In this interview authors of a recent meta-analysis published in Clinical Infectious Diseases discuss their project and provide insights on MRSA nasal colonization screening as an antimicrobial stewardship tool.
Interview with: Diane M. Parente, Pharm.D. and Tristan Timbrook, Pharm.D., MBA, BCPS
Interview by: Timothy P. Gauthier, Pharm.D., BCPS-AQ ID
[Last updated: 2 May 2018]
Does everyone in the hospital with bacterial pneumonia need antibiotic therapy that includes coverage for methicillin resistant Staphylococcus aureus (MRSA)? Of course not, but how do clinicians know who should get MRSA coverage and who should not? In addition, why is covering MRSA such a big deal?
First, let’s focus on that second question. In the hospital setting antibiotic coverage for MRSA typically means a course of intravenous vancomycin. Unfortunately, vancomycin has been associated with nephrotoxicity, which makes many clinicians nervous for their patient’s kidneys when they have to prescribe it. In addition vancomycin requires, patient-specific dosing strategies, therapeutic drug monitoring, and long infusion times. This can all translate to risk for the patient plus a fair deal of work for the prescriber, pharmacist, nurse, and lab. In turn, nobody wants to use vancomycin unless it is truly indicated.
Circling back to that first question, there are a variety of means for differentiating between pneumonia caused by MRSA and pneumonia caused by other pathogens, but this is still an area in which further research is needed. One emerging tool that may be used for this purpose is MRSA nasal colonization status. This is the motivation for this article and the focus of the below interview.
According to CDC, about one in three people is colonized with Staphylococcus aureus in their nose and one in 50 people is colonized with methicillin resistant Staphylococcus aureus (MRSA) in their nose . People that are colonized with MRSA who get pneumonia will not necessarily have MRSA pneumonia, but the chances for it may be greater than people not colonized with MRSA. So, if a patient is found to be negative for MRSA nasal colonization, can the vancomycin therapy be discontinued or maybe never even started? This is one of the big questions people are interested in today.
Recently Parente et al evaluated the diagnostic value of MRSA nasal colonization screening as an antimicrobial stewardship tool for pneumonia. They published their work in Clinical Infectious Diseases:
- Parente DM, Cunha CB, Mylonakis E, Timbrook TT. Clinical utility of methicillin resistant Staphylococcus aureus (MRSA) nasal screening to rule out MRSA pneumonia: a diagnostic meta-analysis with antimicrobial stewardship implications. Clinical Infectious Diseases. 2018. Epub ahead of print.
Since this has become somewhat of a hot topic in the field of antimicrobial stewardship, I reached out to the authors and requested an interview. They were gracious enough to accept and the following was developed.
For the purpose of this article the following definitions are provided:
- Negative predictive value (NPV): the probability that a negative test result is accurate. The higher the value, the more reliable the test.
- Positive predictive value (PPV): the probability that a positive test result is accurate. The higher the value, the more reliable the test.
- HAP = hospital acquired pneumonia
- VAP = ventilator associated pneumonia
Here are insights on MRSA nasal colonization screening as an antimicrobial stewardship tool…
1. What prompted undertaking the task of performing a meta-analysis on the clinical utility of MRSA nasal screening to rule out MRSA pneumonia?
For us, it was reading the Infectious Diseases Society of America (IDSA) HAP/VAP guideline  with a nod on page 23 for MRSA avoidance based on NPV, but no official recommendation on avoidance of antibiotic coverage based on the NPV of MRSA nasal PCR, leaning heavily towards MRSA coverage based on risk factors including overall prevalence of methicillin resistance among S. aureus isolates, antibiotic use within last 90 days, and either previous positive culture or screens for MRSA.
Moreover, on page 12, the IDSA HAP/VAP guidelines note “However, to our knowledge, there are no studies that have prospectively evaluated the use of MRSA screening to inform empiric treatment choices.” which appeared to be very short sighted, as Boyce AAC 2013  clearly evaluated this approach and is well recognized in the literature being cited >30 times.
Further, while not prospective we realized there was a decent amount of literature evaluating the clinical utility of MRSA nares screens for MRSA pneumonia.
Overall, we felt the guidelines missed out on a major opportunity for antimicrobial stewardship and avoidance of unnecessary patient exposure to anti-MRSA antibiotics; specifically, the potential nephrotoxicity of vancomycin and associated healthcare costs in a large number of patients, all in the face of readily available and good data.
2. From your research, what is the main take home point about using MRSA nasal colonization status as it relates to treating pneumonia?
No MRSA nares colonization = no vancomycin in the absence of persistent hemodynamic instability, VAP, structural lung disease, or other exclusion/strong indication.
3. Is there anything that you found particularly interesting or surprising in the process of completing this meta-analysis?
While less related to the meta-analysis and more related to the practical implications thereof and consideration for implementation, vancomycin has very little if any effect on colonization and therefore conversations about post-antibiotic specimen obtainment are a nonstarter [4-7].
4. What should antimicrobial stewards know about the NPV and PPV of MRSA nasal colonization status to rule out MRSA pneumonia?
Similar to procalcitonin, think not only about the test but also about what patients with MRSA pneumonia look like – think severely ill with the exception of patients with structural lung disease.
