NEW YORK (January 27, 2020)—New peer-reviewed research has evaluated the efficacy of different doses and schedules of linezolid for the treatment of tuberculosis (TB). The greatest level of efficacy was found at a 1200 mg daily dose. Linezolid is currently used as part of regimens that treat drug-resistant strains of TB. The research appeared in the 19th issue of Antimicrobial Agents and Chemotherapy (AAC).
While linezolid’s efficacy against TB infections has been evaluated in many peer-reviewed studies, there is little information in the literature that provides data on the effectiveness of different doses of linezolid. The research published today in AAC presents the results of a clinical trial sponsored by the non-profit TB Alliance that treated 114 drug-sensitive TB patients for two weeks with one of six possible linezolid dosing strategies. The study evaluated the effect of linezolid without other drugs and used the current standard of care for drug sensitive TB —a combination of isoniazid, rifampicin, pyrazinamide and ethambutol—as a control.
The early bactericidal activity trial, known as LIN-CL001, found higher doses of linezolid to be more active during the two-week treatment period. The activity of linezolid increased with increasing doses. Activity was highest for a 1200 mg total daily dose, followed by 600 mg per day and then by 300 mg taken daily. Activity was similar whether the total daily dose was taken once a day or divided into two during the day.
“As linezolid is increasingly used to treat resistant forms of TB, we need more research to determine how best to use this important drug,” said Mel Spigelman, President and CEO, TB Alliance. “We must continue to explore the dose response characteristics of linezolid to help refine treatment regimens that include it.”
Linezolid was first developed to treat infections caused by gram positive organisms, but was later found to have activity against TB. It has been increasingly added to treatment regimens over the past ten years and is now recommended by the World Health Organization for the treatment of multidrug-resistant TB. Reported side effects include optic or peripheral neuropathy and suppression of the bone marrow (myelosuppression), leading to problems such as anemia. These potential side effects require monitoring while patients are treated with linezolid. Understanding the safety and efficacy of various doses is important to managing these issues and choosing the right balance between the risks and benefits in treating patients.
TB Alliance’s ZeNix trial is exploring the safety and efficacy of different linezolid dosing schemes as part of a treatment regimen for extensively drug-resistant TB (XDR-TB), pre-XDR-TB, or treatment-intolerant/non-responsive multi-drug-resistant TB (MDR-TB).
Tuberculosis is a global disease, found in every country in the world. It is the leading infectious cause of death worldwide. In 2018, an estimated 10 million people fell ill from active TB and 1.5 million died. It is an airborne disease that can be spread by coughing or sneezing. Cases of drug-resistant TB continue to increase, with approximately half a million cases of drug-resistant TB developed in 2018 and 127 countries reporting cases of XDR-TB.
TB, in all forms, must be treated with a combination of drugs; the most drug-sensitive forms of TB require six months of treatment using four anti-TB drugs. Treatment of XDR-TB or treatment-intolerant/non-responsive MDR-TB has historically been lengthy and complex; most XDR-TB patients currently take a combination of as many as eight antibiotics, some involving daily injections, for 18 months or longer.