title: In vitro activity of telavancin in combination with colistin versus Gram-negative bacterial pathogens.
abstract: The treatment of Gram-negative infections is increasingly compromised by the spread of resistance. With few agents currently in development, clinicians are now considering the use of unorthodox combination therapies for multidrug-resistant strains. Here we assessed the in vitro activity of the novel lipoglycopeptide telavancin (TLV) when combined with colistin (COL) versus 13 Gram-negative type strains and 66 clinical isolates. Marked synergy was observed in either checkerboard (fractional inhibitory concentration index [FICI], <0.5; susceptibility breakpoint index [SBPI], >2) or time-kill assays (>2-log reduction in viable counts compared with starting inocula at 24 h) versus the majority of COL-susceptible enterobacteria, Stenotrophomonas maltophilia, and Acinetobacter baumannii isolates, but only limited effects were seen against Pseudomonas aeruginosa or strains with COL resistance. Using an Etest/agar dilution method, the activity of TLV was potentiated by relatively low concentrations of COL (0.25 to 0.75 μg/ml), reducing the MIC of TLV from >32 μg/ml to ≤ 1 μg/ml for 35% of the clinical isolates. This provides further evidence that glycopeptide-polymyxin combinations may be a useful therapeutic option in the treatment of Gram-negative infections.
authors.affiliation: Antimicrobial Research Group, Centre for Immunology and Infectious Disease, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Hornsey
authors.forename: Christopher
authors.initials: C
authors.lastname: Longshaw
authors.forename: Lynette
authors.initials: L
authors.lastname: Phee
authors.forename: David W
authors.initials: DW
authors.lastname: Wareham
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects; D000617:Aminoglycosides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D003091:Colistin / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D000077427:Lipoglycopeptides; D008826:Microbial Sensitivity Tests; D011113:Polymyxins / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000077427:Lipoglycopeptides; D011113:Polymyxins; C487637:telavancin; D003091:Colistin