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

Ceftazidime-avibactam, a new ß-lactam-ß-lactamase inhibitor combination, is active against multidrug-resistant Enterobacterales 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 Enterobacterales and 182 P. aeruginosa nonduplicate clinical isolates. The results of antimicrobial susceptibility testing indicated that the categorical agreement (CA) of ceftazidime-avibactam 10/4-µg disk testing for all tested Enterobacterales isolates was 99.8%, with 0.5% very major errors (VMEs) and no major error (ME). The CA of ceftazidime-avibactam 10/4-µg disk testing for all tested P. aeruginosa isolates was 87.9%, with 15.5% MEs and no VME. The CA of ceftazidime-avibactam 30/20-µg disk testing for all tested Enterobacterales isolates was 99.4%, with 1.5% VMEs and no ME. The CA of ceftazidime-avibactam 30/20-µg disk testing for all tested P. aeruginosa isolates was 91.8%, with 2.5% VMEs and 9.9% MEs. Overall, ceftazidime-avibactam 10/4-µg disk testing showed superior performance and was more suitable for assessment of the susceptibility of Enterobacterales and P. aeruginosa isolates. IMPORTANCE Multidrug-resistant Enterobacterales and P. aeruginosa strains have become a global public threat, with the emergence and prevalence of plasmid-mediated extended-spectrum ß-lactamases (ESBLs), AmpC cephalosporinases, and carbapenemases disseminated worldwide. Ceftazidime-avibactam, which is commercially available, has shown excellent in vitro activity against multidrug-resistant and carbapenem-resistant Enterobacterales and P. aeruginosa isolates. Moreover, ceftazidime-avibactam has shown promise in treating infections caused by multidrug-resistant and carbapenem-resistant isolates. The disk diffusion test for ceftazidime-avibactam is the most common antimicrobial susceptibility testing method in most laboratories in China. The accurate detection of ceftazidime-avibactam susceptibility is of great significance for the rational clinical application of drugs. Here, we evaluated the performance of the ceftazidime-avibactam 10/4-µg and 30/20-µg disk diffusion tests, compared with the reference broth microdilution method, with clinical Enterobacterales and P. aeruginosa isolates.

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

To evaluate in vitro antibacterial activity of MRX-8 against gram-negative bacteria recently isolated from China, 765 clinical isolates were collected randomly from 2017 to 2020, including Enterobacterales and P. aeruginosa and A. baumannii, S. maltophilia, B. cepacia, Alcaligenes app. and Haemophilus spp. isolates. All strains were performed with antimicrobial susceptibility testing by broth microdilution method according to the CLSI 2021. Antimicrobial agents included MRX-8, polymyxin B, colistin, amikacin, ceftriaxone, ceftazidime, cefepime, ceftazidime-avibactam, cefoperazone-sulbactam, meropenem, ciprofloxacin, ampicillin, ampicillin-sulbactam and levofloxacin. For carbapenem-susceptible and carbapenem-resistant E.coli isolates, the MIC50/90 of MRX-8 was 0.125/0.25 mg/L and 0.06/0.125 mg/L, respectively. For carbapenem-susceptible and carbapenem-resistant K. pneumoniae isolates, the MIC50/90 of MRX-8 was 0.25/0.5 mg/L and 0.125/0.5 mg/L, respectively. For polymyxins (polymyxin B and colistin)-resistant E. coli and K. pneumoniae, MIC50 of MRX-8 was 4-16 mg/L and MIC90 was >32 mg/L. The MIC50 and MIC90 of MRX-8 for other Klebsiella spp. except K. pneumoniae, Citrobacter spp., S. enterica and Shigella spp. isolates ranged 0.06-0.125 mg/L and 0.06-0.25mg/L, respectively. For Morganella spp., Proteus spp., Providencia spp., Serratia spp., S. maltophilia and B. cepacia, all MIC50 of MRX-8 was >32mg/L. For carbapenem susceptible and resistant P. aeruginosa, the MIC50 and MIC90 of MRX-8 was both 1mg/L, and that for A. baumannii was 0.5mg/L and 0.5-1mg/L. For Alcaligenes spp. and Haemophilus spp., MIC50/90 was 1/4 mg/L and 0.25/0.5 mg/L. MRX-8 was more effective against most clinically isolated gram-negative isolates, including carbapenem-resistant E. coli, K. pneumoniae, P. aeruginosa and A. baumannii, highlighting its potential as valuable therapeutics.

In Vitro 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 in vitro activity of KBP-7072 and several comparators against clinical A. baumannii isolates collected from China. A collection of 536 A. baumannii clinical isolates were isolated from 20 hospitals across 13 provinces and cities in China between 2018 and 2019. Antimicrobial susceptibility testing of 12 antimicrobial agents was performed utilizing the broth microdilution method recommended by CLSI. KBP-7072 has shown active antibacterial activity against 536 A. baumannii isolates. It inhibited the growth of all isolates at 4 mg/liter, including 372 carbapenem-resistant isolates, 37 tigecycline MIC ≥ 4 mg/liter isolates, and 138 omadacycline MIC ≥ 4 mg/liter isolates. Compared with other expanded spectrum tetracyclines, KBP-7072 (MIC90, 1 mg/liter) outperformed 2-fold and 4-fold more active against 536 A. baumannii isolates than tigecycline (MIC90, 2 mg/liter) and omadacycline (MIC90, 4 mg/liter). KBP-7072 was as equally active as colistin (MIC90, 1 mg/liter, 99.4% susceptible). Doxycycline (33.4% susceptible), gentamicin (31.3% susceptible), meropenem (30.6%, susceptible), imipenem (30.2% susceptible), ceftazidime (27.8% susceptible), piperacillin-tazobactam (27.2% susceptible), and levofloxacin (27.2% susceptible) showed marginally poor antibacterial activity against tested isolates according to CLSI breakpoints, except for minocycline (73.7% susceptible). KBP-7072 is a potential alternative agent for the treatment of infection caused by A. baumannii, including carbapenem-resistant species. IMPORTANCE It is reported that A. baumannii has emerged as an intractable nosocomial pathogen in hospitals especially when it develops resistance to carbapenems and other antibiotics, which limits treatment options and leads to high mortality. In February 2017, the WHO published a list of ESKAPE pathogens designated "priority status" for which new antibiotics are urgently needed. Therefore, the epidemiological surveillance and new therapeutic development of A. baumannii must be strengthened to confront an emerging global epidemic. KBP-7072 is a novel, expanded spectrum tetracycline antibacterial and has demonstrated good in vitro activity against recent geographically diverse A. baumannii isolates collected from North America, Europe, Latin America, and Asia-Pacific. This study has shown excellent in vitro activity of KBP-7072 against clinical A. baumannii isolates collected from different regions of China, regarded as supplementary to KBP-7072 pharmacodynamics data, which is of great significance, as it is promising an alternative treatment in CRAB isolates infections in China.