Medical centres in eight countries in the Asia-Pacific region provided 2391 isolates for the SENTRY Antimicrobial Surveillance Program during 2003-2004 to determine their susceptibility to several antimicrobial classes, including daptomycin. Daptomycin, vancomycin and teicoplanin minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined for 120 isolates of Staphylococcus aureus, which included wild-type (WT) methicillin-resistant S. aureus (MRSA) and strains with decreased susceptibility to vancomycin (hetero-vancomycin-intermediate S. aureus (hVISA)). Oxacillin-resistant staphylococcal isolates were much less susceptible to the other tested agents compared with oxacillin-susceptible strains. Vancomycin resistance was higher among Enterococcus faecium (10.3%) than Enterococcus faecalis (0.4%), and macrolide resistance was high both for beta-haemolytic (17.7%) and viridans group (48.7%) streptococci. Daptomycin (MIC for 90% of the organisms (MIC(90))=0.5-1mg/L) was two-fold more potent than vancomycin, with >99% susceptibility when tested against staphylococci. All tested isolates of E. faecalis (MIC(90)=2mg/L) and beta-haemolytic streptococci (MIC(90)=0.5mg/L) were susceptible to daptomycin. Daptomycin MIC and MBC values were slightly higher for the hVISA isolates compared with WT-MRSA, with MBC/MIC ratios of only 1-2 for both groups. The MBC/MIC ratio for vancomycin was often greater when tested against these strains, particularly hVISA. In contrast, teicoplanin MBC/MIC ratios were significantly higher, with many of the strains showing values consistent with tolerance (>or=32). Daptomycin was demonstrated to have excellent in vitro activity when tested against Gram-positive isolates collected from Asia-Pacific countries, including hVISA strains.