treatment of drug-resistant tuberculosis

Last reviewed 01/2018

treatment of multi drug resistant tuberculosis

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In 2013, out of the reported 136,000 MDR-TB patients, just over 71% (97,000) started on  treatment. This is a three-fold increase compared with 2009 (1).

Access to quality-assured drug susceptibility testing (DST) is a critical component of TB treatment. Furthermore it is important that drug resistant TB programmes to have knowledge about:

• the prevalence of drug resistance in new patients, as well as in different groups of retreatment cases
• which and with what frequency second-line anti-TB drugs have been used within a given area served by a programmatic strategy

Treatment strategies for MDR-TB can be

• standardised
• data on historical resistance patterns and drugs which have been used in that region are used as the basis for regimen design
• all patients in a defined group or category receive the same regimen
• suspected MDR-TB should be confirmed by DST whenever possible
• individualized
• each regimen is designed based on the patient's past history of TB treatment and individual DST results (1,2)

Current recommendation requires 18-24 months of treatment for MDR-TB (2).

• empiric standardized regimens often need to be adjusted based on patient clinical history, once additional history or when DST results becomes available
• individual regimens are designed based on DST of the infecting strain, patient's history of TB treatment and contact history.

The following steps can be uses to build a regimen for drug-resistant TB treatment.

• step 1 - choose an injectable agent such as amikacin, kanamycin, or capreomycin
• Streptomycin is generally not used because of high rates of resistance in patients with MDR-TB
• step 2 - choose a higher generation fluoroquinolone
• use a later generation fluoroquinolone. If levofloxacin (or ofloxacin) resistance is documented, use moxifloxacin
• avoid moxifloxacin if possible when using bedaquiline or delamanid
• step3 - choose two or more oral bacteriostatic second-line anti-TB drugs
• e.g. - Cycloserine/terizidone, Para-aminosalicylic acid (PAS), Ethionamide/prothionamide
• Ethionamide/prothionamide is considered the most effective
• DST is not considered reliable for the drugs in this group
• step 4 - Add Group 1 drugs. Pyrazinamide, Ethambutol
• Pyrazinamide is routinely added in most regimens
• step 5 - consider adding a new antituberculosis drug
• e.g. - Bedaquiline, Delamanid, Linezolid, Clofazimine
• consider if four second-line anti-TB drugs are not likely to be effective
• if drugs are needed from this group, it is recommended to add two or more

Treatment of MDR-TB can be divided into:

• intensive phase
• consist of at least four second-line anti-TB drugs that are likely to be effective (including an injectable anti-TB drug), as well as pyrazinamide
• lasts at least eight months in total, but the duration can be modified according to the patient's response to treatment
• continuation phase
• continuation of treatment with other drugs

Reference:

• (1) Millard J, Ugarte-Gil C, Moore DA. Multidrug resistant tuberculosis. BMJ. 2015;350:h882. 
• (2) World Health Organization (WHO) 2014. Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis