Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal Colonization Predicts Intensive Care Unit-Acquired MRSA Infections: True Or False?

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) infections are a focus of national attention because of their potentially lethal complications and evidence that their frequency has been increasing in U.S. hospitals [1]. Although better infection control and other best practices may finally be stemming the tide, at least for blood stream infections (BSI) [2], the problem remains pervasive and serious. Hospitalizations with infections caused by MRSA increased steadily between 2000 and 2005, nearly doubling in many areas of the country [3]. Currently, MRSA accounts for more than 60% of the S. aureus infections in intensive care units (ICUs) [4,5]. Several recent investigations have attempted to define the benefits of routine MRSA surveillance as a tactic to prevent MRSA infections among hospitalized patients. Unfortunately, the results of these studies have been mixed, and the benefits of routine MRSA screening at the time of hospital or ICU admission are still debated [6 –9].

Another potential role for MRSA screening in the ICU is as a guide for empiric antimicrobial therapy of suspected infections. Several studies have demonstrated that prior MRSA colonization is a risk factor for subsequent infection with MRSA [10,11]. Unfortunately, the overall accuracy of MRSA screening as a predictor of subsequent ICU-acquired infections necessitating empiric antimicrobial coverage for MRSA is unknown.

In this issue of Surgical Infections, Byrnes et al. describe their experience with MRSA surveillance in the ICU setting [12]. In a retrospective study of critically ill surgical patients with proved MRSA infections, the results of MRSA nasal swab surveillance at ICU admission were correlated. Detection of MRSA by polymerase chain reaction (PCR) was significantly more sensitive than a chromogenic assay, but the detection of MRSA colonization by surveillance had limited clinical utility for two reasons. First, screening was significantly more sensitive when performed within six days prior to the development of clinical infection, indicating that many cases of MRSA infection truly are ICU-acquired. Second, in corroboration, 30% of MRSA infections were not preceded by nasal colonization.

Another recent study of screening for MRSA nasal colonization as a predictor of the subsequent occurrence of MRSA infection in the ICU helps to clarify this important issue. These data demonstrate that MRSA nasal colonization is a poor predictor of subsequent MRSA infection requiring antimicrobial treatment among ICU patients. In a study conducted in the medical ICU of Barnes-Jewish Hospital in St. Louis, 164 of 749 patients (21.9%) were found to have nasal colonization with MRSA at the time of ICU admission [13]. The predictive accuracy of colonization for ICU-acquired MRSA infections, either lower respiratory tract infection (LRTI) or BSI, was poor. For LRTI: Sensitivity, 24.2%; specificity, 78.5%; positive predictive value, 17.7%; and negative predictive value, 84.4%. For BSI: Sensitivity, 23.1%; specificity, 78.2%; positive predictive value, 11.0%; and negative predictive value, 89.7%. Addition of nasal colonization results obtained later during the ICU stay did not change the predictive accuracy of this test appreciably for identification of subsequent LRTIs and BSIs attributed to MRSA that required antimicrobial therapy. Had MRSA nasal swab results been used to determine the requirement for MRSA empiric treatment, then 72.5% of patients with MRSA LRTIs and 73.1% of patients with MRSA BSIs would not have received appropriate anti-MRSA antimicrobial therapy at the time infection was suspected clinically. In view of these findings, clinicians should not employ the nasal swab colonization data alone in determining the need for empiric anti-MRSA therapy of ICU-acquired infections.

To date, most studies among hospitalized patients have focused on identifying MRSA colonization as a predictor of infection for the entire population cohort [14 –18]. Croft et al. demonstrated that MRSA colonization was a predictor of subsequent MRSA infection among trauma patients [19]. Thirty-six of 355 trauma patients (10.1%) had MRSA colonization, of whom 13 (36.1%) developed an MRSA infection. The other 21 MRSA infections identified in this population occurred among the 319 patients not colonized with MRSA. Similarly, Chen et al. examined nasal carriage of S. aureus in otherwise healthy children presenting with skin and soft tissue infections [20], finding high rates of nasal colonization with S. aureus but significant discordance between nasal and wound isolates. Schweizer et al. found that prior MRSA colonization or infection was predictive of subsequent MRSA BSIs and that physicians appeared to use this documentation when prescribing empirical therapy for suspected bacteremia [21]. However, as with the previous two studies, most MRSA BSIs (212/287) occurred in patients who were not colonized with MRSA. These investigations also demonstrate the limited overall utility of prior documentation of MRSA colonization as a determinant for empiric MRSA antimicrobial therapy in an individual patient.

