Resistance (R) among Gram-positive cocci has escalated in the last two decades to levels necessitating the development and use in the newer drug classes, oxazolidinones (linezolid) and streptogramins (quinupristin/dalfopristin [Q/D]). The SENTRY Antimicrobial Surveillance Program has monitored these classes before, during and after their release by various regulatory agencies. Over 30,000 Gram-positive strains were tested against > 30 drugs by reference broth microdilution methods between 1998-2000 in four geographic regions (Asia-Western Pacific [APAC], Europe [EU], Latin America [LA], North America [NA]). The tested strains were 23,188 staphylococci; 5,103 enterococci and 2,045 streptococci. Among staphylococci, linezolid was active against all isolates (MICs, less than or equal to 4 mug/ml) regardless of susceptibility patterns of other antimicrobial agents. Similar results were noted for vancomycin (includes one VISA from Hong Kong), teicoplanin, and Q/D (< 1% R). Gatifloxacin had the widest spectrum among fluoroquinolones (FQ) against Staphylococcus aureus (1.5-9.2% R) and coagulase-negative staphylococci (0.8-4.0%). Linezolid was also active against all enterococci (MIC50 and (90) 2 mug/ml). Q/D was active against only 75.3% of vancomycin-resistant enterococci (VRE). The VRE rate was highest in NA (12.4%) > EU (3.2%) > LA (1.6%) > APAC (1.3%). Among streptococci, linezolid wits consistently active (MIC90, 1 mug/ml) as were the glycopeptides and Q/D. Variable penicillin-R (MIC, greater than or equal to 2 mug/ml) was observed among regions: EU (32.5%) > APAC (15.1%) > LA (13.8%) > NA (9.6%), and macrolide-R was higher in EU (40.3%). Ciprofloxacin-R at greater than or equal to4 mug/ml in streptococcal strains was noted world wide highest in viridans group streptococci (18.4-25.6%). Linezolid remained active (MIC, less than or equal to 4 mug/ml) against all Gram-positive species strains tested in the SENTRY Program (1998-2000). Q/D, glycopeptides and newer FQ compounds were generally less effective in vitro. It remains a prudent practice to continue surveillance programs to detect emerging resistance patterns and recognize significant regional variations in the oxazolidinone susceptibilities. (C) 2002 Elsevier Science Inc. All rights reserved.