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Ethionamide and Prothionamide
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
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.
Management of complex tuberculosis cases: a focus on drug-resistant tuberculous meningitis
Published in Expert Review of Anti-infective Therapy, 2018
Ravindra Kumar Garg, Imran Rizvi, Hardeep Singh Malhotra, Ravi Uniyal, Neeraj Kumar
Updated guidelines of WHO recommend at least five effective antituberculosis drugs for multidrug-resistant tuberculosis regimen during the intensive phase. They include pyrazinamide and four core second-line drugs (one from Group A, one from Group B, and at least two from Group C). Intensive phase lasts for 8 months, while the continuation phase lasts for a minimum of 12 months for the oral agents, making the total duration of treatment 20 months. An ideal multidrug-resistant tuberculosis regimen, therefore, consists of pyrazinamide, a fluoroquinolone, an injectable antituberculosis drug, ethionamide (or prothionamide), and cycloserine, or para-aminosalicylic acid if cycloserine cannot be used. A shorter regimen with seven drugs and a treatment duration of 9–12 months has recently been recommended by WHO but is not recommended for extra-pulmonary disease [1]. Current WHO recommendations mandate that an appropriate regimen for multidrug-resistant meningitis should consist of a fluoroquinolone (levofloxacin or moxifloxacin), ethionamide and/or cycloserine, pyrazinamide, an injectable drug (kanamycin or amikacin) as a supportive drug, and linezolid, despite the limited evidence for the latter drug. Most of these drugs have an excellent CSF penetration profile. (Table 4) An algorithm for the diagnosis and management of drug-resistant tuberculous meningitis are shown in Figure 2.
Clinical pharmacokinetics of drugs in cardiopulmonary associated cachexia without hepatorenal pathology: a systematic review
Published in Drug Metabolism Reviews, 2019
Buileta et al. conducted studies on two antibiotics in the cephalosporin class, which were cefipirome, a poorly lipophilic drug, and ceftazidime, a hydrophilic antibiotic (Nix et al. 1992; Pea et al. 2005). They concluded that there were reductions of 36% and 6% in the volume of distribution for both ceftazidime and cefipirome, respectively, in cachetic patients with cystic fibrosis (Bulitta et al. 2010; Bulitta et al. 2011). This leads to a high concentration of the drug in the plasma (Figure 2). Similarly, there was a reduced volume of distribution for prothionamide in wasted tuberculosis patients compared with non-wasted tuberculosis patients but the difference was not statistically significant.