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The Clinical Utility of Methicillin Resistant Staphylococcus aureus (MRSA) Nasal
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Screening to Rule Out MRSA Pneumonia: A Diagnostic Meta-analysis with Antimicrobial
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Stewardship Implications
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Diane M. Parente1, Cheston B. Cunha2,3, Eleftherios Mylonakis2,3, Tristan T. Timbrook4
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1. Department of Pharmacy, The Miriam Hospital, Providence, RI, USA
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2. Infectious Disease Division, Rhode Island Hospital and The Miriam Hospital, Providence, RI,
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USA 3. Division of Infectious Diseases, Brown University, Warren Alpert Medical School, Providence, RI, USA 4. Department of Pharmacy, University of Utah Health Care, Salt Lake City, UT, USA
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Corresponding Author: Diane M. Parente, PharmD, Infectious Diseases and Antimicrobial
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Stewardship Clinical Pharmacist, Department of Pharmacy, The Miriam Hospital, 164 Summit
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Avenue, Providence, RI 02906, Tel: (401) 793-3306; E-mail:
[email protected]
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Alternate Corresponding Author: Tristan T. Timbrook, PharmD, MBA, BCPS, Antimicrobial
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Stewardship Clinical Pharmacist, University of Utah Health Care, 50 N. Medical Drive,
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Pharmacy Administration, Room A-050, Salt Lake City, UT 84132, Tel: (502) 608-7817, E-mail:
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[email protected]
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Keywords: MRSA nasal screening, pneumonia, antimicrobial stewardship, meta-analysis
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Running title: MRSA nasal screen meta-analysis
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Summary: MRSA nares screening had a high NPV for ruling out MRSA pneumonia but a low
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PPV for predicting MRSA pneumonia. MRSA nares screening can be a stewardship tool to
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streamline empiric antibiotic therapy among those not nares colonized with MRSA.
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ABSTRACT
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Background: Recent literature has highlighted MRSA nasal screening as a possible
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antimicrobial stewardship program (ASP) tool for avoiding unnecessary empiric MRSA therapy
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for pneumonia, yet current guidelines recommend MRSA therapy based on risk factors. The
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objective of this meta-analysis was to evaluate the diagnostic value of MRSA nasal screening in
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MRSA pneumonia.
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Methods: Pubmed and EMBASE were searched from inception to November 2016 for English
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studies evaluating MRSA nasal screening and development of MRSA pneumonia. Data analysis
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was performed using a bivariate random-effects model to estimate pooled sensitivity, specificity,
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and positive (PPV) and negative (NPV) predictive values.
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Results: Twenty-two studies, comprising of 5,163 patients met our inclusion criteria. Pooled
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sensitivity and specificity of MRSA nares screen for all MRSA pneumonia types was 70.9% and
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90.3%, respectively. With a 10% prevalence of potential MRSA pneumonia, the calculated PPV
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was 44.8% while the NPV was 96.5%.
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community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) were at
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85% and 92.1%, respectively. For CAP and HCAP both the PPV and NPV increased to 56.8%
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and 98.1%, respectively. In comparison, for MRSA ventilated-associated pneumonia (VAP), the
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sensitivity, specificity, PPV, NPV was 40.3%, 93.7%, 35.7%, and 94.8%, respectively.
The pooled sensitivity and specificity for MRSA
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Conclusion: Nares screening for MRSA had a high specificity and NPV for ruling out MRSA
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pneumonia, particularly in cases of CAP/HCAP. Based on the NPV, utilization of MRSA nares
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screening is a valuable tool for AMS to streamline empiric antibiotic therapy, especially among
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patients with pneumonia that are not colonized with MRSA.
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BACKGROUND
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Current guidelines for the treatment of pneumonia published by the American Thoracic Society
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(ATS) and Infectious Diseases Society of America (IDSA) recommend empiric methicillin-
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resistant Staphylococcus aureus (MRSA) coverage in at-risk patients, yet MRSA pneumonia
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has a low prevalence [1, 2]. While initiating appropriate empiric antibiotics in a timely manner is
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critical, prescribers are often challenged on whom to initiate anti-MRSA coverage to and when
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therapy should be de-escalated. Current guidelines do not provide guidance on de-escalation
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before the availability of respiratory culture results; which may take up to 96 hours to process, or
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in the absence thereof. As a result, patients are frequently continued on anti-MRSA therapy,
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such as vancomycin, thereby contributing to unfavorable consequences of antimicrobial
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overuse, including increased risk of adverse events, antimicrobial resistance, drug-drug
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interactions, and increased expense [3].
