Tuberculosis (TB) remains one of the leading infectious causes of morbidity and mortality worldwide. Drug-resistant tuberculosis poses a major challenge to global tuberculosis elimination strategies, especially in developing countries with a high disease burden. Among various forms of drug resistance, isoniazid mono/poly drug resistant tuberculosis (Hr-TB) has gained increasing attention due to its association with poor treatment outcomes and progression to multidrug-resistant tuberculosis (MDR-TB). [1]

According to the World Health Organization (WHO) Global Tuberculosis Report 2024, approximately 1.4 million new cases of isoniazid-resistant tuberculosis are reported annually worldwide. India contributes nearly one-fourth of the global Hr-TB burden, accounting for approximately 25–27% of all cases. The National Tuberculosis Elimination Programme (NTEP) emphasizes early diagnosis through molecular methods such as Line Probe Assay (LPA) and implementation of standardized treatment regimens including Rifampicin, Ethambutol, Pyrazinamide, and Levofloxacin. [1,2,4]

Isoniazid resistance may occur due to mutations in the katG gene, inhA promoter region, or both. The katG mutation is commonly associated with high-level isoniazid resistance, while inhA mutations are generally associated with low-level resistance and possible cross-resistance to ethionamide. Early identification of mutation patterns is important for optimizing treatment strategies and preventing amplification of resistance. [9,10]

Several studies have reported treatment success rates ranging from 70% to 75% among Hr-TB patients, while unfavourable outcomes such as treatment failure, death, and loss to follow-up continue to remain substantial. Factors including previous tuberculosis treatment, co-morbidities such as diabetes mellitus and HIV infection, malnutrition, extensive pulmonary involvement, and delayed diagnosis contribute significantly to poor outcomes. [5,7,8,10]

Despite increasing recognition of Hr-TB under NTEP, data regarding treatment outcomes and adverse drug events from Odisha and Eastern India remain sparse. Therefore, this study was undertaken to evaluate treatment outcomes and adverse drug reactions among patients receiving isoniazid mono/poly drug resistant regimen in a tertiary care centre of Odisha. [4,7]

.

MATERIALS AND METHODS

Study Design and Setting

This retrospective cohort study was conducted in the Department of Respiratory Medicine, Post Graduate Institute of Medical Education and Research (PGIMER) and Capital Hospital, Bhubaneswar, Odisha.

Study Duration

The study duration extended from January 2023 to December 2024 (24 months).

Study Population

The study population consisted of all patients diagnosed with isoniazid mono/poly drug resistant tuberculosis registered under the Drug Resistant Tuberculosis (DR-TB) registry and Intermediate Reference Laboratory during the study period.

Sample Size

A total of 22 patients fulfilling the inclusion criteria were included in the study.

Inclusion Criteria

1. Patients diagnosed with isoniazid mono/poly drug resistant tuberculosis.
2. Patients registered under DR-TB treatment registry.
3. Patients with mutation in katG gene and/or inhA gene.
4. Patients receiving standardized Hr-TB treatment regimen under NTEP.

Exclusion Criteria

1. Patients diagnosed with multidrug-resistant tuberculosis (MDR-TB).
2. Patients with pre-XDR or XDR tuberculosis.
3. Patients with incomplete treatment records.

Study Parameters

The following parameters were evaluated:

1. Demographic characteristics including age and gender.
2. Site of tuberculosis involvement.
3. Genotypic mutation patterns.
4. Radiological findings.
5. Previous history of tuberculosis treatment.
6. Co-morbid conditions.
7. Treatment outcomes.
8. Adverse drug events.

Methodology

Detailed patient information was retrieved from DR-TB treatment records and hospital medical records. Baseline clinical and demographic characteristics were recorded. Diagnostic evaluation included sputum examination, molecular diagnostic methods, and radiological investigations.

Mutation analysis was performed using genotypic methods identifying katG and inhA mutations. Radiological assessment included evaluation for unilateral or bilateral lesions and extent of pulmonary involvement.

Treatment outcomes were categorized according to NTEP guidelines as:

• Cured
• Treatment completed
• Treatment failure
• Died
• Lost to follow-up (LTFU)

Favourable outcomes included cured and treatment completed categories, whereas treatment failure, death, and loss to follow-up were considered unfavourable outcomes.

