We assessed MICs and minimal bactericidal concentrations of vancomycin, daptomycin, and nine other antimicrobials against methicillin-resistant Staphylococcus aureus isolates obtained from 1999 through 2006. No vancomycin, daptomycin, or linezolid resistance was observed. Clindamycin, gentamicin, and ciprofloxacin resistance decreased significantly. No tolerance to vancomycin or daptomycin was observed, nor was MIC creep seen.The increasing prevalence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has been accompanied by debate over the effectiveness of vancomycin, perhaps due to diminished inhibitory or bactericidal activity that may have occurred in recent years. Some recent studies have differed with respect to the stability of vancomycin MICs over time (5,8,9,18,21). An earlier study from University of Texas Health Science Center and University Hospital indicated that the activity of vancomycin against MRSA did not change between the years 1987 and 1999, during a period of increasing resistance to other drug classes (e.g., macrolides, lincosamides, and fluoroquinolones) (9).The presence and/or significance of antimicrobial tolerance remains an area of controversy (15,20). Vancomycin tolerance was not related to outcome in an animal model of S. aureus endocarditis (20). However, reduced bactericidal activity of vancomycin (using a high-inoculum method) correlated with worse outcome in bacteremic patients treated with vancomycin (15).The purpose of this study was to assess the inhibitory and bactericidal activities of vancomycin and daptomycin and inhibitory activities of nine other commonly used antimicrobial agents against isolates of MRSA recovered from bacteremic patients at a university hospital during an 8-year period from 1999 through 2006.The first 30 MRSA isolates recovered from bacteremic patients each year were retrieved from the frozen isolate bank of the University Hospital Microbiology Laboratory during the years 1999 through 2006. Vancomycin troughs have been carefully monitored for approximately the last 2 years of the study period. These strains represented the first isolate recovered from each patient (not posttherapy), had been stored in skim milk at Ϫ70°C since isolation, and had been subcultured a minimum of two times.Isolates were tested by the CLSI (formerly NCCLS) broth microdilution procedure (3); the test medium was cation-adjusted Mueller-Hinton broth. Panels incorporated 1/2-log 2 dilutions of vancomycin (range of concentrations, 0.12 to 8 g/ ml). Also incorporated were standard dilutions of daptomycin (0.12 to 8 g/ml, with 50 g/ml calcium added to each daptomycin well), linezolid (0.06 to 16 g/ml), erythromycin (0.06 to 64 g/ml), clindamycin (0.03 to 16 g/ml), doxycycline (0.06 to 16 g/ml), minocycline (0.06 to 16 g/ml), trimethoprim-sulfamethoxazole (0.03 to 8 g/ml), gentamicin (0.06 to 8 g/ml), rifampin (0.25 to 8 g/ml), and ciprofloxacin (0.06 to 16 g/ ml). Microdilution panels were incubated at 35°C in air for 20 to 22 h prior to visual determinat...