Complex evolutionary trajectories in vivo of two novel KPC variants conferring ceftazidime-avibactam resistance.

More and more ceftazidime-avibactam-resistant KPC-producing Klebsiella pneumoniae have been reported with its widespread use, and the detection rate of KPC variants has increased dramatically. However, the evolutionary mechanism and fitness effects during KPC mutation remained unknown. Here, we report the complex in vivo evolutionary trajectories of two novel KPC variants, KPC-155 (L169P/GT242A) and KPC-185 (D179Y/GT242A), from K.

A multicentre, randomised, double-blind, double-dummy, parallel-controlled, phase 3 clinical trial assessing the efficacy and safety of intravenous nemonoxacin malate vs. levofloxacin for community-acquired pneumonia in adult patients.

Background: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3, multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin vs. levofloxacin for the treatment of community-acquired pneumonia (CAP) in adult patients.

Multicenter Antimicrobial Resistance Surveillance of Clinical Isolates from Major Hospitals - China, 2022.

What Is Already Known About This Topic?: Bacterial resistance surveillance is crucial for monitoring and understanding the trends and spread of drug-resistant bacteria.

What Is Added By This Report?: The number of strains collected in 2022 increased compared to 2021. The top five bacteria, including , , , , and Acinetobacter baumannii, remained largely unchanged.

A modified Kirby-Bauer disc diffusion (mKB) method for accurately testing tigecycline susceptibility: a nation-wide multicenter comparative study.

Tigecycline is one of the important antibiotics available for treating infection caused by multiple-drug resistant pathogens. However, the conventional AST methods which are commonly used in clinical microbiology laboratories usually lead to false intermediate or resistant results in testing tigecycline susceptibility, and further mislead clinical antimicrobial therapies. The modified Kirby-Bauer disc diffusion (mKB) method was performed based on the traditional standard Kirby-Bauer disc diffusion (sKB) method.

Integrative population pharmacokinetic/pharmacodynamic analysis of nemonoxacin capsule in Chinese patients with community-acquired pneumonia.

Nemonoxacin is an innovative quinolone antibiotic for treatment of community-acquired pneumonia (CAP). As more data are available from clinical studies, it is necessary to perform an integrative pharmacokinetic/pharmacodynamic (PK/PD) analysis to support and justify the optimal dosing regimen of nemonoxacin in clinical practice. We developed a population PK model using non-linear mixed effect model based on the data of 195 Chinese subjects receiving nemonoxacin in phase I to III clinical trials.

Setting of the tentative epidemiological cut-off values of contezolid for Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Streptococcus pneumoniae and Streptococcus agalactiae.

Objectives: To set the tentative epidemiological cut-off values (TECOFFs) of contezolid for Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Streptococcus pneumoniae and Streptococcus agalactiae based on the distributions of inhibition zone diameters and MICs.

Methods: A total of 1358 non-duplicate clinical isolates of Gram-positive bacteria were collected from the patients across China from 2017 to 2020. The isolates were tested for susceptibility to contezolid and the comparator linezolid by broth microdilution and disc diffusion methods in three microbiology laboratories.

Performance of Ceftazidime-Avibactam 30/20-μg and 10/4-μg Disks for Susceptibility Testing of and Pseudomonas aeruginosa.

Ceftazidime-avibactam, a new β-lactam-β-lactamase inhibitor combination, is active against multidrug-resistant and Pseudomonas aeruginosa isolates and has became available for clinical use in China in the latter half of 2019. In this study, we evaluated the performance of the disk diffusion test with ceftazidime-avibactam 10/4-μg and 30/20-μg disks, compared with the reference broth microdilution method, with a collection of 467 and 182 P. aeruginosa nonduplicate clinical isolates.

A multicenter investigation of 2,773 cases of bloodstream infections based on China antimicrobial surveillance network (CHINET).

Background: Bloodstream infections (BSIs), especially hospital-acquired BSIs, are a major cause of morbidity and mortality. However, the details about the pathogens and antimicrobial resistance profile of BSIs across China are still lacking.

Methods: An investigation was conducted in 10 large teaching hospitals from seven geographic regions across China in 2016 based on China Antimicrobial Surveillance Network (CHINET) to profile the clinical and etiological features of BSIs.

Antimicrobial activity of ceftobiprole and comparator agents when tested against gram-positive and -negative organisms collected across China (2016-2018).

