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Fluoroquinolone and Second-Line Injectable Resistance Among Rifampicin- and Isoniazid-Resistant Mycobacterium
Rosângela Siqueira Oliveira1, Angela Pires Brandao1,2, Fabiane Maria de Almeida Ferreira1
1Núcleo de Tuberculose e Micobacterioses, Centro de Bacteriologia, Instituto Adolfo Lutz (IAL), São Paulo 01246-000, Brazil.
Microorganisms
|November 27, 2025
Summary
Drug-resistant tuberculosis (DR-TB) surveillance in Brazil found low second-line drug resistance overall. However, fluoroquinolone resistance was high among multidrug-resistant tuberculosis (MDR-TB) strains, indicating a need for advanced molecular testing.
Area of Science:
- Microbiology and Infectious Diseases
- Molecular Epidemiology
- Public Health
Background:
- Drug-resistant tuberculosis (DR-TB) poses a significant global health threat, complicating treatment and control efforts.
- Rifampicin (RIF) and isoniazid (INH) resistance are key indicators of DR-TB, often preceding resistance to second-line drugs.
- Accurate molecular detection of resistance is crucial for effective DR-TB management.
Purpose of the Study:
- To determine the prevalence and molecular characteristics of second-line drug resistance in Mycobacterium tuberculosis complex (MTBC) isolates resistant to RIF and/or INH in São Paulo, Brazil.
- To evaluate the utility of the MTBDRsl line-probe assay and Sanger sequencing for detecting resistance to fluoroquinolones (FQ) and injectable drugs.
Main Methods:
- Analysis of 728 MTBC isolates resistant to RIF and/or INH (2019-2021) identified by GenoType MTBDRplus or phenotypic testing.
- Subsequent testing of these isolates using the MTBDRsl v. 2.0 assay for FQ and injectable drug resistance.
- Confirmation of detected mutations via Sanger sequencing for isolates with inferred resistance.
Main Results:
- Of 728 RIF- and/or INH-resistant isolates, 6.6% (41/623) showed mutations indicative of second-line drug resistance via MTBDRsl.
- Fluoroquinolone resistance was detected in 92.7% (38/41) of these isolates, primarily associated with gyrA mutations.
- Two multidrug-resistant tuberculosis (MDR-TB) isolates harbored the rrs a1401g mutation, associated with injectable drug resistance. Most MDR strains with second-line mutations (97%) were pre-extensively drug-resistant (pre-XDR-TB).
Conclusions:
- While overall second-line drug resistance prevalence was low, fluoroquinolone resistance is a significant concern among MDR-TB isolates in São Paulo.
- The findings underscore the importance of integrating molecular assays and sequencing for precise DR-TB detection and patient management.
- Early identification of pre-XDR-TB strains through molecular tools is vital for targeted interventions and preventing further resistance.
Keywords:
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