Phenotypic and Molecular Characterization of Mycobacterium tuberculosis Isolates Resistant to both Isoniazid and Ethambutol

• DOI: 10.1128/aac.49.6.2218-2225.2005
• Publication Date: 2005-05-25T23:07:56Z
• Authors: Linda M. Parsons; Max Salfinger; Anne Clobridge; Jillian Dormandy; Lisa Mirabello; Valerie L. Polletta; Ahmet Sanic; Oleg Sinyavskiy; Susan C. Larsen; Jeffrey Driscoll; Genet Zickas; Harry W. Taber
• Keywords: DNA, Bacterial; 0301 basic medicine; Genotype; Antitubercular Agents; Oligonucleotides; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Catalase; Polymerase Chain Reaction; 3. Good health; 03 medical and health sciences; Phenotype; Bacterial Proteins; Drug Resistance, Multiple, Bacterial; Mutation; Tuberculosis, Multidrug-Resistant; Isoniazid; Humans; Pentosyltransferases; Radiometry; Ethambutol

In performing radiometric susceptibility testing on over 2,000 patient isolates of Mycobacterium tuberculosis during the past 6 years, we found that resistance to 7.5 microg/ml ethambutol (EMB) occurred only in are also resistant 0.4 isoniazid (INH). Using 157 selected present study, performed and agar proportion tests DNA sequencing genetic regions associated with these two drugs. The goal was study occurrence common mutations each drug determine whether any particular INH-resistance-associated mutation more often combination EMB-resistance-associated mutation. an analysis 128 INH, a at katG Ser315 EMB (61 67=91.0%) than either susceptible or 2.5 (39 60=65.0%). These observations suggest INH-resistant strains likely acquire other sites. addition, 64 67 (95.5%) contained codon 306 406 embB. Met306Val most embB mutation, 52 (77.6%) isolates. Most occurrences this (49 52=94.2%) were Ser315Thr Finally, region appears be sufficiently sensitive for use as rapid screening tool detection high-level EMB.