Background: Ceftobiprole is a fifth-generation cephalosporin which has been reported to have broad antibacterial spectrum when tested against bacteria collected from other countries except China. This study evaluated the in vitro activity of ceftobiprole in comparison with other comparators against clinically significant isolates collected across from China.

Results: Susceptibility testing of ceftobiprole and comparators against 1163 clinically isolated Gram-positive and Gram-negative bacteria was performed with broth micro dilution method following the CLSI guidelines.

Activities of Eravacycline, Tedizolid, Norvancomycin, Nemonoxacin, Ceftaroline, and Comparators against 1,871 and 1,068 Species Isolates from China: Updated Report of the CHINET Study 2019.

To evaluate the activities of eravacycline, tedizolid, nemonoxacin, norvancomycin, and ceftaroline against Staphylococcus and species isolates were collected as part of the China Antimicrobial Surveillance Network (CHINET) in 2019 to provide susceptibility data for Staphylococcus spp. and spp. for their future development and application in clinical practice.

Activity of New β-Lactam-β-Lactamase Inhibitor Combinations and Comparators against Clinical Isolates of Gram-Negative Bacilli: Results from the China Antimicrobial Surveillance Network (CHINET) in 2019.

Novel β-lactam-β-lactamase inhibitor combinations (BLBLIs) are in clinical development for the treatment of infections caused by carbapenem-resistant and difficult-to-treat resistant (DTR) (defined as resistance to all tested β-lactams and fluoroquinolones) Gram-negative bacilli. This study evaluated the activities of cefepime-zidebactam, ceftazidime-avibactam, cefepime-tazobactam, ceftolozane-tazobactam, and other comparators against 4,042 nonduplicate Gram-negative clinical isolates collected from different regions of China (46 hospitals) in 2019. Based on the pharmacokinetic-pharmacodynamic (PK-PD) breakpoints, cefepime-zidebactam inhibited 98.

Activity of MRX-8 and Comparators Against Clinical Isolated Gram-Negative Bacilli in China.

To evaluate antibacterial activity of MRX-8 against gram-negative bacteria recently isolated from China, 765 clinical isolates were collected randomly from 2017 to 2020, including and and , and spp. isolates. All strains were performed with antimicrobial susceptibility testing by broth microdilution method according to the CLSI 2021.

Activity of KBP-7072 against 536 Acinetobacter baumannii Complex Isolates Collected in China.

Acinetobacter baumannii has emerged globally as a difficult-to-treat nosocomial pathogen and become resistant to carbapenems, resulting in limited treatment options. KBP-7072 is a novel semisynthetic aminomethylcycline, expanded spectrum tetracycline antibacterial agent with completed phase 1 clinical development studies. This study aimed to evaluate the activity of KBP-7072 and several comparators against clinical A.

Assessment of Ceftazidime-Avibactam 30/20-μg Disk, Etest versus Broth Microdilution Results When Tested against Clinical Isolates.

The objective of this research was to evaluate the correlation between inhibitory zones and MIC when testing ceftazidime-avibactam using disk diffusion, Etest, and broth microdilution method established by the Clinical and Laboratory Standards Institute (CLSI). Four-hundred and 58 isolates of isolated from 54 medical centers from the China Antimicrobial Surveillance Network (CHINET) in 2016 to 2020 were collected. Antimicrobial susceptibility testing using broth microdilution, Etest, and disk diffusion were performed according to the CLSI.

Comparison of Four Carbapenemase Detection Methods for Variants.

Recently, various variants resistant to ceftazidime-avibactam have begun to emerge in clinical settings, but it is unclear which testing method is most appropriate for detecting these variants. Strains were subjected to antimicrobial susceptibility testing using the broth microdilution method. Four carbapenemase detection methods, modified carbapenem inactivation method (mCIM) and EDTA carbapenem inactivation method (eCIM), APB/EDTA (carbapenemase inhibitor APB [3-aminophenylboronic acid] and EDTA enhancement method), NG-test Carba 5, and GeneXpert Carba-R were used to try to detect KPC-2 variants in 19 Klebsiella pneumoniae isolates.

Comparative activities of sitafloxacin against recent clinical isolates in hospitals across China.

