Nosing around for staphylococci

In my last post about the newly described MRSA strains that carry the mecA_LGA251, I referred again to the “empty cassette variants” (or “mecA dropouts”) that are missed by commercial MRSA PCR tests that target the orfX gene but don’t contain mecA primers. I also mentioned that we’d soon be publishing our first year of experience with this. Well, here is the short report I was talking about, describing our ~8% rate of false positivity due to empty cassette variants, and characterizing the strains in question. We found substantial genetic diversity among the “drop-out” strains, meaning that the problem wasn’t due to the introduction of a single clone. When we tested these MSSA isolates using the newer GeneXpert MRSA/SA Nasal Assay (the “Nasal Complete” assay), they were correctly identified as S. aureus but not MRSA (this new assay has primers for the mecA gene). Even the “Nasal Complete” assay is susceptible to false positives, though, from the simultaneous presence of an MSSA and a methicillin-resistant coagulase-negative staphylococcus (MR-CoNS) in the same nose (the prevalence of MR-CoNS + MSSA co-colonization was 3.4% in one study). Indeed, the package insert describes a PPV of about 75% for the Nasal Complete—for MRSA, the 25% “false positives” divide equally between those for which culture was negative (which might reflect increased sensitivity of PCR) and those for which the culture grew only MSSA (which may reflect MR-CoNS/MSSA co-colonization). Who knew the nares would be such a vexing place for those who design and market PCR tests?

WHO backs rapid test for TB - If only we had rapid treatment

I heard on NPR this morning that the WHO (Keith Moon died 32 years ago) is supporting the new rapid TB test made by Cepheid (MTB/RIF test).  You can read more about the test characteristics in the recent NEJM article. They reported 98% sensitivity in smear-positive patients but only 73% sensitivity in smear-negative patients after a single test.  Sensitivity rises to 85% after a second test and to 90% after a third test.  The test was very good at identifying rifampin-resistant and rifampin-sensitive strains (both around 98% of the time).

The NPR article states that the processor costs $64,000 in US but could be $17,000 for developing countries.  Tests will cost $17.  If you need to do three tests in smear-negative patients to rule out TB with a sensitivity of 90%, it would cost $51. I wonder if developing country budgets can absorb that cost?

Heads, MRSA. Tails, possibly MRSA.

Cepheid just issued a recall notice on the Xpert MRSA/SA BC test, the rapid, real-time assay that is designed to quickly identify MRSA vs. MSSA in positive blood cultures. Seems MRSA can evolve (!), and there are now some isolates that are not detected, resulting in false-negative results (that's what us clin micro types call a "very major error"). Here is the text of the notification:

Dear Valued Customer:

Based on the recall announced July 1, 2010, Cepheid is initiating a recall of all lots of Xpert MRSA/SA BC (blood culture) product. The recall is a corrective action, which does not require return of product to the manufacturer. Customers may continue to use the product; however, when a MRSA negative/SA positive result is obtained, the results should be interpreted as MRSA indeterminate/Staphylococcus aureus positive, antimicrobial susceptibility testing pending. Further testing should be performed using an FDA-cleared, phenotypic antimicrobial susceptibility testing method on isolated colonies recovered from the blood culture bottle. MRSA positive/SA positive results can still be reported as such. The new instructions will be incorporated in the product labeling. The Xpert MRSA/SA BC product produces false-negative MRSA results, which could potentially contribute to incorrect treatment of an MRSA infection.

The following statement will be added to the Interpretation of Results section of the package insert for "MRSA Negative/SA Positive" results:

The results should be interpreted as "MRSA indeterminate/SA Positive, antimicrobial susceptibility testing pending". Further testing should be performed using a FDA-cleared, phenotypic antimicrobial susceptibility testing method on isolated colonies recovered from the blood culture bottle.

Although the product appears to continue to meet performance claims as outlined in the current product labeling, an ongoing failure investigation has identified the emergence of novel MRSA strain types as one of the causes of false-negative MRSA results. The failure investigation has not fully determined the remaining causes of the false-negative MRSA results. To date, one adverse event has been reported to the FDA through the MDR process.