Whole-genome sequencing shows that patient-to-patient transmission rarely accounts for acquisition of Staphylococcus aureus in an Intensive Care Unit

Staphylococcus aureus is a leading cause of healthcare associated infection. Efforts to reduce the burden of S. aureus infections in healthcare settings have targeted patient carriage and preventing person-to-person transmission. These measures have only been partially successful. Our understanding of S. aureus transmission is limited by low discrimination of currently available typing techniques. The high resolution offered by whole-genome sequencing (WGS) has the potential to overcome these limitations. We investigated the role of colonised patients as the source of new S. aureus acquisition in a hospital setting. Over the study period all patients admitted to an adult intensive care unit (ICU) were assessed for carriage, acquisition and their role in transmission. The primary objectives of the study were to determine the rate of S. aureus acquisition in patients admitted to ICU and investigate the role of colonised patients as a source of these acquisitions. In achieving these objectives we also established the ability of WGS to differentiate carriage strains of S. aureus by evaluating within and between host diversity, and establish the reliability of conventional approaches (spa-typing combined with overlapping patient stay) to detect transmission by comparing with WGS. We found that WGS disproved transmission events indicated by conventional methods. In addition WGS revealed both transmission and acquisition events invisible by conventional methods. Furthermore, WGS has the resolution to differentiate carriage strains within and between hosts allowing thresholds to be established to interpret the relationship of transmission pairs. This represents the first systematic evaluation of nosocomial patient-to-patient transmission of S. aureus using WGS. These results challenge previous assumptions about the role of patients in S. aureus transmission routes in hospital settings.