Tuberculosis
Treatment
For standard treatment of TB in persons with HIV, including appropriate choice of ARVs, see table below and ART in TB/HIV Co-infection
See online video lectures from the EACS online course Clinical Management of HIV
Susceptible Mycobacterium tuberculosis
| Drug / Dose(i) | Comments* | |
|---|---|---|
| Initial phase |
rifampicin Dosing is weight-based |
Initial phase for 2 months. Corticosteroids are recommended as adjuvant treatment in TB meningitis and TB with CNS involvement |
| Alternative Initial phase |
rifabutin Dosing is weight-based |
Initial phase for 2 months. |
| Continuation phase |
rifampicin/rifabutin Dosing is weight-based |
Total duration of therapy: 1. Pulmonary, drug susceptible TB: 6 months 2. Pulmonary TB & positive culture at 8 weeks of TB treatment: 9 months 3. Extrapulmonary TB with CNS involvement or disseminated TB: 9-12 months 4. Extrapulmonary TB with bone/joint involvement and in other sites: 6-9 months |
An alternative shorter regimen (only in patients with CD4>100) of rifapentine, isoniazid, pyrazinamide and moxifloxacin for 2 months, followed by rifapentine, isoniazid and moxifloxacin for 2 months can be used, if rifapentine is available (see WHO Guidelines, 2022) Evidence on efficacy of this regimen in extrapulmonary TB is limited.
* Intermittent regimens (2 or 3 times per week) are contraindicated in persons with HIV. Missed doses can lead to treatment failure, relapse or acquired drug resistance. Insufficient evidence is available to recommend any ultra-short (<4 months) regimens in HIV patients.
i For dose details, please see separate table TB Drug Doses, below
Diagnosis: MDR-TB, XDR-TB
Multidrug Resistant TB (MDR-TB) or Extensively Drug-Resistant TB (XDR-TB)
MDR-TB/XDR TB should be suspected in case of:
- Previous TB treatment
- Contact with MDR/XDR-TB index case
- Birth, travel or work in an area endemic for MDR-TB
- History of poor adherence
- No clinical improvement on standard therapy and/or sputum smear positive after 2 months of TB therapy or culture positive at 3 months
- Homelessness/hostel living and, in some countries, recent/current incarceration
- In areas with very high MDR/XDR-TB prevalence
MDR-TB: Resistance to isoniazid AND rifampicin
XDR-TB - since 2021: Resistance to isoniazid AND rifampicin AND fluoroquinolones AND at least one additional Group A drug, see below
Rapid detection
Gene Xpert or similar technology has the advantage of rapid detection of rifampicin resistance. Drug susceptibility testing is important for optimizing treatment
Treatment of resistant TB
Isoniazid-resistant TB
-
rifampicin/rifabutin + pyrazinamide + ethambutol + levofloxacin or moxifloxacin for 6 months, WHO 2020 recommendations
Rifampicin-resistant (RR) and MDR/XDR-TB
-
Treatment of MDR/XDR-TB is a specialist area. WHO has published new Guidelines (2022)
Currently recommended all-oral regimen:
Can be used in persons with confirmed RR/MDR-TB who have not been exposed to bedaquiline, pretomanid, linezolid for > 1 month
- 6 months of bedaquiline, pretomanid, linezolid (600 mg qd) and moxifloxacin (BPaLM). This regimen may be used without moxifloxacin if resistance to fluoroquinolones (pre-XDR-TB) is documented (BPaL). In this case consider extension of 3 months. Data on the effectiveness of this regimen in extensive pulmonary TB disease or severe extra-pulmo-nary TB are currently not available (see WHO Guidelines 2022)
Alternative all oral regimen:
Can be used in persons with MDR/RR-TB without resistance to fluoroquinolones and without previous exposure to second-line drugs and without extensive pulmonary TB or severe extra-pulmonary TB
- 4-6 months bedaquiline (6 months) + levo-/ moxifloxacin + ethionamide** + ethambutol + isoniazid (high-dose) + pyrazinamide + clofazimine followed by
- 5 months levo-/ moxifloxacin + ethambutol + pyrazinamide + clofazimine
**4 months of ethionamide can be replaced by 2 months of linezolid (600 mg qd)
Longer TB treatment regimens (>18 months)
Patients with XDR-TB and those not eligible to or failing all-oral short regimens may benefit from individualized longer treatment.
All three Group A drugs and at least one Group B drug should be included to ensure that treatment starts with at least four TB drugs likely to be effective, and that at least three agents are included for the rest of treatment if bedaquiline is stopped.
If only one or two Group A drugs are used, both Group B drugs are to be included.
If the regimen cannot be composed with drugs from Groups A and B alone, Group C drugs are added to complete it.
The duration of longer regimens must be individualized. For details, see WHO Guidelines 2022.
Treatment compliance is crucial. If needed, each dose of medicines should be given as DOT throughout the whole treatment period.
