This study aimed to investigate the dissemination and characteristics of bla_KPC, bla_NDM, bla_OXA-48-like, bla_IMP, and bla_VIM among the carbapenem-resistant Enterobacteriaceae (CRE) strains isolated from adult and children patients. A total of 935 non-duplicate CRE strains were collected from 36 hospitals in 24 provinces or cities across China from 2016 to 2018. Antimicrobial susceptibility testing was performed by broth microdilution method and carbapenemase genes bla_KPC, bla_NDM, bla_OXA-48-like, bla_IMP, and bla_VIM were screened by PCR and confirmed by DNA sequencing. Overall, carbapenemases were produced in 97.4% (911/935) of CRE strains, including KPC-2 (51.6%, 482/935), NDM (35.7%, 334/935), and OXA-48-like carbapenemases (7.3%, 68/935). Overall, the most prevalent carbapenemase gene was bla_KPC-2 among Klebsiella pneumoniae (64.6%, 457/709) and the CRE strains isolated from adult patients (70.3%, 307/437), and bla_NDM among Escherichia coli (96.0%, 143/149) and the CRE strains from children (49.0%, 247/498). The bla_OXA-232-positive carbapenem-resistant K. pneumoniae (9.3%, 66/709) were all isolated from children. Sixteen strains were positive for bla_IMP and 9 strains produced multiple carbapenemases. No strain was positive for bla_VIM. Most of the CRE strains (>90%) were resistant to cephalosporins and carbapenems, more than half (>50%) were resistant to aminoglycosides and fluoroquinolones, but the majority (95.8 and 98.4%) were susceptible to polymyxin B and tigecycline. Ceftazidime-avibactam showed excellent in vitro activity against bla_KPC-2 and bla_OXA-48-like positive strains (100% susceptible). In China, KPC-2, NDM, and OXA-48-like carbapenemases were predominant among CRE clinical isolates. The most prevalent carbapenemase gene was bla_KPC-2 among K. pneumoniae isolates from adult patients, and bla_NDM among E. coli isolates from children.

Epidemiological knowledge of circulating carbapenem-resistant Klebsiella pneumoniae (CRKP) is needed to develop effective strategies against this public health threat. Here we present a longitudinal analysis of 1,017 CRKP isolates recovered from patients from 40 hospitals across China between 2016 and 2020. Virulence gene and capsule typing revealed expansion of CRKP capsule type KL64 (59.5%) alongside decreases in KL47 prevalence. Hypervirulent CRKP increased in prevalence from 28.2% in 2016 to 45.7% in 2020. Phylogenetic and spatiotemporal analysis revealed Beijing and Shanghai as transmission hubs accounting for differential geographical prevalence of KL47 and KL64 strains across China. Moderate frequency capsule or O-antigen loss was also detected among isolates. Non-capsular CRKP were more susceptible to phagocytosis, attenuated during mouse infections, but showed increased serum resistance and biofilm formation. These findings give insight into CRKP serotype prevalence and dynamics, revealing the importance of monitoring serotype shifts for the future development of immunological strategies against CRKP infections.

SUMMARY: Klebsiella pneumoniae carbapenemase (KPC) variants, which refer to the substitution, insertion, or deletion of amino acid sequence compared to wild bla _KPC type, have reduced utility of ceftazidime-avibactam (CZA), a pioneer antimicrobial agent in treating carbapenem-resistant Enterobacterales infections. So far, more than 150 bla _KPC variants have been reported worldwide, and most of the new variants were discovered in the past 3 years, which calls for public alarm. The KPC variant protein enhances the affinity to ceftazidime and weakens the affinity to avibactam by changing the KPC structure, thereby mediating bacterial resistance to CZA. At present, there are still no guidelines or expert consensus to make recommendations for the diagnosis and treatment of infections caused by KPC variants. In addition, meropenem-vaborbactam, imipenem-relebactam, and other new β-lactam-β-lactamase inhibitor combinations have little discussion on KPC variants. This review aims to discuss the clinical characteristics, risk factors, epidemiological characteristics, antimicrobial susceptibility profiles, methods for detecting bla _KPC variants, treatment options, and future perspectives of bla _KPC variants worldwide to alert this new great public health threat.

