MRSA transmission on a neonatal intensive care unit: epidemiological and genome-based phylogenetic analyses

Abstract

Background: Methicillin-resistant Staphylococcus aureus (MRSA) may cause prolonged outbreaks of infections in neonatal intensive care units (NICUs). While the specific factors favouring MRSA spread on neonatal wards are not well understood, colonized infants, their relatives, or health-care workers may all be sources for MRSA transmission. Whole-genome sequencing may provide a new tool for elucidating transmission pathways of MRSA at a local scale.

Methods and findings: We applied whole-genome sequencing to trace MRSA spread in a NICU and performed a case-control study to identify risk factors for MRSA transmission. MRSA genomes had accumulated sequence variation sufficiently fast to reflect epidemiological linkage among individual patients, between infants and their mothers, and between infants and staff members, such that the relevance of individual nurses' nasal MRSA colonization for prolonged transmission could be evaluated. In addition to confirming previously reported risk factors, we identified an increased risk of transmission from infants with as yet unknown MRSA colonisation, in contrast to known MRSA-positive infants.

Conclusions: The integration of epidemiological (temporal, spatial) and genomic data enabled the phylogenetic testing of several hypotheses on specific MRSA transmission routes within a neonatal intensive-care unit. The pronounced risk of transmission emanating from undetected MRSA carriers suggested that increasing the frequency or speed of microbiological diagnostics could help to reduce transmission of MRSA.

Figure 1. Definition of MRSA-related patient status.

Initially, birth or a negative swab result in the status “MRSA-negative”. A few days later another swab is taken, which turns out MRSA-positive. MRSA is presumed to have been acquired latest one day before the positive swab was taken, because it takes time for the bacteria to multiply and spread from the location of transmission to the location being swabbed. Therefore, the infant’s status is “unknown MRSA-positive” from one day before the positive swab until the positive result is received on the ward. Thereafter, the infant’s status is “known MRSA-positive”.

Figure 2. Maximum clade credibility tree based on BEAST analysis of MRSA genome sequences.

Tips of the tree are constrained by bacterial isolation dates, the time scale is shown at the bottom. Node support is indicated for posterior probabilities ≥0.9. The case-control study period (February 8 to August 31, 2010) is indicated by grey shading. MRSA from patients (patient numbers are indicated), healthcare workers (HCW A, HCW B) and two mothers of patients are included. Colours indicate patient positions on wards A, B, and C, respectively. Blue bars indicate 95% Bayesian credibility intervals of bacterial divergence dates (node heights).