Impact of Methicillin-Resistant Staphylococcus aureus Nasal Polymerase Chain Reaction Screening Tests on Duration of Vancomycin Therapy for Skin and Soft Tissue Infections

Abstract

Background: Recent literature demonstrated a 24-hour reduction in vancomycin duration of therapy (DOT) for skin and soft tissue infections (SSTIs) with a negative methicillin-resistant staphylococcus aureus (MRSA) nasal screening versus a positive nasal screening. Objective of this study was to investigate vancomycin DOT in patients with SSTIs who received MRSA nasal polymerase chain reaction (PCR) screening versus those who did not receive MRSA nasal PCR screening. Methods: A retrospective, multi-center, cohort study was completed in admitted adult patients on vancomycin for SSTI from 01/01/2020 to 09/30/2022. Hospital policy permits any clinician to order a MRSA nasal PCR screening test for various indications, including SSTIs, pneumonia and sepsis. Results: One-hundred-fifty-one patients were included, of which 71 had MRSA nasal PCR screening tests obtained, and 80 did not. The median vancomycin DOT in patients with MRSA nasal PCR screening tests was 19.9 versus 36.7 hours (P = .014) in patients without screening tests. Conclusion: Patients with SSTIs who receive MRSA nasal PCR screening tests have a shortened vancomycin DOT. These results contribute to current data in support of the efficacy and clinical utility of obtaining MRSA nasal PCR screening tests for SSTIs.

Introduction

The skin is the largest organ in the body and acts as a protective barrier. Disruptions in the skin integrity may lead to infection. Methicillin resistant Staphylococcus aureus (MRSA) is one of many bacteria that can be found in normal skin flora and may contribute to skin and soft tissue infections (SSTIs). ¹ According to Ray et al., ² a study of over 300 000 patients taking place from 2009 to 2011, the rate of clinically diagnosed MRSA SSTIs is 496 per 10 000 person-years. ² The need for broad spectrum antibiotics for empiric SSTI coverage, including MRSA coverage, is determined by the patient’s clinical presentation and MRSA risk factors. ³ Absence of MRSA nasal colonization has been correlated with ability to rule out MRSA related infections. ² Multiple studies have found a high negative predictive value (NPV) of ~97% and a variable positive predictive value (PPV) of ~40% to 60% when using MRSA nasal PCR tests in lower respiratory tract infections.^1,4,5 MRSA nasal PCR testing typically results within 2 hours compared to 24 hours for MRSA nasal cultures and 3 to 5 days for SSTI cultures.

Timely PCR turnaround time results facilitate early interventions and potential shorter durations of MRSA antibiotic coverage.^5,6 Overuse of broad-spectrum antibiotics, including vancomycin, has led to increasing bacterial resistance.^6,7 Currently vancomycin is the most prevalent parenteral anti-MRSA agent used in the United States.^7-9 Use of vancomycin is associated with adverse effects including acute kidney injury and infusion reactions. Due to labor-intensive administration and monitoring and increased risk of adverse events, vancomycin has been associated with increased healthcare costs. ⁶ Woolever et al., ⁵ demonstrated a statically significant decrease in vancomycin duration of therapy (DOT) with implementation of a pharmacist-driven-protocol for ordering MRSA nasal tests in lower respiratory tract infections.

Burgoon et al. ¹ demonstrated the utility of MRSA nasal tests results, obtained for general MRSA screening upon admission and assessed patients with SSTIs noting a reduction in vancomycin DOT of 1 day when a negative swab was obtained. Although MRSA infections are closely correlated with purulent infections, Hitchcock et al. ¹⁰ looked at PPV and NPV in non-severe purulent versus non-severe non-purulent SSTIs and found similar results. A significant knowledge gap exists in analysis of MRSA nasal PCR tested versus non-tested cohorts for SSTIs and the overall clinical impact of obtaining a MRSA nasal PCR test in SSTIs. This study investigates the utility of MRSA nasal PCR tests in patients with SSTIs who received and did not receive testing and to determine the impact on DOT for vancomycin.

Methods

Study Design and Study Location

A retrospective, multi-center, cohort analysis at Mayo Clinic Health System (MCHS) La Crosse and Sparta, Wisconsin, and consists of 1 community teaching hospital and 1 critical access hospital with over 7000 admissions per year and has been recognized by the Infectious Disease Society of America for Centers of Excellence for Antimicrobial Stewardship. The rate of MRSA at our healthcare facility in 2023 was 30%. Institutional guidelines for SSTI infections recommend use of first generation cephalosporins (eg, cefazolin) for patients with non-purulent SSTI and without a history of MRSA colonization or risk factors. Vancomycin is recommended in patients with known MRSA colonization, MRSA risk factors, or purulent SSTIs. In patients who may have a diabetic foot infection, vancomycin may be added to broad spectrum antibiotic therapy, if MRSA colonization or risk factors were present.

