High prevalence of carbapenem-resistant and identification of a novel VIM-type metallo-β-lactamase, VIM-92, in clinical isolates from northern China.

Carbapenem-resistant (CRPA) has become a serious global health concern due to the limited treatment options. The primary resistance mechanism in CRPA involves the production of metallo-β-lactamases (MBLs), making MBL-producing a significant component of CRPA cases. To understand the prevalence of CRPA in hospitals in northern China, we conducted a preliminary screening and identification of CRPA in 143 clinical isolates of collected from various departments of a tertiary hospital between 2021 and 2023, analyzing CRPA resistance trends in certain regions of northern China during this period.

Effectiveness and safety of ceftazidime-avibactam in Chinese patients with hospital-acquired pneumonia, including ventilator-associated pneumonia: a Phase 4, multi-centre, open-label study.

Background: Ceftazidime-avibactam was approved in patients with hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), based on the multinational Phase 3 REPROVE study. This study assessed efficacy and safety of ceftazidime-avibactam in Chinese adults with HAP/VAP.

Methods: This was a Phase 4, prospective, multi-centre, open-label study, conducted at 42 sites in China.

Clinical outcomes and pharmacokinetics/pharmacodynamics of intravenous polymyxin B treatment for various site carbapenem-resistant gram-negative bacterial infections: a prospective observational multicenter study.

Polymyxin B, a last resort for carbapenem-resistant gram-negative bacteria (CRGNB) infections, has infection site-specific pharmacokinetic/pharmacodynamic (PK/PD) properties. However, there is little clinical evidence to support optimal exposures of polymyxin B for different site infections. We performed a prospective, observational, multicenter study to evaluate the clinical outcomes and PK/PD of intravenous polymyxin B treatment for various site CRGNB infections.

Global emergence of Carbapenem-resistant Hypervirulent Klebsiella pneumoniae driven by an IncFII KPC-2 plasmid.

Background: Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) has been increasingly reported worldwide, posing a severe challenge to public health; however, the mechanisms driving its emergence and global dissemination remain unclear.

Methods: We analysed CR-hvKp strains derived from canonical hvKp backgrounds, and acquired a carbapenemase-encoding gene. These strains were identified from 485 CRKp isolates in the CRACKLE-2 China cohort, 259 CRKp isolates from a multi-centre study, and 67,631 K.

Performance of ddPCR-GNB for microbial diagnosis of suspected bloodstream infection due to the four most common gram-negative bacteria: a prospective, multicenter study.

Unlabelled: We aimed to validate the performance of ddPCR-GNB, a plasma droplet digital PCR panel targeting the four most common gram-negative bacteria, for patients with suspected bloodstream infection (BSI). Patients suspected of having BSIs were prospectively enrolled. The results of blood culture and ddPCR-GNB were compared, and cases with discordant results were arbitrated on the basis of additional microbiological results and clinical evidence.

"Seesaw effect" between daptomycin and ceftobiprole in daptomycin-resistant methicillin-resistant staphylococcus aureus isolates.

Objectives: This study aimed to investigate the "seesaw effect" of daptomycin (DAP) and ceftobiprole (BPR) on DAP-resistant (DAP-R) methicillin-resistant Staphylococcus aureus (MRSA) isolates.

Methods: Broth microdilution minimum inhibitory concentrations (MICs) of DAP and BPR were tested for laboratory-derived and clinical DAP-R MRSA isolates to estimate the "seesaw effect". Time-kill curves for seven representative DAP-R isolates were obtained using DAP and BPR to validate their synergistic activity in vitro.

Genomic characterization of healthcare-associated ST5 MRSA causing severe pseudomembranous enteritis in intensive care unit.

Background: Methicillin resistant Staphylococcus aureus (MRSA) is one of the main causes of hospital-acquired infections, but the diagnosis of MRSA pseudomembranous enteritis has faded in recent years. Here, we reported a pseudomembranous enteritis case in a young male patient caused by ST5 MRSA.

Methods: Clinical data of the patient were collected from medical records.

Global phylogeography and genetic characterization of carbapenem and ceftazidime-avibactam resistant KPC-33-producing Pseudomonas aeruginosa.

Ceftazidime-avibactam (CZA) is currently one of the last resorts used to treat infections caused by carbapenem-resistant Enterobacteriaceae and Pseudomonas aeruginosa. However, KPC variants have become the main mechanism mediating CZA resistance in KPC-producing gram-negative bacteria after increasing the application of CZA. Our previous study revealed that CZA-resistant KPC-33 had emerged in carbapenem-resistant P.

Mechanisms of bla dissemination across diverse carbapenem-resistant clinical isolates.

Objective: The IMP-4 carbapenemase is an endemic cause of carbapenem resistance in the Asia-Pacific region. Our aim was to determine the dissemination mechanism of the bla gene.

Methods: Twelve representative Australian IMP-4 clinical isolates from The Alfred Hospital (Victoria, Australia) were characterised using antimicrobial susceptibility testing, with their genome and plasmid assemblies analysed.

