Geographic patterns of global isolates of carbapenem-resistant Klebsiella pneumoniae and the activity of ceftazidime/avibactam, meropenem/vaborbactam, and comparators against these isolates: Results from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program, 2020

Abstract

Carbapenem-resistant Enterobacterales (CRE) are a growing threat to public health. This study was conducted to determine the prevalence of carbapenem-resistant Klebsiella pneumoniae (CR-KP) and the associated carbapenemase genes using data from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program, 2020. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method, and carbapenemase genes were detected using multiplex polymerase chain reaction (PCR). Clinical and Laboratory Standards Institute breakpoints were used for interpretation of susceptibility. A total of 6753 K. pneumoniae isolates were collected from 57 countries in six regions worldwide. Of these, 1118 (16.6%) were CR-KP isolates. Among 1079 of the tested CR-KP isolates, 1017 (94.3%) had at least one of the class A (41.0%, 417/1017), B (39.3%, 400/1017), and D (38.8%, 395/1017) carbapenemase genes. The resistance patterns and associated genes differed significantly between the participating countries. India, Greece, and Argentina had the highest rates of carbapenem resistance. Susceptibility to the β-lactamase inhibitor combination, ceftazidime/avibactam was greater than that to meropenem/vaborbactam in all K. pneumoniae (93.7% vs. 90.3%, P < 0.05), CR-KP (63.3% vs. 41.5%, P < 0.05), CR-KP with genes for Klebsiella pneumoniae carbapenemase-like carbapenemase (99.5% vs. 96.0%, P < 0.05), oxacillinase-like carbapenemase (98.7% vs. 4.6%, P < 0.05), and CR-KP without carbapenemase genes (93.5% vs. 79.0%, P < 0.05). CR-KP was the only exception with class B carbapenemase, with susceptibility rates of 1.4% and 9.4% to ceftazidime/avibactam and meropenem/vaborbactam, respectively (P < 0.05). Overall, surveillance results are important for guiding empirical antimicrobial therapy in different regions and for monitoring the global transmission of CR-KP with varying resistance mechanisms.

Keywords: Carbapenem-resistant; Carbapenemase; Ceftazidime/avibactam; Klebsiella pneumoniae; Meropenem/vaborbactam; β-lactamase inhibitor combination.