The third of four Singapore papers in the latest supplementary issue of Clinical Infectious Diseases on Infection Prevention in the Asia-Pacific is also based on work funded by the now defunct Communicable Diseases Public Health Research Grant from the Ministry of Health. The lead investigator – A/Prof Angela Chow from the Department of Clinical Epidemiology at Tan Tock Seng Hospital – performed a cross-sectional study (repeated over 3 years – only the first year’s results were reported in the paper) to investigate the transmission of methicillin-resistant Staphylococcus aureus (MRSA) between an acute care hospital and its “network” of closely affiliated three community hospitals and two nursing homes.

It is quite well known that nursing homes and community hospitals serve as reservoirs for multidrug-resistant bacteria because of the relative lack of resources for infection prevention in these settings, and also because the average length of stay at these institutions is far longer than in acute hospitals, increasing the opportunity for transmission of bacteria. If multidrug-resistant bacteria such as MRSA become endemic at these institutions – also termed intermediate-long term care facilities (ILTCs) – any attempt to control their spread becomes multiply more complicated at the national level.

Previously, I had mentioned that our hospitals harboured two major healthcare-associated MRSA clones (HA-MRSA_, based on various work done between 2005 and 2010. Since 2010 however, another new global clone of HA-MRSA – ST45-MRSA – had appeared and made rapid inroads into our hospitals. This clone appeared in the 1990’s in Germany (therefore named the “Berlin clone”), spread throughout many parts of Europe in the early 2000’s, appeared in Hong Kong by the late 2000’s, and was noticed by us in Singapore in 2010. This current study then gave us a chance to update ourselves on the relative distribution of the three major HA-MRSA clones in Singapore not just in the acute hospitals but also in the ILTCs.

The field study team undertook the herculean task of recruiting 999, 358 and 343 subjects respectively from the acute care hospital, 3 community hospitals and 2 nursing homes, all over a 6-week period in 2014. Nasal, axillary and groin swabs were obtained from all subjects, and cultured for MRSA. The MRSA isolates obtained were subject to whole genome sequencing. We were fortunate to be able to partner the Wellcome Trust Sanger Institute for this part of the work, as well as Prof Matthew Holden from the University of St Andrews – a world renowned expert on MRSA genomics – for the bioinformatics work. There is an interesting side story here: the funding agency was initially not keen to support the collaboration with Sanger, because sequencing capability is available in a few research institutions in Singapore. However, the price of whole genome sequencing at Sanger was approximately a third of the “best price” in Singapore (a significant price differential remains even today), while MRSA-specific genomic expertise was lacking, hence “market forces” prevailed.

The results were certainly interesting but sobering:

  • The percentage of inpatients colonised with MRSA at the acute care hospital was high (11.8%) but nonetheless far lower than inpatients at the community hospitals (29.9%) or nursing homes (20.4%).
  • The majority of MRSA clones belonged to ST22, ST45 and ST239 as expected, but the number of isolates belonging to the Berlin clone (ST45) far exceeded those of the older  ST239.
  • There were far more and varied MRSA clones (including those belonging to community-associated MRSA lineages such as ST59 and ST30) in community hospitals and nursing homes. This can be interpreted in several ways, but our hypothesis was that the relatively poorer infection prevention practices in these settings permitted more MRSA clones to be established.
Distribution of MRSA clones in the different healthcare settings. ST22 (EMRSA-15) was the predominant clone in each setting, although a greater variety of clones were seen in nursing home and community hospital settings.
  • If we accept the premise that 60 SNPs defined a “recent transmission cluster” (and Prof Holden’s team did a lot of work in this area), then virtually all of such clusters involved inpatients from at least 2 different healthcare settings. Suggesting that there is frequent transmission of MRSA between the acute hospital, community hospitals and nursing homes.
  • The subsequent network analysis (using genomic differences to reconstruct transmission events) is speculative, but suggested that the acute hospital was both the source of MRSA to the community hospitals and also the reservoir for MRSA in the nursing homes.
Transmission dynamics of MRSA in the healthcare facilities evaluated. The thicker the arrow, the greater the number of transmission events.

It remains to be seen if the results of the next two years (2015 and 2016 – the study is now completed) will validate these findings, but the implications are clear: interconnected infection prevention strategies – including rapid sharing of information and best practices – should be implemented in healthcare networks, rather than let each institution define how best to practice infection prevention.