Predictive Value of the Methicillin-Resistant Staphylococcus aureus Nasal Swab for Methicillin-Resistant Staphylococcus aureus Ventilator-Associated Pneumonia in the Trauma Patient

Abstract

Background:

Many trauma centers have empiric treatment algorithms for ventilator-associated pneumonia (VAP) treatment prior to culture results that include antibiotic agents for methicillin-resistant Staphylococcus aureus (MRSA) coverage that can have adverse effects. This is the only study to evaluate risk factors and MRSA nasal swabs to risk-stratify trauma patients for MRSA VAP, thereby potentially limiting the need for empiric vancomycin.

Patients and Methods:

This was a single institution retrospective cohort study. Adult patients admitted to the trauma intensive care unit (ICU) between January 2013 and December 2017 who had a MRSA nasal swab and subsequently met criteria for VAP were included. Demographics, risk factors for MRSA pneumonia, and culture results were collected.

Results:

A total of 140 patients met inclusion criteria. The negative predictive value (NPV) of MRSA nasal swab at predicting subsequent MRSA pneumonia was 97%. The sensitivity, specificity, and positive predictive value were 50.0%, 96.2%, and 44.4%, respectively. Smokers were more likely to develop MRSA pneumonia, odds ratio: 7.0 (p = 0.02). When considering non-smokers with a negative MRSA nasal swab, NPV was 100%.

Conclusions:

This is the only study to date that assesses the utility of MRSA nasal swab and risk factor data to guide empiric VAP antibiotic therapy in trauma patients. Smoking was found to be a risk factor for MRSA pneumonia. The use of MRSA nasal swabs in combination with smoking status to guide empiric use of MRSA coverage antibiotic agents is recommended because of a 100% NPV. When utilized, as many as 68% of patients may safely be spared MRSA coverage antibiotic agents and the related adverse effects.

Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia has been associated with worse outcomes compared with other types of pneumonia [1]; as such, treatment guidelines for health care-associated pneumonia (HCAP), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP) recommend the use of empiric MRSA coverage antibiotic agents pending culture results [2,3]. The empiric use of MRSA coverage antibiotic agents is not benign. Vancomycin-induced kidney injury has been associated with a greater incidence of end-stage renal disease and mortality [4], leading to an interest in identifying patients with pneumonia at low risk for MRSA pneumonia to limit empiric MRSA coverage antibiotic agents.

Many studies have demonstrated that MRSA colonization of the nares is associated with subsequent MRSA infections [5 –10]. The validity of MRSA polymerase chain reaction (PCR) nasal swabs to diagnose MRSA nasal colonization has been demonstrated [11,12]. A 2014 study by Dangerfield et al. [13] that evaluated the use of MRSA nasal swabs as a predictor of MRSA pneumonia in patients with pneumonia, determined that MRSA nasal swabs had a 99.2% negative predictive value for MRSA pneumonia. A similar study by Chou et al. [14] also estimated that MRSA nasal swabs had a 97% NPV for MRSA pneumonia.

The predictive value of MRSA nasal swabs for MRSA pneumonia has not been studied in trauma patients. Known risk factors for MRSA pneumonia include: tobacco use, illicit drug use, advanced age, recent nursing home stay, chronic obstructive pulmonary disease (COPD), recent antibiotic exposure, and homelessness [15,16]. It has been proposed that trauma patients have a higher incidence of some of these risk factors compared with the general population [17], limiting the generalizability of previous studies to trauma patients. In this study we evaluated the predictive value of MRSA nasal swabs for MRSA VAP among trauma patients.

Patients and Methods

We conducted a single institution retrospective observational cohort study in a 920-bed level 1 trauma center, approved by the hospital Institutional Review Board. The primary objective was to establish the positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of MRSA nasal swab results for subsequent MRSA VAP among trauma patients. A secondary objective was to identify risk factors associated with MRSA VAP among this patient population. Data were collected from a single tertiary care center and included all adult trauma patients (>18 years old) admitted to the trauma intensive care unit (ICU) between January 2013 and December 2017 who subsequently developed MRSA VAP. Patients had to be intubated for longer than 48 hours to be included in the study, with pneumonia diagnosed by positive bronchoalveolar lavage (BAL) and MRSA nasal swab prior to BAL. Data were collected from the electronic medical record (EMR).

