9.1 Standard first-line treatment regimens

Standard first-line regimens are used for patients with presumed drug-susceptible tuberculosis (TB), documented drug-susceptible TB or while waiting for drug susceptibility testing (DST) results when drug-resistant (DR) TB is unknown but considered a low probability.

9.1.1 New patient regimens

New patients are defined as those who have no history of anti-TB treatment or who have received less than one month of anti-TB drugs. New patients may have smear positive or smear negative pulmonary TB (PTB) or extrapulmonary TB (EPTB).

Pulmonary TB and extrapulmonary TB

(except TB meningitis and osteoarticular/spinal TB)1,2

2 (HRZE)/4 (HR)

The treatment lasts 6 months with an intensive phase of 2 months with 4 anti-TB drugs and a continuation phase of 4 months with 2 anti-TB drugs.

In lymph node TB, adenopathies usually disappear in less than 3 months after treatment initiation. Paradoxical reactions may be observed at the beginning of treatment (appearance of abscesses, fistulas or other lymph nodes) and should not lead to a change in treatment. Non-steroidal anti-inflammatory drugs can be used in patients that experience paradoxical reactions.

This regimen should NOT be used :
– In patients who develop active TB after close contact with a known DR-TB case:
Obtain DST and while waiting for results, start a regimen based on the DST of the presumed source case (Chapter 10).

– In areas with high prevalence of resistance to isoniazid:
In these areas, all patients should get a DST at the start of treatment. The regimen 2 (HRZE)/4 (HR)E can be used1 in places where DST is not available or while waiting for DST result. This recommendation is based only on expert opinion. As a result, many patients will receive ethambutol unnecessarily if the DST is not available, but this could prevent rifampicin resistance in theory.

– An 8-month regimen 2 (HRZE)/6 (HE) or 2 S(HRZ)/6 (HE) is still used by some countries however, it has been demonstrated that it gives more frequent relapses and failures than the 6-month regimen. It should be replaced by the above 6-month regimen.
– Three times a week regimens are not recommended as a routine practice. However, for patients who are: (1) under strict directly observed therapy and (2) not HIV-infected, three times a week regimen for the continuation phase can be considered. Three times weekly administration during the intensive phase should not be done in any situation.

TB meningitis and osteoarticular/spinal TB

2 (HRZE)/10 (HR)

TB meningitis
Treatment of TB meningitis lasts 12 months2,3. Although 6 months are probably sufficient in most cases, treatment lasts longer because of the uncertain cerebrospinal fluid penetration of some anti-TB drugs. It is also recommended that all patients with TB meningitis receive a course of corticosteroids (Section 9.3).

Osteoarticular TB and spinal TB (Pott’s disease)
Although there is limited evidence to the benefit of extending the treatment, treating for 12 months with 2 (HRZE)/10 (HR)2,3 is recommended mainly because it is difficult to assess the response to the treatment. Pott's disease is a severe form of TB that should be treated as a priority because of the risk of neurological sequelae due to the chronic compression of the spinal nerve. In the absence of significant deformity and neurological deficit, most cases of spinal TB can be successfully treated with rest, back support bracing and anti-TB drugs. Surgery should be considered for patients with neurological deficit, an unstable spine lesion, and/or when they are not responding to therapy.

9.1.2 Previously treated patient regimens

See reference 1

Previously treated patients are defined as those who have received one month or more of anti-TB drugs in the past. It is critical in these patients to detect drug resistance, especially multidrug-resistant TB (MDR-TB) so that an effective drug regimen can be used. First-line drug regimens are not effective against MDR strains and their use can result in mortality and morbidity, amplification of resistance and spread of MDR-TB.

Strategy in previously treated patients:

Drug-resistance should be determined in all previously treated patients at or before the start of treatment. Xpert MTB/RIF is the preferred screening method for MDR-TB because of its sensitivity and quick turnaround time. The following are strategies depending on the availability of DST:

1 - Xpert MTB/RIF is available4: Xpert MTB/RIF indicating rifampicin resistance in previously treated patients should lead to an empiric MDR regimen (see Adult and adolescent diagnostic algorithm 3, Chapter 4). Previously treated patients with an Xpert MTB/RIF test indicating no rifampicin resistance should have DST to first-line drugs and be started on a first-line retreatment regimen1 .

2 - Only conventional DST is available: Patients whose treatment has failed2 3 or other patients with a high likelihood of MDR-TB (close contacts) should be started on an empiric MDR regimen while waiting for DST results. Relapse patients or patients returning after interruption may receive a retreatment regimen with first-line drugs1  while waiting DST5. When DST result becomes available, the regimen should be adjusted. If the clinical condition does not improve or deteriorates on the retreatment regimen with first-line drugs while waiting DST results, change to an empiric MDR regimen.

3 - DST is not available: Strategies without DST for previously treated patients are not recommended. Some programmes may have no choice but to care for patients under these circumstances. In this case, it is advised for TB patients whose previous treatment has failed2 3 or other patients with a high likelihood of MDR-TB (close contacts) to be started on an empiric MDR regimen. Patients with low to moderate risk of having MDR-TB (relapse or returning after interruption) may receive a retreatment regimen with first-line drugs: 2 (HRZE)4 /1 (HRZE)/5 (HR)E. If no response is seen, the patient should be switched to an empiric MDR regimen. The MDR regimen should be continued throughout the course of treatment.

Empiric MDR regimens are described in Chapter 10.

Ref Notes

Most national TB programmes use 2 S(HRZE)/1 (HRZE)/5 (HR)E while waiting DST. These guidelines suggest using HRZE until DST returns, as the benefits of streptomycin are minimal and the daily injections discomforting.

[ a b ]

For PTB, failure should be confirmed with either: a positive culture OR a positive smear and the presence of clinical deterioration. This indicates that the patient is a true failure and not a case of being smear-positive with dead bacilli.

[ a b ]

MDR-TB rates of failures should be documented in all programmes to determine if their rates of MDR-TB are high enough to warrant empiric MDR-TB treatment while waiting DST.

[ a b ]

Most national TB programmes use 2 S(HRZE)/1 (HRZE)/5 (HR)E. These guidelines suggest using HRZE as the benefits of streptomycin are minimal and the daily injections discomforting.