Adverse drug events were identified from treatment records and categorized based on clinical presentation.

Statistical Analysis

Data were entered into Microsoft Excel and analysed using descriptive statistical methods. Categorical variables were expressed as frequencies and percentages. Odds ratios with confidence intervals were calculated for factors associated with unfavourable outcomes. A p-value less than 0.05 was considered statistically significant.

Ethical Considerations

Confidentiality of patient information was strictly maintained throughout the study. Institutional ethical principles for retrospective data analysis were followed.

RESULTS AND OBSERVATIONS

Table 1: Gender-wise Distribution of Study Participants

Table 2: Distribution of Study Participants by Site of Disease

Table 3: Distribution According to Genotypic Mutation Pattern

Table 4: Distribution According to Radiological Findings

Table 5: Treatment Outcomes by Gender

Table 6: Treatment Outcomes by Age Group

Table 7: Treatment Outcomes According to Mutation Pattern

Table 8: Treatment Outcomes According to History of TB Treatment

Table 9: Impact of Co-morbid Conditions on Treatment Outcomes

Table 10: Distribution of Adverse Drug Events

Table 11: Post-treatment Follow-up Outcomes

Table 12: Factors Associated with Unfavourable Outcomes

Figures and Charts

Figure 1: Gender-wise Distribution of Study Participants

Figure 2: Distribution According to Genotypic Mutation Pattern

Figure  3: Impact of Previous TB Treatment on Outcomes

Figure 4Impact of Co-morbid Conditions on Treatment Outcomes

Figure 5 Distribution of Adverse Drug Events

DISCUSSION

The present study evaluated treatment outcomes and adverse drug events among patients receiving isoniazid mono/poly drug resistant tuberculosis regimen in a tertiary care hospital of Odisha. The study provides important regional data regarding Hr-TB treatment outcomes, mutation patterns, and factors associated with poor prognosis.

In the present study, males constituted 68.2% of the study population, which is comparable to previous Indian studies reporting higher prevalence of tuberculosis among males. Increased occupational exposure, smoking, alcohol consumption, and delayed healthcare seeking behaviour among males may contribute to this observation.

Pulmonary tuberculosis accounted for 95.5% of cases, indicating that Hr-TB predominantly affects the pulmonary system. The predominant mutation identified was katG mutation (68.2%), followed by inhA mutation (22.7%). Similar findings have been reported in previous Indian studies and global meta-analyses demonstrating katG mutation as the commonest mechanism of isoniazid resistance. Since katG mutations are associated with high-level isoniazid resistance, early molecular detection is crucial for timely initiation of appropriate therapy.

Radiologically, bilateral lesions were observed in 59.1% of participants, indicating moderate to extensive pulmonary involvement. Similar findings have been reported from AIIMS and NIRT cohorts where bilateral disease was observed in approximately 55–65% of Hr-TB cases.

The overall favourable treatment outcome in the present study was 72.7%, which is comparable with global studies reporting treatment success rates between 70% and 75%. However, unfavourable outcomes were observed in 27.3% of participants, primarily due to treatment failure, death, and loss to follow-up.

Previously treated patients demonstrated significantly higher unfavourable outcomes (38.5%) compared to new cases (11.1%). This finding suggests that prior tuberculosis treatment is an important predictor of poor outcome, possibly due to delayed diagnosis, poor adherence, residual lung damage, and higher bacillary burden. Similar observations have been reported by Patel et al. and Khan et al., who reported poor outcomes ranging from 30% to 40% among previously treated Hr-TB cases.

Co-morbid conditions were strongly associated with poor treatment outcomes. Patients with diabetes mellitus, HIV infection, chronic kidney disease, and multiple co-morbidities had significantly higher unfavourable outcomes compared to patients without co-morbidity. Co-morbid illnesses impair immunity, complicate treatment adherence, and increase susceptibility to adverse drug reactions.

Adverse drug events were common but generally manageable. Gastrointestinal upset was the most frequently observed adverse event (45.5%), followed by rash/hypersensitivity and hepatotoxicity. No serious adverse event was observed during the study period. These findings are comparable with previous studies evaluating adverse events among Hr-TB patients receiving fluoroquinolone-based regimens.

