Table 1

Reasons for drug resistance and how to avoid them

Reasons for drug resistanceAction
Adding a single drug to a failing regimenAlways add two or more drugs
Inadequate or intermittent drug supplyPolitical commitment
Maintain stocks
NonadherenceFixed drug combination tablets
Individual support (e.g. DOT)
Quality of drugs for TBMonitoring system
Pharmacodynamics: how a drug affects the patientAdverse effects should be managed promptly (e.g. antiemetics)
Pharmacokinetics: how human metabolism affects the drugCheck drug levels with high individual variation (e.g. rifampicin and moxifloxacin#)

DOT: directly observed therapy. #: although there is a 100-fold difference in plasma values of these drugs, routine measurement is not required for rifampicin except in isoniazid-resistant (pre-MDR-TB) disease and in those with fully sensitive strains who fail to show a significant improvement at 2 months (i.e. before starting the continuation phase of treatment). The usual effective dose of moxifloxacin for TB to achieve serum levels of 1–2 mg⋅L−1 is 600 mg, for which there is no formulation; 800 mg is therefore required and only if there is a problem with this dose would levels need to be measured for a 400 mg dose, to ensure efficacy.