Watch out for the drop outs!

Some of you astute readers may have noticed that in my photo (to the right), there is a Cepheid GeneXpert machine in the background. I didn’t choose this photo with that in mind—I simply thought the last photo was too close up, and I look much better from a distance (a long distance).

I should make clear, however, that this photo should not imply my support for this product over other available diagnostic products. Nor have I received honoraria from the makers of any rapid MRSA detection test (unlike, say, 5 of the 8 authors of a widely-cited study supporting active MRSA surveillance….but I digress……).

As further evidence of my neutrality regarding diagnostic devices, I’m going to point out an annoying little problem we’ve been having lately with the MRSA Xpert assay—false positive tests due to so-called “MRSA drop outs”. This phenomenon results from the fact that the currently FDA-approved assay doesn’t detect the mecA gene itself (the one that encodes resistance), but rather a sequence that includes part of the staphylococcal chromosomal cassette mec element (SCCmec) and the S. aureus orfX gene. Since the SCCmec element is the cassette that carries the mecA complex, the assay should be good—that is, unless the mecA complex has “dropped out”, resulting in an "empty cassette", leaving a methicillin-susceptible S. aureus that tests positive by the Xpert assay. The manufacturer claims that these “drop out” strains are very rare in North America, and there is some data to support this claim. However, MRSA epidemiology is a moving target, and if you don’t run culture in parallel with this assay you’d never know if such strains were becoming more common. In addition, I’m not sure how the manufacturer can know that this is a rare phenomenon unless they’ve sampled very widely across the continent—data I have not seen. In fact, their recently published multicenter trial did not carefully assess for the prevelance of such strains, a limitation they point out in their discussion.

We’ve had several false positives in the past two months due to these MRSA drop-outs. By DNA fingerprinting the isolates are different (meaning we haven’t had one “drop-out” strain emerge, but are seeing several). We don’t do a lot of screening at our University Hospital, and our rate of positivity in the screened population is fairly these false positives are messin' with our positive predictive value.

Cepheid has a new assay nearing FDA approval, one that contains mecA-specific primers. That should solve this problem. But until then, if you are using this assay for MRSA screening, you may wish to periodically (or continuously) perform culture in parallel, to see if you have any of these isolates circulating in your hospital.


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