The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) is a growing concern due to its high mortality and limited treatment options. Although hypermucoviscosity is crucial for CR-hvKp infection, the role of changes in bacterial mucoviscosity in the host colonization and persistence of CR-hvKp is not clearly defined. Herein, we observed a phenotypic switch of CR-hvKp from a hypermucoviscous to a hypomucoviscous state in a patient with scrotal abscess and urinary tract infection (UTI). This switch was attributed to decreased expression of rmpADC , the regulator of mucoid phenotype, caused by deletion of the upstream insertion sequence IS Kpn26 . Postswitching, the hypomucoid variant showed a 9.0-fold decrease in mice sepsis mortality, a >170.0-fold reduction in the ability to evade macrophage phagocytosis in vitro, and an 11.2- to 40.9-fold drop in growth rate in normal mouse serum. Conversely, it exhibited an increased residence time in the mouse urinary tract (21 vs. 6 d), as well as a 216.4-fold boost in adhesion to bladder epithelial cells and a 48.7% enhancement in biofilm production. Notably, the CR-hvKp mucoid switch was reproduced in an antibiotic-free mouse UTI model. The in vivo generation of hypomucoid variants was primarily associated with defective or low expression of rmpADC or capsule synthesis gene wcaJ , mediated by IS Kpn26 insertion/deletion or base-pair insertion. The spontaneous hypomucoid variants also outcompeted hypermucoid bacteria in the mouse urinary tract. Collectively, the IS Kpn26 -associated mucoid switch in CR-hvKp signifies the antibiotic-independent host adaptive evolution, providing insights into the role of mucoid switch in the persistence of CR-hvKp.

Antimicrobial resistance (AMR) is a pressing issue in China, with antibiotic therapy becoming less effective against bacterial infections. To address this challenge, the China Antimicrobial Surveillance Network (CHINET) was established in 2005 to monitor antimicrobial resistance in the country. This study analyzed the CHINET data from teaching hospitals and evaluated the trends of AMR in China from 2018 to 2022. A range of 163,636 to 301,917 isolates was obtained per year, with the majority being Gram-negative bacilli (69.0% to 71.8%). The proportion of important multidrug-resistant pathogens remained stable over the years. While the analysis showed diverse AMR profiles for different bacterial species. Over the five years, generally decreased resistance rates were observed from the majority of the tested species. For example, resistance to ceftriaxone decreased in Escherichia coli and Klebsiella pneumoniae, while resistance to imipenem and meropenem decreased in Pseudomonas aeruginosa. Moreover, resistance to methicillin, gentamicin, fosfomycin, and clindamycin also decreased in clinical Staphylococcus aureus isolates. On the other hand, resistance levels of Acinetobacter baumannii remained stable. Our study provides a comprehensive overview of the AMR profiles of common bacterial species in China and highlights the ongoing efforts to address this challenge.

This study aimed to monitor clinical isolate susceptibility to antimicrobial agents in healthcare facilities in 31 provinces or cities of China in 2024. Antimicrobial susceptibility of clinical isolates from 74 hospitals was tested using disc diffusion automated systems. The data were interpreted using the 2024 Clinical and Laboratory Standards Institute breakpoints. A total of 458,271 clinical isolates were collected, of which 28.3% were Gram-positive and 71.7% were Gram-negative. Methicillin-resistant Staphylococcus aureus , S. epidermidis, and other coagulase-negative Staphylococcus strain prevalence was 28.4%, 76.5%, and 70.2%, respectively. No vancomycin-resistant clinical Staphylococcus spp. were found. Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than E. faecium , with a few vancomycin-resistant strains of both identified. The prevalence of penicillin-susceptible Streptococcus pneumoniae was 97.5% in isolates from children and 96.1% in those from adults. The carbapenem resistance rate was < 15.0% for most Enterobacterales species except Klebsiella ; 22.6% and 23.4% of Klebsiella were resistant to imipenem and meropenem, respectively. Most Enterobacterales were highly susceptible to tigecycline (≤ 3.1%) and colistin (≤ 4.2%). Pseudomonas aeruginosa imipenem and meropenem resistance rates were 21.3% and 17.3%, respectively; those of Acinetobacter baumannii were 64.5% and 64.7%, respectively. In 2024, antimicrobial resistance in clinically isolated bacteria in major regions of China remained high. Antimicrobial agents must be rationally selected based on monitoring to effectively control the development of bacterial resistance.