Treating tuberculosis without rifampicin: an open dilemma

Area of Science:

• Infectious Diseases
• Pulmonology
• Antimicrobial Resistance

Background:

• Tuberculosis (TB) treatment guidelines by the World Health Organization (WHO) recommend similar regimens for rifampicin-monoresistant (RR) and multidrug-resistant (MDR) TB.
• Rifampicin is a crucial first-line anti-TB drug, but its use can be limited due to patient allergy, intolerance, or drug-drug interactions, leading to functional rifampicin mono-resistance (fRR-TB).
• There is uncertainty regarding the optimal treatment strategies for patients with RR-TB and fRR-TB.

Purpose of the Study:

• To conduct a literature review on the epidemiology and diagnostic tools for RR-TB and fRR-TB.
• To assess available treatment options and associated costs for managing RR-TB and fRR-TB.
• To provide guidance on managing TB cases where rifampicin cannot be used.

Main Methods:

• A narrative literature review was performed, searching English-language articles from 1960 to 2025.
• Keywords used included "tuberculosis", "rifampicin", "mono-resistance", and "tuberculosis".
• Bibliographies of selected articles were manually reviewed for additional relevant studies.

Main Results:

• The review covered the role of rifampicin, epidemiology of RR-TB, diagnostic methods for rifampicin resistance, and evolving treatment guidelines.
• Studies reporting non-standard treatment regimens for RR-TB or fRR-TB were analyzed.
• Potential alternative treatment options, their advantages, and disadvantages were summarized, with a proposed management flowchart.

Conclusions:

• WHO-recommended regimens for RR/MDR-TB remain the primary treatment approach.
• Despite data heterogeneity, scenarios exist where rifampicin can be substituted with alternative drugs.
• Alternative drugs can be added to first-line regimens for patients with RR-TB or fRR-TB.