ABSTRACT
Ethionamide (2-ethyl-4-pyridmecarbothioamide) is a derivative of isonicotinic acid that was first synthesized in France in 1956 and quickly shown to be an effective antituberculosis agent (Brouet et al., 1959; Riddell et al., 1960). It is closely related to isoniazid in both structure and function, but is far more difficult for patients to tolerate, principally because of dose-related gastrointestinal side effects. Subsequently, an n-propyl derivative, prothionamide, was developed in an attempt to improve tolerability (Batten, 1968). Ethionamide and prothionamide frequently retain activity against isoniazid-resistant isolates of Mycobacterium tuberculosis, hence their important role in the management of multidrug-resistant tuberculosis (MDR-TB) (Caminero et al., 2010). In clinical practice, ethionamide and prothionamide (together called thioamides) are generally regarded as equivalent (Crofton, 1969), although there are subtle differences of uncertain significance (Fajardo et al., 2006; Jenner et al., 1984). The ecological cutoff for resistance to prothionamide (ECOFF) may be slightly lower than for ethionamide, which occasionally generates differential susceptibility results (i.e. susceptible to prothionamide, resistant to ethionamide). This is a laboratory issue that depends on the critical concentrations used to define resistance (Schon et al., 2011), but from a clinical perspective there is complete cross-resistance between ethionamide and prothionamide (Steenken and Montalbine, 1960). Figure 132.1 shows ethionamide and prothionamide in comparison to isoniazid. The information that follows describing ethionamide also applies to prothionamide unless otherwise stated. Skeleton diagrams of ethionamide, prothionamide, and isoniazid. https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781315152110/08d8042d-9481-4a8d-8c27-9bd589f6de6b/content/fig132_1.tif" xmlns:xlink="https://www.w3.org/1999/xlink"/>