Surgery
Surgical resection may be part of the management for selected persons with focal pulmonary MDR-TB
Drug Choices
Each empiric regimen should be reassessed and modified if needed once drug sensitivity results become available
| Each empiric regimen should be reassessed and modified if needed once drug sensitivity results become available | |
| Group A: Include all three drugs |
|
|
Group B: |
|
|
Group C: |
|
Pretomanid is recommended but not yet included in Group A drugs
Drug interactions with ART and MDR/XDR regimens
When treating RR/MDR/XDR-TB careful review of DDIs and potential toxicities is mandatory before initiating ART,
see Drug-drug Interactions between Anti-tuberculosis Drugs and ARVs
Latent tuberculosis
Indication: TST > 5 mm or positive IGRA or close contacts to persons with sputum smear positive tuberculosis. See Assessment at Initial & Subsequent Visits
Some national guidelines consider the ethnicity, CD4 count and ART usage to define indication for latent tuberculosis treatment
| Regimen* | Comments |
|---|---|
|
isoniazid |
6-9 months |
| rifampicin 600 mg qd po or rifabutin** po (dose according to current ART) |
4 months, check interactions with ARVs, see Drug-drug Interactions between ARVs and Non-ARVs and table on drug-drug interaction relevant ART co-administered with rifampicin and rifabutin |
|
rifampicin 600 mg/day po |
3 months, check interactions with ARVs, see Drug-drug Interactions between ARVs and Non-ARVs and table on drug-drug interaction relevant ART co-administered with rifampicin and rifabutin |
|
rifampicin |
3 months, check interactions with ARVs, see Drug-drug Interactions between ARVs and Non-ARVs |
|
rifapentine*** |
3 months, rifapentine is not yet available in Europe |
|
rifapentine*** |
4 weeks, rifapentine is not yet available in Europe |
* Other preventive regimens may be considered if high risk of latent infection with MDR/XDR-TB
** Rifabutin is not a WHO recommended regimen
*** Rifapentine is not approved by EMA
TB Drug Doses
First line drugs
| Drug name | Dose | Comments | |
| Isoniazid | 5 mg/kg qd (usual dose 300 mg) | Max 375 mg qd Caution: neurotoxicity, add pyridoxine 20 mg qd |
|
| Rifampicin | 10 mg/kg qd (usual dose 600 mg) | Rifampicin is not recommended in persons receiving PIs, DOR, ETR, NVP, RPV, FTR, BIC, CAB, CAB/ RPV LA, EVG/c. see Drug-drug Interactions between Anti-tuberculosis Drugs and ARVs and ART in TB/HIV Co-infection |
|
| Rifabutin | without PIs, EFV, RPV | 5 mg/kg qd (usual dose 300 mg) | |
| with PIs | 150 mg qd | ||
| with EFV | 450-600 mg qd | ||
| with TAF or EVG/c | Not recommended | ||
| Pyrazinamide | 40-55 kg | 1000 mg qd | |
| 56-75 kg | 1500 mg qd | ||
| 76-90 kg | 2000 mg qd | ||
| > 90 kg | 2000 mg qd | ||
| Ethambutol | 40-55 kg | 800 mg qd |
Max 1600 mg qd |
| 56-75 kg | 1200 mg qd | ||
| > 75 kg | 1200 mg qd | ||
Other Drugs
| Drug Name | Dose | Comments | |
| Levofloxacin | 30-45 kg | 750 mg qd | Max 1500 mg qd |
| > 46 kg | 1000 mg qd | ||
| Moxifloxacin | 400 mg qd |
Max 800 mg qd (used in the standardized shorter MDR-TB regimen) Monitor ECG in respect of QT prolongation |
|
| Bedaquiline |
400 mg qd for 2 weeks 200 mg qd three times weekly for 22 weeks |
EFV, ETV: potential reduction of bedaquiline exposure and activity. Not recommended Boosted regimens: increase in bedaquiline exposure. Potential risk of QT interval prolongation, ECG monitoring recommended. Avoid coadministration > 14 days |
|
| Linezolid | 600 mg qd |
Max 1200 mg qd Caution: hematological side effects and neurotoxicity, including optic neuropathy |
|
| Clofazimine | 100 mg qd |
Alternative: 200 mg for 2 months then 100 mg qd Caution: skin toxicity Monitor ECG in respect of QT prolongation |
|
| Cycloserine or terizidone | 30-45 kg | 500 mg qd |
Max 1000 mg qd Caution: neurotoxicity; add pyridoxine, up to 50 mg/250 mg cycloserine |
| > 46 kg | 750 mg qd | ||
| Delamanid | 100 mg bid for 24 weeks | Monitor ECG in respect of QT prolongation | |
| Imipenem/cilastatin | 1000/1000 mg bid iv | To be used with clavulanic acid | |
| Meropenem | 1000 mg tid iv | To be used with clavulanic acid | |
| Amikacin | 30-35 kg | 625 mg qd iv |
After initial period can be reduced to thrice weekly Baseline audiometry should be performed Caution: monitor renal function, audiometry and |
| 36-45 kg | 750 mg qd iv | ||
| 46-55 kg | 750-1000 mg qd iv | ||
| > 55 kg | 1000 mg qd iv | ||
| Streptomycin | 12-18 mg/kg qd iv | Max 1000 mg qd iv | |
| Ethionamide or prothionamide | 30-45 kg | 500 mg qd | Caution: gastrointestinal toxicity; add pyridoxine, up to 50 mg/250 mg prothionamide |
| 46-70 kg | 750 mg qd | ||
| > 70 kg | 1000 mg qd | ||
| Para-aminosalycilic acid | 4000 mg bid |
In weight > 70 kg can be increased to 4000-6000 mg bid Caution: gastrointestinal toxicity |
|
| Pretomanid | 200 mg qd |
Use with bedaquiline and linezolid for 26 weeks Monitor ECG in respect of QT prolongation Peripheral neuropathy is common adverse effect |
|