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Antimicrob Agents Chemother. 2019 Aug 26. pii: AAC.01622-19. doi: 10.1128/AAC.01622-19. [Epub ahead of print]

Whole Genome Sequencing to Identify Drivers of Carbapenem-Resistant Klebsiella pneumoniae Transmission Within and Between Regional Long-Term Acute Care Hospitals.

Author information

1
Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania.
2
Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania.
3
Department of Biostatistics, Informatics, and Epidemiology, Perelman School of Medicine, University of Pennsylvania.
4
Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, Michigan.
5
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
6
The CHOP Microbiome Center, Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA.
7
R.M. Alden Research Laboratory, Culver City, CA.
8
Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA.
9
Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, GA.
10
Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, Michigan esnitkin@med.umich.edu.
11
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan.
12
Division of Infectious Diseases, Department of Medicine, University of Michigan Medical School, Ann Arbor, Michigan.

Abstract

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an antibiotic resistance threat of the highest priority. Given the limited treatment options for this multidrug-resistant organism (MDRO), there is an urgent need for targeted strategies to prevent transmission. Here, we applied whole-genome sequencing to a comprehensive collection of clinical isolates to reconstruct regional transmission pathways, and analyzed this transmission network in the context of statewide patient transfer data and patient-level clinical data to identify drivers of regional transmission. We found that high regional CRKP burden was due to a small number of regional introductions, with subsequent regional proliferation occurring via patient transfers among healthcare facilities. While CRKP was predicted to be imported into each facility multiple times, there was substantial variation in the ratio of intra-facility transmission events per importation, indicating that amplification occurs unevenly across regional facilities. While myriad factors likely influence intra-facility transmission rates, an understudied one is the potential for clinical characteristics of colonized and infected patient to influence their propensity for transmission. Supporting the contribution of high-risk patients to elevated transmission rates, we observed that CRKP colonized and infected patients in high transmission facilities had higher rates of carbapenem use, malnutrition, old age and dialysis. This study highlights the potential for regional infection prevention efforts that are grounded in genomic epidemiology to identify patients and facilities that make the greatest contribution to regional MDRO prevalence, thereby facilitating the design of precision interventions of maximal impact.

PMID:
31451495
DOI:
10.1128/AAC.01622-19

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