Treating pulmonary MDR-TB depends on whether the resistance is primary (infection with a drug-resistant strain before antibiotic therapy) or secondary (selective resistance by mutated strains acquired during therapy from inadequate dosage or discontinued drug regimen).
- In either case, administration of four or more second-line anti-TB drugs is usually necessary.
- Second-line drugs required for MDR-TB include high-dosage isoniazid (INH), high-dosage ethambutol (EMB), amikacin, capreomycin, ethionamide, kanamycin (the injectables), levofloxacin, ofloxacin (quinolones), para-aminosalicylic acid (PAS), rifabutin, and streptomycin (SM).
- A treatment regimen monitored by the directly observed treatment short-course (DOTS) program is the only effective method of tracking patients whose treatment may extend from 12 to 18 months to control the selective resistance and reinfection known to develop.
New anti-tuberculosis drugs
Despite the cost and complexity associated with side effects, newer drugs for both susceptible and resistant strains of MTB are expected to have greater bactericidal action and less cross-reaction with existing therapy than previous drugs. New classes of medications include diarylquinoline, nitroimidazole, and oxazolidine (e.g., linezolid).
Bedaquiline fumarate is one of the newest drugs in the arsenal for use against multidrug-resistant tuberculosis. According to WHO, 109 countries had started using bedaquiline to improve the effectiveness of MDR-TB treatment by the close of 2020.
WHO recommends the following regimens for drug-resistant TB treatment, depending on factors related to patient tolerance, comorbidities, prior treatment, etc.:
- Shorter regimen for MDR/RR-TB: shorter all-oral bedaquiline-containing regimen
- Shorter regimen for MDR/RR-TB with quinolone resistance: 6–9 month treatment regimen composed of bedaquiline, pretomanid, and linezolid
- Longer regimen for MDR/RR-TB: 18-month treatment regimen composed of bedaquiline for the first 6 months and levofloxacin or moxifloxacin, linezolid, clofazimine for 18 months
- Regimen for isoniazid-resistant TB: 6-month treatment regimen composed of rifampicin, ethambutol, pyrazinamide, and levofloxacin
In 2022, the WHO added/revised the following recommendations for treatment:32
- Updated regimen for MDR/RR-TB: 6-month BPaLM regimen composed of bedaquiline, pretomanid, linezolid, and moxifloxacin
- Longer regimen for MDR/RR-TBupdate: 9-month all-oral regimen in patients with MDR/RR-TB rather than the longer 18-month regimen
- Regimen for isoniazid-resistant TB update:Patients with confirmed rifampicin-susceptible, isoniazid-resistant TB, 6-month regimen of rifampicin, ethambutol, pyrazinamide, and levofloxacin is recommended; it is not recommended to add streptomycin or other injectable agents to the treatment regimen
Because second-line drugs are expensive, toxic, and less effective, the dosage and duration of the regimen mandate the expertise of physician specialists in tuberculosis. Questions about specific medications to use, the number of drugs, the duration of therapy, and the outcome were subjected to a meta-analysis with methods recommended by the Cochrane group. Their analysis, which included 9,153 MDR-TB patients, determined that four drugs should be used initially, with at least three continuing throughout treatment. Routine susceptibility testing was assumed as part of the evaluation. The duration of therapy was initially seven to eight months, but it changed to 18–20 months in the succeeding phase. Clinical trials to answer questions and gain more information were highly recommended by the researchers to determine the optimal treatment of MDR-TB patients.33
Surgery
A last resort treatment is the surgical removal of the TB-infected tissue of individuals infected with strains resistant to all known treatments.
32. World Health Organization. (2022). Module 4: treatment - drug-resistant tuberculosis treatment. In WHO operational handbook on tuberculosis. https://www.who.int/publications/i/item/978924006511633. Ahuja, S. D., Ashkin, D., et al. (2012). Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: An individual patient data meta-analysis of 9,153 patients. PLoS Medicine, 9(8), e1001300. https://doi.org/10.1371/journal.pmed.1001300
