Occurrence and Characteristics of Mcr s among Gram-Negative Bacteria Causing Bloodstream Infections of Infant Inpatients between 2006 and 2019 in China

• Published in: Microbiology spectrum Vol. 10; no. 1; p. e0193821
• Main Authors: Wu, Lijuan, Xu, Tingting, Ji, Yang, Song, Jingjie, Wang, Feiling, Huang, Junxi, Zhou, Kai
• Format: Journal Article
• Language: English
• Published: United States 23-02-2022
• Subjects: Anti-Bacterial Agents - pharmacology; China - epidemiology; Colistin - pharmacology; Drug Resistance, Bacterial - drug effects; Drug Resistance, Bacterial - genetics; Enterobacter - genetics; Escherichia coli - genetics; Escherichia coli Proteins - genetics; Female; Gram-Negative Bacteria - genetics; Humans; Infant, Newborn; Inpatients; Klebsiella pneumoniae - genetics; Male; Microbial Sensitivity Tests; Plasmids; Sepsis - epidemiology; Sepsis - microbiology; China; bloodstream infections; infant; mcr-9; mcr-1
• ISSN: 2165-0497; 2165-0497
• DOI: 10.1128/spectrum.01938-21

The aim of this study was to determine the occurrence of mobilized colistin resistance (
) genes in Gram-negative bacteria causing bloodstream infections of child inpatients in China. Bacteria were collected between 2006 and 2019 in a maternal and child health hospital, and
genes were screened by PCR. Five of 252 isolates were
-positive, including one
-positive colistin-resistant Escherichia coli isolate, two
-positive colistin-susceptible Salmonella enterica isolates, and two
-positive colistin-susceptible Enterobacter hormaechei isolates. These were obtained from two neonate and three infant patients admitted between 2009 and 2018. The E. coli isolate was obtained from a neonate aged 20 min, suggestive of a possible mother-to-neonate transmission. The five
-positive isolates were multidrug resistant, and two S. enterica and one
isolate showed a hypervirulent phenotype compared to a hypervirulent Klebsiella pneumoniae type strain in a Galleria mellonella infection model. The
gene was carried by an IncX4-type pA1-like epidemic plasmid, and the
gene was detected on IncHI2/2A-type novel plasmids co-carrying multiple resistance genes. The four IncHI2/2A-type plasmids shared a backbone and a high similarity (≥77% coverage and ≥ 90% nucleotide identity), suggesting that they were derived from a common ancestor with cross-species transmission and have circulated locally over a long period. The conjugation assay showed that the
-encoding plasmid and one
-encoding plasmid were self-transmissible to E. coli with high conjugation frequencies. Our findings demonstrate that
genes have disseminated in the community and/or hospitals, mediated by epidemic/endemic plasmids over a long period. The study shows that continuous monitoring of
genes is imperative for understanding and tackling their dissemination.
Antimicrobial resistance, especially the spread of carbapenemase-producing
(CPE), represents one of the largest challenges to One Health coverage of environmental, animal, and human sectors. Colistin is one of the last-line antibiotics for clinical treatment of CPE. However, the emergence of the mobilized colistin resistance (
) gene largely threatens the usage of colistin in the clinical setting. In this study, we investigated the existence of
genes in 252 Gram-negative bacteria collected between 2006 and 2019 which caused bloodstream infections of child inpatients in China. We found a high prevalence of
carriage among children inpatients in the absence of professional exposure, and
might have widely disseminated in the community via different routes. This study emphasizes the importance of rational use of colistin in the One Health frame, and highlights both the urgent need for understanding the prevalence and dissemination of
genes in different populations and the importance of effective measures to control their spread.