Our objective was to evaluate and compare the in vitro activity of daptomycin, linezolid, and quinupristin/dalfopristin against clinical bloodstream isolates of Grain-positive pathogens from a large cancer center in the Northeastern United States. Minimum inhibitory concentrations (MICs) were determined for daptomycin, quinupristin/dalfopristin, and linezolid against 258 isolates; bactericidal activity was evaluated using time-kill experiments against 14 representative pathogens. Vancomycin-resistant enterococci represented the largest proportion of bacteria tested (32% of the isolates), followed by inethicillin-resistant coagulase-negative staphylococci (23%), and vancomycin sensitive enterococci (14%). Against staphylococci, the MIC(90) was 1 mu g/mL for both daptomycin and quinupristin/dalfopristin and 4 mu g/mL for linezolid. Against enterococci, the MIC(90) for both daptomycin and linezolid was 4 mu g/mL and was 16 mu g/mL for quinupristin/dalfopristin. The quinupristin/dalfopristin MlC(90) for Enterococcus faecium was 2 mu g/mL. Two enterococci were linezolid resistant and remained susceptible to daptomycin. In vitro time-kill studies found daptomycin to be rapidly bactericidal against the majority of organisms tested, killing 99.9% of bacteria within 6 h. Quinupristin/dalfopristin was bactericidal against staphylococci and bacteriostatic against most enterococci. Linezolid was bacteriostatic against all organisms evaluated. Daptomycin, quinupristin/datfopristin, and linezolid each demonstrated in vitro activity against this collection of organisms. Future clinical Studies to evaluate a potential role for these agents in the management of infections in cancer patients, including the treatment of febrile neutropenia, appear warranted. (c) 2005 Elsevier Inc. All rights reserved.