Antimicrobial resistance among imipenem-non-susceptible Escherichia coli and Klebsiella pneumoniae isolates, with an emphasis on novel β-lactam/β-lactamase inhibitor combinations and tetracycline derivatives

Background: To determine susceptibility of imipenem-non-susceptible Escherichia coli (INS-EC) and Klebsiella pneumoniae (INS-KP) isolates collected during 2020–2022 through a national surveillance program in Taiwan to novel antibiotics, and to compare the results with those obtained during 2012–2018. Methods: Minimum inhibitory concentrations were determined by broth microdilution methods. Genes encoding carbapenemases including blaKPC, metallo-β-lactamase (MBL) genes, and blaOXA-48 were detected via multiplex PCR. Data retrieved from our 2012–2018 study were used for comparison. Results: Of 3260 E. coli and 1457 K. pneumoniae isolates collected during 2020–2022, 0.9 % and 9.5 %, were INS-EC and INS-KP, respectively. Cefepime-zidebactam, ceftazidime-avibactam, imipenem-relebactam, and meropenem-vaborbactam were active against 100 %, 75.9 %, 65.5 %, and 79.3 % of 29 INS-EC isolates respectively; and against 100 %, 90.6 %, 64.5 %, and 67.4 % of 138 INS- KP isolates, respectively. Susceptibility was contingent upon carbapenemase types. Susceptibility rates of cefepime-zidebactam and ceftazidime-avibactam remained constant from 2012 to 2018 through 2020–2022 but those of imipenem-relebactam and meropenem-vaborbactam decreased significantly, which may be partially attributable to the increasing prevalence of blaOXA-48. Eighteen MBL-gene-positive isolates and two blaKPC-positive isolates were resistant to ceftazidime-avibactam, whereas all were susceptible to cefepime-zidebactam. Tigecycline had a higher susceptibility rate than eravacycline and omadacycline for K. pneumoniae isolates. Lascufloxacin and delafloxacin were effective against fewer than 10 % of INS isolates. Susceptibilities to novel tetracyclines and fluoroquinolones remained similar from 2012 to 2018 through 2020–2022. Conclusions: This study highlights significant resistance patterns of INS-EC and INS-KP isolates in Taiwan. The declining susceptibility rates and the rising prevalence of genetic resistance determinants highlight the importance of ongoing surveillance and antimicrobial stewardship.