title: Comparative in vitro activities of linezolid, telithromycin, clarithromycin, levofloxacin, moxifloxacin, and four conventional antimycobacterial drugs against Mycobacterium kansasii.
abstract: Mycobacterium kansasii is one of the most pathogenic and frequent nontuberculous mycobacteria isolated from humans. Patients with adverse drug reactions, resistant isolates, or suboptimal response require alternative treatment regimens. One hundred forty-eight consecutive clinical isolates of M. kansasii were tested for antimicrobial susceptibilities by the BACTEC 460 system (NCCLS) with two different inoculation protocols, one conventional and one alternative. In the alternative protocol, the inoculum 12B vial was incubated until the growth index was between 250 and 500. Four conventional antimycobacterial drugs (isoniazid, rifampin, streptomycin, and ethambutol) were studied with standard critical concentrations. The in vitro activities of linezolid, telithromycin, clarithromycin, levofloxacin, and moxifloxacin were determined by measuring radiometric MICs. All isolates tested were identified as M. kansasii genotype I and were resistant to isoniazid at a concentration of 0.4 mug/ml. One hundred twenty isolates (81.1%) were inhibited by 1 microg of isoniazid per ml. A high level of resistance to isoniazid (>10 microg/ml) was observed in six isolates (4.1%). Only five strains (3.4%) were resistant to rifampin (>1 microg/ml). All isolates studied were susceptible to streptomycin and ethambutol. The MICs at which 90% of the isolates were inhibited (in micrograms per milliliter) were as follows: linezolid, 1 (range, < or =0.25 to 2); telithromycin, >16 (range, 4 to >16); clarithromycin, 0.5 (range, < or =0.03 to 1); levofloxacin, 0.12 (range, 0.12 to 0.25); and moxifloxacin, 0.06 (range, < or =0.06 to 0.12). The susceptibility testing results with both inoculation protocols showed perfect correlation. In conclusion, all M. kansasii isolates showed decreased susceptibility to isoniazid, but resistance to rifampin was infrequent. Quinolones, especially moxifloxacin, were the most active antimicrobial agents tested, followed by clarithromycin. Linezolid also showed good activity against these microorganisms, but telithromycin's in vitro activity was poor.
authors.affiliation: Department of Microbiology, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain. falcaide@csub.scs.es
authors.forename: Fernando
authors.initials: F
authors.lastname: Alcaide
authors.forename: Laura
authors.initials: L
authors.lastname: Calatayud
authors.forename: Miguel
authors.initials: M
authors.lastname: Santín
authors.forename: Rogelio
authors.initials: R
authors.lastname: Martín
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology; D006801:Humans; D018942:Macrolides / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009164:Mycobacterium Infections / Q000382:microbiology; D019909:Mycobacterium kansasii / Q000187:drug effects* / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D018942:Macrolides; D011500:Protein Synthesis Inhibitors