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.
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.
|Resistance to which first-line drugs:||Drugs to drop||Drugs to add||Regimen||Total duration|
|INH||INH||FQN||6 months daily RMP + EMB + PZA + FQN||6 months from date FQN started|
|INH||FQN||2 months daily RMP + EMB + PZA + FQN/4 months daily RMP + EMB + FQN||6 months from date FQN started|
|RMP||RMP||FQN||2 months daily INH + EMB + PZA + FQN /10-16 months daily INH + EMB + FQN||18 months from date FQN started|
|RMP||None||2 months daily INH + EMB + PZA / 16 months INH + EMB daily or thrice weekly||18 months from start of therapy|
|EMB||EMB||None||2 months daily INH + RMP + PZA /4 months INH + RMP daily or thrice weekly||6 months from start of therapy|
|PZA||PZA||None||2 months daily INH + RMP + EMB /7 months INH + RMP daily or thrice weekly||9 months from start of therapy|
|INH + EMB||INH + EMB||FQN||6 months daily RMP + PZA + FQN||6 months from date FQN started|
|INH + PZA||INH + PZA||FQN||9 months daily RMP + EMB + FQN||9 months from date FQN started|
|INH + EMB + PZA||INH + EMB + PZA||FQN + injectable||2 months daily RMP + FQN + injectable /7 months daily RMP + FQN||9 months from date FQN started|
Abbreviations: TB, tuberculosis; INH, isoniazid; FQN, fluoroquinolone (moxifloxacin or levofloxacin); RMP, rifampin; EMB, ethambutol; PZA, pyrazinamide.
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