title: In vitro activity of linezolid in combination with doxycycline, fosfomycin, levofloxacin, rifampicin and vancomycin against methicillin-susceptible Staphylococcus aureus.
abstract: The objective of this paper was to investigate the in vitro effects of linezolid combined with five antistaphylococcal antibiotics--doxycycline, fosfomycin, levofloxacin, rifampicin and vancomycin--upon methicillin-susceptible Staphylococcus aureus (MSSA). Five MSSA isolates from clinical specimens of human infections--hf008, hf095, hf295, hf602 and hf946--were used in this study. The checkerboard method was used to assess synergism between linezolid and the five antibiotics, and time-kill curves were carried out with the most active combinations. Indifference was the most common result achieved by the checkerboard method when linezolid was combined with rifampicin, vancomycin or doxycycline. The combination with levofloxacin yielded antagonism for two of the five isolates. However, four isolates showed synergy for the combination of linezolid plus fosfomycin with a fractional inhibitory concentration index (FICI) > or = 0.5. Neither linezolid nor fosfomycin alone inhibited growth at 1/4x minimum inhibitory concentration (MIC); but the combination of both drugs at 1/4 the respective MIC showed a synergistic bacteriostatic effect, a 2-3 log(10) decrease with respect to the most active antibiotic alone. In summary, the combination of subinhibitory.
authors.affiliation: Department of Clinical Microbiology, Hospital La Fe, Avda. Campanar 21, 46009 Valencia, Spain. wadjur@hotmail.com
authors.forename: J M
authors.initials: JM
authors.lastname: Sahuquillo Arce
authors.forename: E
authors.initials: E
authors.lastname: Colombo Gainza
authors.forename: A
authors.initials: A
authors.lastname: Gil Brusola
authors.forename: R
authors.initials: R
authors.lastname: Ortiz Estévez
authors.forename: E
authors.initials: E
authors.lastname: Cantón
authors.forename: M
authors.initials: M
authors.lastname: Gobernado
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology; D004318:Doxycycline / Q000494:pharmacology; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005578:Fosfomycin / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D064704:Levofloxacin; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000494:pharmacology; D023303:Oxazolidinones / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects*; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; D023303:Oxazolidinones; D005578:Fosfomycin; D064704:Levofloxacin; D014640:Vancomycin; D015242:Ofloxacin; D000069349:Linezolid; D004318:Doxycycline; D012293:Rifampin