Utilizing MRSA Nasal Screening for Antimicrobial Stewardship

Highlighted Study:

Carr, AL, Daley, MJ, Givens Merkel, K, Rose, DT. Clinical utility of methicillin-resistant staphylococcus aureus nasal screening for antimicrobial stewardship: a review of current literature. Pharmacotherapy. 2018 Dec;38(12):1216-1228. doi: 10.1002/phar.2188. Epub 2018 Oct 29.

Staphylococcus aureus is a common pathogen in health care-associated infections (HAIs).¹ Upwards of 40% of deep-seated S aureus infections confer methicillin-resistance. Patients with methicillin-resistant S aureus (MRSA) bacteremia and endocarditis may carry a mortality rate of 40%.^1,4 Current guidelines from the Infectious Diseases Society of America (IDSA) recommend empiric MRSA coverage in patients with certain risk factors.^2-6 Even without risk factors, most patients receive empirical vancomycin therapy. MRSA nasal screening, with clinical context, can be utilized to prevent unnecessary exposure, adverse events, and increased expense. ⁷ MRSA colonization can be detected via culture (1-3 days; 86.9% sensitivity) or polymerase chain reaction (PCR) (<1 day; 92.5% sensitivity). ^8,9 The prevalence of MRSA directly impacts the performance of the nasal screen in predicting clinical MRSA infection. A higher prevalence will result in lower negative predictive value. This systematic review by Carr et al., summarized available literature on adult inpatients for whom MRSA nasal swab screening was conducted.¹⁰

Evidence by Infection Type

Pulmonary Infections

The IDSA community-acquired pneumonia (CAP) and hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP) guidelines highlight MRSA risk factors and need for empirical therapy. The HAP/VAP guidelines even suggest that a negative MRSA nasal screening may be utilized to withhold empiric anti-MRSA therapy. A meta-analysis of 22 studies comprising 5243 patients found that nasal screening had a pooled sensitivity of 70.9%, specificity of 90.3%, positive predictive value (PPV) of 44.8%, and negative predictive value (NPV) of 96.5% for MRSA pneumonia. Although sensitivity for VAP was lower (40.3%) compared with CAP/health care-associated pneumonia (85%), NPV remained high at 94.8%. Two studies with pharmacist-driven protocols to order MRSA nasal screens for all suspected pneumonias and even chronic obstructive pulmonary disease exacerbations resulted in significant declines in duration of vancomycin therapy (74 hours to 27.4 hours, p<0.0001 and 4.2 days to 2.1 days, p<0.0001), and therapeutic drug monitoring (48.1% to 16.7%, p = 0.02). With reliable NPV across all forms of pneumonias, MRSA nasal screening can be a great tool for de-escalation of anti-MRSA therapy. However, variable PPV of a positive MRSA nasal screen should not be used as a rule-in or prompt initiation of targeted therapy.

Nonspecific (Any Source) Infections

Impact of MRSA nasal screening and correlation with blood, wound, or respiratory cultures was studied in 7 retrospective studies. In 1 study of swab and culture collection within 48 hours of admission, nasal screening predicted MRSA infection with sensitivity of 58.3%, specificity of 93.9%, PPV of 30.4%, and NPV of 98.0%. Another retrospective review also showed a higher NPV of 94%. Subgroup analysis of sterile vs. non-sterile sites had poor sensitivity (45%) and PPV (83%), but maintained high specificity (99%) and NPV (94%). Some Veterans Affairs (VA) hospitals screen all patients universally for MRSA at admission. In a retrospective review of 326,282 patients, MRSA nasal screening demonstrated high sensitivity of 65.1%, specificity of 85.7%, PPV of 21.8%, and NPV of 97.6%. Additionally, the NPV remained high at 99.4% in 11,882 intensive care unit (ICU) patients, with only 0.22% of negative screens developing clinically significant MRSA infections. An estimated 7364 days of vancomycin could have been avoided if discontinuation was based on these results. The NPV of the MRSA screen to rule out MRSA infection may be highest within 14 days (94%), as sensitivity and NPV trended down past 48 hours of screening and culture collection.

Bloodstream Infections

A retrospective review found that MRSA screening obtained within the past 30 days had an NPV > 95% when the prevalence of MRSA bloodstream isolates was 19.3%. This decreased with higher prevalence (NPV of 90%, MRSA prevalence 33.5%). Another retrospective cohort found that NPV in community-acquired (93%) and heath care-associated (95%) bloodstream infections (BSI) was higher than in nosocomial (85%) BSIs. Median time between MRSA screening and blood culture collection was 1.0 days (IQR 0.0-12.0 days). False-negatives resulted in 8.3% of patients. Although not robust enough to rule out MRSA BSI based on NPV, this study suggests that a positive result may warrant empiric anti-MRSA therapy. Comparatively, a prospective cohort of ICU patients with MRSA nasal PCR obtained at admission or weekly thereafter yielded a sensitivity of 26.9%, specificity of 75.9%, PPV of 11.5%, and an NPV of 89.9% for MRSA BSI. The timing of swab collection may be key. Two studies with screening cultures obtained within 24 and 48 hours found similar sensitivity (80.5% and 71.4%, respectively) and NPV (99.6% and 99.2%, respectively).

