Drug resistant tuberculosis (DR-TB)

Drug resistant tuberculosis (DR-TB) must be presumed (suspected) in persons who remain bacteriologically positive (either smear positive, culture positive or Gene Xpert positive) after intensive phase of standard first-line TB treatment with or without clinical improvement. Persons who test rifampicin resistance positive at initial diagnosis with Gene Xpert must also be treated as cases of DR-TB. These persons must be further evaluated using TB culture and Drug Susceptibility Testing (DST) or newer molecular diagnostic tests such as Line Probe Assays (LPA).

Persons at high risk of drug resistance are TB patients failing Category I+III or Category II treatment, contacts of confirmed DR-TB patients and TB/HIV co-infected patients not improving on treatment.

Persons at medium risk of drug resistance are relapsed TB patients, return after lost-to-follow up and health care workers newly diagnosed with TB. Patients are classified according to the pattern of documented drug resistance profile.

The drug regimen for treatment is selected based on the following principles:

History of drugs used to treat TB patients, profile of drug resistance in Ghana and/or DST profile of the patient
A minimum of four new core medicines that are known to be effective
Kanamycin/Capreomycin an injectable medicine, is the backbone of the four core medicines and should be used in the intensive phase
An effective fluoroquinolone should be used due to the extensive use of earlier generation fluoroquinolones
May include a first line drug to which the strain is susceptible.
Cross-resistance may occur between drugs of the same group and this is taken into consideration.
Drugs are administered daily under strict DOT throughout the injectable and continuation phases.

Treatment of Multi Drug Resistant-TB (MDR-TB) and Rifampicin Resistant-TB (RR-TB) patients is prioritised. Treatment duration is 20-24 months and is determined by sputum smear and culture (bacteriological) conversion (Treatment lasts 16-18 months after bacteriological conversion). Progression from initial to continuation phase is dependent on at least four (4) consecutive months of negative sputum cultures.

Community-based care is promoted in Ghana over facility-based care except in situations requiring admission for management of complications. The practice of infection prevention and control should be maintained at all times during treatment of these patients.

Treatment adherence is critical in the treatment of DR-TB due to limited number of available, effective medicines. Treatment is challenging due to long duration, drug toxicities and side effects. Clinical teams must use a patient-centred care approach and support patients throughout treatment until cured. Psychosocial and economic support is required from treatment supporters, patient families and clinical teams throughout treatment. Early detection and prompt management of drug side effects ensures successful outcomes.

Treatment Pharmacological treatment

Multi Drug Resistant-TB (MDR-TB)

TB Treatment Category	TB Patient Type	Treatment Regimen		Comments
Adults and Children		Initial Phase	Continuation Phase
Multi Drug Resistant Tuberculosis (MDR-TB)	All Newly Diagnosed MDR-TB with or without HIV & Symptomatic contacts of Confirmed MDR-TB with or without HIV	8 months of Z-Cm-Lfx-Pto-Cs#(PAS*)	12 months Z-Lfx-Pto-Cs# (PAS*)	Treatment is daily (Treatment month is 28 days). Modify treatment according to culture results.

# For every 250mg of Cycloserine give 50mg of Pyridoxine (Vitamin B6) to prevent Peripheral Neuropathy. Dose of Pyridoxine should be doubled in HIV patients.
* PAS is an alternative to Cs

Treatment Protocol for Other Resistant Types
Treatment Protocol for Other Resistant Types

Resistance Pattern	TB Patient Type	Treatment Regimen		Comments
Adults and Children		Initial Phase	Continuation Phase
Streptomycin resistant (S)	Mono-Resistant	2 months of HRZE	4 months of HR
Ethambutol resistant (E)	Mono-Resistant	3 months of HRZ	6 months of HR
Isoniazid resistant (H)	Mono-Resistant	9 months of HRZE		Add extra dose of Isoniazid up to a maximum of 300mg daily for treatment duration
Streptomycin and Isoniazid resistant (S-H)	Poly-Resistant TB	9 months of HRZE		Add extra dose of Isoniazid up to a maximum of 300mg daily for treatment duration
Isoniazid and Ethambutol resistant (H-E)	Poly-Resistant TB	9 months of R-Z-Lfx		Extend treatment to 12 months if extensive lung destruction from x-ray image
H, E, and S (±Z)	Poly-Resistant TB	3 months of Km-Pto-Lfx-R-Z	15 months of Pto-Lfx-R-Z	Modified MDR regimen plus R
R mono- or poly-resistance	Rifampicin-Resistant TB	8 months of H-Z-Cm-Lfx-Pto-Cs (PAS*)	12 months of H-Z-Lfx-Pto-Cs (PAS*)	Full MDR regimen plus H

* PAS is alternative to Cs

Definitions:
Mono-resistant TB: TB bacilli have resistance to only one from the first line anti-tuberculosis medicines: streptomycin, isoniazid, rifampicin, pyrazinamide or ethambutol.
Poly-Resistant: TB bacilli have resistance to at least two medicines but not to both isoniazid and rifampicin.
Rifampicin-Resistant (RR-TB): TB bacilli have resistance to rifampicin, with or without resistance to other first line anti-tuberculosis medicines. This may be mono, poly, multi or extensively drug resistant TB.
Multi-Drug Resistant (MDR-TB): TB bacilli have resistance to at least both rifampicin and isoniazid.
Extensively Drug Resistant (XDR-TB): TB bacilli have resistance to one of the fluoroquinolones and at least one of the three injectable second-line drugs (kanamycin, capreomycin or amikacin), in addition to MDR TB.

Dosing of Second-Line Medicines

Anti-TB Drug (Abbreviation)	Recommended Daily Dosage (Maximum Dose)
Anti-TB Drug (Abbreviation)	Adult Dosing	Children Dosing
Pyrazinamide (Z)	20-30 mg/kg once daily (2000 mg)	30-40 mg/kg once daily (2000 mg)
Kanamycin (Km)	15-20 mg/kg once daily (1000 mg)	15-30 mg/kg once daily (1000 mg)
Capreomycin (Cm)	15-20 mg/kg once daily (1000 mg)	15-30 mg/kg once daily (1000 mg)
Levofloxacin (Lfx)	750-1000 mg once daily (1000 mg)	15-20 mg/kg/day in 2 divided doses (1000 mg)
Ethionamide (Eto)	500-750 mg daily in 2 divided doses (1000 mg)	15-20 mg/kg/day in 2 divided doses (1000 mg)
Prothionamide (Pto)	500-750 mg daily in 2 divided doses (1000 mg)	15-20 mg/kg/day in 2 divided doses (1000 mg)
Cycloserine (Cs)	500-750 mg daily in 2 divided doses (1000 mg)	10-20 mg/kg/day in 2 divided doses (1000 mg)
Para-aminosalicylic acid (PAS)	8g once daily or in 2 divided doses (12g)	200-300 mg/kg/day in 2-3 divided doses (8g)

Ghana will be adopting a shorter treatment regime (9-12 months) for management of DR-TB. Please keep checking with the National TB Control programme.

Referral Criteria Refer all patients to a DOTS treatment centre for management and monitoring under Ghana National Tuberculosis Programme.