Linezolid and Delamanid for XDR-TB

Drug-resistant TB is a global crisis. Treatment is prolonged and poorly tolerated because of side effects. In addition, research on new regimens has been slow. Today’s NEJM has two letters regarding treatment for extensively drug-resistant tuberculosis (XDR-TB).

First, a letter from South Korea, regarding final study outcomes of a previously published clinical trial of Linezolid. Interestingly, 27 of 38 patients (71%) with chronic XDR-TB were cured of the infection. Adverse events were frequent and many of the patients required a dose reduction from 600 to 300 mg daily but most were able to tolerate two years of treatment. Resistance was found in 11% of patients. Beyond efficacy, safety, and resistance, I wonder about the cost of linezolid. Linezolid costs $364/day in the United States. Unless Pfizer is going to provide a major discount, two years of linezolid would come to to $265,720 per patient, atop the other costs of XDR-TB treatment. That’s not affordable for any tuberculosis program I’m aware of. Finally, the authors state that newer oxazolidinones (i.e. tidezolid) might be effective in XDR-TB. Research on newer oxazolidinones for XDR-TB has not been conducted yet, but my understanding is the skin/soft tissue infection trials that got tidezolid approved only gave 6 days of drug (3 weeks outside the trials). Will 2 years of tidezolid be safe and tolerable? No one has any idea.

Second, a letter from Otsuka researchers regarding Delamanid. In “Trial 204” of delamanid, the primary end point was 2-month sputum-culture conversion, which was defined as a negative culture for 5 consecutive weeks. I wonder about 2-month sputum-culture conversion as a surrogate end point. Will 2-month conversion really correlate with durable cure of XDR-TB? And the number of patients here is so small, it is hard to know what to make of these data.

My friend Anthony Cannella from the University of Florida replied to my post. He said that cost of drugs and resistance will remain major issues in the fight against drug-resistant TB. We really need a T-cell vaccine for TB. I couldn’t agree more.

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