It is standard practice in the study ICU for all patients to undergo MRSA nasal swab on ICU admission. Indication for BAL is a fever at least 72 hours after admission with a sputum sample positive for bacteria or white blood cells on gram stain. Broad-spectrum antibiotic agents are then started and are narrowed to the culture results of the BAL specimen. As a first step to identify eligible subjects, patients admitted to the ICU and undergoing a BAL during the study time period were pulled from the trauma registry. Those with a positive BAL result, as defined as quantitative culture result of >100,000 colony-forming units (CFU), were then identified by EMR review and entered in the study database. Demographic characteristics and MRSA nasal swab results were collected from the EMR for these patients, as well as data regarding the presence of the following risk factors: active skin infection, recent (within one year) hospital admission, history of MRSA, end-stage renal disease (ESRD), spinal cord injury), incarceration, homelessness, immunosuppression, home wound care, dialysis, home infusion, long-term care facility (LTCF), and hospital length of stay (HLOS) ≥2 days. Comorbidities were further collected, and included drug use, smoking status, COPD, congestive heart failure, HLOS, ICU, and intermediate care (IMC) days, ventilator days, and injury severity score (ISS). A receiver operating characteristic (ROC) curve was produced and used to quantify the PPV, NPV, sensitivity, specificity, and area under the curve.

Results

During the study period, 284 patients underwent BAL. Of these, 142 (50%) had positive results. Of those with positive results, all but two had MRSA nasal swabs performed prior to BAL, resulting in 140 eligible subjects (Table 1). As presented in the table, the median age was 50 years (interquartile rage [IQR], 33.5–65.0), with 85% male (n = 119). On evaluation of comorbidities (Table 2), 32.1% of the study population were smokers, which is twice the national average, according to 2019 U.S. Centers for Disease Control and Prevention (CDC) estimates [18]. Patients who developed MRSA VAP had a lower ISS compared with MRSA-negative VAP: 13.5 versus 26, respectively (p = 0.015). The majority of patients (58%) had a single-organism VAP whereas the remaining 42% of patients had a polymicrobial VAP. The most common organism identified was methicillin-susceptible Staphylococcus aureus (MSSA; Table 3). The second most common organisms were Haemophilus influenzae and Klebsiella pneumoniae. Both MRSA and Pseudomonas were found in 5.6% of the patients, respectively.

Table 1.

Demographics

	All	Swab negative, culture negative	Swab negative, culture positive	Swab positive, culture negative	Swab positive, culture positive
n	140	127	4	5	4
Age (y)	50 (33.5–65.0)^a	51 (35.5–65.5)	40 (26.8–55.5)	25 (24.0–31.0)	48 (29.5–69.0)
Gender, n (%)
Male	119 (85%)	106 (83.5%)	4 (100%)	5 (100%)	4 (100%)
Female	21 (15%)	21 (16.5%)	0 (0%)	0 (0%)	0 (0%)
Race, n (%)
White	82 (61.7%)	73 (60.3%)	4 (100%)	3 (60%)	2 (66.7%)
Black	15 (11.3%)	14 (11.6%)	0 (0%)	1 (20%)	0 (0%)
Asian	17 (12.8%)	16 (13.2%)	0 (0%)	1 (20%)	0 (0%)
Hispanic	13 (9.8%)	13 (10.7%)	0 (0%)	0 (0%)	0 (0%)
Other	6 (4.5%)	5 (4.1%)	0 (0%)	0 (0%)	1 (33.3%)

Medians and interquartile ranges are presented.

Table 2.

Comorbidities

	All	Swab negative, culture negative	Swab negative, culture positive	Swab positive, culture negative	Swab positive, culture positive
n	140	127	4	5	4
Drug	15 (10.7%)	14 (11.0%)	0 (0%)	0 (0%)	1 (25%)
Smoker	45 (32.1%)	37 (29.1%)	4 (100%)	2 (40%)	2 (50%)
COPD	4 (2.9%)	3 (2.4%)	0 (0%)	0 (0%)	1 (25%)
CHF	2 (1.4%)	2 (1.6%)	0 (0%)	0 (0%)	0 (0%)
LOS (days)	23 (16–31)^a	23 (16.0–31.5)	24.5 (20.8–28)	15 (10–17)	26.5 (25.0–32.8)
ICU days	18 (13–25)	18 (13–25)	22.5 (20.3–24.3)	12 (9–14)	21 (19.3–22.0)
IMC days	2 (0–5.8)	1.5 (0–4.8)	1.5 (0.8–3.0)	2 (1–4)	8 (5.5–8.5)
Ventilator days	15 (11.0–19.3)	15 (11.0–21.5)	15.5 (12.5–17.3)	8 (6–11)	15 (9.5–19.3)
ISS	26 (17.0–30.8)	26 (17.0–31.5)	13.5 (9.8–19.3)	29 (26–38)	13.5 (9.8–21.0)

COPD = chronic obstructive pulmonary disease; CHF = congestive heart failure; LOS = length of stay; ICU = intensive care unit; IMC = intermediate care unit; ISS = injury severity score.

