Frequency, genetic mechanisms and factors associated with fluoroquinolone (pre-XDR) and aminoglycoside resistance among multidrug-resistant tuberculosis cases in Northwestern Nigeria.

BACKGROUND

Rifampicin-resistant Mycobacterium tuberculosis (MTB), a critical priority pathogen, becomes highly complicated when it develops into pre-extensively drug-resistant (pre-XDR) and is an exceptional challenge for global TB control efforts. This study aims to determine the frequency and mutations associated with fluoroquinolone (FLQ) and aminoglycoside (AMG) resistance in MTB isolates from patients with pulmonary illnesses in Kaduna State, Nigeria. MATERIALS AND

METHODS

A total of 144 MDR-TB-positive sputum samples previously collected from 360 individuals were processed using the NaOH-Na-citrate-NALC method. All isolates were tested for MTB complex using TB Ag MPT64 (SD Bioline), and GenoType MTBDRsl VER 2.0 was used to identify chromosomal mutations in gyrA, gyrB, rrs and eis genes. Risk associated with FLQ- and AMG-resistant MDR-TB was assessed using a structured questionnaire, and the resulting data were statistically analysed.

RESULTS

The occurrence rate of FLQ resistance (preXDR) in MDR-TB was 12.5% (n = 18), which was mediated by diverse mutations and missing regions WT1 and WT2 in gyrA (n = 14) and N538D in gyrB (n = 4). The frequency of AMG resistance among MDR-TB strains was 11.8% (7/144), and the predominant mechanisms of resistance were MUT1 (A1401G) and MUT2 (G1484T) in the rrs gene. Moreover, the MUT1 (C-14T) mutation (23.5%, 4/17) was observed in the eis promoter region. Remarkably, among these strains, 2 MDR-TB (1.4%) exhibited resistance to both FLQ and AMG. Histories of contact with TB patients (OR = 8.94, 95% CI: 4.1-19.49, p < 0.0001) and prior anti-tuberculosis treatment (OR = 2.36, 95% CI: 1.13–4.94, p = 0.00233) were associated with FLQ- and AMG-resistant MDR-TB.

CONCLUSION

This study revealed a high occurrence of pre-XDR-TB in the study population and among the MDR strains, which could lead to treatment failures and a higher public health threat. To stop pre-XDR-TB from spreading and growing and to improve treatment outcomes in this and other regions where it is more prevalent, it is imperative to diagnose resistance to second-line anti-tuberculosis drugs quickly before beginning treatment and activate pre-XDR-TB surveillance systems. CLINICAL TRIAL NUMBER: Not applicable.