Dataset Information

Whole Genome Sequencing detects Inter-Facility Transmission of Carbapenem-resistant Klebsiella pneumoniae.

ABSTRACT: OBJECTIVES:To identify transmission patterns of Carbapenem-resistant Klebsiella pneumoniae infection during an outbreak at a large, tertiary care hospital and to detect whether the outbreak organisms spread to other facilities in the integrated healthcare network. METHODS:We analyzed 71?K. pneumoniae whole genome sequences collected from clinical specimens before, during and after the outbreak and reviewed corresponding patient medical records. Sequence and patient data were used to model probable transmissions and assess factors associated with the outbreak. RESULTS:We identified close genetic relationships among carbapenem-resistant K. pneumoniae isolates sampled during the study period. Transmission tree analysis combined with patient records uncovered extended periods of silent colonization in many study patients and transmission routes that were likely the result of asymptomatic patients transitioning between facilities. CONCLUSIONS:Detecting how and where Carbapenem-resistant K. pneumoniae infections spread is challenging in an environment of rising prevalence, asymptomatic carriage and mobility of patients. Whole genome sequencing improved the precision of investigating inter-facility transmissions. Our results emphasize that containment of Carbapenem-resistant K. pneumoniae infections requires coordinated efforts between healthcare networks and settings of care that acknowledge and mitigate transmission risk conferred by undetected carriage and by patient transfers between facilities.

SUBMITTER: Spencer MD

PROVIDER: S-EPMC6408229 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Whole Genome Sequencing detects Inter-Facility Transmission of Carbapenem-resistant Klebsiella pneumoniae.

Spencer Melanie D MD Winglee Kathryn K Passaretti Catherine C Earl Ashlee M AM Manson Abigail L AL Mulder Holly P HP Sautter Robert L RL Fodor Anthony A AA

The Journal of infection 20181129 3

<h4>Objectives</h4>To identify transmission patterns of Carbapenem-resistant Klebsiella pneumoniae infection during an outbreak at a large, tertiary care hospital and to detect whether the outbreak organisms spread to other facilities in the integrated healthcare network.<h4>Methods</h4>We analyzed 71 K. pneumoniae whole genome sequences collected from clinical specimens before, during and after the outbreak and reviewed corresponding patient medical records. Sequence and patient data were used ...[more]

PMID: 30503842

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Project description:Carbapenem-resistantKlebsiella pneumoniae(CR-Kp) is significant threat to public health worldwide. The primary reservoir for CR-Kp is the intestinal tract, where the bacterium is usually present at low density, but can bloom following antibiotic treatment, mostly in hospital settings. The impact of disturbances in the intestinal environment on the fitness, survival, expansion, and drug susceptibility of this pathogen is not well-understood. Nevertheless, gaining such knowledge could lead to innovative intervention strategies for addressing colonization and infection. Here, we adopted anin vivomodel to examine the transcriptional adaptation of a CR-Kp clinical isolate to immune activation in the intestine. We report that as early as 6 hours following host treatment with anti-CD3 antibody, CR-Kp underwent rapid transcriptional changes including downregulation of genes involved in sugar utilization and amino acid biosynthesis, and upregulation of genes involved in amino acid uptake and catabolism, antibiotic resistance, and stress response. In agreement with these findings, the concentration of oxidative species and amino acids was increased in the mouse intestine following treatment. Genes encoding for proteins containing the domain of unknown function (DUF) 1471 were particularly upregulated, however their deletion did not impair CR-Kp fitness in vivoupon immune activation. Transcription factor enrichment analysis identified the global regulator cAMP-Receptor Protein CRP as a potential orchestrator of the observed transcriptional signature. In keeping with the recognized role of CRP in regulating utilization of alternative carbon sources, CRP deletion in CR-Kp resulted in strongly impaired gut colonization, but this effect was not amplified by immune activation. Thus, following intestinal colonization, which occurs in a CRP-dependent manner, CR-Kp can rapidly respond to immune cues by implementing a well-defined and complex transcriptional program whose direct relevance towards bacterial fitness remains cryptic. Further analyses utilizing this model may identify key factors to tackle the intestinal stage of CR-Kp colonization.

Dataset Information

Whole Genome Sequencing detects Inter-Facility Transmission of Carbapenem-resistant Klebsiella pneumoniae.

Publications

Whole Genome Sequencing detects Inter-Facility Transmission of Carbapenem-resistant Klebsiella pneumoniae.

Similar Datasets

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