Treatment outcomes of multi-drug-resistant and rifampicin-resistant tuberculosis with and without isolation of nontuberculous mycobacteria between 2018-2021: A retrospective cohort study in Ghana

Multi-drug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB) pose an urgent health threat in Ghana. Despite ongoing interventions, the outcomes for MDR/RR-TB in Ghana have remained suboptimal over recent years. During this period, there has been an increasing detection of nontuberculous mycobacteria (NTM) in mycobacterial cultures. We sought to examine if the isolation of NTM could be a factor contributing to unfavourable MDR/RR-TB treatment outcomes. We also estimated predictors of NTM isolation, including using the short-course injectable-containing regimen (SCI) versus the all-oral bedaquiline (SCO) regimen and other covariates. This retrospective cohort study analysed MDR/RR-TB patients in Ghana from 2018 to 2021 across four regions. Demographic, clinical, and diagnostic data were collected under the National Tuberculosis Control Program framework. Mycobacterial smears and cultures were used to monitor treatment response, with further identification of NTM using line probe assays and Sanger sequencing. Multivariable logistic regression models evaluated predictors of NTM isolation and having an unfavourable outcome. Of 427 identified MDR/RR-TB patients, 380 were included for analysis: 76.3% were male, the mean age was 43.9 years, and 18.9% were people living with HIV. NTM were isolated in 7.1% of cases, primarily Mycobacterium intracellulare and M. fortuitum, with higher odds of isolation in individuals from the Eastern Region (aOR:14.18, 95% CI: 3.95-50.92). Overall, 67.9% achieved favourable outcomes: 71.4% (185/259) in those on the SCO versus 60.3% (73/121) on the SCI regimen. People living with HIV (aOR 14.18, 95% CI: 3.95-50.92) had an increased odds of having an unfavourable outcome. NTM isolation was not associated with unfavourable outcomes. Our study results suggest that although NTM isolation may occur during the course of MDR/RR-TB treatment, it does not affect MDR/RR-TB treatment outcome. Future research should further explore the implications of NTM co-infection on longer-term MDR/RR-TB outcomes, such as post-TB lung disease, to refine management strategies tailored to the reality of low-resource, high-burden settings.

Author Summary

Despite improvements in tuberculosis (TB) treatment protocols, multi-drug-resistant and rifampicin-resistant (MDR/RR)-TB outcomes remain suboptimal. Nontuberculous mycobacteria (NTM), environmental organisms opportunistically capable of causing lung disease in susceptible individuals, are increasingly identified from sputum specimens in regions with high TB prevalence. Yet, their clinical impact on MDR/RR-TB outcomes is not well understood. Pulmonary NTM disease often presents with symptoms similar to pulmonary TB, complicating diagnosis and potentially leading to treatment modifications that may not always be warranted.

In Ghana, where MDR/RR-TB cases are on the rise, standardised short-course injectable (SCI) and all-oral bedaquiline-based (SCO) treatment regimens have been in place. However, there is no data on how the presence of NTM may influence MDR/RR-TB treatment response, particularly within different geographic and environmental contexts. There have, however, been reports of NTM emergence in people undergoing treatment for MDR/RR-TB using a bedaquiline-containing regimen in China. We present this gap in the management of MDR/RR-TB, noting the clinical implications of NTM isolation during the course of TB treatment is not well-defined. This study sought to fill existing knowledge gaps by identifying predictors of NTM isolation in sputum samples from patients undergoing treatment for MDR/RR-TB using either the SCO or SCI. Additionally, we evaluated whether the presence of NTM was associated with unfavourable TB treatment outcomes. Our findings indicate geographic differences in the occurrence of NTM among the study cohort. Also, persons living with HIV were more likely to experience unfavourable TB treatment outcomes. The presence of NTM did not affect the MDR/RR-TB treatment outcomes, regardless of the regimen used in our study. Our findings suggest that routine detection of NTM in MDR/RR-TB patients may not necessitate treatment changes. However, the detection of NTM shows the need for further investigation into how regional characteristics may influence NTM coinfection and potentially NTM pulmonary disease. Addressing this challenge is essential for guiding treatment decisions in resource-limited settings.