Human beings are born with an innate desire, most readily observed in early childhood, to investigate what exactly is inside their noses. For those of us who grow up to be clinical microbiologists or infection preventionists some extend this interest to other people's noses. While many people might wonder why would you want to do that, the question that springs to the clinical microbiologist's mind is: which method should I use?

Why Screen for Nasal Carriage of MRSA?

About 5-10% of people in the US are colonized by methicillin-resistant Staphylococcus aureus (MRSA), and one of the most common locations for colonization is the nares (the holes in your nose). For people who are  seriously ill and require admission to an intensive care unit, or who are undergoing surgery, colonization with MRSA (or even methicillin-susceptible S. aureus, MSSA) is a risk factor for subsequently developing a serious staphylococcal infection that could lead to death. In fact, about 20,000 people per year in the US alone die of serious MRSA infections. So under certain circumstances, if you have MRSA (or MSSA) in your nose, we may want to know about it and help you get rid of it.

Under what circumstances we should screen patients for MRSA (or MSSA) is actively debated – and some argue that in most cases, it isn't worth the significant funds required to carry it out effectively. It has also been noted that funds targeting a single organism (such as S. aureus) may be better spent on interventions, such as a preoperative antiseptic scrub, that would help prevent other types of infections as well. Another reason a clinical microbiologist may want to screen for MRSA in certain patient populations is if it is legally required of healthcare facilities in the state they work in, or has been decided by their institution’s infection control group to test all patient in certain units of the hospital. Some question of the value of legal requirements is a healthy means to ensure effective practices, but unless the law changes, clinical microbiologists should follow these requirements.

To screen other people’s noses for S. aureus, a health care worker first needs to swab the patient’s nares – but with what kind of swab? Rayon tipped swabs or flocked swabs are commonly used. There is evidence that flocked swabs may improve yield for MRSA screening compared to a traditional rayon swab/gel transport system, however in another small laboratory comparison with spiked specimens (not patient samples), results were essentially equivalent between rayon tipped swabs and flocked swabs (in this case, eSwabs). While I think eSwabs are a good collection system and possibly have certain advantages over traditional swabs in this application, my lab uses traditional rayon tipped swabs; I’ve learned from experience that I’d rather jam something up my nose than change a collection device across a large health system, unless the evidence in favor of switching is compelling. It’s worth noting that while I have focused on nasal carriage, swabbing multiple anatomical sites improves sensitivity (and cost).

A major branching point is the decision of how to test the swabs: a molecular test or a culture method. Among hundreds of laboratories that utilize The College of American Pathologists (CAP) for proficiency testing, culture methods predominate relative to molecular methods, particularly culture methods using chromogenic selective media. Regular culture media may also be employed (TSB Sheep’s blood agar, or Columbia nalidixic acid agar), particularly if looking for both MSSA and MRSA. Results from a culture method are generally available in 20-24 hours. Studies have also shown that sensitivity can be improved by performing a broth enrichment first: a short culture in broth media before plating to agar enhances results, although this adds some expense and additional labor and increases the turn-around-time (TAT). Most culture-based methods will detect both mecA- and mecC-mediated resistance (although using media that are not selective for methicillin-resistant organisms and a PBP2a assay would not).

Advantages and Disadvantages of Molecular Testing for MRSA

Molecular testing (nucleic acid amplification based testing, for example PCR) for MRSA/MSSA may offer improved sensitivity and TAT relative to culture-based testing, but at a markedly higher cost per test. Molecular testing in many studies demonstrates improved sensitivity relative to culture, but the specificity is not as good compared to culture.

There are 2 approaches to MRSA molecular test design, each with advantages and drawbacks. Single-locus testing targets sequences spanning the staphylococcal cassette chromosome that typically harbors mecA (SCCmec) and orfX (adjacent to SCCmec in S. aureus). Variability in the SCCmec sequence can lead to false negatives when assay primers are of low binding affinity to the altered sequence, despite the presence of functional mecA. Single-locus testing also leads to some false positives where the SCCmec primer binding sites are intact but mecA is absent or the cassette is partially excised. Multi-locus testing evaluates separately for S. aureus (using thermostable nuclease (nuc) or some other conserved S. aureus gene sequence) and resistance genes (mecA and, in some assays, also mecC). This approach has the drawback that specimens that include both MSSA and another Staphylococcus species which is positive for mecA (S. epidermidis, for example) will report falsely positive for MRSA - some labs follow up all positive molecular results with culture for confirmation.

Perhaps the primary drawback of molecular testing is the cost. Single specimen random access assays offer a great TAT, but cost up to $45 per test, whereas other molecular assays that are more suitable for batch testing (commonly run once or twice per day) are cheaper at around $20-$30 per test. Either way, molecular testing is considerably more expensive than culture-based testing (about $1-3 per test, depending on the method), and the volume of tests run can be enormous depending on the patient populations targeted.

These many factors contribute to the ongoing debate weighing the costs and benefits of screening for MSSA/MRSA. If screening is deemed worthwhile, is the added expense of molecular testing worth the increase in sensitivity? How do we interpret older studies given the significant decreases in the prevalence of MRSA in the last 10-15 years? Should we spend the money instead on reducing healthcare-associated infections, which would address multiple organisms?

What questions does MRSA/MSSA screening raise in your lab? How have you addressed these questions? Continue the discussion by leaving a comment below!