International Journal of Antimicrobial Agents 40 (2012) 108–113 Contents lists available at SciVerse ScienceDirect International Journal of Antimicrobial Agents j our na l ho me p age: http://www.elsevier.com/locate/ijantimicag High vancomycin minimum inhibitory concentration is a predictor of mortality in meticillin-resistant Staphylococcus aureus bacteraemia Yu Mi Wi a,b , June Myung Kim b , Eun-Jeong Joo c , Young Eun Ha c , Cheol-In Kang c , Kwan Soo Ko d , Doo Ryeon Chung c , Jae-Hoon Song c , Kyong Ran Peck c,∗ a Division of Infectious Diseases, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea b Department of Medicine, the Graduate School, Yonsei University, Seoul, Republic of Korea c Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea d Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea a r t i c l e i n f o Article history: Received 3 February 2012 Accepted 12 April 2012 Keywords: MRSA bacteraemia Vancomycin MIC Mortality a b s t r a c t Failure of vancomycin in the treatment of meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia has been reported despite full susceptibility of the organism to vancomycin. A retrospective observational cohort study including 137 patients with MRSA bacteraemia was performed at two centres in South Korea during 2009–2010. A total of 137 patients with MRSA bacteraemia receiving vancomycin therapy were enrolled during the study period. Isolates from 13 (9.5%) of the 137 patients had minimum inhibitory concentrations (MICs) ≥1 g/mL. The 30-day cumulative survival was 53.8% for patients infected with isolates having a MIC ≥ 1 g/mL and 79.8% for patients infected with isolates having a MIC < 1 g/mL (log-rank test, P = 0.026). Vancomycin MIC ≥ 1 g/mL [hazard ratio (HR) = 7.0, 95% confidence interval (CI) 2.2–22.1; P = 0.001], nosocomial acquisition of bacteraemia (HR = 5.4, 95% CI 1.4–20.1; P = 0.013), rapidly fatal underlying diseases (HR = 20.5, 95% CI 3.9–106.4; P < 0.001), presentation with septic shock (HR = 8.4, 95% CI 3.0–23.3; P < 0.001), presence of complicated infections (HR = 5.6, 95% CI 2.0–15.8; P = 0.001) and persistent MRSA bacteraemia for ≥3 days (HR = 4.2, 95% CI 1.4–12.7; P = 0.012) were independent pre- dictors of 30-day mortality in patients with MRSA bacteraemia. In patients with high Pitt bacteraemia scores (Pitt score ≥2), the delay in initiation of vancomycin therapy was significantly different between non-survivors and survivors (2.4 days vs. 1.1 days; P = 0.012). Vancomycin MIC ≥ 1 g/mL had a signifi- cant impact on mortality of patients with MRSA bacteraemia. These findings support early consideration of alternative anti-MRSA agents in patients with MRSA bacteraemia who have high vancomycin MICs as well as prompt initiation of anti-MRSA treatment in patients with MRSA bacteraemia, especially those with high Pitt scores. © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. 1. Introduction Meticillin-resistant Staphylococcus aureus (MRSA) infections are a significant cause of healthcare-associated morbidity [1–3]. Although recent data have shown a decrease in the rate of healthcare-associated MRSA infections, community-associated MRSA has recently emerged in populations that traditionally were not at risk of infection [4,5]. Vancomycin is the most common antimicrobial agent used for the treatment of MRSA infections worldwide. However, reduced susceptibility to vancomycin in S. aureus isolates has been a major medical concern for more than a ∗ Corresponding author. Tel.: +82 2 3410 0329; fax: +82 2 3410 0041. E-mail address: krpeck@skku.edu (K.R. Peck). decade [6–13]. A number of studies have reported that ele- vated vancomycin minimum inhibitory concentrations (MICs) in MRSA isolates are associated with significantly higher mortality in the treatment of MRSA bacteraemia [8–10]. However, several recent reports showed no significant influence of MIC on the treatment outcome of patients infected with high-MIC isolates [11–13]. The association between poor outcome and high vancomycin MIC has been attributed to the difficulty in achieving an optimum vancomycin area under the concentration–time curve (AUC)/MIC ratio [14,15]. The AUC/MIC ratio was proposed to be the best outcome-predictive pharmacokinetic parameter of vancomycin activity against MRSA [16]. An increase in the number of strains with higher vancomycin MICs (MIC creep) has been noted [17,18]. Consequently, it may be anticipated that MIC creep will worsen the outcomes of treatment in patients with MRSA infections receiving 0924-8579/$ – see front matter © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. http://dx.doi.org/10.1016/j.ijantimicag.2012.04.003