# Performance evaluation of alternative bacteriological measures of response to MDR-TB therapy during the initial 16 weeks of treatment

## TL;DR

This study evaluates alternative tests to monitor treatment response in drug-resistant tuberculosis, finding they align well with standard methods.

## Contribution

The study demonstrates that alternative bacteriological measures can reliably replace traditional culture methods for monitoring MDR-TB treatment response.

## Key findings

- Alternative tests like CFM, FDA, and TB-MBLA showed high concordance with MGIT culture at weeks 12 and 16.
- All alternative tests achieved 100% concordance with MGIT culture by week 16 in HIV-positive patients.
- Baseline factors did not affect the concordance of alternative tests with MGIT culture.

## Abstract

Monitoring response to Multi-Drug-Resistant Tuberculosis (MDR-TB) treatment is burdensome to TB programmes and may benefit from alternative effective tools. We evaluated the concordance of alternative bacteriological measures of response to therapy (AMRT) during the initial sixteen weeks of MDR-TB treatment.

In a prospective study of MDR/RR-TB among smear positive adults, aged 18 year and above. Pooled early morning- and spot sputa were obtained before treatment initiation (95% on Bdq, Lzd, Lfx, Cfz, Cs regimen) and at weeks 2, 4, 6, 8, 12, and 16 during treatment between 14/02/2020 and 09/02/2024. Samples were tested using Concentrated Fluorescent Microscopy (CFM), Fluorescein-diacetate (FDA)-Acid Fast Bacilli (AFB) vital smear microscopy, the tuberculosis-Molecular bacterial load assay (TB-MBLA), and Middle brook 7H11 selective (MB7H11S) colony-forming units as the AMRT. Concordance of the AMRT for sputum conversion was compared to Mycobacterial Growth Indicator Tube (MGIT) culture conversion at weeks 12 and 16 of treatment.

A total of 101 MDR/RR-TB patients were screened of which 42 were smear negative. Fifty-nine participants were enrolled, of whom 58 (98%) provided baseline sputa and these were included in the analysis. The concordance, n/N (%) of each AMRT test with MGIT culture conversion at week 12 were: 31/35(88.6%) for CFM, 32/33 (97.0%) for FDA, and 25/26 (96.2%) for TB-MBLA, and 11/11 (100%) for MB7H11S. At week 16, concordance of eachAMRT were: 39/40 (97.5%) for CFM, 35/36 (97.2%) for FDA, 32/32 (100%) for TB-MBLA, and 15/15 (100%) for MB7H11S. Among people living with HIV,the concordances of AMRT with MGIT culture conversion varied at week 8 but was 100% for all tests at weeks 12 and 16. Baseline clinical and/or bacteriological factors did not influence the concordance of AMRT to MGIT culture conversion at weeks 12, and 16.

Our data show that concentrated Fluorescent smear, Fluorescein-di-acetate smear microscopy, and TB-MBLA are suitable alternative measures of response to TB therapy compared to MGIT culture among MDR-TB participants. Use of these alternative rapid methods may allow timely decision making as well as rapid evaluation of alternative MDR-TB treatment regimens.