Interim Guidance: 4-Month Rifapentine-Moxifloxacin Regimen …

Recommendation for Use of the 4-month Rifapentine-Moxifloxacin Regimen

CDC recommends the 4-month RPT-MOX regimen for treating patients aged ≥12 years with body weight ≥40 kg with pulmonary TB caused by organisms that are not known or suspected to be drug-resistant and who have no contraindications to this regimen. The 4-month daily treatment regimen consists of an intensive phase composed of 8 weeks of daily treatment with RPT, MOX, INH, and PZA, followed by a continuation phase of 9 weeks of daily treatment with RPT, MOX, and INH (Table 1). Anti-TB drugs should be administered once daily with food, 7 days per week, for a total of 119 treatment doses; similar to the standard 6-month regimen, at least 5 of 7 weekly doses should be administered under direct observation (2). The 4-month regimen can be used in persons with an HIV infection who have CD4 counts ≥100 cells/μL and are receiving or planning to initiate efavirenz as part of their antiretroviral therapy (ART) regimen in the absence of any other known drug-drug interactions between antituberculosis and antiretroviral medications.

Considerations. The 4-month daily treatment regimen was not studied in, and CDC does not recommend this regimen for, the following patient groups: body weight <40 kg; age <12 years; pregnant or breastfeeding; most types of suspected or documented extrapulmonary TB infection (see exceptions below); history of prolonged QT syndrome or concurrent use of one or more QT-prolonging medications (in addition to MOX); patients receiving medications with known clinically relevant drug-drug interactions with RPT, MOX, INH, or PZA; or patients infected with a baseline Mycobacterium tuberculosis isolate known or suspected to be resistant to INH, PZA, rifampin (RIF), or fluoroquinolones.

The 4-month daily treatment regimen was not studied in, and CDC recommends that clinical consultation be obtained to determine if this regimen is an acceptable treatment option for, patient groups with increased risk for M. tuberculosis resistance to any drug in the regimen, including persons who received >5 doses of treatment directed against TB in the preceding 6 months, who received >5 doses of latent tuberculosis infection treatment in the preceding 6 months, or who received >5 doses of treatment with any one or more of the following drugs for any reason (e.g., urinary tract infection or pneumonia) in the preceding 30 days: INH, RIF, rifabutin, RPT, PZA, or any fluoroquinolone. Other patient groups for whom clinical consultation is recommended include those with serum or plasma alanine aminotransferase or aspartate aminotransferase >3 times the upper limit of normal or total bilirubin >2.5 times the upper limit of normal, or with preexisting advanced liver disease; renal insufficiency or end-stage renal disease, or with serum or plasma creatinine level >2 times the upper limit of normal; plasma potassium level <3.5 mEq/L; who have types of extrapulmonary TB that are likely to be paucibacillary, not pose a substantial risk for death or disability, and not require prolonged treatment (i.e., pleural or lymph node TB); or for whom a specimen was unable to be submitted for any M. tuberculosis resistance testing before initiating treatment.

The 4-month daily treatment regimen was not studied in patients with a negative sputum culture, but who in the judgment of the clinician likely represent paucibacillary or low mycobacterial burden pulmonary TB disease. A 4-month regimen for smear-negative, culture-negative, noncavitary TB exists in the 2016 CDC guidelines (2), and CDC recommends that the 4-month RPT-MOX regimen may also be used unless patients are in one of the nonrecommended patient groups listed above.

Baseline and follow-up evaluations. Microbiology, laboratory, and clinical assessments are recommended before starting and during treatment with the 4-month daily regimen (Table 2). A respiratory specimen for acid-fast bacilli smear microscopy and culture should be obtained at baseline and at monthly intervals during treatment until two consecutive specimens are negative on culture. Baseline molecular drug-susceptibility testing for rapid identification of mutations associated with resistance to at least INH, PZA, RIF, and fluoroquinolones is advisable. Phenotypic DST should follow with a panel to include at least RIF (as surrogate for RPT), INH, PZA, and MOX as the preferred fluoroquinolone. CDC’s Tuberculosis Elimination Laboratory (TBLab@cdc.gov) can assist identifying laboratories to perform this testing for TB programs that intend to implement the 4-month daily treatment regimen.

Duration and definition of completion of therapy. The 4-month daily treatment regimen is considered complete based on the total number of doses taken (119). Recommended treatment duration is independent of any cavitation on baseline chest radiograph. Intensive phase doses (56) should be administered within 70 days from treatment initiation, and continuation phase doses (63) should be administered within 84 days from intensive phase completion, so that the regimen is completed within 5 months. If these targets are not met, the patient should be considered to have interrupted therapy and be managed as described in TB treatment guidelines (2). Confirmation of continued susceptibility to all drugs in the 4-month daily treatment regimen is required before restarting this regimen.

Poor treatment response and treatment failure or discontinuation. Patients with any positive culture at completion of 2 months of therapy, with or without ongoing symptoms, should be carefully evaluated to identify the cause of delayed response (2). Mycobacterial isolates obtained after 2 months should be sent to a reference laboratory for DST. If drug resistance to INH, RIF, PZA, or any fluoroquinolone is detected by any testing method (i.e., phenotypic or molecular) in baseline or follow-up specimens, the 4-month regimen should be stopped, and patients should be started on an appropriate treatment regimen that accounts for the identified drug-resistance pattern (7). Patients who become pregnant while on treatment should receive clinical consultation regarding whether to stop the 4-month daily treatment regimen and be treated with an alternative regimen that is considered safer for pregnant persons (2).