Daptomycin has demonstrated potent in vitro activity against many common staphylococci and streptococci, such as Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA]; MIC 90 , 0.5 g/ml), coagulase-negative staphylococci (Staphylococcus epidermidis [MIC 90 , 0.5 g/ml] and less frequently isolated species), group A and B -hemolytic streptococci (MIC 90 , Յ0.03 g/ml), Enterococcus faecalis (MIC 90 , 1 g/ml), and Enterococcus faecium (MIC 90 , 2 g/ml), in numerous investigations (4, 5). However, limited information exists on the activity of daptomycin tested against less frequently isolated Gram-positive species. We evaluated daptomycin activity tested against uncommonly isolated streptococci and three other Gram-positive groups derived from recent global surveillance programs.A total of 1,356 unique isolates (one per patient) were collected from documented infections and submitted to a monitoring reference laboratory (JMI Laboratories; North Liberty, IA, USA) where species identifications were confirmed using standard algorithms, Vitek systems (bioMérieux, Hazelwood, MO), matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) (Bruker Daltonics, Bremen, Germany), or 16S sequencing methods, when necessary. The organisms were obtained from the SENTRY Antimicrobial Surveillance Program platform from infections cultured in 112 medical centers located worldwide from 2008 to 2011 and stored in Trypticase soy broth with 15% glycerol in temperature-monitored Ϫ80°C freezers. The collection included viridans group streptococci (675 isolates; seven groups or species), -hemolytic streptococci (BHS) other than Streptococcus pyogenes and Streptococcus agalactiae (598 isolates), Corynebacterium spp. (18 isolates; five species), Listeria monocytogenes (39 isolates), and Micrococcus spp. (26 isolates).The majority of isolates were from 77 U.S. medical centers, whereas four less common species isolates were obtained from worldwide hospital locations, including Streptococcus equisimilis, Streptococcus mutans, Corynebacterium spp., and L. monocytogenes.Daptomycin and comparators were tested for susceptibility by the reference Clinical and Laboratory Standards Institute (CLSI) broth microdilution method (6, 7). The cation-adjusted MuellerHinton broth was supplemented with 2.5 to 5% lysed horse blood when fastidious streptococcal species were tested. Also, the test medium was adjusted to contain physiological levels of calcium (50 mg/liter) when daptomycin was tested (6). All quality control results were within published ranges for daptomycin when S. aureus ATCC 29213 and E. faecalis ATCC 29212 were tested (7).Daptomycin exhibited potent in vitro activity when tested against seven groups of viridans group streptococci tested with MIC 50 and MIC 90 results ranging from Յ0.06 and Յ0.06 g/ml (Streptococcus bovis and Streptococcus dysgalactiae groups) to 0.5 and 1 g/ml (Streptococcus mitis, Streptococcus oralis, and Streptococcus parasanguinis), respectively ( Table 1). The highest d...