Epidemic spread of KPC-producing bacteria in the Czech Republic

Abstract

Carbapenems are currently last-resort antibiotics for the therapy of infections caused by multidrug-resistant Gram-negative bacteria. Therefore, the resistence to those drugs represents a significant threat of current medicine. Genes encoding for carbapenemases are mainly spread on mobile-genetic elements, especially plasmids. As demonstrated by several studies, they can be efficiently spread in bacterial populations. For surveillance purpose, it is crucial to under-stand evolution and spread of those resistence determinants on molecular-genetic level. In the Czech Republic, car-bapenemase-producing bacteria are monitored in a routine level by diagnostic clinical laboratories and confirmed at Na-tional Reference Laboratory for Antibiotics of National Insti-tute of Public Health and at Biomedical Center of Faculty of Medicine in Pilsen, Charles University. Whole-genome-sequencing-based molecular surveillance of those bacteria has been established since 2014. Among three main molecular groups of carbapenemases, KPC-type enzymes are spread globally, causing high-level of resistence to carbapenems. In this study we present the ongoing spread of the KPC-producing strains, which is evolving to an epidemic in Czech hospitals. During the period of 2018-2019, a total of 108 KPC-producing Enterobacterales were recovered from 20 hospi-tals. Analysis of long-read sequencing data revealed the pres-ence of several types of blaKPC-carrying plasmids; 19 out of 25 blaKPC-carrying plasmids could be assigned to R (n = 12), N (n = 5), C (n = 1) and P6 (n = 1) incompatibility (Inc) groups. Five of the remaining blaKPC-carrying plasmids were multireplicon, while one plasmid couldn't be typed. Addition-ally, phylogenetic analysis confirmed the spread of blaKPC-carrying plasmids among different clones of diverse Entero-bacterales species. Our findings demonstrated that the in-creased prevalence of KPC-producing isolates was due to plasmids spreading among different species. In some districts, the local dissemination of IncR and IncN plasmids was ob-served. Additionally, the ongoing evolution of blaKPC-carrying plasmids, through genetic rearrangements, favours the preser-vation and further dissemination of these mobile genetic ele-ments. Therefore, the situation should be monitored, and im-mediate infection control should be implemented in hospitals reporting KPC-producing strains.