The rapid diagnosis of isoniazid and rifampicin resistance in Mycobacterium tuberculosis--a molecular story.

Isoniazid and rifampicin resistance are assayed phenotypically by the resistance ratio, absolute concentration or proportion methods. Assay methods are often difficult to standardise and the World Health Organization (WHO) Global Programme on Drug Resistance is attempting to produce standardised drug resistance data worldwide. Broth-based methods are faster than solid media systems, and a commercial radiometric system, the Bactec 460, is arguably the fastest method and permits testing to be completed within 7-14 days; however, this method is expensive and requires disposal of radioactive material. Novel phenotypic methods that utilise mycobacteriophages have shown promise. Other molecular detection systems require knowledge of the genes encoding the drug target (the inhA/mabA, katG, oxyR and ahpC genes for isoniazid; rpoB for rifampicin) and the mutations producing resistance. These genotypic methods are limited in that not all resistance mechanisms are known, but advanced assays for rifampicin resistance that use gene sequencing, heteroduplex analysis, solid-phase hybridisation or single-strand conformation polymorphism analysis are becoming available.