Resistance to pyrazinamide and ethambutol compromises MDR/XDR-TB treatment

Abstract

The rising number of multi-drug resistant tuberculosis (MDR-TB) cases worldwide prompted the World Health Organisation (WHO) to release an emergency update on the guidelines for the management of drug-resistant TB. These guidelines recommended that treatment of MDR-TB should include at least 4 effective drugs and that standardised treatment regimens should be based on resistance patterns for each country/region. Most importantly, treatment regimens should not be dependant on results of drug susceptibility testing (DST) for ethambutol (EMB) or pyrazinamide (PZA). In response, the South African Department of Health has prepared a draft drug-resistant TB treatment policy in which PZA remains one of the 4 effective drugs, while EMB should be replaced with terizidone or cycloserine, if resistant to EMB (disregarding inaccurate DST). Analyses of recent drug-resistance patterns in South Africa indicate a high frequency of undetected EMB and PZA resistance and their association with MDR-TB. Accordingly, we recommend that the WHO guidelines be followed more closely in which 4 other effective drugs are used to treat MDR-TB. EMB and PZA can be included provided they are not counted as one of the four effective drugs. However these guidelines do not address the root cause of the amplification of resistance in undiagnosed MDR-TB patients in South Africa. This can only be achieved by the implementation of rapid DST methods in all TB cases prior to initiation of therapy. Ultimately this would curb the amplification of resistance and the evolution of XDR -TB.