Medians and interquartile ranges (IQRs) were calculated for continuous variables. Frequencies and percentages were summarized for categorical variables

Table 3.

Speciation Found on Bronchoalveolar Lavage Results

	Number positive	Percent positive
MSSA	59	41.6%
Haemophilus influenzae	39	27.5%
Klebsiella pneumoniae	19	13.4%
Escherichia coli	12	8.5%
Streptococcus pneumoniae	12	8.5%
Pseudomonas aeruginosa	8	5.6%
MRSA	8	5.6%
Enterobacter cloacae	6	4.2%
Moraxella catarrhalis	5	3.5%
Acinetobacter baumannii	4	2.8%
Serratia marcescens	4	2.8%
Other	16	11.3%

MSSA = methicillin-susceptible Staphylococcus aureus; MRSA = methicillin-resistant Staphylococcus aureus.

Eight patients were positive for MRSA pneumonia. The MRSA nasal swab was found to be 50.0% sensitive, 96.2% specific, with a 44.4% PPV, and 97% NPV for MRSA VAP (Tables 4 and 5). There was no difference in time from intubation or MRSA nasal swabs to time of positive MRSA culture (Table 6). There was no association between risk factors (Table 7) and MRSA VAP, with the exception of smoking. Smokers were more likely than non-smokers to have a MRSA VAP, odds ratio: 7.05 (95% confidence interval [CI], 1.4–36.4; p = 0.02). The NPV of MRSA nasal swabs among non-smokers was 100%.

Table 4.

Methicillin-Resistant Staphylococcus aureus Nasal Swab and Culture Results

		Culture
		Negative	Positive
Nasal swab	Negative	127	4
Nasal swab	Positive	5	4

Table 5.

Predictive Values

Sensitivity	50.00%
Specificity	96.21%
Positive predictive value	44.44%
Negative predictive value	96.95%

Note: Receiver operating characteristic (ROC) curve was utilized to quantify the predictive ability of the methicillin-resistant Staphylococcus aureus (MRSA) nasal swab. Area under the curve was 0.7311

Table 6.

Median Number of Days between Intubation/MRSA Nasal Swab to Positive MRSA Culture

	Negative culture	Positive culture	p
Median number of days from intubation to culture	5.0	4.0	0.996
Median number of days from nasal swab to culture	5.0	5.5	0.43

MRSA = methicillin-resistant Staphylococcus aureus.

Table 7.

Risk Factors

	All	Swab negative, culture negative	Swab negative, culture positive	Swab positive, culture negative	Swab positive, culture positive
n	140	127	4	5	4
Active skin infection	1 (0.7%)	1 (0.8%)	0 (0%)	0 (0%)	0 (0%)
Health care admission with 1 y	6 (4.3%)	5 (3.9%)	1 (25%)	0 (0%)	0 (0%)
MRSA hx	1 (0.7%)	0 (0%)	0 (0%)	0 (0%)	1 (25%)
ESRD dm	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)
Spine cord injury	6 (4.3%)	6 (4.7%)	0 (0%)	0 (0%)	0 (0%)
Incarcerated	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)
Homelessness	1 (0.7%)	1 (0.8%)	0 (0%)	0 (0%)	0 (0%)
Immunosuppression	13 (9.3%)	12 (9.5%)	1 (25%)	0 (0%)	0 (0%)
Home wound care	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)
Dialysis	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)
Home infusion	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)
LTCF	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)
HLOS> = 2	139 (99.3%)	126 (99.2%)	4 (100%)	5 (100%)	4 (100%)

MRSA = methicillin-resistant Staphylococcus aureus; ESRD = end-stage renal disease; LTCF = long-term care facility; HLOS = hospital length of stay.

Discussion

Many studies have identified worse outcomes among MRSA pneumonia patients compared with other sources of pneumonia [1,19,20]. In light of these findings, guidelines have advocated for empiric MRSA coverage antibiotic use in the treatment of VAP [2,3]. However, MRSA coverage antibiotic agents, such as vancomycin, have a known risk for nephrotoxicity, ototoxicity, and a higher incidence of ESRD and mortality [4]. Studies evaluating the utility of MRSA nasal swabs as a screening tool to guide empiric MRSA coverage antibiotic agents estimate a NPV of 97%–99.2% [13,14].

