Clinical outcomes after initial treatment of methicillin-resistant Staphylococcus aureus infections

Nobuaki Shime,1,2 Nobuyuki Saito,3 Miya Bokui,4 Naoki Sakane,5 Mitsuhiro Kamimura,6 Tsutomu Shinohara,7 Tadashi Kosaka,8 Hisashi Ishikura,9 Atsuko Kobayashi,10 1Department of Emergency and Critical Care Medicine, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan; 2Department of Emergency and Critical Care Medicine, Kyoto Medical Centre, Kyoto, Japan; 3Shock and Trauma Center, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Japan; 4Department of Pharmacy, National Hospital Organization Kyoto Medical Centre, Kyoto, Japan; 5Clinical Research Institute, National Hospital Organization Kyoto Medical Centre, Kyoto, Japan; 6Department of Pulmonology, National Hospital Organization Disaster Medical Centre, Tokyo, Japan; 7Department of Clinical Investigation, National Hospital Organization Kochi Hospital, Kochi, Japan; 8Department of Pharmacy, Kyoto Prefectural University, School of Medicine, Kyoto, Japan; 9Department of Surgery, Tokushima Red Cross Hospital, Komatsushima, Japan; 10Department of Central Laboratory, Takarazuka City Hospital, Hyogo, Japan Objective: To evaluate the clinical outcomes associated with anti-methicillin-resistant Staphylococcus aureus (MRSA) antimicrobials. Methods: We reviewed a prospective database of 247 consecutive patients with clinically and microbiologically confirmed MRSA infections, hospitalized in 7 Japanese hospitals between April 2014 and March 2015, and treated with anti-MRSA pharmaceuticals. Survival was measured at 30 days. We examined the relationships between initial antimicrobial administered and survival and organ toxicity. HR and 95% CIs were calculated. Results: Overall 30-day mortality was 12%. The lungs were infected in 105 (41%), skin and soft tissue in 73 (30%), and bones and joints in 21 (9%) patients. Bacteremia complicated the illness in 69 patients (28%). Among 5 pharmaceuticals, vancomycin was prescribed to 174 (71%), linezolid to 38 (16%), teicoplanin to 22 (9%), and daptomycin to 11 (5%) patients. Vancomycin tended to be associated with the lowest survival (HR=2.47; 95% CI=0.93–6.51; P=0.067), particularly in the lung-infected subgroup (HR=4.85; 95% CI=1.12–20.94; P=0.034) after adjustments for baseline illness severity. The incidence of renal dysfunction tended to be higher in patients with trough serum concentrations of vancomycin >15 mg/dL. Conclusion: In this observational study reflecting real-world conditions, vancomycin was associated with higher 30-day mortality and incidence of kidney dysfunction than other anti-MRSA agents. The significance of the differences observed among antimicrobials other than vancomycin is uncertain. Keywords: methicillin-resistant Staphylococcus aureus, vancomycin, linezolid, infectious mortality, renal dysfunction