Whole-Genome Sequencing Reveals the Contribution of Long-Term Carriers in Staphylococcus aureus Outbreak Investigation

June 23, 2017 at 3:37 pm

Clin. Microbiol. July 2017 55:2188-2197

C. Gordon, B. Pichon, T. Golubchik, D. J. Wilson, J. Paul, D. S. Blanc, K. Cole, J. Collins, N. Cortes, M. Cubbon, F. K. Gould, P. J. Jenks, M. Llewelyn, J. Q. Nash, J. M. Orendi, K. Paranthaman, J. R. Price, L. Senn, H. L. Thomas, S. Wyllie, D. W. Crook, T. E. A. Peto, A. S. Walker, and A. M. Kearns

aNational Institute for Health Research Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, United Kingdom

bNuffield Department of Medicine, University of Oxford, Oxford, United Kingdom

cAntimicrobial Resistance and Healthcare Associated Infections Reference Unit, Public Health England, Colindale, United Kingdom

dPublic Health England, Royal Sussex County Hospital, Brighton, United Kingdom

eLausanne University Hospital, Service of Preventative Medicine, Lausanne, Switzerland

fNewcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, United Kingdom

gPortsmouth Hospitals NHS Trust, Portsmouth, United Kingdom

hBrighton and Sussex University Hospitals NHS Trust, Brighton, United Kingdom

iPlymouth Hospitals NHS Trust, Plymouth, United Kingdom

jBrighton and Sussex Medical School, Falmer, United Kingdom

kEast Kent Hospitals NHS Foundation Trust, Canterbury, United Kingdom

lRoyal Stoke University Hospital, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, United Kingdom

mPublic Health England, London, United Kingdom

nNational Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at University of Oxford, Oxford, United Kingdom

Whole-genome sequencing (WGS) makes it possible to determine the relatedness of bacterial isolates at a high resolution, thereby helping to characterize outbreaks.

However, for Staphylococcus aureus, the accumulation of within-host diversity during carriage might limit the interpretation of sequencing data. In this study, we hypothesized the converse, namely, that within-host diversity can in fact be exploited to reveal the involvement of long-term carriers (LTCs) in outbreaks.

We analyzed WGS data from 20 historical outbreaks and applied phylogenetic methods to assess genetic relatedness and to estimate the time to most recent common ancestor (TMRCA).

The findings were compared with the routine investigation results and epidemiological evidence.

Outbreaks with epidemiological evidence for an LTC source had a mean estimated TMRCA (adjusted for outbreak duration) of 243 days (95% highest posterior density interval [HPD], 143 to 343 days) compared with 55 days (95% HPD, 28 to 81 days) for outbreaks lacking epidemiological evidence for an LTC (P = 0.004). A threshold of 156 days predicted LTC involvement with a sensitivity of 0.875 and a specificity of 1.

We also found 6/20 outbreaks included isolates with differing antimicrobial susceptibility profiles; however, these had only modestly increased pairwise diversity (mean 17.5 single nucleotide variants [SNVs] [95% confidence interval {CI}, 17.3 to 17.8]) compared with isolates with identical antibiograms (12.7 SNVs [95% CI, 12.5 to 12.8]) (P < 0.0001).

Additionally, for 2 outbreaks, WGS identified 1 or more isolates that were genetically distinct despite having the outbreak pulsed-field gel electrophoresis (PFGE) pulsotype.

The duration-adjusted TMRCA allowed the involvement of LTCs in outbreaks to be identified and could be used to decide whether screening for long-term carriage (e.g., in health care workers) is warranted.

Requiring identical antibiograms to trigger investigation could miss important contributors to outbreaks.



Entry filed under: Bacterias, Biología Molecular, Epidemiología, Metodos diagnosticos, Resistencia bacteriana, Sepsis, Update.

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