The spread of carbapenemase-producing Enterobacteriaceae (CPE), contributing to widespread carbapenem resistance, has become a global concern. However, the specific dissemination patterns of carbapenemase genes have not been intensively investigated in developing countries, including Myanmar, where NDM-type carbapenemases are spreading in clinical settings. In the present study, we phenotypically and genetically characterized 91 CPE isolates obtained from clinical (n = 77) and environmental (n = 14) samples in Yangon, Myanmar. We determined the dissemination of plasmids harboring genes encoding NDM-1 and its variants using whole-genome sequencing and plasmid analysis. IncFII plasmids harboring blaNDM-5 and IncX3 plasmids harboring blaNDM-4 or blaNDM-7 were the most prevalent plasmid types identified among the isolates. The IncFII plasmids were predominantly carried by clinical isolates of Escherichia coli, and their clonal expansion was observed within the same ward of a hospital. In contrast, the IncX3 plasmids were found in phylogenetically divergent isolates from clinical and environmental samples classified into nine species, suggesting widespread dissemination of plasmids via horizontal transfer. Half of the environmental isolates were found to possess IncX3 plasmids, and this type of plasmid was confirmed to transfer more effectively to recipient organisms at a relatively low temperature (25°C) compared to the IncFII plasmid. Moreover, various other plasmid types were identified harboring blaNDM-1, including IncFIB, IncFII, IncL/M, and IncA/C2, among clinical isolates of Klebsiella pneumoniae or Enterobacter cloacae complex. Overall, our results highlight three distinct patterns of the dissemination of blaNDM-harboring plasmids among CPE isolates in Myanmar, contributing to a better understanding of their molecular epidemiology and dissemination in a setting of endemicity.
The bacterial enzyme New Delhi metallo-β-lactamase hydrolyzes almost all β-lactam antibiotics, including carbapenems, which are drugs of last resort for severe bacterial infections. The spread of carbapenem-resistant Enterobacteriaceae that carry the New Delhi metallo-β-lactamase gene, blaNDM, poses a serious threat to public health. In this study, we genetically characterized eight carbapenem-resistant Escherichia coli isolates from a tertiary care hospital in Yangon, Myanmar. The eight isolates belonged to five multilocus-sequence types and harbored multiple antimicrobial-resistance genes, resulting in resistance against nearly all of the antimicrobial agents tested, except colistin and fosfomycin. Nine plasmids harboring blaNDM genes were identified from these isolates. Multiple blaNDM genes were found in the distinct Inc-replicon types of the following plasmids: an IncA/C2 plasmid harboring blaNDM-1 (n = 1), IncX3 plasmids harboring blaNDM-4 (n = 2) or blaNDM-7 (n = 1), IncFII plasmids harboring blaNDM-4 (n = 1) or blaNDM-5 (n = 3), and a multireplicon F plasmid harboring blaNDM-5 (n = 1). Comparative analysis highlighted the diversity of the blaNDM-harboring plasmids and their distinct characteristics, which depended on plasmid replicon types. The results indicate circulation of phylogenetically distinct strains of carbapenem-resistant E. coli with various plasmids harboring blaNDM genes in the hospital.
Melioidosis was first identified in Myanmar in 1911 but for the last century it has remained largely unreported there. Burkholderia pseudomallei was first isolated from the environment of Myanmar in 2016, confirming continuing endemicity. Recent genomic studies showed that B. pseudomallei originated in Australia and spread to Asia, with phylogenetic evidence of repeated reintroduction of B. pseudomallei across countries bordered by the Mekong River and the Malay Peninsula. We present the first whole-genome sequences of B. pseudomallei isolates from Myanmar: nine clinical and seven environmental isolates. We used large-scale comparative genomics to assess the genetic diversity, phylogeography and potential origins of B. pseudomallei in Myanmar. Global phylogenetics demonstrated that Myanmar isolates group in two distantly related clades that reside in a more ancestral Asian clade with high amounts of genetic diversity. The diversity of B. pseudomallei from Myanmar and divergence within our global phylogeny suggest that the original introduction of B. pseudomallei to Myanmar was not a recent event. Our study provides new insights into global patterns of B. pseudomallei dissemination, most notably the dynamic nature of movement of B. pseudomallei within densely populated Southeast Asia. The role of anthropogenic influences in both ancient and more recent dissemination of B. pseudomallei to Myanmar and elsewhere in Southeast Asia and globally requires further study.
Pseudomonas asiatica is a recently proposed species of the genus Pseudomonas. This study describes eight isolates of carbapenem-resistant P. asiatica harboring blaNDM-1 and blaVIM-2, genes encoding metallo-β-lactamase (MBL). These isolates were obtained from urine samples of patients hospitalized in Myanmar. These isolates were resistant to carbapenems but susceptible to colistin. All eight isolates were positive for a carbapenemase inactivation method, CIMTrisII, and seven were positive on an immunochromatographic assay for NDM-type MBL. One isolate was highly resistant to aminoglycosides. Whole-genome sequencing showed that seven isolates harbored blaNDM-1 and one harbored blaVIM-2, with these genes located on the chromosome. One isolate harbored blaNDM-1 and rmtC, a gene encoding 16S rRNA methylase. Five types of genomic environments surrounding blaNDM-1 and blaVIM-2 were detected in these eight isolates, with four isolates having the same type. These data indicate that P. asiatica isolates harboring genes encoding carbapenemases, including blaNDM-1 and blaVIM-2, are spreading in medical settings in Myanmar.
Among 42 gram-negative bloodstream isolates from inpatients in 3 hospitals in Yangon, Myanmar, admitted during July–December 2014, 16 (38%) were extended-spectrum β-lactamase–producing Enterobacteriaceae and 6 (14%) produced carbapenemase. The high prevalence of multidrug-resistant gram-negative bacteria raises concerns about the empiric treatment of patients with sepsis in Yangon.
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