Longitudinal genomic surveillance of MRSA in the UK reveals transmission patterns in hospitals and the community

Abstract

Genome sequencing has provided snapshots of the transmission of methicillin-resistant Staphylococcus aureus (MRSA) during suspected outbreaks in isolated hospital wards. Scale-up to populations is now required to establish the full potential of this technology for surveillance. We prospectively identified all individuals over a 12-month period who had at least one MRSA-positive sample processed by a routine diagnostic microbiology laboratory in the East of England, which received samples from three hospitals and 75 general practitioner (GP) practices. We sequenced at least 1 MRSA isolate from 1465 individuals (2282 MRSA isolates) and recorded epidemiological data. An integrated epidemiological and phylogenetic analysis revealed 173 transmission clusters containing between 2 and 44 cases and involving 598 people (40.8%). Of these, 118 clusters (371 people) involved hospital contacts alone, 27 clusters (72 people) involved community contacts alone, and 28 clusters (157 people) had both types of contact. Community- and hospital-associated MRSA lineages were equally capable of transmission in the community, with instances of spread in households, long-term care facilities, and GP practices. Our study provides a comprehensive picture of MRSA transmission in a sampled population of 1465 people and suggests the need to review existing infection control policy and practice.

Fig. 1. Map showing the study catchment area in the East of England.

The locations of hospitals (n=3), GP practices (n=75) and postcode districts are shown for the 1,465 study cases. Postcode districts are color-coded to show the number of MRSA positive cases sampled in each district. A total of 5,012,137 residents lived in the highlighted districts (16,240 km²) according to the 2011 UK Census.

Fig. 2. Pairwise comparison between MRSA relatedness and type of patient contact.

For each case, the most closely related MRSA isolate from another case was identified and the epidemiological contact of each case-pair defined. The number of cases in each epidemiological category is shown as a function of the genetic distance. Panels A to D show the genetic distance distribution for cases with hospital contacts alone. Direct contact refers to a link in the same time and place (ward or hospital). Indirect contact refers to a link in the same place but different time. Panel E shows community contacts. Cases with neither hospital nor community contacts are shown in panel F. Only cases with MRSA isolates from clonal complexes found in at least one other patient in the population are shown (n=1,459).

Fig. 3. Transmission clusters color coded on the CC22 phylogeny.

Maximum likelihood tree generated from 34,600 SNP sites in the core genome is shown for 1,667 CC22 isolates. Colors refer to type of epidemiological links in clusters of genetically related isolates (maximum 50 SNPs) from multiple cases.

Fig. 4. Exemplars of two patterns of nosocomial MRSA spread

(A) Ward-centric pattern. Eight patients in this transmission cluster had ward contacts in ward B2 and B21, including admission overlaps. Of note, the putative epicenter of transmission was in wards B2 or B21, but the outbreak strain was isolated on later admissions in 6 of the 8 patients, 3 of which (1090, 727 and 762) were first detected at a different hospital (hospital A) from where they had putatively acquired it (i.e. in hospital B). B. Patient-centric pattern. Six patients had stayed in wards visited by patient 388 (i.e. A49, A80 and A59) prior to their MRSA isolation date. Negative MRSA screens prior to entry to these wards for some patients (1288, 1057, 1488, 1377 and 942) further supports hospital acquisition. Isolates from patient 388 were the most basal in the phylogenetic tree and their diversity enclosed that of isolates from the other patients, providing further indicators for this patient being the potential source for the transmission cluster. Colored blocks other than grey represent ward contacts, which are labeled by a letter to denote the hospital (A or B) and a number that denotes the anonymised ward.