Subjects

Patients were included if they were 18 years of age or greater and empiric IV vancomycin ordered for a purulent or non-purulent SSTI at time of inpatient hospital admission (January 1st, 2020, to September 30th, 2022). Patients were excluded from the study if vancomycin indication other than SSTI (such as prosthetic joint infection, osteomyelitis, ear, nose and throat infections, dental infections), vancomycin use for perioperative prophylaxis, use of IV anti-MRSA therapy other than vancomycin, severe SSTIs including necrotizing fasciitis and Fournier’s gangrene, human or animal bites, and use of nasal mupirocin within previous 90 days. ¹¹ Study groups evaluated include patients who received a MRSA nasal PCR screening test and those who did not receive an MRSA nasal screening test. Patients previously known to be MRSA colonized historically were included in our study. These patients are not considered colonized for life and our healthcare facility utilizes MRSA decolonization procedures. A report using electronic health record (EHR) data of patients with IV vancomycin ordered for the indication of SSTI was used to identify patients for the study. The study was determined to be Mayo Clinic Institutional Review Board exempt.

Variables

The primary outcome of the study is difference in DOT of vancomycin in patients who received a MRSA nasal PCR test screening test versus those who did not. Secondary outcomes evaluated include rate of adverse drug events, length of stay, and 30-day re-admission rates. Additional analysis was performed on patients who received a MRSA nasal PCR screening test with a positive result compared to those with a negative result. The results of MRSA nasal PCR tests and SSTI culture results were compared to calculate the PPV and NPV. At our sites, hospital policy permits any clinician to order a MRSA nasal PCR screening test for various indications, including SSTIs, pneumonia, and sepsis. Pharmacists have a collaborative practice agreement to order MRSA nasal PCR screening test for patients with empiric IV vancomycin indicated for an SSTI. Pharmacists receive an alert in the electronic health record to order a MRSA nasal PCR screening test when vancomycin is ordered for an SSTI and a MRSA nasal PCR screening test is not already ordered.

Terms and Measures

Data collection was performed via retrospective EHR review. Duration of therapy for vancomycin is defined as the initial order time to time of discontinuation. Purulent SSTIs were defined as any pustule, abscess, furuncle, or folliculitis. Non-purulent SSTIs were defined as cellulitis without noted purulent material. Acute kidney Injury (AKI) was defined as an increase in serum creatinine by ≥0.3 mg/dL within 48 hours or an increase of serum creatinine of ≥1.25 or ≥1.5 times the patient’s baseline. ¹²

Data Collection

A standardized data collection form was used by a small investigator group. Questions and discrepancies were directed to the primary investigator for further guidance. Demographic data was obtained, including age, sex, weight, type of residence, diabetes, lymphedema, IV drug use, history of MRSA infection or SSTIs, antibiotic allergies, prior hospitalization, and area of admission were obtained. Clinical data, including type and location of SSTI, vancomycin order and discontinuation time, rate of AKI or infusion reactions, transitioned to oral anti-MRSA antibiotic, wound culture results, date and time of admission and discharge, and MRSA nasal PCR test screening result and timing, ordering clinician, and rate of 30-day unplanned hospital utilization, were obtained.

Statistical Analysis

Descriptive statistics were used to summarize the demographic characteristics of the sample. The primary outcome was assessed using a 2-sample t-test. Using preliminary data, the standard deviation (SD) of vancomycin DOT was 84 hours. One hundred ninety-four patients in each group (388 total) are required to detect a mean difference of 24 hours with 80% power using a 2-sample t-test (SD = 84, type 1 error = .05). The length of stay was assessed using a 2-sample t-test. Vancomycin DOT between those who received a positive MRSA nasal PCR screening test and those who had a negative MRSA nasal PCR screening test was assessed using a 2-sample t-test (or Wilcoxon rank-sum test). Pearson’s Chi-square test was used to compare adverse drug event rates and 30-day readmission rates. Positive and negative predictive values with 95% confidence intervals were computed based on the result of the nasal PCR test and the gold standard culture result.

Results

Two hundred seventy-nine patients were assessed, and 151 patients were included in analysis (see Figure 1). The most common exclusion criteria met was vancomycin ordered for an indication other than SSTI (N = 127). Of the patients included in the study, 71 had MRSA nasal PCR screening tests obtained and 80 did not have a MRSA nasal PCR test obtained. Baseline characteristics between the groups had minimal differences (see Table 1). Majority of patients were male (68.9%), mean age was 60 years, mean weight was 105.8 kg and mean body mass index (BMI) was 35.5.

Figure 1.

Study flow diagram.

SSTI = skin and soft tissue infection; MRSA = methicillin resistant Staphylococcus aureus.