These studies did not include trauma patients, raising concerns that their results may not predict the outcomes for that population adequately because of the presumed high incidence of risk factors for MRSA pneumonia [17]. The primary objective of this study was to establish the predictive value of MRSA nasal swabs among trauma patients, with a secondary objective of identifying risk factors associated with MRSA pneumonia in the trauma population. The patient population in this study was predominantly middle-aged white males with an incidence of risk factors similar to the general population, with the exception of smoking. Patients included in this study were found to be twice as likely as the general population to be smokers, according to 2019 CDC estimates [18].

Despite the higher incidence of smoking in this study population the NPV of MRSA nasal swabs to predict subsequent MRSA VAP was 97%. When accounting for smoking status, the NPV was 100%. This is a similar result to those seen in the previous studies of non-trauma patients.

Limitations of this research should be considered for the generalizability of our findings. In studies of this nature, the incidence of MRSA pneumonia varies between patient populations. One large study found MRSA accounted for 8.9% of community-acquired pneumonia, 26.5% of HCAP, and 22.9% of HAP [21]. Other studies have reported as low as 0.9% MRSA CAP and 2%–5.5% for HCAP [13,22 –25]. In this study population, 5.6% of VAP was caused by MRSA. Furthermore, although we were concerned that the time from MRSA nasal swab to time of culture would impact the predictive value of the MRSA nasal swab, we calculated no difference in median days between nasal swab and culture results among those with or without MRSA VAP (5.5 vs. 5; p = 0.43). Finally, our findings report nasal swab screening only; other methods of screening, such as pulsed field gel electrophoresis or multilocus sequence typing, may yield different results.

A review of demographic data and risk factors revealed a high prevalence of smokers. Analysis of the data identified that smoking was positively associated with MRSA pneumonia; smokers with pneumonia were seven times more likely to be diagnosed with MRSA. Patients positive for MRSA pneumonia had lower ISS compared with MRSA-negative patients. The reason for this difference is unclear, and as this was not a primary end point of the study, caution should be given to this result. Although our study focused narrowly on patients diagnosed with MRSA VAP, we identify a number of interesting topics for future study, including the efficacy of preventive measures to clear the skin of nasal colonization, the identified risk factors' effect on other organisms, and whether the organism present upon admission was the same strain causing the infection.

Conclusions

Methicillin-resistant Staphylococcus aureus coverage antibiotic agents, such as vancomycin, have been associated with kidney injury, greater incidence of ESRD, and a higher mortality rate [4]. The use of MRSA nasal swab data to guide use of empiric MRSA coverage antibiotic agents has been studied in non-trauma patients [13,14]. This is the first study to evaluate the use in trauma patients. This study suggests that the MRSA nasal swab has a high NPV of 97% for MRSA pneumonia among this trauma population. Smoking was found to be twice as prevalent in this population as compared to the general population and was noted to be a significant risk factor for MRSA pneumonia, with an odds ratio of 7.05. When considering only non-smokers with a negative MRSA nasal swab, the NPV for MRSA pneumonia was 100%. As such, we assert that the results of a MRSA nasal swab can safely be used to limit the use of empiric MRSA coverage antibiotics for non-smokers. Although further multi-institutional study assessing these results across multiple trauma patient populations is needed, this study supports the use of smoking status and MRSA nasal swab data to guide the use of empiric MRSA coverage antibiotics thus decreasing the risk for harmful side effects among trauma patients.

Footnotes

Acknowledgment

The abstract was presented at the 50th Critical Care Congress, virtual meeting, January 31, 2021.

Funding Information

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author Disclosure Statement

The authors have no competing interests to declare.

References

Minejima

, Lou

, Nieberg

, Wong-Beringer

. Patients presenting to the hospital with MRSA pneumonia: Differentiating characteristics and outcomes with empiric treatment. BMC Infect Dis, 2014; 14:252.

American Thoracic Society. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med, 2005; 171:388–416.

Kalil

, Metersky

, Klompas

, 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. Clin Infect Dis, 2016; 63:e61–111.

Bamgbola

. Review of vancomycin-induced renal toxicity: An update. Ther Adv Endocrinol Metab, 2016; 7:136–147.

National Nosocomial Infections Surveillance System. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control, 2004; 32:470–485.