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S. aureus, including MRSA, is a common colonizer of the nares. The absence of MRSA nares
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colonization has reported to be a negative predictor of MRSA pulmonary infections, specifically
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pneumonia.
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prevention purposes. However, recent literature has highlighted MRSA nasal screening as a
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useful antimicrobial stewardship screening test for avoiding unnecessary empiric MRSA
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therapy, including vancomycin [4, 5]. The objective of this meta-analysis was to evaluate the
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diagnostic value of MRSA nasal screening in ruling out potential MRSA pneumonia.
Traditionally, nares surveillance for MRSA is used for infection control and
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METHODS
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Literature Review
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We reviewed Pubmed and EMBASE from 1971 and 1974, respectively, to March 1, 2017 for
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studies in English evaluating MRSA nasal screening and development of MRSA pneumonia.
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We used the search string: (Methicillin-resistant Staphylococcus aureus OR MRSA) AND (nasal
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OR nares) AND (pneumonia OR respiratory OR lower respiratory tract infections). Citation titles
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and abstracts were reviewed for relevance, and subsequently, full-text reviews were performed
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on all potentially relevant studies. Bibliographies of included articles were reviewed for
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additional studies of relevance. Conference proceedings from IDWeek, the Interscience
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Conference on Antimicrobial Agents and Chemotherapy, and the European Congress of Clinical
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Microbiology and Infectious Diseases from 2007 to 2016 were also reviewed utilizing the
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keywords “nares” and “nasal” to identify unpublished studies.
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Inclusion and Exclusion Criteria
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Studies were included if they contained information on both positive rates of MRSA nasal
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surveillance screenings either using culture or polymerase chain reaction (PCR) and reported
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the rates of culture confirmed MRSA pneumonia for community-acquired pneumonia (CAP),
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hospital-acquired pneumonia (HAP), healthcare-associated pneumonia (HCAP), or ventilator-
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associated pneumonia (VAP). Studies were excluded if they were non-English, only utilized
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MRSA surveillance culture studies from other body sites (e.g. throat swab), or zero event
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studies (e.g. absence of MRSA pneumonia diagnosed).
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Outcomes
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Outcomes evaluated for the clinical utility of MRSA nasal screening for predicting MRSA
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pneumonia included the performance characteristics of sensitivity, specificity, diagnostic odds
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ratios, likelihood ratios, positive predictive values (PPVs), and negative predictive values
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(NPVs). Additionally, factors affecting test performance and heterogeneity among studies were
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assessed.
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Data Extraction and Quality Assessment
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Two investigators (D.M.P. and T.T.T.) independently reviewed the literature. Differences in
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article selection were resolved by consensus. Each investigator evaluated the included studies
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for possible sources of bias using the QUADAS-2 checklist [6]. Data were extracted from the
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studies on rates of positive MRSA nasal surveillance screens, rates of MRSA pneumonia, study
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designs, setting, patient population and sample size, pneumonia classification and assessment
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definitions if present, respiratory culture type, and timing of surveillance screens.
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Data Analysis
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Performance characteristics were evaluated using a bivariate model for diagnostic meta-
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analysis to calculate the pooled sensitivities, specificities, diagnostic odds ratio, likelihood ratios,
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PPVs, and NPVs. Random effects modeling was employed on the assumption of heterogeneity
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in measurements among studies. PPVs and NPVs were calculated using the pooled MRSA
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pneumonia prevalence among the included studies overall and by pneumonia type for
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CAP/HCAP, HAP, and VAP. Pooled prevalence was calculated using a random effects model
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and excluded studies of only S. aureus pneumonia cohorts. Publication bias was assessed with
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the Deeks test [7]. Possible sources of heterogeneity were evaluated using meta-regression.
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Heterogeneity was determined with a Cochran’s Q statistic of p
