Molecular and Phenotypic characterization of Mycobacterium tuberculosis resistant to anti-tuberculosis drugs

B IMPERIALE; M. ZUMÁRRAGA; B DI GIULIO; A. CATALDI; N MORCILLO

INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE

INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D)

Lugar: Paris; Año: 2013 vol. 17 p. 1088 - 1093

1027-3719

SETTING. Dr. Cetrángolo Hospital, Buenos Aires, Argentina. OBJECTIVES. To characterize drug-resistant (DR), multidrug-resistant and extensively drug-resistant (M/XDR) M. tuberculosis isolates identifying its genetic profiles, drug-resistance levels and mutations conferring resistance. DESIGN. Phenotypic drug susceptibility testing methods were used to determine drug-resistance profiles. Minimal inhibitory concentrations (MICs) of isoniazid (INH), rifampicin (RIF) and levofloxacin (LX) from 169 DR isolates, 78 of them mono-resistant to INH (INH-R), 13 to RIF (RIF-R), 7 to LX (LX-R) and 71 MDR, was determined. A Multiplex-Allele-Specific-PCR and DNA sequencing were used to detect mutations in katG, rpoB and gyrA/B genes. Genotyping was performed by spoligotyping and IS6110-RFLP. RESULTS. A total of 38.9% of INH-R isolates showed MIC≥32.0 µg/mL; 61.3% of RIF-R had MIC: 64.0 µg/mL and 5/9 LX-R, MIC: 16.0µg/mL. The main mutations found in INH-R isolates were katG315 (53.7%) and inhAP-15 (25.5%), in RIF-R isolates were rpoB531 (61.9%) followed by rpoB526 (16.7%). LX-R isolates showed mutations in gyrA94/90. Haarlem, LAM and T were the main spoligotyping families found. KatG315 was mainly associated with Haarlem and LAM, while inhAP-15 with T. CONCLUSIONS. Several isolates showed association between high INH-R level and katG mutation, others from Haarlem were prone to become MDR and continue to circulate in the community