title: [Effect of linezolid in combination with isoniazid and rifampicin against multidrug resistant Mycobacterium tuberculosis clinical isolates].
abstract: Tuberculosis continues to be a serious public health problem worldwide. Since multi-drug resistant strains of Mycobacterium tuberculosis constitutes a serious problem in tuberculosis control, new and more effective chemotherapeutic agents are required. This study was aimed to investigate the in vitro effect of linezolid alone and in combination with isoniazid and rifampicin against 10 multidrug resistant M. tuberculosis isolates by using the checkerboard method. Checkerboard testing was performed by the broth microdilution method, using Middlebrook 7H9 broth with 10% oleic acid-albumin-dextrose-catalase. Antibiotic combinations were tested at concentrations of 0.06-4 microg/ml for linezolid and 0.03-32 mg/ml for isoniazid and rifampicin. The results were evaluated according to the calculated fractional inhibitory concentration (FIC) index. All clinical isolates were found to be susceptible to linezolid; MICs of linezolid were 0.25 microg/ml for two strains and 0.5 microg/ml for the other strains. While rifampicin MIC values were >32 microg/ml for all the isolates, isoniazid MIC values were 4 microg/ml for two isolates, 8 microg/ml for six isolates, 16 microg/ml for one isolate and 32 microg/ml for one isolate. In this study, synergism was detected in only one strain between linezolid and isoniazid (FIC index: 0.265). Although synergy was observed between linezolid and isoniazid just for one strain, further larger scale in vitro and in vivo studies are necessary to evaluate the effect of different drug combinations against multidrug-resistant M. tuberculosis strains.
authors.affiliation: Ondokuz Mayis Universitesi Tip Fakültesi, Mikrobiyoloji ve Klinik Mikrobiyoloji Anabilim Dali, Samsun. cobanay2003@yahoo.com.tr
authors.forename: Ahmet Yilmaz
authors.initials: AY
authors.lastname: Coban
authors.forename: Kemal
authors.initials: K
authors.lastname: Bilgin
authors.forename: Meltem
authors.initials: M
authors.lastname: Uzun
authors.forename: Belma
authors.initials: B
authors.lastname: Durupinar
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000904:Antibiotics, Antitubercular / Q000494:pharmacology; D000995:Antitubercular Agents / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D023303:Oxazolidinones / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000382:microbiology*
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D023303:Oxazolidinones; D000069349:Linezolid; D007538:Isoniazid; D012293:Rifampin