Safdar and Bradley performed a systematic review to estimate the risk of MRSA infection following colonization with MRSA compared with methicillin-susceptible S. aureus (MSSA) [14]. Colonization with MRSA was associated with a four-fold increase in infection risk. In this analysis, four studies evaluated the role of MRSA colonization as a determinant of subsequent occurrence of MRSA infections in the ICU setting, demonstrating similar results [22 –25]. Pujol et al. found that 147 of 488 patients (30.1%) were nasal carriers of S. aureus; 84 patients (17.2%) harbored MRSA, whereas 63 (12.9%) harbored MSSA [22]. Nosocomial S. aureus bacteremia was diagnosed in 38 patients (7.7%): 24 (38%) of the MRSA carriers, eight (9.5%) of the MSSA carriers, and six (1.7%) of the non-carriers. This same group of investigators demonstrated that nasal colonization with S. aureus identified a group of ICU patients at high risk for subsequent infection with S. aureus [23]. Squier et al. found that 103 of 204 surgical ICU/liver transplant ICU patients (50.5%) were colonized with S. aureus [24]. Forty-four (42.7%) were nasal carriers only, whereas seven (6.8%) were rectal carriers only, and 52 (50.5%) were both nasal and rectal carriers. Infections caused by S. aureus developed in 32 patients (15.7%), including three non–carriers.

Taken together, the extant studies suggest that patients colonized with MRSA at the time of ICU admission are at greater risk for the subsequent development of an MRSA infection. The addition of rectal cultures to nasal cultures may increase the identification of MRSA colonization and thereby improve the diagnostic accuracy of such data for decision-making regarding the need for subsequent empiric anti-MRSA treatment. This is likely the most important explanation for the poor performance of nasal swabs alone in predicting subsequent MRSA infections. If more extensive surveillance swabs are obtained from stool, gastric aspirate, groin, oropharynx, and axilla, the predictive accuracy might be expected to increase, albeit at an exponential increase in cost. This has been demonstrated for other types of nosocomial infections such as Candida BSIs, where colonization indices employing multiple-site surveillance cultures have been good predictors of subsequent infection [26]. However, investigations of MRSA surveillance in the ICU make clear the limited ability of nasal swabs alone to predict the presence or absence of an MRSA infection in an individual patient.

The fact that nasal colonization may not be predictive of subsequent MRSA infections in the individual patient suggests that prophylactic upper airway decontamination may not be useful either; findings of clinical trials employing upper airway decontamination in the ICU setting [27 –29] have produced conflicting results. Additionally, nasal colonization may be a transient phenomenon; patients who have negative nasal swabs at ICU admission may acquire MRSA subsequently [12]. Therefore, negative results of nasal swabs may support de-escalation of empiric MRSA coverage if all clinical cultures are found subsequently to be negative for MRSA. However, clinicians cannot use the results of initial negative MRSA nasal swabs reliably to withhold empiric MRSA coverage for patients who otherwise are at risk for MRSA infection.

In summary, MRSA nasal swab colonization data are a poor predictor of subsequent MRSA infection requiring treatment in the individual patient and may not be useful for decision-making regarding the need for empiric antimicrobial therapy. However, routine surveillance for MRSA and other important antibiotic-resistant pathogens often is an important element of effective infection control programs [7,30 –32]. When it comes to individual patient decision-making regarding the need for antimicrobial treatment, a policy of de-escalation probably is the most logical approach in the ICU [33,34], balancing the need for appropriate antimicrobial treatment with the need to minimize the unnecessary use of antimicrobial agents in order to reduce the emergence of resistance.

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