Tuesday, March 4, 2014

Staphylococcus aureus: Here, there and everywhere

To spend any time on our infectious diseases consult service is to be knee-deep in invasive, difficult-to-treat S. aureus disease. Most S. aureus (including MRSA) disease is caused by a strain previously colonizing the host, and given that up to a third of the human population carries S. aureus it is easy to understand why the disease is so common. Exposure to healthcare is a major risk factor for invasive S. aureus disease, simply because so many healthcare interventions (surgery, device use, antibiotic exposure) provide opportunities for the organism to invade. 

Nonetheless, the conventional wisdom still holds that a large proportion of healthcare-associated S. aureus disease results from patient-to-patient transmission events—the corollary being that prevention of S. aureus disease should focus primarily on preventing transmission (including active detection and isolation). However, a careful assessment may demonstrate that interventions solely designed to interrupt transmission are responsible for only a small portion of disease reduction in observational studies (for an example, see my previous post on the VA MRSA directive). This is important, as it should focus our attention on preventing disease among those at risk for colonization (everyone), via such horizontal measures as device-associated infection prevention bundles, chlorhexidine bathing, and suppression/eradication of the carrier state during high-risk intervals

A study by UK investigators published in Clinical Infectious Diseases provides further evidence that patient-to-patient S. aureus transmission is a relatively uncommon event, even as an explanation for S. aureus “acquisition” events in the ICU. Using whole genome sequencing (WGS), the investigators found that only 7 of 37 ICU patients who “newly acquired” S. aureus were colonized with strains that were closely related to other patients who had an overlapping ICU stay. There are several limitations to the work, most of which are outlined by the authors in their discussion and by the excellent accompanying editorial by David and Daum. The limitation most concerning to me is the assumption that a single nares + perineum culture plated directly to solid agar media (chromogenic agar and Columbia CNA) is a sensitive method for detection of S. aureus carriers. It isn’t. Failure to perform a throat culture or to use broth enrichment probably reduced sensitivity by 30-50% (explaining their overall carriage rate of only 16.7%, when most published studies demonstrate S. aureus colonization rates of closer to 30%). We recently performed a study wherein we cultured 500 pregnant women at 5 body sites—the table below is taken from our presentation at the Decennial meeting in 2010 in Atlanta. The bottom line? Using only nares and perineal cultures directly plated to solid agar media would have missed more than half of our S. aureus carriers. Achieving 90% sensitivity (using a positive culture at any of the five body sites as the gold standard) required sampling both the nares and the throat and using overnight broth enrichment.
So what about all those “acquirers” carrying isolates that didn’t match other ICU patients? In addition to implicating other potential reservoirs (personnel, visitors, etc.), I’d wager that some were prior carriers who were newly detected due to sampling issues, increase in CFU associated with healthcare exposure, etc. Intermittent detection of S. aureus carriage is well described, and would be magnified using the microbiological techniques in this study.

Finally, while I agree with the authors that WGS is the new gold standard for assessing genetic relatedness, the use of spa typing as the “conventional method” comparator is too easy. As we found in our recently published study, roughly half of all MRSA isolated from epidemiologically unrelated clinical infections in 43 US hospitals were from a single spa type! (How’s that for discriminatory power?) If you’re going to write off the conventional methods, at least use a method with better discrimination, such as PFGE!

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