Skin and Soft Tissue Infections/Bone and Joint Infection

One VA study of 216 patients with a skin and soft tissue infection (SSTI) found an NPV of 98.1% but did not report MRSA prevalence. A larger VA study of patients with SSTI reported a lower NPV of 90.3% (MRSA prevalence 17.7%). In 57 patients with diabetic foot infections (DFI) (MRSA prevalence 29.8%), sensitivity of 41%, specificity of 90%, PPV of 67%, and NPV of 80% was reported. Ten of 17 patients with initial negative swabs had MRSA as a causative pathogen. Conversely, a positive nasal culture was associated with an increased risk of MRSA DFI (odds ratio [OR] 8.0, 95% CI, 2.05—31.02). Another study of 102 patients with prosthetic joint infections (MRSA prevalence 37%) reported overall poor performance in sensitivity and NPV (~80%).

Intra-abdominal Infections

A retrospective review of 240 general, transplant, and trauma surgery patients with intra-abdominal infections (IAIs) and MRSA nasal PCR obtained within 14 days reported a sensitivity of 87% and NPV of 97%. A prospective cohort of 73 surgical ICU patients with postoperative IAIs and nasal cultures obtained within 1 week of onset of illness showed only 1 of the 12 patients who developed a MRSA infection had a negative MRSA screen. MRSA colonization prior to infection onset was an independent risk factor for post-operative infections due to MRSA (OR 4.72, 95% CI, 1.17—19.0, p = 0.029).

Urinary Tract Infections

Retrospective reviews including subgroup analyses for patients with urinary tract infections (UTI) reported a sensitivity of 71.0%, specificity of 79.3%, PPV of 13.3%, and NPV of 98.4%. Another study of 2948 patients had similar results, with sensitivity of 77%, specificity of 87%, PPV of 11%, and NPV of 99%. Although these suggest that MRSA nasal screening can be a reliable tool to guide empirical antibiotic therapy, it is important to keep in mind that MRSA is an uncommon urinary pathogen, with prevalence less than 5%.

Central Nervous System Infections

There is a lack of evidence for the performance and safety of MRSA nasal screening in patients with meningitis.

Clinical Implications and Antimicrobial Stewardship

The aforementioned studies provide evidence for the use of MRSA nasal screen across many infections, however, swabs may be inappropriate to collect in all patients, including those with nasal obstruction, heavy nasal bleeding, or burns, ulcers, fractures, or open wounds within the nasal cavity. Additionally, evidence for the clinical utility of patients with septic shock, febrile neutropenia, cystic fibrosis, and chronic bronchiectasis is lacking.

Results of the MRSA screening may be compromised if the specimen is collected after intranasal mupirocin or systemic anti-MRSA therapy. Some studies reported delayed decolonization (1-4 weeks), with systemic vancomycin. Differences in infection control measures, geographic prevalence of MRSA, surveillance screening practices, and laboratory processing must be noted for external validity of the discussed studies. To account for low NPV in MRSA infections with high prevalence, one can apply the results in combination with clinical risk factors.

Pharmacists are optimally placed to aid in development and implementation of MRSA screening protocols and treatment pathways. They can utilize existing results, order a MRSA nasal swab if appropriate, and recommend discontinuation of anti-MRSA therapy based on implemented protocols. Furthermore, pharmacists are able to educate on and curb increased antimicrobial use secondary to positive test results. This directly leads to cost savings on both drug and therapeutic drug monitoring, as well as from adverse events.

Dr. Krutika N. Mediwala is an Infectious Diseases/Antimicrobial Stewardship Clinical Pharmacy Specialist at the Medical University of South Carolina (MUSC) in Charleston, SC. Her areas of interest include antimicrobial stewardship process improvement, Gram-negative resistance and infections, leadership and mentorship.

References:

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3. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):147—59.
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8. Trevino SE, Pence MA, Marschall J, Kollef MH, Babcock HM, Burnham CD. Rapid MRSA PCR on respiratory specimens from ventilated patients with suspected pneumonia: a tool to facilitate antimicrobial stewardship. Eur J Clin Microbiol Infect Dis. 2017;36(5):879—85.
9. Luteijn JM, Hubben GA, Pechlivanoglou P, Bonten MJ, Postma MJ. Diagnostic accuracy of culture-based and PCR based detection tests for methicillin-resistant Staphylococcus aureus: a meta-analysis. Clin Microbiol Infect. 2011;17(2):146—54.
10. Carr, AL, Daley, MJ, Givens Merkel, K, Rose, DT. Clinical utility of methicillin-resistant staphylococcus aureus nasal screening for antimicrobial stewardship: a review of current literature. Pharmacotherapy. 2018 Dec;38(12):1216-1228. doi: 1002/phar.2188. Epub 2018 Oct 29.