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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| + | |||
| + | === BPaLM === |
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| + | * [[Bedaquiline]], [[pretomanid]], [[linezolid]], and [[moxifloxacin]] (BPaLM) for 6 months<ref>Nyang'wa BT, Berry C, Kazounis E, Motta I, Parpieva N, Tigay Z, Solodovnikova V, Liverko I, Moodliar R, Dodd M, Ngubane N, Rassool M, McHugh TD, Spigelman M, Moore DAJ, Ritmeijer K, du Cros P, Fielding K; TB-PRACTECAL Study Collaborators. A 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis. N Engl J Med. 2022 Dec 22;387(25):2331-2343. doi: [https://doi.org/10.1056/NEJMoa2117166 10.1056/NEJMoa2117166]. PMID: 36546625.</ref> now [https://www.who.int/publications/i/item/9789240065116 recommended by WHO] |
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| + | * Should be avoided in CNS disease, disseminated TB, children, or pregnant patients |
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| + | |||
| + | === Specific Resistance Patterns === |
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{| class="wikitable" |
{| class="wikitable" |
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!Resistance To |
!Resistance To |
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| + | !Replace With |
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| − | !Drug to Stop |
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| − | !Drug to Add |
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!Regimen |
!Regimen |
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!Total Duration |
!Total Duration |
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|- |
|- |
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| − | |INH |
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|INH |
|INH |
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|FQN |
|FQN |
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|6 months from date FQN started |
|6 months from date FQN started |
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|- |
|- |
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| − | |INH |
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|INH |
|INH |
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|FQN |
|FQN |
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|6 months from date FQN started |
|6 months from date FQN started |
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|- |
|- |
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| − | |RMP |
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|RMP |
|RMP |
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|FQN |
|FQN |
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|18 months from date FQN started |
|18 months from date FQN started |
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|- |
|- |
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| − | |RMP |
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|RMP |
|RMP |
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|None |
|None |
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|18 months from date FQN started |
|18 months from date FQN started |
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|- |
|- |
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| − | |EMB |
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|EMB |
|EMB |
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|None |
|None |
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|6 months from start of therapy |
|6 months from start of therapy |
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|- |
|- |
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| − | |PZA |
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|PZA |
|PZA |
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|None |
|None |
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|9 months from start of therapy |
|9 months from start of therapy |
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|- |
|- |
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| − | |INH+EMB |
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|INH+EMB |
|INH+EMB |
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|FQN |
|FQN |
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|6 months from date FQN started |
|6 months from date FQN started |
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|- |
|- |
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| − | |INH+PZA |
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|INH+PZA |
|INH+PZA |
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|FQN |
|FQN |
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|9 months from date FQN started |
|9 months from date FQN started |
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|- |
|- |
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| − | |INH+EMB+PZA |
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|INH+EMB+PZA |
|INH+EMB+PZA |
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|FQN+injectable |
|FQN+injectable |
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|9 months from date FQN started |
|9 months from date FQN started |
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|} |
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| − | * |
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[[Category:Tuberculosis]] |
[[Category:Tuberculosis]] |
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Latest revision as of 21:48, 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
BPaLM
- Bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) for 6 months[1] now recommended by WHO
- Should be avoided in CNS disease, disseminated TB, children, or pregnant patients
Specific Resistance Patterns
| 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 |
- ↑ Nyang'wa BT, Berry C, Kazounis E, Motta I, Parpieva N, Tigay Z, Solodovnikova V, Liverko I, Moodliar R, Dodd M, Ngubane N, Rassool M, McHugh TD, Spigelman M, Moore DAJ, Ritmeijer K, du Cros P, Fielding K; TB-PRACTECAL Study Collaborators. A 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis. N Engl J Med. 2022 Dec 22;387(25):2331-2343. doi: 10.1056/NEJMoa2117166. PMID: 36546625.
