Mycobacterium avium sp. avium (MAA), M. avium sp. hominissuis (MAH), and M. avium sp. paratuberculosis (MAP) are the main members of the M. avium complex (MAC) causing diseases in several hosts. The aim of this study was to describe the genetic diversity of MAC isolated from different hosts. Twenty-six MAH and 61 MAP isolates were recovered from humans and cattle, respectively. GenoType CM® and IS1311-PCR were used to identify Mycobacterium species. The IS901-PCR was used to differentiate between MAH and MAA, while IS900-PCR was used to identify MAP. Genotyping was performed using a mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) scheme (loci: 292, X3, 25, 47, 3, 7, 10, 32) and patterns (INMV) were assigned according to the MAC-INMV database (http://mac-inmv.tours.inra.fr/). Twenty-two (22/26, 84·6%) MAH isolates were genotyped and 16 were grouped into the following, INMV 92, INMV 121, INMV 97, INMV 103, INMV 50, and INMV 40. The loci X3 and 25 showed the largest diversity (D: 0·5844), and the global discriminatory index (Hunter and Gaston discriminatory index, HGDI) was 0·9300. MAP (100%) isolates were grouped into INMV 1, INMV 2, INMV 11, INMV 8, and INMV 5. The HGDI was 0·6984 and loci 292 and 7 had the largest D (0·6980 and 0·5050). MAH presented a higher D when compared with MAP. The MIRU-VNTR was a useful tool to describe the genetic diversity of both MAH and MAP as well as to identify six new MAH patterns that were conveniently reported to the MAC-INMV database. It was also demonstrated that, in the geographical region studied, human MAC cases were produced by MAH as there was no MAA found among the human clinical samples.

Several isolates showed an association between high INH(R) levels and katG mutation; others from the Haarlem family were prone to becoming MDR-TB and continue to circulate in the community.

This test was safe, cheap, and easily implemented without requiring hospitalization. This research could represent a significant step forward to diagnose and rapidly detect drug-resistant TB in children.

The emergence of drug-resistant, multidrug-resistant and extensively drug-resistant tuberculosis (TB) is of major public health concern in several countries. In this study, the pharmacodynamic relationships among the structural analogs of antibiotics belonging to the same family were taken into consideration. The aim of this study was to compare the susceptibility of Mycobacterium tuberculosis to isoniazid (INH), rifampicin and levofloxacin (LX) to their respective structural analogs, which are frequently used as second-line agents. The microplate colorimetric method was used to determine the MIC to INH, ethionamide (ETH), rifampicin, rifabutin, LX and moxifloxacin (MOX) in clinical isolates previously shown to be drug resistant. Mutations conferring drug resistance were detected by GenoType MTBDR plus and DNA sequencing. INH and ETH cross-resistance was found in 95.12% (39/41) of the INH-resistant isolates harboring a mutation in inhAP or inhA open reading frame, but rifabutin cross-resistance was observed in 90.0% (63/70) of the clinical isolates originally shown to be resistant to rifampicin. Isolates with high LX-resistance levels also showed high MIC to MOX. Fluoroquinolone cross-resistance was verified in isolates containing the gyrA94 and the gyrA90 mutation. In general, isolates with high INH, rifampicin and LX-resistance levels also displayed high MIC values for their structural analogs. These findings suggest the need to test in vitro the second-line drugs before their incorporation in the therapeutic schemes.

No abstract