Changing the paradigm for hospital outbreak detection by leading with genomic surveillance of nosocomial pathogens

The current paradigm for hospital outbreak detection and investigation is based on methodology first developed over 150 years ago. Daily surveillance to detect patients positive for pathogens of particular importance for nosocomial infection is supported by epidemiological investigation to determine their relationship in time and place, and to identify any other factor that could link them. The antibiotic resistance pattern is commonly used as a surrogate for bacterial relatedness, although this lacks sensitivity and specificity. Typing may be used to define bacterial relatedness, although routine methods lack sufficient discriminatory power to distinguish relatedness beyond the level of bacterial clones. Ultimately, the identification of an outbreak remains a predominately subjective process reliant on the intuition of experienced infection control professionals. Here, we propose a redesign of hospital outbreak detection and investigation in which bacterial species associated with nosocomial transmission and infection undergo routine prospective whole-genome sequencing. Further investigation is based on the probability that isolates are associated with an outbreak, which is based on the degree of genetic relatedness between isolates. Evidence is provided that supports this model based on studies of MRSA (methicillin-resistant Staphylococcus aureus), together with the benefits of a ‘Sequence First’ approach. The feasibility of implementation is discussed, together with residual barriers that need to be overcome prior to implementation.

[1]  J. Parkhill,et al.  Building a genomic framework for prospective MRSA surveillance in the United Kingdom and the Republic of Ireland , 2016, Genome research.

[2]  Thomas R Rogers,et al.  Rapid, comprehensive, and affordable mycobacterial diagnosis with whole-genome sequencing: a prospective study , 2016, The Lancet. Respiratory medicine.

[3]  Julian Parkhill,et al.  Whole-genome sequencing for analysis of an outbreak of meticillin-resistant Staphylococcus aureus: a descriptive study , 2013, The Lancet. Infectious Diseases.

[4]  Phelim Bradley,et al.  Whole-genome sequencing for prediction of Mycobacterium tuberculosis drug susceptibility and resistance: a retrospective cohort study , 2015, The Lancet. Infectious diseases.

[5]  Tamara Munzner,et al.  Evidence-based design and evaluation of a whole genome sequencing clinical report for the reference microbiology laboratory , 2017, bioRxiv.

[6]  Daniel J. Wilson,et al.  Diverse sources of C. difficile infection identified on whole-genome sequencing. , 2013, The New England journal of medicine.

[7]  Julian Parkhill,et al.  Rapid whole-genome sequencing for investigation of a neonatal MRSA outbreak. , 2012, The New England journal of medicine.

[8]  Julian Parkhill,et al.  Evolution of MRSA During Hospital Transmission and Intercontinental Spread , 2010, Science.

[9]  J. Parkhill,et al.  Investigation of a Cluster of Sequence Type 22 Methicillin-Resistant Staphylococcus aureus Transmission in a Community Setting , 2017, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[10]  Steven J. M. Jones,et al.  Whole-genome sequencing and social-network analysis of a tuberculosis outbreak. , 2011, The New England journal of medicine.

[11]  G. Smith,et al.  Rapid single-colony whole-genome sequencing of bacterial pathogens , 2013, The Journal of antimicrobial chemotherapy.

[12]  Zena Lapp,et al.  Integrated genomic and interfacility patient-transfer data reveal the transmission pathways of multidrug-resistant Klebsiella pneumoniae in a regional outbreak , 2017, Science Translational Medicine.

[13]  S. Peacock,et al.  Local Persistence of Novel MRSA Lineage after Hospital Ward Outbreak, Cambridge, UK, 2011–2013 , 2016, Emerging infectious diseases.

[14]  C. Churcher,et al.  Are commercial providers a viable option for clinical bacterial sequencing? , 2018, Microbial genomics.

[15]  M. Quail,et al.  Zero tolerance for healthcare-associated MRSA bacteraemia: is it realistic? , 2014, The Journal of antimicrobial chemotherapy.

[16]  David J. Edwards,et al.  Gastrointestinal Carriage Is a Major Reservoir of Klebsiella pneumoniae Infection in Intensive Care Patients , 2017, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[17]  G. Smith,et al.  Rapid bacterial whole-genome sequencing to enhance diagnostic and public health microbiology. , 2013, JAMA internal medicine.

[18]  Francesc Coll,et al.  Longitudinal genomic surveillance of MRSA in the UK reveals transmission patterns in hospitals and the community , 2017, Science Translational Medicine.

[19]  J. Snow On the Mode of Communication of Cholera , 1856, Edinburgh medical journal.