A Quicker Cure for Multidrug-Resistant TB

SEPTEMBER 15, 2016
Standard treatment for multidrug-resistant (MDR) tuberculosis (TB) lasts 2 years or more with complicated regimens of toxic medications that are sometimes ineffective and often widely unavailable.
 
Half a million individuals develop MDR TB each year. It’s prevalent in American homeless shelters, the former Soviet Union, South Asia, and South America. The drug resistance can either be transferred at the time of infection or develop after insufficient therapy. The insidious nature of TB allows latent MDR strains in the lungs of immigrants and refugees to travel overseas.

The World Health Organization recommends a new, faster, less expensive, and easier to self-administer regimen for patients with MDR TB or rifampicin-resistant TB. Of note, though, is pregnancy, extra-pulmonary disease, and second-line treatment resistance are contraindications.1

This new regimen includes a 4-drug initiation phase for 4 to 6 months, followed by a 2-drug continuation phase for 5 months, costing less than $1000 per patient. Initiation phase drugs include kanamycin, moxifloxacin, prothionamide, clofazimine, pyrazinamide, high-dose isoniazid, and ethambutol. Continuation phase drugs include moxifloxacin, clofazimine, pyrazinamide, and ethambutol. Providers may substitute in linezolid, delamanid, or bedaquiline if the patient’s strain has documented resistance to one of the new regimen’s components, but research on these substitutions is limited.

Members of the International Carbapenem Study Group recently examined the shorter MDR TB regimen.2 This multicenter, observational, retrospective, cohort study enrolled MDR-/XDR-TB patients 16 years and older in 8 European and 3 South American countries. The study centers specialized in complicated TB cases, and the patient populations weren’t generally representative of European or South American TB patients.

Resistance to ethambutol and pyrazinamide, prothionamide, fluoroquinolones, and kanamycin were widespread in European patients. Only 4% of patient strains were susceptible to all of the short-regimen medications. Drug susceptibility testing was used to guide treatment selection in MDR TB cases; however, no testing currently exists for clofazimine or prothionamide. Extensive fluoroquinolone resistance, with concomitant pyrazinamide resistance especially, predicts treatment failure.

This new regimen hasn’t been selected for extensively drug-resistant (XDR) TB in the available literature, but it reduces the risk of XDR TB selection compared with standard of care. Patients are more likely to finish therapy due to the shorter course of the new regimen; therefore, it decreases the prevalence of patients at risk of MDR TB.

Drug susceptibility testing, disease extent, toxicity concerns, medication availability, previous antituberculosis medication exposure, and expected adherence should guide treatment selection.
 
References
  1. World Health Organization. The Shorter MDR-TB Regimen. WHO website. who.int/tb/Short_MDR_regimen_factsheet.pdf. Accessed September 11, 2016.
  2. Sotgiu G, et al. Faster for less: the new "shorter" regimen for multidrug-resistant tuberculosis. Eur Respir J. 2016;48(3).


Daniel Holland, PharmD
Daniel Holland, PharmD
Daniel Holland, PharmD, is a graduate and medical writer from the University of Connecticut School of Pharmacy. Connect with him on LinkedIn or at daniel.holland222@gmail.com
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