EC Pulmonology and Respiratory Medicine

Background: Multi-Drug Resistance Tuberculosis (MDR-TB) is a global health problem. Rifampicin resistance (RR) is caused by mutations in the rpoB gene, resistance of INH is caused by mutations in katG or inhA. Fitness is defined as the ability of pathogens to survive, replication and transmission. The fitness of drug resistance strain is one of the determinants MDR-TB/RR spreading. Estimation of strain MDR-TB fitness were assessed by the gradation of AFB smear in new case and previous treatment of MDR-TB Pulmonary TB patients

Method: The study was conducted at RSUD Dr. Soetomo Surabaya from November 2021 to March 2022. To detect genetic mutations conducted by Line Probe Assay (Genoscholar^TMNTM+MDR TB II, NIPRO Japan), and AFB examination using Ziehl Neelsen staining microscopy. Analyze correlation of resistance gene with AFB gradation using chi square test and Fischer’s exact

Results: There were 33 subjects recruited, 16 MDR/RR-TB patients new cases and 17 MDR-TB/RR patients with previously treatment. The new cases patients had more rpoB mutations, while patients with previously treatment had more double mutations (rpoB+katG/inhA). Higher AFB smear grades were significant associated with MDR/RR-TB previously treatment, otherwise no significant correlation in all TB cases of resistance in RR and HR with AFB gradation. Among the lower AFB grades revealed rpoB and rpoB+katG/inhA mutations were 57,14% and 42,86%. In the Higher AFB grades revealed rpoB and rpoB+katG/inhA mutations were 47,37% and 52,63% respectively.

Conclusion: There is no correlation between profile resistance of rifampicin and INH with AFB gradation.

 Keywords: TB-MDR/RR; rpoB; inhA; katG; AFB

1. World Health Organization. Global Tuberculosis Report (2021).
2. Soedarsono S. “Tuberculosis: Development of New Drugs and Treatment Regimens”. Jurnal Respirasi 1 (2021): 36.
3. Rufai SB., et al. “Comparison of xpert MTB/RIF with line probe assay for detection of rifampin-monoresistant Mycobacterium tuberculosis”. Journal of Clinical Microbiology 6 (2014): 1846-1852.
4. Grosset JH and Chaisson RE. “Handbook of Tuberculosis” (2017).
5. Soedarsono S., et al. “First line anti-tuberculosis drug resistance pattern in multidrug-resistant pulmonary tuberculosis patients correlate with acid fast bacilli microscopy grading”. Indonesian Journal of Tropical and Infectious Disease 2 (2020): 83.
6. Rokhmah D. “Gender and tuberculosis disease: implications for low access to poor health services”. Kesmas: National Public Health Journal 10 (2013): 447.
7. Muslih M., et al. “Factors affecting the incidence of tuberculosis in women (Case study at brebes regency hospital)”. Journal of Epidemiology and Community Health 1 (2018): 48.
8. Dheda K., et al. “The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis”. Lancet Respiratory Medicine 4 (2017): 291-360.
9. Saktiawati A and Subroto Y. “Influence of diabetes mellitus on the development of multidrug resistant-tuberculosis in Yogyakarta”. Acta Medica Indonesiana, Indonesian Journal of Internal Medicine 1 (2018): 11-17.
10. Nijland HMJ., et al. “Exposure to rifampicin is strongly reduced in patients with tuberculosis and type 2 diabetes”. Clinical Infectious Diseases 7 (2006): 848-854.
11. Kabir S., et al. “Variations in rifampicin and isoniazid resistance associated genetic mutations among drug naïve and recurrence cases of pulmonary tuberculosis”. International Journal of Infectious Diseases 103 (2021): 56-61.
12. Naidoo K and Dookie N. “Insights into recurrent tuberculosis: relapse versus reinfection and related risk factors”. Tuberculosis 1 (2018): 3-36.
13. Shariq Ahmed., et al. “Profile of drug‑resistant‑conferring mutations among new and previously treated pulmonary tuberculosis cases from Aligarh Region of Northern India”. International Journal of Mycobacteriology 4 (2018): 315-327.
14. Alvarez-Uria G and Reddy R. “Differences in rpoB, katG and inhA mutations between new and previously treated tuberculosis cases using the GenoType MTBDR plus assay”. Infection, Genetics and Evolution 59 (2018): 48-50.
15. Gagneux S. “Fitness cost of drug resistance in Mycobacterium tuberculosis”. Clinical Microbiology and Infection 1 (2009): 66-68.
16. Kassa GM., et al. “Sputum smear grading and associated factors among bacteriologically confirmed pulmonary drug-resistant tuberculosis patients in Ethiopia”. BMC Infectious Diseases 1 (2021): 238.
17. Borrell S and Gagneux S. “Infectiousness, reproductive fitness and evolution of drug-resistant Mycobacterium tuberculosis”. International Journal of Tuberculosis and Lung Disease 12 (2009): 1456-1466.
18. Song T., et al. “Fitness costs of rifampicin-resistance in Mycobacterium tuberculosis are amplified under conditions of nutrient starvation and compensated by mutation in the β’ subunit of RNA polymerase”. Molecular Microbiology 6 (2015): 1106-1119.
19. Vilchèze C and Jacobs WR. “Resistance to isoniazid and ethionamide in Mycobacterium tuberculosis: Genes, mutations, and causalities”. Molecular Genetics of Mycobacteria 4 (2015): 431-453.
20. Cohen T., et al. “The effect of drug resistance on the fitness of Mycobacterium tuberculosis”. Lancet Infectious Diseases 1 (2003): 13-21.