Drug-resistant tuberculosis: Difference between revisions
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+ | == Background == |
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− | * [[Mycobacterium tuberculosis]] infection that is resistant to both first-line drugs, isoniazid and rifampin |
+ | * [[Mycobacterium tuberculosis]] infection that is resistant to both first-line drugs, isoniazid and [[rifampin]] |
− | == Classification == |
+ | === Classification === |
* '''Multidrug resistant tuberculosis (MDR-TB)''': resistance to [[isoniazid]] and [[rifampicin]] |
* '''Multidrug resistant tuberculosis (MDR-TB)''': resistance to [[isoniazid]] and [[rifampicin]] |
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+ | ** Rifampin monoresistance is quite rare, so MDR is usually inferred from rifampin resistance alone |
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* '''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 |
* '''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 |
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* '''Totally drug-resistant tuberculosis (TDR-TB)''': not well-defined |
* '''Totally drug-resistant tuberculosis (TDR-TB)''': not well-defined |
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+ | |||
+ | === Resistance Mechanisms === |
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+ | |||
+ | * 90% of isoniazid resistance is from known mutations in either the katG or InhA genes |
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+ | * 95% of rifampin resistance is from known mutations in the rpoB gene |
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+ | |||
+ | === Risk Factors === |
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+ | |||
+ | * The strongest predictor of MDR-TB is prior TB treatment (increases from 3% to 18% of cases) |
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+ | * 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) |
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+ | * Exposure to person with MDR-TB |
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+ | * HIV infection |
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+ | * Other risk factors include younger age and more recent arrival from endemic country |
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== Management == |
== Management == |
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+ | * '''Rapid PCR testing for rifampin resistance''' should be considered in all patients, but definitely done if at increased risk of MDR-TB |
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⚫ | |||
+ | * Referral to a specialized TB program |
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− | ** Any first-line agents to which it is still susceptible |
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+ | * First-line is generally a [[Fluoroquinolones|fluoroquinolone]], [[bedaquiline]], [[linezolid]], [[clofazimine]], and [[cycloserine]] |
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− | ** A fluoroquinolone (except ciprofloxacin) |
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⚫ | |||
− | ** An injectable: kanamycin, or other parenteral agent |
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+ | ** Group A: [[fluoroquinolones]] (except [[ciprofloxacin]]), [[bedaquiline]], [[linezolid]] |
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− | ** Other second-line agents, starting with ethionamide |
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+ | ** Group B: [[clofazimine]], [[cycloserine]] (or [[terizidone]]) |
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− | * Followed by 12 months of a less intensive regimen (at least three effective drugs), for a total of at least 20 months |
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+ | ** Group C: [[ethambutol]], [[pyrazinamide]], [[delamanid]], [[amikacin]] (or [[streptomycin]]), [[imipenem-cilastatin]] (or [[meropenem)]], [[ethionamide]], [[p-aminosalicylic acid]] |
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+ | * For low-burden disease, can consider a 4-drug regimen |
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+ | * Duration |
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+ | ** Intensive phase (5 drugs) of 5 and 7 months after culture conversion, followed by consolidation phase with 4 drugs |
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+ | ** Total treatment duration between 15 and 21 months after culture conversion |
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Revision as of 21:39, 1 April 2023
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 |