Harris

, Furuno

, Roghmann

, et al. Targeted surveillance of methicillin-resistant Staphylococcus aureus and its potential use to guide empiric antibiotic therapy. Antimicrob Agents Chemother, 2010; 54:3143–3148.

Safdar

, Bradley

. The risk of infection after nasal colonization with Staphylococcus aureus. Am J Med, 2008; 121:310–315.

Byrnes

, Adegboyega

, Riggle

, et al. Nasal swabs collected routinely to screen for colonization by methicillin-resistant Staphylococcus aureus in intensive care units are a sensitive screening test for theorganism in clinical cultures. Surg Infect, 2010; 11:511–515.

Robicsek

, Suseno

, Beaumont

, et al. Prediction of methicillin-resistant Staphylococcus aureus involvement in disease sites by concomitant nasal sampling. J Clin Microbiol, 2008; 46:588–592.

10.

Sarikonda

, Micek

, Doherty

, et al. Methicillin-resistant Staphylococcus aureus nasal colonization is a poor predictor of intensive care unit-acquired methicillin-resistant Staphylococcus aureus infections requiring antibiotic treatment. Crit Care Med, 2010; 38:1991–1995.

11.

Kelley

, Grabsch

, Howden

, et al. Comparison of the Xpert methicillin-resistant Staphylococcus aureus (MRSA) assay, BD GeneOhm MRSA assay, and culture for detection of nasal and cutaneous groin colonization by MRSA. J Clin Microbiol, 2009; 47:3769–3772.

12.

Andersen

, Tollefsen

, Seljordslia

, et al. Rapid MRSA test in exposed persons: costs and savings in hospitals. J Infect, 2010; 60:293–299.

13.

Dangerfield

, Chung

, Webb

, Seville

. Predictive value of methicillin-resistant Staphylococcus aureus (MRSA) nasal swab PCR assay for MRSA pneumonia. Antimicrob Agents Chemother, 2014; 58:859–864.

14.

Chou

, Eskandarian

, Jung

, et al. Predictive values of methicillin-resistant staphylococcus aureus (MRSA) nasal swab PCR assay for MRSA pneumonia. Open zforum Infect. Dis. 2018 Nov;5(Suppl 1):S449–S449.

15.

Wooten

, Winston

. Risk factors for methicillin-resistant Staphylococcus aureus in patients with community-onset and hospital-onset pneumonia. Respir Med, 2013; 107:1266–1270.

16.

Poonja

, Mashruwala

, Kim

, et al. Risk factors for pseudomonas MRSA in healthcare-associated pneumonia. The Hospitalist 2016. www.the-hospitalist.org/hospitalist/article/121661/antimicrobial-resistant-infections/risk-factors-pseudomonas-mrsa (Last accessed March 31, 2021).

17.

Loberg

, Hayward

, Fessler

, Edhayan

. Associations of race, mechanism of injury, and neighborhood poverty with in-hospital mortality from trauma: A population-based study in the Detroit metropolitan area. Medicine (Baltimore), 2018; 97:e12606.

18.

Cornelius

, Wang

, Jamal

, et al. Tobacco product use among adults–United States. Morbid Mortal Wkly Rep, 2020; 69:1736–1742.

19.

Jeffres

, Isakow

, Doherty

, et al. Predictors of mortality for methicillin-resistant Staphylococcus aureus health-care-associated pneumonia: Specific evaluation of vancomycin pharmacokinetic indices. Chest, 2006; 130:947–955.

20.

Taneja

, Haque

, Oster

, et al. Clinical and economic outcomes in patients with community-acquired Staphylococcus aureus pneumonia. J Hosp Med, 2010; 5:528–534.

21.

Kollef

, Shorr

, Tabak

, et al. Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture-positive pneumonia. Chest, 2005; 128:3854–3862.

22.

Grenier

, Pepin

, Nault

, et al. Impact of guideline-consistent therapy on outcome of patients with healthcare-associated and community-acquired pneumonia. J Antimicrob Chemother, 2011; 66:1617–1624.

23.

Lobo

, Reed

, Wunderink

. Expanded clinical presentation of community-acquired methicillin-resistant Staphylococcus aureus pneumonia. Chest, 2010; 138:130–136.

24.

Moran

, Krishnadasan

, Gorwitz

, et al. Prevalence of methicillin-resistant Staphylococcus aureus as an etiology of community-acquired pneumonia. Clin Infect Dis, 2012; 54:1126–1133.

25.

Shindo

, Sato

, Maruyama

, et al. Health-care-associated pneumonia among hospitalized patients in a Japanese community hospital. Chest, 2009; 135:633–640.