Drug-resistant infections are becoming one of the scariest epidemics since the advent of antibiotic discovery. Although microbes like methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci*, and multidrug-resistant Pseudomonas aeruginosa are responsible for 23,000 deaths in the US alone, they don’t garner the headlines of a disease like Ebola, which although clearly a devastating outbreak in Africa, affected far fewer people within North America.
If “outbreak” doesn’t imply people walking around in orange biohazard suits, it does mean a sudden increase in infection. Before any infection control measures can be implemented, the source of the outbreak has to be identified – often easier said than done. A new research paper published in mBio this week covers identification of a MRSA strain, ST228, within a hospital setting.
The research was performed by a team of clinician scientists in Switzerland’s University Hospital of Lausanne, including lead scientist Dominique Blanc and first author Laurence Senn. 1600 patients were diagnosed with MRSA between 2008 and 2012, and sequencing showed the majority of these was due to a single clone, ST228, indicating that these patients were infected after being admitted to the hospital (rather than newly admitted patients bringing in new MRSA strains as they were admitted). Incidence of hospital-acquired MRSA cases peaked around 2010, but ST228 remained the prevalent isolate even after the number of MRSA cases dropped (see figure, right). How was this strain maintained among patients?
Super spreaders are a potent source of hospital-acquired infections (HAIs). These individuals, like Typhoid Mary, are often asymptomatically colonized by the epidemic strain. A single health-care worker in the hospital system was found in 2009 to carry the ST228 clone and treated to eliminate the colonization. Yet as the bar graph indicates, the ST228 strain continued to circulate within the hospital, so this individual was not the original source.
As patients were screened for MRSA carriage, the researchers noted a high number of groin samples were positive. This is unusual, because S. aureus is often associated with skin or nasal carriage, and is not normally considered part of the gut microbiome. Further investigation revealed 70% of ST228 carriers had positive rectal swabs, suggesting this strain has a different niche preference than other S. aureus strains. To get a better idea of how ST228 might differ from other strains, the scientists performed whole-genome sequencing on 228 patient isolates, and alignment was performed using the core genome (omitting mobile genetic elements).
Their results showed two major clusters: one with moderate diversity from isolates collected from before the outbreak (cluster 1, see figure at left), and one with very low diversity, suggesting patient-to-patient transfer (cluster 2). Analysis of patient movement was able to show that the beginning of the outbreak was associated with shared wards between infected patients, the septic surgery ward and the ENT ward. As the outbreak progressed, the association with a single ward was lost. However, pinpointing these two wards informs hospital surveillance staff that septic surgery wards, not always intuited as a source of MRSA, can indeed harbor and disseminate this pathogen.
How was this outbreak able to continue for so long? Several traits of this particular strain may have allowed it to persist in a hospital setting. This includes acquisition of two genes, which confer resistance to mupirocin, often used to decolonize MRSA carriers, and chlorhexidine, often used to disinfect health-care settings. Additionally, the strain had a proclivity for enteric colonization. Finally, the strain likely colonized a number of individuals, such as the health-care worker mentioned above, without causing disease. This silent transmission of MRSA with an uncommon niche propensity and genetic adaptation specific for a health-care setting set the stage for a difficult-to-identify outbreak origin.
Fortunately, the researchers were able to use sequencing technology to find the source, allowed infection-control specialists to better prepare themselves. As WGS continues to decrease in price, labor, and time-to-answer, it may become the strongest weapon we have in future outbreaks against organisms able to rapidly adapt to our cleverest prevention attempts.
-- Julie Wolf
* Originally posted as vancomycin-resistant Klebsiella pneumoniae, when the most prevalent forms of resistant bacteria are vancomycin-resistant Enterococcus faecium and faecalis, and carbapenem-resistant Klebsiella pneumoniae