Ching-Yen Tsai,1 Chen-Hsiang Lee,1,2 I-Ling Chen3 1Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 2College of Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 3Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan Background: Recent reports have described decreased effectiveness of teicoplanin in the treatment of bacteremia due to methicillin-resistant Staphylococcus aureus (MRSA) with teicoplanin minimal inhibitory concentration (MIC) ≥1.5 mg/L. Consensus guidelines recommend considering use of alternative agents for MRSA infections involving a higher teicoplanin MIC, despite of limited data to support this recommendation. Patients and methods: To compare the clinical outcome among patients with bacteremia due to MRSA with teicoplanin MIC ≥1.5 mg/L, we included patients who received high-dose daptomycin (≥8 mg/kg/day) and those who received standard-dose (6 mg/kg/day) or high-dose (6 mg/kg/12 hours) maintenance teicoplanin. The primary endpoint was a favorable outcome, defined as the resolution of clinical signs and symptoms and a negative culture report at the end of therapy. Adjusted analyses were performed by multivariate analysis and propensity score-based matching. Results: Of 142 patients eligible for inclusion, 28 (19.7%) were treated with high-dose daptomycin, 27 (19.0%) with high-dose teicoplanin, and 87 (61.3%) with standard-dose teicoplanin. In multivariate regression analysis, Pittsburgh bacteremia score ≥4 (OR, 5.3; 95% CI, 1.9–14.5) was independently associated with an unfavorable outcome. After propensity-score matching with age and Pittsburgh bacteremia score ≥4, patients on high-dose daptomycin were more likely to have favorable outcomes than those on standard-dose teicoplanin (74.1% vs 42.6%; P=0.02). However, there was no significant difference in terms of favorable outcomes (P=0.12) between patients receiving high-dose daptomycin and those receiving high-dose teicoplanin after the same propensity-score matching. Conclusion: Treatment with high-dose daptomycin resulted in significantly better outcomes than with standard-dose teicoplanin in the treatment of MRSA bacteremia with teicoplanin MIC ≥1.5 mg/L. However, the clinical outcome of the patients receiving high-dose teicoplanin was similar to that of the patients receiving high-dose daptomycin. Keywords: gram-positive bacteria, antimicrobial susceptibility, pharmacodynamics, glycopeptide, lipopeptide