Table 1.

Baseline Characteristics.

Characteristic	MRSA nasal PCR screening tests obtained (n = 80)	MRSA nasal PCR screening tests not obtained (n = 71)	P-value
Age (years, min, max)	60 (47, 72)	60 (44, 75)	0.86
Body mass index (kg/m2, min, max)	31.9 (28.3, 39.9)	31.9 (27.3, 39.9)	0.72
Sex
Male (n, %)	49 (61%)	40 (56%)	0.54
Body weight (kg, mean, SD)	106.2 (37.3)	105.4 (32.5)	0.86
Residential demographics
Community dwelling (n, %)	70 (88%)	65 (92%)	0.07
Nursing home (n, %)	2 (2%)	5 (7%)
Homelessness (n, %)	8 (10%)	0
Prison (n, %)	0	1 (1%)
Comorbid conditions
Diabetes mellitus (n, %)	28 (35%)	33 (46%)	0.21
Lymphedema (n, %)	17 (21%)	17 (24%)
BMI > 40 kg/m2 (n, %)	20 (25%)	18 (25%)
History of intravenous drug use (n, %)	13 (16%)	6 (8%)
Admitted to intensive care unit (n, %)	6 (8%)	7 (10%)	0.61
Any antibiotic allergy	31 (39%)	29 (41%)	0.79
Penicillin allergy (n, %)	15 (18%)	16 (23%)	0.06
Cephalosporin allergy (n, %)	8 (10%)	5 (7%)	0.42
Hospitalization in preceding 90 days (n, %)	13 (16%)	23 (32%)	0.02
MRSA infection in preceding 2 years (n, %)	4 (5%)	8 (11%)	0.16
MRSA SSTI in preceding 2 years (n, %)	1 (1%)	2 (3%)	0.96
Purulent infection (n, %)	25 (31%)	42 (59%)	<0.001
Non-purulent infection (n, %)	53 (66%)	27 (38%)
Unknown/combination (n, %)	2 (3%)	2 (3%)

SSTI = skin and soft tissue infection; MRSA = methicillin resistant Staphylococcus aureus.

The median vancomycin DOT in patients without MRSA nasal PCR screening tests was 16.8 hours longer than that in patients with MRSA nasal PCR screening tests, 36.7 (17.7, 48.1) hours versus 19.9 (8.8, 37.8) hours (P = 0.014) (see Figure 2). Adverse events and readmission rates between the study groups were similar 6 (8%) versus 3 (4%) (P = 0.4) and 10 (13%) versus 9 (13%) (P = 0.97) respectively. Length of stay was longer in the MRSA nasal PCR test obtained group, 3.7 (2.6, 6.8) days versus 2.9 (1.9, 4.60) (P = 0.03) (see Table 2). Both purulent and non-purulent SSTIs were evaluated and demonstrated similar NPV (see Table 3).

Figure 2.

Vancomycin duration of therapy (hours).

Note. Vancomycin duration of therapy (hours) in patients with and without MRSA nasal PCR screening is detailed. In patients who received MRSA nasal PCR screening, vancomycin duration of therapy (hours) between positive and negative results is shown. MRSA = methicillin resistant Staphylococcus aureus; PCR = polymerase chain reaction.

Table 2.

Secondary Outcomes.

Outcome	MRSA nasal PCR screening tests obtained (n = 80)	MRSA nasal PCR screening tests not obtained (n = 71)	P-value
Length of hospital stay (days) (median, min, max)	3.7 (2.6, 6.8)	2.9 (1.9, 4.6)	0.03
Unplanned healthcare utilization related to SSTI (n, %)	10 (13%)	9 (13%)	0.97
SSTI culture obtained (n, %)	36 (45%)	40 (56%)	0.46
Any adverse event related to vancomycin (n, %)	6 (8%)	3 (4%)	0.40
Acute Kidney injury (n, %)	2 (3%)	2 (3%)	0.90
Vancomycin infusion syndrome (n, %)*	2 (3%)	1 (1%)	0.63
Received oral anti-MRSA step-down antibiotics (n, %)	13 (16%)	13 (18%)	0.74
Duration of oral anti-MRSA step down therapy (days, %)	7 (9%)	8 (11%)	0.11

SSTI = skin and soft tissue infection; MRSA = methicillin resistant Staphylococcus aureus.

^*Vancomycin is administered at a rate of 1000 mg per hour at our healthcare center.

Table 3.

Positive Predictive Value and Negative Predictive Value of MRSA Nasal Screening Tests in Patients with Skin and Soft Tissue Infections.

