CDC Releases Interim Guidance on a Novel Treatment Regimen for Drug-Susceptible Tuberculosis

The Centers for Disease Control and Prevention (CDC) has issued a treatment recommendation for patients infected with drug-susceptible pulmonary tuberculosis (TB). This interim guidance was published in the Morbidity and Mortality Weekly Report.

For this interim guidance, investigators at the CDC performed a systematic review using data from an international, open-label, phase 3 inferiority study (31/A5349), pharmacokinetic and pharmacodynamic modeling, and clinical trials that assessed patients with drug-susceptible pulmonary TB.

The CDC recommends a 4-month daily treatment regimen of high-dose rifapentine (RPT) with moxifloxacin (MOX), isoniazid (INH), and pyrazinamide (PZA) for patients aged 12 years and older with drug-susceptible TB infection. This regimen comprises 8 weeks of treatment with all 4 medications, followed by a 9-week course of RPT, MOX, and INH. Medications should be taken with food under direct observation.

This novel treatment regimen is not recommended for patients younger than 12 years, those who weigh less than 88.2 lb (40 kg), women who are pregnant and/or breastfeeding, patients with extrapulmonary TB infection, and those with a history of prolonged QT syndrome.

For patients with HIV infection, treatment with this 4-month regimen may be considered among those with CD4 counts greater than or equal to 100 cells/mL and those who are planning to initiate antiretroviral therapy with efavirenz.

Patients should undergo microbiologic, laboratory, and clinical evaluations prior to treatment initiation and throughout the treatment course. In addition, a respiratory specimen should be obtained for acid-fast Bacilli smear microscopy and culture testing, with continued drug-susceptibility testing throughout the course of treatment. If drug-resistant TB infection is detected, treatment with this novel regimen should discontinued.

Treatment should be considered as complete after a patient has received 119 total doses within 70 days of initiation.

For patients who either are unresponsive or discontinue treatment after 2 months, repeat culture specimens should be obtained with samples sent to a reference laboratory for additional drug-susceptibility testing.

The investigators acknowledged that RPT and MOX are not indicated for a 4-month treatment course for TB infection. However, RPT is recommended for the prevention of TB infection among patients with latent TB, and MOX is recommended for the treatment of TB infection.

Of note, RPT has recently been found to contain a decreased concentration of nitrosamines. Additional information about nitrosamines can be found at the Food and Drug Administration’s (FDA) drug safety and availability website.

According to the investigators, “clinicians should carefully review a patient’s clinical history, [current medication regimen], social determinants of health, and risk factors for adverse drug reactions when making the decision to use this regimen.”

Reference

Carr W, Kurbatova E, Starks A, Goswami N, Allen L, Winston C. Interim guidance: 4-month rifapentine-moxifloxacin regimen for the treatment of drug-susceptible pulmonary tuberculosis-United States, 2022. MMWR Morb Mortal Wkly Rep. Published online March 1, 2022. doi:10.7326/M21-4784