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Partial intermittent linezolid dose effective against XDR-TB

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CHICAGO — Once-daily 800 mg linezolid, followed by a 1,200-mg three-times weekly dose, was effective against extensively drug-resistant tuberculosis.

"Clinical pharmacokinetics help evaluate and substantiate clinical observations," Kwok Chiu Chang, MD, senior medical and health officer of the Tuberculosis and Chest Service Center for Health Protection in the Hong Kong Department of Health, told Infectious Disease News. "We have provided some pharmacokinetic findings that support the use of an intermittent dosing schedule to strike a balance between efficacy and toxicity in treating extensively drug-resistant tuberculosis with linezolid."

Chang and colleagues measured the 2-hour level penetrability of linezolid in paired serum and sputum samples among seven patients with XDR-TB. Seven patients harbored bacilli with minimum inhibitory concentrations of 0.5 mg/L to 1 mg/L for linezolid.

Four patients were cured of XDR-TB after 16 to 19 months of treatment with linezolid and other TB therapies. After 2 to 4 months of daily treatment, nadirs of hemoglobin levels reached 8.7 g/dL to 12.1 g/dL and subsequently normalized during intermittent treatment. Median ratio of sputum-to-serum linezolid levels was 1.3 mg/L.

Six patients had serum linezolid levels of at least 1 mg/L in a median of 83% of the inter-dosing time interval with a median estimated 2-hour serum linezolid level to MIC ratio of 57 mg/L.

Adverse events included mild peripheral neuropathy 3 or more months after initiation of daily treatment and remained stable in three patients.

“Linezolid-associated peripheral neuropathy probably occurs with inhibition of mitochondrial protein synthesis,” the researchers wrote in a press release. “Clinical and pharmacokinetic findings suggest that XDR-TB may be cured with minimal adverse events related to linezolid, by its dosing in a partially intermittent schedule.” - by Jennifer Henry

For more information:

• Chang KC. #L1-1488. Presented at: the 2011 ICAAC; Sept. 17-20; Chicago.

Disclosures: Dr. Chang reports no relevant financial disclosures.

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