Single-dose suraxavir marboxil for acute uncomplicated influenza in adults and adolescents: a multicenter, randomized, double-blind, placebo-controlled phase 3 trial.

Suraxavir marboxil (GP681) is an antiviral drug inhibiting the polymerase acidic protein (PA) of RNA polymerase, of influenza. It has shown therapeutic activity against influenza A and B virus infections in preclinical studies. In this multicenter randomized, double-blind, placebo-controlled, phase 3 trial, we aimed to investigate the efficacy and safety of single-dose suraxavir marboxil (40-mg oral dose) in otherwise healthy outpatients aged 5-65 years with uncomplicated influenza unaccompanied by severe issues.

Phenotypic and genotypic characterization of clinical carbapenem-resistant species harboring the metallo-beta-lactamases IMP-8 or NDM-1 in China.

Unlabelled: Carbapenem-resistant spp. pose a significant challenge in clinical settings due to limited treatment options for nosocomial infections. Carbapenem-hydrolyzing class D beta-lactamases are the primary cause for carbapenem resistance, while metallo-beta-lactamases (MBLs) New Delhi metallo beta-lactamase (NDM) and imipenemase (IMP) also contribute.

Decadal Evolution of KPC-related plasmids in Pseudomonas aeruginosa high-risk clone ST463 in Zhejiang, China.

Klebsiella pneumoniae carbapenemase-producing Pseudomonas aeruginosa (KPC-PA) isolates have quickly expanded in China, especially the high-risk clone ST463. We aimed to explore the evolution of KPC-related plasmids driving ST463 clone success. Whole-genome sequencing of 1258 clinical P.

Susceptibility of various Gram-negative bacteria to antibacterial agents: SMART in China 2019-2020.

Background: The Study for Monitoring Antimicrobial Resistance Trends (SMART) is an international surveillance program longitudinally monitoring aerobic and facultative Gram-negative bacteria (GNB) involvement in infections and their antimicrobial resistance profiles. Here the incidence and resistance patterns of Chinese GNB isolates from bloodstream infections (BSI), intraabdominal infections (IAI), respiratory tract infections (RTI) and urinary tract infections (UTI) to commonly used antibacterial agents has been updated. 4,975 GNB isolates collected from 22 hospitals across 7 regions of China from 2019 to 2020 were analyzed.

Establishment of epidemiological cut-off values of etimicin: a new fourth-generation aminoglycoside, against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus aureus.

Objective: To determine the epidemiological cut-off (ECOFF) values of etimicin against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus aureus.

Methods: We selected 1500 isolates from five hospitals throughout five cities in China spanning from January 2018 to December 2021 in the study. Minimal inhibit concentrations (MICs) of etimicin were determined using the broth microdilution method.

Ceftolozane/tazobactam disrupts Pseudomonas aeruginosa biofilms under static and dynamic conditions.

Background: Pseudomonas aeruginosa biofilms limit the efficacy of currently available antibacterial therapies and pose significant clinical challenges. Pseudomonal biofilms are complicated further when other markers of persistence such as mucoid and hypermutable phenotypes are present. There is currently a paucity of data regarding the activity of the newer β-lactam/β-lactamase inhibitor combination ceftolozane/tazobactam against P.

In vivo divergent evolution of cross-resistance to new β-lactam/β-lactamase inhibitor combinations in Pseudomonas aeruginosa following ceftazidime/avibactam treatment.

Purpose: To describe and characterize the evolutionary process of cross-resistance to ceftazidime/avibactam, ceftolozane/tazobactam and imipenem/relebactam of a carbapenem-resistant Pseudomonas aeruginosa (CRPA) lineage isolated from a patient receiving two courses of ceftazidime/avibactam treatment.

Methods: The minimum inhibitory concentrations (MICs) of strains were determined by broth microdilution methods. The mutant genes were identified by the whole genome sequencing results.

Clinical characteristics and prognosis of bloodstream infections with carbapenem-resistant Gram-negative organisms in patients with hematological malignancies: A multicenter case-control study in China.

Objective: To investigate clinical characteristics of hematological malignancy (HM) patients with carbapenem-resistant gram-negative organism (CRO) bloodstream infections (BSI) in China, and to elucidate the prognostic risk factors of CRO BSI.

Methods: We conducted a multicenter case-control study of 201 HM patients with CRO BSI between 2018-2020. Antimicrobial susceptibility testing and whole genome sequencing were performed for CRO isolates.

Efficacy and safety of ZX-7101A, an inhibitor of influenza cap-dependent endonuclease, in adults with uncomplicated influenza: a randomized, double-blind, placebo-controlled phase 2/3 trial.

Objectives: To evaluate the efficacy and safety of ZX-7101A: an inhibitor of influenza viral cap-dependent endonuclease, in adults with uncomplicated influenza and explore treatment-emergent resistance.

Methods: We conducted a randomized, double-blind, placebo-controlled, adaptive-design phase 2 and phase 3 studies (ZX-7101A-202) in adults with uncomplicated influenza. Eligible patients were randomized 1:1:1 to receive a single dose of 40 or 80 mg ZX-7101A or placebo, stratified by body weight and baseline composite symptom score.