Sitafloxacin is one of the newer generation fluoroquinolones. Considering the ever-changing antimicrobial resistance, it is necessary to monitor the activities of sitafloxacin against recent pathogenic isolates. Therefore, we determined the minimum inhibitory concentrations (MICs) of sitafloxacin and comparators by broth microdilution or agar dilution method against 1101 clinical isolates collected from 2017 to 2019 in 31 hospitals across China.

A randomized, controlled, multicenter clinical trial to evaluate the efficacy and safety of oral sitafloxacin versus moxifloxacin in adult patients with community-acquired pneumonia.

Objectives: To evaluate the efficacy and safety of oral sitafloxacin versus oral moxifloxacin in the treatment of Chinese adults with community-acquired pneumonia (CAP).

Patients And Methods: This is a multicenter, randomized, open-label, positive-controlled clinical trial (chinadrugtrials.org.

Activity of Cefepime-Zidebactam, Ceftazidime-Avibactam, and Other Comparators against Clinical Isolates of , Pseudomonas aeruginosa, and Acinetobacter baumannii: Results from China Antimicrobial Surveillance Network (CHINET) in 2018.

This study evaluated the activity of cefepime-zidebactam in comparison with that of ceftazidime-avibactam and other comparators against clinically significant Gram-negative bacillus isolates. A total of 3,400 nonduplicate Gram-negative clinical isolates were collected from 45 medical centers across China in the CHINET Program in 2018, including ( = 2,228), ( = 657), and ( = 515). The activities of cefepime-zidebactam and 20 comparators were determined by broth microdilution as recommended by the Clinical and Laboratory Standards Institute.

Activity of Lefamulin Against the Common Respiratory Pathogens Isolated From Mainland China During 2017-2019.

Purpose: Lefamulin is a novel antibiotic approved by the U.S. Food and Drug Administration in 2019 for the treatment of community-acquired bacterial pneumonia (CABP).

Comparative Activities of Ceftaroline and Tedizolid against Clinical Strains of Staphylococcus aureus and : Results from the China Antimicrobial Surveillance Network (CHINET) in 2018.

The activities of ceftaroline and tedizolid were compared against , , and clinical isolates collected from the China Antimicrobial Surveillance Network. Ceftaroline demonstrated potent activity against isolates (MIC, ≤0.25/1 mg/liter).

In vitro activity of omadacycline against pathogens isolated from Mainland China during 2017-2018.

Antibiotic resistance of bacterial pathogens isolated in China is a major concern. Omadacycline is a novel tetracycline derivative that has been approved for use in skin infections and community-acquired pneumonia. This study was conducted to determine the in vitro activity of omadacycline against a large collection of patient isolate medical centers across Mainland China.

Study of Synergistic Bactericidal Activity of Dual β-Lactam Antibiotics Against KPC-2-Producing .

To study the synergistic bactericidal activity of dual β-lactam antibiotics against KPC-2-producing and to explore the new therapeutic regimens for infections caused by carbapenem-resistant strains. The antimicrobial susceptibility testing of imipenem, meropenem, ceftazidime, and clavulanic acid on 40 clinically isolated strains of KPC-2-producing from 5 cities across the country was performed by microdilution broth method. The synergistic bactericidal activity of combined antibiotics mentioned above was determined at various concentrations using checkerboard techniques.

Resistance reported from China antimicrobial surveillance network (CHINET) in 2018.

The aim of this study is to investigate the antimicrobial susceptibility of strains isolated from the major hospitals in China. A total of 44 teaching hospitals were involved. Antimicrobial susceptibility testing was conducted by Kirby-Bauer automated systems, and results were interpreted using CLSI criteria.

Tolerability and Pharmacokinetics of Contezolid at Therapeutic and Supratherapeutic Doses in Healthy Chinese Subjects, and Assessment of Contezolid Dosing Regimens Based on Pharmacokinetic/Pharmacodynamic Analysis.

Purpose: This study assessed the tolerability and pharmacokinetic (PK) properties of a new-generation oxazolidinone, contezolid (MRX-I), and its major inactive metabolite, M2, after single oral administrations of 800, 1200, and 1600 mg in the fed state, and compared the efficacy of 3 dosing regimens in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection based on PK/pharmacodynamic (PD) analysis.

Methods: A Phase I study at a single study center was conducted with 2 parts. In the first part, 20 healthy subjects received a single oral dose of 1200 or 1600 mg of contezolid or placebo in the fed state in a double-blind, placebo-controlled, dose-escalation tolerance study.