TB Manual

Resistance to RMP, in 95% of cases,⁷⁴ is due to point mutations in the rpo gene in the beta subunit of DNA-dependent RNA polymerase. Resistance to RMP results in cross-resistance to rifabutin in most (∼80%) cases and to rifapentine in all (100%) cases. With one exception, RMP mono-resistance is uncommon, and intolerance and/or allergic reactions to it are more common clinical scenarios. RMP mono-resistance has been seen in patients with advanced HIV disease (CD4 counts in cases of acquired RMP resistance have all been <200 cells × 10⁶/L and usually <50 cells × 10⁶/L) who were taking rifabutin as prophylaxis against M. avium complex, or received an intermittent anti-TB regimen during the initial phase of treatment. ^75–81 Treatment options for patients determined to be RMP mono-resistant are given in Table 4.^56,82,83

In 2013, the WHO simplified definitions and reporting requirements to include RMP-resistant TB cases with MDR-TB. Currently, neither the WHO or ATS/CDC/ERS/IDSA guidelines address management of RMP resistance in the absence of INH resistance.

Recommendation

• We conditionally recommend, in patients with isolated resistance (or intolerance) to rifampin, either: 1) isoniazid, ethambutol and a fluoroquinolone daily for 12 to 18 months, supplemented with pyrazinamide for at least 2 months during the intensive phase; 2) isoniazid and ethambutol for 18 months, supplemented with pyrazinamide for at least 2 months during the intensive phase; or 3) treatment as MDR-TB (poor evidence).

Table 4. Treatment regimens for the management of mono or polydrug-resistant TB.

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