title: Comparative in vitro activities of daptomycin, linezolid, and quinupristin/dalfopristin against Gram-positive bacterial isolates from a large cancer center.
abstract: Our objective was to evaluate and compare the in vitro activity of daptomycin, linezolid, and quinupristin/dalfopristin against clinical bloodstream isolates of Gram-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 methicillin-resistant coagulase-negative staphylococci (23%), and vancomycin sensitive enterococci (14%). Against staphylococci, the MIC90 was 1 microg/mL for both daptomycin and quinupristin/dalfopristin and 4 microg/mL for linezolid. Against enterococci, the MIC90 for both daptomycin and linezolid was 4 microg/mL and was 16 microg/mL for quinupristin/dalfopristin. The quinupristin/dalfopristin MIC90 for Enterococcus faecium was 2 microg/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/dalfopristin, 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.
authors.affiliation: Applied Pharmacodynamics Laboratory, University at Buffalo School of Pharmacy and Pharmaceutical Sciences, Buffalo, NY 14260, USA. pfsmith@buffalo.edu
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Smith
authors.forename: Brent M
authors.initials: BM
authors.lastname: Booker
authors.forename: Abayomi B
authors.initials: AB
authors.lastname: Ogundele
authors.forename: Pamela
authors.initials: P
authors.lastname: Kelchin
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017576:Daptomycin / Q000494:pharmacology*; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology*; D006801:Humans; D016867:Immunocompromised Host; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D009369:Neoplasms / Q000276:immunology / Q000382:microbiology*; D023303:Oxazolidinones / Q000494:pharmacology*; D014769:Virginiamycin / Q000494:pharmacology*
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D014769:Virginiamycin; C062940:quinupristin-dalfopristin; D000069349:Linezolid; D017576:Daptomycin