Management of Drug-Resistant Tuberculosis - Policy Guidelines

EXECUTIVE SUMMARY
Key Issues in the Management of Drug-Resistant Tuberculosis

1. Multidrug-resistant tuberculosis (MDR-TB) is defined as tuberculosis (TB) disease where there is in vitro resistance to both isoniazid and rifampicin, with or without resistance to other anti-TB drugs. As isoniazid and rifampicin are the two most important first-line TB drugs, their removal through resistance from the anti-TB drug armamentarium has serious implications.

2. Extensively drug-resistant tuberculosis (XDR-TB) is defined as MDR-TB and in vitro resistance to any of the fluoroquinolones and any injectable (i.e., kanamycin, amikacin or capreomycin).
XDR-TB is extremely difficult and expensive to treat and an exceptionally high mortality (exceeding 90%) has been reported in HIV co-infected XDR-TB patients in Tugela Ferry, KwaZulu-Natal.

3. Prevention is the key to effective control of DR-TB. MDR-TB arises as a result of poor management of TB patients and most cases of XDR-TB arise as a result of poor MDR-TB management.

4. DR-TB is a laboratory diagnosis and therefore quality-assured laboratory services are of paramount importance. All laboratories that perform drug susceptibility testing (DST) must have internal quality assurance measures in place and participate in external proficiency testing programmes.

5. Management of MDR-TB will be conducted in dedicated MDR-TB units, in other health care facilities and in the community by trained health care workers in an environment with appropriate infection control measures to prevent nosocomial transmission of DR-TB. All smear negative, TB culture positive patients should be started on MDR-TB community
treatment. TB microscopy positive patients who refuse to be admitted may not be denied MDR-TB treatment. All GeneXpert positive patients with resistance to rifampicin should be started on MDR-TB treatment. MDR-TB diagnosis should be confirmed after initiating on treatment.

6. Uninterrupted supply of appropriate drugs, treatment under direct supervision with proper education and counselling of patients are also required.

7. All provinces must have DR-TB Clinical Review Committees, which are responsible for making recommendations on difficult patients, and make decisions on termination of treatment.

8. All MDR-TB hospitals must have multidisciplinary clinical management teams. These teams will take collective decisions on the comprehensive management of patients in the hospitals and review clinical progress on a regular basis.

9. Infection control officers and committees must ensure that TB risk assessments are conducted on an annual basis, infection control plans developed and monitored on a regular basis to monitor the effectiveness of the interventions implemented.

10. Mono-and poly-drug-resistant TB require individualised treatment based on the resistance profile to first-line anti-TB drugs. These patients need to be managed as outpatients but treatment must be initiated by a doctor in the MDR-TB hospital’s outpatients department and the patient registered in the drug resistant TB register. Mono-drug resistance to INH should
be treated with the following fixed combination drugs: rifampicin + isoniazid + pyrazinamide + ethambutol (RHZE).

11. A standardised approach to MDR-TB treatment is recommended for all newly diagnosed MDR- or XDR-TB patients. The standardised MDR-TB regimen consists of an intensive phase also called ‘injectable phase’ of at least six months with five drugs followed by a continuation phase of 18 months (or less) with four drugs. Treatment should be given at least six days
per week. The drugs used are kanamycin or amikacin, moxifloxacin, ethionamide, terizidone or cycloserine and pyrazinamide during the injectable phase. Moxifloxacin, ethionamide, terizidone or cycloserine and pyrazinamide are given during the continuation phase. In patients who were previously exposed to second-line anti-TB drugs for a month or more; the
standardised regimen will be modified based on the history of drug usage and DST results.

12. The duration of the injectable phase will be determined by adding four months to the TB culture conversion date (date of collection of the first sputum that turned TB culture negative); it has to be six months or more.

13. The duration of treatment will be determined by adding 18 months to the date of TB culture
conversion.

14. XDR-TB requires an individualised approach based on the previous history of drug use in a patient and the results of drug susceptibility testing (DST). However, DST for second-line anti-TB drugs is technically complex and much less reliable than DST for first-line anti-TB drugs. Therefore, treatment of XDR-TB should always be initiated under guidance of the clinical
management team and the review committees. Practitioners need to remember that DST for injectables and fluoroquinolones are the most reliable of all second-line anti-TB drugs.

15. All patients with DR-TB must be offered HIV counselling and testing, and those who are coinfected must be started on cotrimoxazole and antiretroviral treatment (ART) as soon as ARV adherence counselling is completed. All co-infected MDR/XDR-TB/HIV patients qualify to receive antiretroviral therapy (ART) regardless of their CD4 count.

16. On-going adherence, counselling and psychosocial support must be provided to patients and reinforced throughout treatment. Patients must also be educated about TB prevention and cough hygiene

17. Suspected but unconfirmed MDR- and XDR-TB patients must be isolated in a well-ventilated side ward in a TB or district hospital, if space allows. If at home, they must be educated about cough hygiene and infection control at home. Treatment needs to be initiated as soon as diagnosis is confirmed. Use of line probe assay and GeneXpert are recommended for quicker
diagnosis.

18. Close contacts of patients diagnosed with DR-TB must be screened and tested for DR-TB. Those who do not have TB must be routinely screened for DR-TB at six-monthly intervals. Currently, there is, no evidence to support TB preventive therapy.

19. Occupational health services for all staff must be provided in all the hospitals. A register of all health workers who develop TB or DR-TB should be kept at the hospital in order to help determine the risk involved and to inform future policy.

20. DR-TB registers should be kept at the MDR-TB hospitals and all centres that will be initiating MDR- and XDR-TB treatment including district hospitals, health centres and updated regularly.

21. Cohort analyses of DR-TB case finding, interim outcomes and final outcomes should be provided at regular intervals to enable assessment of performance and facilitate appropriate corrective action.

22. In order to increase access to care for MDR-TB patients in South Africa, nurse-initiated treatment is an option that has proven successful in HIV management throughout the world.  Nurse-initiated MDR-TB treatment will be part of decentralised MDR-TB services.