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ZeNix trial shows lower dose of linezolid can be used for treating highly drug resistant tuberculosis

21 Jul 2021

Results from the ZeNix trial show that the BPaL combination of drugs remains effective against highly drug resistant tuberculosis (TB) with reduced dosage or duration of the linezolid part of the regimen. These results were presented today at the International AIDS Society Conference.

Drug resistant TB is a major public health problem, according to the World Health Organisation. Around 600,000 people developed multidrug-resistant (MDR) TB in 2016, and 8,000 cases were reported of extensively drug-resistant (XDR) TB, which is resistant to at least four of the core anti-TB drugs. These types of TB are hard to treat, as there are few drugs available, and outcomes are often poor. Treatment can take 18 months or longer, and may include up to eight different drugs.

The previous Nix-TB trial had shown that treatment with a combination of the drugs bedaquiline, pretomanid and linezolid for six months led to nine in 10 people with highly drug resistant TB having a favourable treatment outcome. However, many of those people also experienced side-effects from the drug linezolid.

The ZeNix trial was carried out to see if the same combination of drugs would remain effective at treating highly drug resistant TB, with fewer side-effects, if the dose of linezolid was reduced, or if the length of time people took linezolid for was reduced.

181 people with highly drug resistant TB took part in ZeNix from South Africa, Georgia, Russia and Moldova. They were randomly allocated to one of four groups:

  • One group had the current standard BPaL treatment, with 1200mg of linezolid a day for six months
  • One group had BPaL treatment with 1200mg of linezolid a day for two months, continuing on bedaquiline and pretomanid for a further four months
  • One group had BPaL treatment with 600mg of linezolid a day for six months
  • One group had BPaL treatment with 600mg of linezolid a day for two months, continuing on bedaquiline and pretomanid for a further four months

The results presented at the IAS conference showed that patients in all four groups had a high chance of cure. Fewer patients had linezolid side-effects in the groups that had the lower dose or shorter length of treatment with the drug.

The ZeNix trial is funded and sponsored by the TB Alliance. The MRC CTU at UCL led the statistical work within the trial, and the UCL Centre for Clinical Microbiology (CCM) was the central laboratory / laboratory monitoring lead.

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