Ethionamide microbiology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]
Microbiology
In Vitro Activity
Ethionamide exhibits bacteriostatic activity against extracellular and intracellular Mycobacterium tuberculosis organisms. The development of ethionamide resistant M. tuberculosis isolates can be obtained by repeated subculturing in liquid or on solid media containing increasing concentrations of ethionamide. Multi-drug resistant strains of M. tuberculosis may have acquired resistance to both isoniazid and ethionamide. However, the majority of M. tuberculosis isolates that are resistant to one are usually susceptible to the other. There is no evidence of cross-resistance between ethionamide and para-aminosalicylic acid (PAS), streptomycin, or cycloserine. However, limited data suggest that cross-resistance may exist between ethionamide and thiosemicarbazones (i.e., thiacetazone) as well as isoniazid.
In Vivo Activity
Ethionamide administered orally initially decreased the number of culturable Mycobacterium tuberculosis organisms from the lungs of H37Rv infected mice. Drug resistance developed with continued ethionamide monotherapy, but did not occur when mice received ethionamide in combination with streptomycin or isoniazid.
Susceptibility Testing
Ethionamide susceptibility testing should only be performed by qualified or reference laboratories.
Two standardized in vitro susceptibility methods are available for testing ethionamide against M. tuberculosis organisms. The modified proportion method (CDC or NCCLS M24-P) utilizes Middlebrook and Cohn 7H10 agar medium impregnated with ethionamide at a final concentration of 5.0 μg/mL. After 2 to 3 weeks of incubation, MIC99 values are calculated by comparing the quantity of organisms growing in the medium containing drug to the control cultures. Mycobacterial growth in the presence of drug, of at least 1% of the growth in the control culture, indicates resistance.
The radiometric broth method employs the BACTEC 460 machine to compare the growth index from untreated control cultures to cultures grown in the presence of 5.0 μg/mL of ethionamide. Strict adherence to the manufacturer's instructions for sample processing and data interpretation is required for this assay.
Susceptibility test results obtained by these two different methods cannot be compared unless equivalent drug concentrations are evaluated.
The clinical relevance of in vitro susceptibility test results for mycobacterial species other than M. tuberculosis using either the radiometric or the proportion method has not been determined.[1]
References
- ↑ "TRECATOR (ETHIONAMIDE) TABLET, FILM COATED [WYETH PHARMACEUTICALS COMPANY, A SUBSIDIARY OF PFIZER INC.]". Text " accessdate " ignored (help)
Adapted from the FDA Package Insert.