to prevent transmission are needed urgently.

Huang Y ，Li J ，Wang Q ，Tang K ，Cai X ，Li C ... -  《-》