The present study emphasizes the importance of early molecular diagnosis, individualized treatment approaches, adherence counselling, and close follow-up among high-risk patients. Strengthening management of co-morbid conditions and implementing digital adherence strategies may further improve treatment outcomes.

Limitations

The present study has certain limitations. First, the study was conducted at a single tertiary care centre with a relatively small sample size, limiting generalizability of findings. Second, the retrospective study design depended upon the accuracy of medical records and treatment registers. Third, long-term follow-up beyond treatment completion was limited.

Future multicentric studies with larger sample sizes and long-term follow-up are required to better understand treatment outcomes and resistance patterns among Hr-TB patients.

CONCLUSION

Treatment success in isoniazid mono/poly drug resistant tuberculosis is achievable with early diagnosis, treatment adherence, and close follow-up. Previously treated patients and those with co-morbid conditions are at significantly higher risk for poor outcomes and require intensified supervision.

The predominance of katG mutation highlights the need for early molecular diagnostic testing and individualized therapeutic approaches. Most adverse drug events observed during treatment were mild and manageable, suggesting that the standardized Hr-TB regimen is generally well tolerated.

Strengthening molecular diagnostic facilities, co-morbidity management, patient counselling, and long-term follow-up may significantly improve outcomes among Hr-TB patients.

Ethics Approval and Consent to Participate

This retrospective study was conducted using hospital and DR-TB registry records while maintaining strict confidentiality of patient information.

Conflicts of Interest

The authors declare that there is no conflict of interest regarding the publication of this paper.

Funding Statement

No external funding was received for this study.

Authors’ Contributions

Dr. Ashish Anshuman Panda (AAP) contributed to data collection, analysis, manuscript drafting, and preparation of tables and figures. Dr. Biswal Pradipta Trilochan (BPT) contributed to study supervision and manuscript review. Dr. Nirmal Chandra Satapathy (NCS) contributed to clinical evaluation and data interpretation. Prof. Dr. Geetanjali Panda (GP) contributed to academic supervision and final manuscript revision. All authors approved the final manuscript

Acknowledgments

The authors express their sincere gratitude to the Department of Respiratory Medicine, PGIMER and Capital Hospital, Bhubaneswar, for providing necessary facilities and support during the study. The authors also acknowledge the contribution of all healthcare workers and staff involved in maintaining the DR-TB registry and patient records.

REFERENCES

1. World Health Organization. Global Tuberculosis Report 2024. Geneva: WHO; 2024.
2. National TB Elimination Programme (NTEP), Central TB Division, Ministry of Health and Family Welfare. National Guidelines for Management of Drug Resistant Tuberculosis. New Delhi: Government of India; 2024.
3. Revised National Tuberculosis Programme. National Strategic Plan for Tuberculosis Elimination 2017–2025.
4. Central TB Division. India TB Report 2023.
5. Araújo-Pereira M, et al. Isoniazid Monoresistance and Antituberculosis Treatment Outcome in Persons With Pulmonary Tuberculosis in Brazil. Open Forum Infectious Diseases.
6. Bharath Kathi, et al. Clinico-radiological Profile of Drug Resistant Tuberculosis in a Tertiary Care Centre in Tirupati, Andhra Pradesh.
7. Patel K, et al. Assessing Treatment Efficacy and Determinants of Outcome in Isoniazid Monoresistant Tuberculosis Patients. Acta Medica International. 2024.
8. Khan S, et al. Treatment Outcomes Among Patients with Isoniazid Mono-Resistant Tuberculosis, Mumbai, India. MSF Retrospective Cohort. 2021.
9. Indian Journal of Tuberculosis. Genotypic Characterization of Isoniazid Mono-resistant TB Strains in India.
10. PLOS ONE. Global Meta-analysis of Isoniazid-resistant TB Outcomes and Mutation Patterns. PLoS ONE. 2023;18(5):e0284123.
11. Ramappa V, Aithal GP. Hepatotoxicity Related to Anti-tuberculosis Drugs. World Journal of Gastroenterology. 2012;18(23):2952–2960.