Journal
GENOME BIOLOGY
Volume 20, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13059-019-1785-1
Keywords
Resistance mechanisms; Population dynamics; Intrinsic resistance; Plasmid diversity
Funding
- Wellcome Trust [098051]
- PHE [108077]
- UKCRC Translational Infection Research Initiative [G1000803]
- Biotechnology and Biological Sciences Research Council
- National Institute for Health Research on behalf of the Department of Health
- Chief Scientist Office of the Scottish Government Health Directorate
- Health Protection Agency
- NIHR Cambridge Biomedical Research Centre
- Wellcome Sanger Institute PhD studentship
- Australian Research Council DECRA fellowship [DE180100929]
- NIHR Biomedical Research Centres in Cambridge (NIHR Cambridge BRC AMR Theme)
- Academy of Medical Sciences
- Health Foundation
- Medical Research Council [G1000803]
- MRC [MR/N029399/1, G1000803] Funding Source: UKRI
- Australian Research Council [DE180100929] Funding Source: Australian Research Council
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Background Two of the most important pathogens contributing to the global rise in antimicrobial resistance (AMR) are Klebsiella pneumoniae and Enterobacter cloacae. Despite this, most of our knowledge about the changing patterns of disease caused by these two pathogens is based on studies with limited timeframes that provide few insights into their population dynamics or the dynamics in AMR elements that they can carry. Results We investigate the population dynamics of two priority AMR pathogens over 7 years between 2007 and 2012 in a major UK hospital, spanning changes made to UK national antimicrobial prescribing policy in 2007. Between 2006 and 2012, K. pneumoniae showed epidemiological cycles of multi-drug-resistant (MDR) lineages being replaced approximately every 2 years. This contrasted E. cloacae where there was no temporally changing pattern, but a continuous presence of the mixed population. Conclusions The differing patterns of clonal replacement and acquisition of mobile elements shows that the flux in the K. pneumoniae population was linked to the introduction of globally recognized MDR clones carrying drug resistance markers on mobile elements. However, E. cloacae carries a chromosomally encoded ampC conferring resistance to front-line treatments and shows that MDR plasmid acquisition in E. cloacae was not indicative of success in the hospital. This led to markedly different dynamics in the AMR populations of these two pathogens and shows that the mechanism of the resistance and its location in the genome or mobile elements is crucial to predict population dynamics of opportunistic pathogens in clinical settings.
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