Increased mortality associated with meticillin-resistant Staphylococcus aureus (MRSA) infection in the Intensive Care Unit: results from the EPIC II study

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Abstract

Controversy continues regarding whether the presence of meticillin resistance increases mortality risk in Staphylococcus aureus infections. In this study, we assessed the role of meticillin resistance in survival of patients with S. aureus infection included in the EPIC II point-prevalence study of infection in critically ill patients performed on 8 May 2007. Demographic, physiological, bacteriological and therapeutic data were collected for 13 796 adult patients in 1265 participating Intensive Care Units (ICUs) from 75 countries on the study day. ICU and hospital outcomes were recorded. Characteristics of patients with meticillin-sensitive S. aureus (MSSA) and meticillin-resistant S. aureus (MRSA) infections were compared. Co-morbidities, age, Simplified Acute Physiology Score (SAPS) II, site of infection, geographical region and MRSA/MSSA were entered into a multivariate model, and adjusted odds ratios (ORs) [95% confidence interval (CI)] for ICU and hospital mortality rates were calculated. On the study day, 7087 (51%) of the 13 796 patients were classified as infected. There were 494 patients with MRSA infections and 505 patients with MSSA infections. There were no significant differences between the two groups in use of mechanical ventilation or haemofiltration/haemodialysis. Cancer and chronic renal failure were more prevalent in MRSA than in MSSA patients. ICU mortality rates were 29.1% and 20.5%, respectively (P < 0.01) and corresponding hospital mortality rates were 36.4% and 27.0% (P < 0.01). Multivariate analysis of hospital mortality for MRSA infection showed an adjusted OR of 1.46 (95% CI 1.03–2.06) (P = 0.03). In ICU patients, MRSA infection is therefore independently associated with an almost 50% higher likelihood of hospital death compared with MSSA infection.

Introduction

Staphylococcus aureus is a common cause of infection in intensive care patients and in many cases it is resistant to meticillin [1]. However, whether meticillin resistance increases mortality in patients with S. aureus infection remains controversial. Some investigations and meta-analyses have reported that meticillin resistance does increase the mortality risk [2], [3], [4], [5], [6], [7], whereas others have been unable to demonstrate any difference in mortality between meticillin-resistant S. aureus (MRSA) and meticillin-sensitive S. aureus (MSSA) infections [8], [9], [10], [11], [12], [13], [14], [15]. The conflicting results may be explained by differences in setting, sample size, case mix, strain virulence, minimum inhibitory concentration (MIC), antibiotic choice, antibiotic dosage and timing of appropriate antimicrobial therapy.

The 1-day point-prevalence Extended Prevalence of Infection in the ICU (EPIC II) study showed that, on the day of the study, 7087 (51%) of 13 796 patients were classified as infected, and 70% of these had positive cultures; 47% of the positive isolates were Gram-positive [16]. The five most commonly isolated organisms were S. aureus (20.5%), Pseudomonas spp. (19.9%), Candida spp. (17.0%), Escherichia coli (16%) and Klebsiella spp. (12.7%); 49.4% of the S. aureus isolates were MRSA [16].

The purpose of the present study was to compare the characteristics of patients with MRSA and MSSA infections in the EPIC II study cohort and to assess the independent role of meticillin resistance in mortality in these patients.

Section snippets

Methods

The EPIC II 1-day point-prevalence study of infection in critically ill patients was performed on 8 May 2007 [16]. Demographic, physiological, bacteriological and therapeutic data were collected from 13 796 adult (>18 years) patients in 1265 participating Intensive Care Units (ICUs) (Supplementary Appendix A) from 75 countries on the study day, as described previously [16]. Simplified Acute Physiology Score (SAPS) II and Sequential Organ Failure Assessment (SOFA) scores were calculated for the

Characteristics of patients with MRSA versus MSSA infections

There was considerable variation in the percentages of patients with MRSA/MSSA according to geographical region (Fig. 1). The characteristics of patients with MRSA (n = 494) and MSSA (n = 505) infections are shown in Table 1. There were no differences in SAPS II and SOFA scores on admission between groups. Patients with MRSA were slightly older and had longer ICU stays prior to the study date than those with MSSA [median (IQR) 10 days (3–22 days) vs. 7 days (3–14 days); P < 0.001]. Patients with MSSA

Discussion

The main findings of this study are that, in ICU patients, MRSA infections are more frequent in patients with underlying co-morbid conditions, such as cancer and chronic renal failure, and are associated with a 50% greater likelihood of hospital death compared with MSSA infections. Patients with MRSA infection are also more likely to have concomitant infection with Pseudomonas spp., Enterococcus, Acinetobacter spp. or Candida spp. These findings are in agreement with several other studies [6],

Acknowledgment

The authors thank Hassane Njimi, MSc, PhD (Department of Intensive Care, Erasme University Hospital, Brussels, Belgium) for help with data management and statistical analyses.

Funding: No funding sources.

Competing interests: JR participated as a consultant and as a member of the speaker's bureau for Pfizer. All other authors declare no competing interests.

Ethical approval: Ethics committee approval was obtained from individual centers.

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