Multi-Drug resistant tuberculosis

Grouping of second-line drugs

Second line drugs are grouped as shown in Table below

Pretomanid is a new drug that has not yet been assigned to a group

Shorter regimen for MDR/RR-TB and Pre-XDR-TB 

The Preferred oral shorter regimen has a duration of 6 months, consisting of Bedaquiline (Bdq), Pretomanid (Pa), Linezolid (Lzd) and Moxifloxacin (Mfx) (BPaLM) for patients with MDR/RR TB and BPaL for patients with Pre-XDR

Eligibility criteria for Pretomanid

Patient eligibility
Patients with moxifloxacin resistance should be prescribed BPaL instead of BPaLM

The alternative shorter regimen is a 9-month regimen preferred in adults, children and pregnant women

Intensive and continuation phases for shorter regimen 

 NB: Initial phase: 4-6 Bdq [6]-Lfx [Mfx]-Lzd [2]-E-Z-Hh-Cfz then Continuation phase 5 Lfx [Mfx]-Cfz-Z-E

Refer to dosing chart under DR TB treatment in special populations

All oral longer treatment regimen
Patients who do not qualify for all oral shorter regimen receive 18-20 months all oral longer regimen based on WHO drug grouping as follows:

• Initial phase: 6Bdq-Lzd-Cfz-Lfx (Mfx) then
• Continuation phase: 12Lzd-Cfz-Lfz (Mfx)

Intensive and continuation phases for longer regimen

DR-TB treatment in special populations

All these patient categories MUST be discussed at provincial and/or national DR-TB CEC meetings

DR TB treatment in special populations

Pretomanid is abbreviated Pa, Hh indicates high-dose isoniazid

Note:

• All treatments for these patients should be guided by DR CEC (district, provincial or national)
• An individualized regimen can be designed for a patient when pDST results are available. The regimen should compose of at least 5 effective drugs This must be done in conjunction with the national CEC
• There is more than one possible combination for the longer regimen
• All patients on DRTB treatment must be followed up monthly with sputum culture/DST
• All patients on DRTB drugs must be monitored closely for adverse drug reactions and Grade 3-4 adverse reaction reported to the CEC and ZAMRA
• Ambulatory model of care is preferred over the inpatient model of care unless there are compelling indications for patient admission

Tuberculosis and Immunocompromised Patients
Immunocompromised patients may develop tuberculosis owing to reactivation of previously latent disease or due to new infection. All TB diagnosed patients should be counselled and tested for HIV. The infection may be caused by other mycobacteria e.g. M. avium complex in which case specialist advice is needed.

Management of TB/HIV co-infected patients

• TB treatment should be initiated first, followed by ART as soon as the patient can tolerate ART, preferably within the first 2 weeks of TB treatment, except for TB meningitis (start after 8 weeks).
• All TB patients with HIV should start ART regardless of CD4 count.
• Modifications to the ARV regimen should be made to avoid overlapping toxicities and drug-drug interactions between ART and TB medications (ART guidelines).
• Co-infected patients have an increased risk of drug toxicity and TB Immune Reconstitution Inflammatory Syndrome (IRIS).
• Prednisolone 40 mg twice daily for 2 weeks then 20 mg once daily for 2 weeks for TB IRIS Prevention.

Extensively Drug-Resistant Tuberculosis (XDR-TB)

Recognized earlier in 2006 in South Africa, extensively drug-resistant TB (XDR-TB) is MDR-TB that is also resistant to three or more of the six classes of second-line drugs.

Monitoring

Required monitoring and frequency:

Since Isoniazid and Rifampicin are associated with liver toxicity, the hepatic function should be checked before
and during treatment with these drugs. Patients on dual treatment of HIV and TB are likely to have liver/renal toxicity and should therefore be monitored closely.