What the MRSA PCR? The Role of Nose PCR Swabs in Stewardship.

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How I felt when I found out you can use nose swabs for stewarship.

I recently wrote about the fact that all pneumonia are aspiration events. Depending on the colonization of the oropharynx and the volume of aspirate material plays a role in the development of subsequent disease. It stands to reason that, if we are able to figure out what is colonizing the oropharynx, we may be able to target our antibiotics more appropriately at least on the empiric front. Indeed, this has been attempted for methicillin-resistant staphylococcus aureus. Stewardship programs across the nation have implemented MRSA screening with PCR in those who receive empiric vancomycin for possible HAP/VAP, with negative PCR testing being used to de-escalate anti-MRSA therapy. Indeed, there seems to be a correlation between PCR testing of the nares and subsequent isolation of MRSA in clinical isolates. A prospective study of 1266 patients found that MRSA nasal colonization was 16.4% (1). In multivariate analysis, nasa colonization was associated with increased risk of developing MRSA infection (RR 2.50, 95% CI 1.9-3.27). Another cohort of over 14,000 patients (2) found that colonization of nares was associated with a RR of 3.0 for developing bacteremia (95% CI 2.0-4.7). This was also seen in a cohort of soldiers, with colonization being associated with higher rates of skin-soft tissue infection with MRSA (3).

Obtaining sputum cultures is difficult under the best of circumstances. Initial studies on the implementation of screening evaluated the use of nasal cultures, which tend to have an advantage in its ease of use when compared to sputum cultures, but tend to have a slower turnaround time when compared to its more modern counterpart, the PCR. In a cohort using MRSA nasal culture (4), anti-MRSA therapy was shorter in the intervention group (those who had nasal cultures reported to physicians) compared to the control group (1 day vs 3 days). There was notably, no difference in mortality (14% in control vs 19% in intervention group, p = 0.29). Another cohort compared the nasal culture with PCR (5) in 259 paired samples and found high concordance even when patients took antibiotics, 93.7% in the presence (95% CI 88-96.8%) and 90.9% in the absence (95% CI 84.8%-94.7%) of antibiotics.

Utility of PCR in Relationship to Sputum Cultures

Before going any further, I think it is helpful to put the following data into context. The value of the screening PCR lays on its ability to rule out MRSA pneumonia. Indeed, we are using the assumption that a negative nasal PCR = no colonization and low risk of MRSA pneumonia. If the patient tests positive for nasal MRSA PCR, then who knows what is going on in the lungs. But if they test negative, we can be fairly certain that their pneumonia is not caused by MRSA. Here, we would like to ensure our negative predictive value, the likelihood that someone who tests negative does not have the disease, is as high as possible. It is related to specificity, however while specificity/sensitivity tend to be static numbers that are related to the particular test in question, positive and negative predictive values take into account the disease prevalence (6). Why is this important? Because the PPV and NPV (in particular, the latter which is what we’re focusing) are related to the disease prevalence: 

As you can see, the more common the disease is in your population, then the higher the PPV of that specific test. Indeed, the opposite is true with lower disease prevalence being correlated with higher NPV. Given that MRSA is not quite common, this makes the PCR a good “rule out” tool unless your disease prevalence goes beyond 10% (which is what I was able to find as being the more common prevalence in these studies). Having gotten that out of the way, we can go into a bit more detail about the relationship between nasal PCR and respiratory specimens. In one retrospective study of 435 patients who had either a PCR and a concomitant blood or pulmonary culture (7), the test performed fairly well when the prevalence was 5.7%:

Another retrospective study of 72 patients (8) similarly found good sensitivity/specificity and NPV/PPV, though here there is no mention of prevalence:

In a VA study of 297 paired nasal samples and cultures (9), surveillance MRSA nasal swabs yielded a PPV of 37.5% (95% CI 21.1-56.3) and NPV of 99.3 (95% CI 97.3-99.9%). Sensitivity was 85.7% while specificity was 92.9%. Another retrospective study of 400 critical care patients found a NPV of 99.03, PPV of 37.36, sensitivity 91.89, specificity 84.3% (10). In a similar study, a matched-case control study of 4317 critically ill patients, nasal MRSA cultures yielded a sensitivity/specificity of 72.2% (95% CI 62-81%) and 96.8% (95% CI 96-97%), respectively and PPV and NPV of 32.3% (95% CI 26-39) and 99.4% (99.1-99.6%) when using receipt of vancomycin as a surrogate for suspicion for MRSA (11). A single-center retrospective cohort compared MRSA nasal swab PCR with respiratory culture (12). 200 patients were included, and found that overall, sensitivity and NPV were fairly high (prevalence 10.5%):

While these data seem to suggest a fairly good correlation, one  single-center prospective study enrolling 1083 medical ICU patients,found there was no difference in MRSA infection (either pneumonia or bacteremia) between those who were colonized (27.4%) or not (22.7%) as determined by nasal MRSA cultures (13). Indeed, the sensitivity for swabs that were obtained either at the start or later on during the ICU admission were poor but NPV tended to increase in this population:

The prevalence of MRSA infection in this cohort, however, was 24% which highlights the above point I made about its role in NPV. A meta-analysis that pooled the vast majority of these studies (14) which included over 5160 patients, found that the NPV of MRSA nasal PCR screen was 90.3% when the prevalence was 10%. The NPV increased to 98.1% for CAP/HCAP:

Again, one should note there is a difference in the prevalence of disease and comparators, however in the right population this can be a fairly useful tool to de-escalate antibiotics.

Real-Life Applications:

I am a proponent of hard clinical outcomes. These tend to be either mortality, ICU stay, time in the hospital, etc. Antibiotic use as a primary outcome leaves a lot to be desired and I think this is where I find the data to fall short. Of course, if you implement a study designed to make people use less antibiotics, don’t be surprised when you get a positive result. These can be a bit tricky to design and power to mortality. The data on applicability, however, tends to show the obvious. A retrospective, multicenter study (15) evaluated the implementation of MRSA nasal swab PCR screening by pharmacists for patients who got empiric vancomycin for possible pneumonia. Two implementation periods were evaluated, with median vancomycin duration being shorter after the implementation of MRSA nasal swab PCR to guide therapy (24 hours vs 14.3 hours). A similar single center study of 418 total patients (16) among pre-implementation and post-implementation cohorts found that those in the latter had shorter length of vancomycin duration (1.44 days vs 2.59 days, p < 0.01). Rates of AKI were lower in the post-protocol group (13% vs 24%, p=0.01). Here, the calculated sensitivity, specificity, PPV and NPV were 100%, 95.6%, 36.8% and 100%, respectively. In a study that used both nasal and throat cultures (17), the recommendation to stop vancomycin when both of these were negative was not associated with higher overall in-hospital mortality (7.7%). These are of course helpful data for the stewardship standpoint and allows us to have a tool to prevent overuse of antibiotics, however I would like to see further data on mortality going forward. 

Having said that, it seems that colonization has been looked at as a surrogate for other types of infections. A very thorough review (18) has looked at the role of MRSA nasal swab PCR and subsequent infections including bacteremia. Color me skeptic at this point (I mean, how does nose colonization translate to bacteremia???) but I think it may pan out at the end of the day:


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