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Friday, December 23, 2016 Written by Fred C. Tenover, Ph.D., D(ABMM), Senior Director for Scientific Affairs and Consortium Director

The Cepheid HAI Consortium (A User-Based Resource)

INTRODUCTION

The theme of the Cepheid Healthcare Associated Infection (HAI) Consortium is “Our Customers as Collaborators.” Our vision is to enlist our customers as partners to answer key questions about the changing epidemiology of healthcare-associated infections and resistance patterns of HAI-associated microorganisms. Consortium members provide Cepheid with organisms of interest during defined time periods. All isolates Cepheid receives have been de-identified and coded so that there is no link to patients’ protected health information. We have received and studied more than 500 isolates to date. The results of our studies are not only of scientific interest but they help Cepheid keep abreast of changing strain patterns that may influence our Xpert® assays. This has been particularly helpful in addressing the changing epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) isolates with the recognition of both “empty cassette” strains (where mecA is lost from the SCCmec cassette) and the emergence of SCCmec variants.

The Consortium currently includes 26 hospitals with broad geographic representation of the continental United States and Hawaii that have donated isolates for the study (see map). The initial focus of the consortium is to explore issues associated with MRSA. The objectives of the first study were to: (1) determine shifts in major MRSA clonal types seen in the U.S., (2) identify novel antimicrobial resistance patterns, (3) characterize changes in SCCmec profiles, and (4) compare the strain types and resistance patterns of nasal and blood culture isolates. The results were presented at the 50th ICAAC meeting in Boston in September 2010. For typing studies, Cepheid chose staphylococcal protein A gene (spa) typing as its primary method, with additional typing of selected isolates by pulsed-field gel electrophoresis (PFGE). Spa typing is a DNA sequence-based typing method that is commonly used in Europe and elsewhere around the world to characterize MRSA isolates.1 However, there is little information about the distribution of spa types in the United States. Correlations between strain types determined by spa and PFGE have been established and we wanted to validate those relationships.2 In addition, the study examined the antimicrobial susceptibility patterns of the MRSA isolates tested with a series of older and newer agents to screen for emerging resistance profiles in collaboration with scientists from Achaogen, a South San Francisco pharmaceutical company. Finally, we characterized the staphylococcal cassette chromosome (SCC)mec types of the isolates. SCCmec is the genetic element in the chromosome that encodes the methicillin resistance gene.

BACKGROUND TO THE STUDY

During the last decade, a novel MRSA strain type, USA300, emerged and spread across the United States, becoming the most common cause of community-associated MRSA (CA-MRSA) infections in the country.3,4 USA300 replaced other MRSA strain types, which had become established in many U.S. regions, including the original CA-MRSA strain from the Midwestern U.S., i.e., USA400 (MW2). The proportion of USA300 isolates recovered from the nares of healthy people in the United States also rose significantly from 2001–2002 to 2003–2004 according to the data published from the National Health and Nutrition Examination Survey (NHANES) conducted by the Centers for Disease Control and Prevention.5

USA300 isolates have spread into healthcare centers and now cause a significant portion of healthcare-associated MRSA infections.3 This strain appears to be displacing the traditional multi-drug resistant healthcare associated MRSA strain USA100. As USA300 has spread across the United States, it has also become more resistant to antimicrobial agents. Indeed, multi-drug resistant strains of USA300 have been recognized in San Francisco, Boston, and other centers.6 The emergence of USA300 represents an impressive biological success story.

THE RESULTS

Although the details are being submitted for publication, the data showed a surprising shift in the strain types of invasive (blood) isolates of MRSA away from spa type 2 (t002) (using the Kreiswirth/Ridom nomenclature), which is also SCCmec II (i.e., USA100), to spa type 1 (t008) SCCmec IV (i.e., USA300). Nasal isolates were just the opposite with USA100 predominating. A limitation of the study is that it is a convenience sample of isolates and is not population based. Nonetheless, the shift in strain types is intriguing.

THE FUTURE

We will continue to collect and characterize MRSA isolates beginning again in 2011, but we will also begin a second Consortium project. Another major area of concern in the field of HAIs is the changing epidemiology of Clostridium difficile infections. There is, at present, little information available on the C. difficile strain types circulating in the United States, although according to data from Cepheid’s Xpert clinical trials, strain types likely affect the sensitivity of many antigen-based detection assays, so the data are of practical significance.7 Thus, the next study on the HAI Consortium agenda is to survey C. difficile strain types among Consortium member hospitals. Stay tuned for what should be a very eye-opening investigation.

On behalf of the scientific and medical affairs teams at Cepheid, we thank you for your interest in our technology and hope that you will consider joining with us in our HAI Consortium efforts.

REFERENCES

1. Harmsen, D., et al. 2003. Typing of methicillin-resistant Staphylococcus aureus in a university hospital setting by using novel software for spa repeat determination and database management. J Clin Microbiol. 41: 5442-5448.
2. Goering, R. V., et al. 2008. Molecular epidemiology of methicillin-resistant and methicillin-susceptible Staphylococcus aureus isolates from global clinical trials. J Clin Microbiol. 46: 2842-2847.
3. Klevens, R. M., et al. 2007. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA. 298: 1763-1771.
4. Moran, G. J., et al. 2006. Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med. 355: 666-674.
5. Tenover, F. C., et al. 2008. Characterization of Staphylococcus aureus isolates from nasal cultures collected from individuals in the United States in 2001 to 2004. J Clin Microbiol. 46: 2837-2841.
6. Diep, B. A., et al. 2008. Emergence of multidrug-resistant, community-associated, methicillin-resistant Staphylococcus aureus clone USA300 in men who have sex with men. Ann Intern Med. 148: 249-257.
7. Tenover, F. C., et al. 2010. Impact of strain type on detection of toxigenic Clostridium difficile: comparison of molecular diagnostic and enzyme immunoassay approaches. J Clin Microbiol. 48: 3719-3724.