With the likely incidence of MRSA pneumonia being 5% or less and true MRSA pneumonia epidemiology suggesting ~90% admitted to ICU, the conditional probabilities of a MRSA pneumonia in a medical floor patient is probably half a percent or less (10% x 5% = 0.5%).
In terms of NPV and PPV of MRSA nasal colonization status, for CAP/HAP there is a high NPV (98.1%) meaning that if the MRSA nares test is negative then it is highly unlikely the patient has MRSA pneumonia and therefore in a patient who is clinically stable without structural lung disease discontinue or do not initiate anti-MRSA therapy.
There is a low PPV of MRSA nasal colonization status to rule in MRSA pneumonia (44.8%), meaning when the result of an MRSA nares test is positive, there is not certainty that the patient does or does not have MRSA pneumonia and therefore the MRSA nares results should not weigh as heavily when making the decision to start or continue anti-MRSA therapy.
It is important to note CA-MRSA pneumonia should be suspected in patients with multilobular cavitating alveolar infiltrates or necrotizing pneumonia seen on imaging, preceding a recent infection with influenza, hemoptysis, severe hypoxemia, high fever, leukopenia, hypotension, or cyanosis. Again, emphasizing these patients will look severely ill.
5. Are there clinical circumstances when you would give considerably less weight to MRSA nasal colonization status for determining whether or not to cover MRSA empirically for pneumonia?
Note above discussion.
Patients with a positive MRSA nares test, VAP, structural lung disease (e.g., cystic fibrosis or bronchiectasis), recent nasal decolonization prior to nares screen, or an MRSA infection within 30 days.
6. What future research is needed when it comes to using MRSA nasal colonization status for managing patients with suspected or confirmed pneumonia?
It would be nice to see a large study with propensity matching, the effect on LOS and nephrotoxicity by doing early de-escalations, and outcomes in those with early de-escalations versus those without.
2. Kalil AC et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clinical Infectious Diseases. 2016;63(5):e61–111.
3. Boyce JM et al. A trial of discontinuation of empiric vancomycin therapy in patients with suspected methicillin-resistant Staphylococcus aureus health care-associated pneumonia. Antimicrobial Agents and Chemotherapy. 2013; 57(3): 1163-8.
5. Vikram HR et al. Discontinuation of contact precautions for patients no longer colonized with methicillin-resistant Staphylococcus aureus. Infection Control and Hospital Epidemiology. 2010; 31(5): 541-3.
7. Bernard L et al. Effect of vancomycin therapy for osteomyelitis on colonization by methicillin-resistant Staphylococcus aureus: lack of emergence of glycopeptide resistance. Infection Control and Hospital Epidemiology. 2003; 24(9): 650-4.
ADDITIONAL RELEVANT RESOURCES
- Willis C et al. Impact of a pharmacist-driven methicillin-resistant Staphylococcus aureus surveillance protocol. American Journal of Health-System Pharmacy. 2017; 74(21): 1765-1773.
- Smith EA, et al. Nasal methicillin-resistant Staphylococcus aureus screening in patients with pneumonia: A powerful antimicrobial stewardship tool. American Journal of Infection Control. 2017; 45(11): 1295-1296.
- Acuna-Villaorduna C, et al. Active identification of patients who are methicillin-resistant Staphylococcus aureus colonized is not associated with longer duration of vancomycin therapy. America Journal of Infection Control. 2017; 45(10): 1081-1085.
- Stanford Health Care. Vancomycin De-Escalation Guide.
I would like to express my utmost appreciation to Dr. Parente and Dr. Timbrook for taking the time to complete this interview and share their perspectives.
ABOUT THE INTERVIEWEES
Diane M. Parente, Pharm.D. is the clinical pharmacist specialist in infectious diseases and antimicrobial stewardship at The Miriam Hospital in Providence, RI. Her primary responsibilities include antimicrobial stewardship, participation on adult infectious diseases consultation rounds, precepting pharmacy students and residents, and lecturing at the University of Rhode Island, Bryant University, and Johnson and Wales University.
Diane received her PharmD degree at the University of Rhode Island in 2012. She then completed a PGY-1 Pharmacy Practice Residency at UF Health Jacksonville in Jacksonville, FL followed by a Post-Doctoral Fellowship in outcomes and antimicrobial stewardship at the Providence VA Medical Center in Providence, RI.
Her research and practice interests include antimicrobial stewardship quality improvement and outcomes.
Tristan Timbrook, Pharm.D., MBA, BCPS is an Antimicrobial Stewardship Pharmacist at University of Utah Health (Salt Lake City, UT).
Dr. Timbrook obtained his PharmD and MBA at Sullivan University (Louisville, KY). He then completed his PGY-1 Pharmacy Practice Residency and PGY-2 Infectious Diseases Pharmacy Residency at Medical University of South Carolina (Charleston, SC). He is a former Post-Doctorl Outcomes Pharmacy Fellow in Antimicrobial Stewardship at the Providence VA Medical Center (Providence, RI).
His primary interests include integrations of rapid diagnostics and antimicrobial stewardship, comparative effectiveness research, and medical informatics with particular interest given to clinical decision support systems.
You can find him on Twitter @TimbrookTT.
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