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.

A 22-year-old man, after a hematopoietic stem cell transplant, suffered long-term pneumonia caused by bla_KPC-2-positive K. pneumoniae and bla_KPC-33-positive K. pneumoniae alternately and finally achieved pathogenic clearance and improvement of clinical infectious conditions after using ceftazidime–avibactam in combination with imipenem as salvage therapy. This case provides a reference for treating infection caused by K. pneumoniae with a KPC variant in countries lacking new antimicrobial agents.

The aim of this study was to evaluate the correlation between inhibitory zones and minimum inhibitory concentrations (MICs) when testing cefiderocol against Acinetobacter baumannii complex using disk diffusion and the broth microdilution (BMD) method according to the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. Four-hundred and sixty-eight non-duplicated A. baumannii complex clinical isolates were collected from 56 hospitals of the China Antimicrobial Surveillance Network from 2019 to 2021. BMD using iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB) and standard disk diffusion methods were performed according to CLSI guidelines. Results were interpreted according to the CLSI and EUCAST breakpoints. Categorical agreement (CA), minor error (mE), major error (ME), and very major error (VME) were calculated for disk diffusion methods. The susceptibilities of all A. baumannii complex isolates by BMD were 98.7% (CLSI) and 97.6% (EUCAST). For all A. baumannii complex isolates, CA was 98.1% (CLSI) and 97.0% (EUCAST), with 0.9% (CLSI) and 1.9% (EUCAST) of VME, respectively. For the carbapenem-susceptible A. baumannii complex, the CA was 100%, with no mE or VME using both CLSI and EUCAST breakpoints. For carbapenem-resistant A. baumannii complex, CA was 97.5% (CLSI) and 96.2% (EUCAST), with 1.1% (CLSI) and 2.5% (EUCAST) of VME, respectively. Regarding the difficult-to-treat resistance A. baumannii complex isolates, CA was 97.6% (CLSI) and 95.7% (EUCAST), with 1.2% (CLSI) and 3.1% (EUCAST) of VME, respectively. Cefiderocol disk diffusion was difficult to assess in this study. Very few isolates were resistant to cefiderocol by BMD using CLSI breakpoint, and these were categorized as susceptible with the disk diffusion test. This study did, however, show that the main proportion of A. baumannii isolates were susceptible to cefiderocol by BMD, including carbapenem-resistant A. baumannii . IMPORTANCE: Carbapenem-resistant Acinetobacter baumannii is a major global health concern due to its high prevalence and limited treatment options. Cefiderocol is the only novel Food and Drug Administration (FDA)-approved β-lactam agent for the salvage treatment of carbapenem-resistant A. baumannii infection. Currently, a commercial automated susceptibility testing panel of cefiderocol is unavailable. Both the preparation of iron-depleted cation-adjusted Mueller-Hinton broth and the performance of broth microdilution are cumbersome in routine microbiology laboratories. A disk diffusion method is convenient for cefiderocol antimicrobial susceptibility testing, but limited data are available specifically for A. baumannii clinical isolates. Moreover, the Clinical and Laboratory Standards Institute published revisions to the A. baumannii cefiderocol disk diffusion breakpoints in 2022. Hence, we evaluated the performance of cefiderocol disk diffusion compared with the reference BMD against A. baumannii clinical isolates, especially those with cefiderocol zone diameters ≤ 14 mm.

With the wide use of carbapenems, carbapenem-resistant Enterobacterales have been increasingly reported worldwide. In this study, one bla_OXA-181-positive Pseudocitrobacter faecalis strain was isolated from the blood culture of a patient with a bloodstream infection in China, which was its first clinical report outside Pakistan. Species identification of P. faecalis was initially performed using MALDI-TOF/MS and further confirmed by 16S rRNA gene and housekeeping gene sequencing. The antimicrobial susceptibility testing was determined through the broth microdilution method, and their clonal relationship was analyzed by pulsed-field gel electrophoresis. To study the transmission and genetic structure of the bla_OXA-181 gene, a transformation test and whole-genome sequencing (WGS) were performed. The results of the antimicrobial susceptibility testing indicated this P. faecalis was resistant to carbapenems, quinolones, and commonly used β-lactam/β-lactamase inhibitor combinations. Through WGS and transformation experiments, bla_OXA-181 and qnrS1 genes causing antibiotic resistance were located on a 55,148-bp length IncX3 type plasmid with a truncated ColKp3 replicon gene. As a rare species of Enterobacterales, P. faecalis was clinically reported in China for the first time, and the bla_OXA-181 gene it carried was located on a globally disseminated IncX3 plasmid. The spread of such bacteria and antibiotic resistance requires more clinical attention.

Objective: To monitor the trends of carbapenem-resistant gram-negative bacteria to antimicrobial agents in healthcare facilities in major regions of China between 2015 and 2024. Methods: Carbapenem-resistant gram-negative isolates from 74 hospitals in the country were tested for antimicrobial susceptibility using an automated method (imported or domestic AST instruments) supplemented by the disc diffusion method. Results were evaluated using the 2024 CLSI breakpoint. Results: A total of 339 513 clinical isolates were collected between 2015 and 2024. Among clinical Enterobacterales isolates, the rate of carbapenem resistance was generally below 13%, except for Klebsiella spp., where it ranged from 20.4% to 21.9%. Most clinical Enterobacterales isolates are highly susceptible to tigecycline, colistin, and polymyxin B, with resistance rates ranging from 0.1% to 15.4%. The detection rate of meropenem-resistant Pseudomonas aeruginosa has decreased over six consecutive years, from 31.4% in 2018 to 21.5% in 2024. The detection rate of meropenem-resistant Acinetobacter baumannii remained modest, from 64.9% in 2015 to 68.3% in 2024. Conclusions: Multidrug-resistant bacteria remain a significant challenge in clinical anti-infective treatment, and the surveillance of bacterial resistance and the rational use of antimicrobial agents need to be further strengthened to combat bacterial resistance.