Drug-resistant tuberculosis
From IDWiki
Background
- Mycobacterium tuberculosis infection that is resistant to both first-line drugs, isoniazid and rifampin
Classification
- Multidrug resistant tuberculosis (MDR-TB): resistance to isoniazid and rifampicin
- Rifampin monoresistance is quite rare, so MDR is usually inferred from rifampin resistance alone
- Extensively drug-resistant tuberculosis (XDR-TB): resistance to at least isoniazid and rifampicin, and to any fluoroquinolone, and to any of the three second-line injectables
- Totally drug-resistant tuberculosis (TDR-TB): not well-defined
Resistance Mechanisms
- 90% of isoniazid resistance is from known mutations in either the katG or InhA genes
- 95% of rifampin resistance is from known mutations in the rpoB gene
Risk Factors
- The strongest predictor of MDR-TB is prior TB treatment (increases from 3% to 18% of cases)
- Residence in country with higher rate of MDR-TB: India (8%/13% new/previous treatment), Philippines (12%/15%), China (7%/8%), Viet Nam (14%/10%), Pakistan (8%/7%), Ethiopia (6%/13%), Somalia (6%/8%), Haiti (unclear), Hong Kong (5%/7%), Afghanistan (unclear)
- Exposure to person with MDR-TB
- HIV infection
- Other risk factors include younger age and more recent arrival from endemic country
Management
- Rapid PCR testing for rifampin resistance should be considered in all patients, but definitely done if at increased risk of MDR-TB
- Referral to a specialized TB program
- First-line is generally a fluoroquinolone, bedaquiline, linezolid, clofazimine, and cycloserine
- Other regimens are any five drugs to which it is susceptible, in order of preference:
- Group A: fluoroquinolones (except ciprofloxacin), bedaquiline, linezolid
- Group B: clofazimine, cycloserine (or terizidone)
- Group C: ethambutol, pyrazinamide, delamanid, amikacin (or streptomycin), imipenem-cilastatin (or meropenem), ethionamide, p-aminosalicylic acid
- For low-burden disease, can consider a 4-drug regimen
- Duration
- Intensive phase (5 drugs) of 5 and 7 months after culture conversion, followed by consolidation phase with 4 drugs
- Total treatment duration between 15 and 21 months after culture conversion
| Resistance To | Replace With | Regimen | Total Duration |
|---|---|---|---|
| INH | FQN | 6 months RMP+EMB+PZA+FQN | 6 months from date FQN started |
| INH | FQN | 2 months RMP+EMB+PZA+FQN then 4 months RMP+EMB+FQN | 6 months from date FQN started |
| RMP | FQN | 2 months daily INH+EMB+PZA+FQN then 10-16 months INH+EMB+FQN | 18 months from date FQN started |
| RMP | None | 2 months INH+EMB+PZA, then 16 months INH+EMB | 18 months from date FQN started |
| EMB | None | 2 months INH+RMP+PZA, then 4 months INH+RMP | 6 months from start of therapy |
| PZA | None | 2 months INH+RMP+EMB, then 7 months INH+RMP | 9 months from start of therapy |
| INH+EMB | FQN | 6 months daily RMP+PZA+FQN | 6 months from date FQN started |
| INH+PZA | FQN | 9 months RMP+EMB+FQN | 9 months from date FQN started |
| INH+EMB+PZA | FQN+injectable | 2 months TMP+FQN+injectable, then 7 months RMP+FQN | 9 months from date FQN started |