Skin and Soft Tissue Infection	Positive predictive value (%, n)	Negative predictive value (%, n)	Sensitivity (%)	Specificity (%)
All SSTIs	67 (4/6)	81 (26/32)	40	93
Purulent SSTIs	80 (4/5)	88 (14/16)	67	93
Non-purulent SSTIs	—	80 (13/16)	—	92

SSTI = skin and soft tissue infection; MRSA = methicillin resistant Staphylococcus aureus.

Discussion

The clinical impact of MRSA nasal PCR screening tests in respiratory infections has been well established however, the clinical utility and impact of obtaining MRSA nasal PCR screening tests for the indication of SSTIs is limited.^4-6 This study demonstrated a reduction in vancomycin DOT of 16.8 hours by use of MRSA nasal PCR screening tests in patients with SSTIs, regardless of negative or positive results further providing input on the utility of MRSA nasal PCR screening in patients with SSTI beyond the benefit noted by Burgoon et al. ¹ They demonstrated a decrease of vancomycin DOT of >24 hours with a negative nasal test results vs a positive nasal test result when a PCR was obtained. ¹ The median DOT of vancomycin was less than 48 hours at our practice site and use of the MRSA nasal PCR screening drove that duration to less than 24 hours. This is impactful because shortened vancomycin DOT can lead to a decrease in adverse effects, healthcare associated costs, and bacterial resistance.^5-7

This study also demonstrated obtaining MSRA nasal PCR screening tests for SSTIs does not negatively impact clinical outcomes including unplanned healthcare utilization 30 days post hospitalization. In MRSA nasal PCR screened patients, purulent infections had a longer duration of vancomycin. A longer duration of vancomycin would be expected as Methicillin-Resistant Staphylococcus aureus usually causes purulent SSTIs.^9,10

Literature has demonstrated a comparable NPV and PPV for MRSA nasal PCR screening test results in SSTIs and respiratory tract infections. NPV is a measure used to evaluate the effectiveness of a diagnostic test. It represents the probability that patients with a negative test result truly do not have the disease. ⁸ Results of MRSA nasal PCR screening was compared to results of cultures in patients when cultures were obtained. Despite limited cultures available for analysis (38), this study demonstrated similar trends for NPV, PPV, sensitivity, and specificity found in other studies for MRSA nasal PCR tests in SSTIs.^1,6,10 Both purulent and non-purulent SSTIs were evaluated and demonstrated similar NPV. Sixteen culture samples were available in patients classified to have had a non-purulent SSTI and in these cases, swabs were collected from serosanguinous drainage from SSTI sites. In general, swabbing of serosanguinous fluid for culture is not recommended as it may not yield useful microbiological information. ⁹ Despite this, use of MRSA nasal PCR tests helped to reduce vancomycin DOT in both purulent and non-purulent SSTIs.

This study was able to demonstrate the clinical utility of obtaining MRSA nasal PCR screening tests in SSTIs and clinician receptivity to withdrawal vancomycin coverage based on the test results. This study also supports the benefit of utilizing MRSA nasal PCR screening tests by demonstrating a statistically significant decrease in vancomycin DOT despite all study groups having a shorter vancomycin DOT when compared to previous studies that had used MRSA nasal culture screening tests. ¹ Literature has shown that decreasing vancomycin DOT results in decreased healthcare costs, rate of adverse effects, and bacterial resistance.^5-7

Limitations of this study included data abstraction was completed on less patients (n = 151) than required to meet power calculations (n = 383). Despite this, data collected provides an insight into the benefit of MRSA nasal PCR screening testing, and the value of a negative MRSA nasal PCR screening test, on vancomycin DOT in patients with skin and soft tissue infections (Figure 2). Less patients received a MRSA nasal PCR screening test if they were hospitalized in the preceding 90 days (16% vs 32%, P = .02) and also in those patients who presented with purulent SSTIs (31% vs 59%, P < .00). In this study clinicians may have opted for wound cultures instead of MRSA nasal PCR screening tests and may explain why MRSA nasal PCR screening tests were less utilized in these 2 groups. We also observed an increased length of stay of 19 hours in patients who received a MRSA nasal PCR screening test versus those who did not receive a screening test (See Table 3). Although, this may not be representative of obtaining MRSA nasal PCR screening tests in SSTIs as confounding factors that can greatly impact length of stay were not assessed in this study and is a limitation of our study. Other limitations of this study include inability to evaluate patients readmitted or vancomycin use at an outside facility without electronic health record sharing. The duration of time assessed may not be sufficient to assess long-term implications and parenteral anti-MRSA agents other than vancomycin were not evaluated.

Conclusion

This study demonstrated a significant reduction vancomycin DOT for SSTIs when MRSA nasal swab PCR screening tests are obtained. The reduction in vancomycin DOT did not negatively impact rate of adverse events or 30-day unplanned healthcare utilization. These results contribute to current data in support of the efficacy and clinical utility of obtaining MRSA nasal PCR screening tests for SSTIs.