Determination of ethambutol MICs for Mycobacterium tuberculosis and Mycobacterium avium isolates by resazurin microtitre assay.

Department of Microbiology and Molecular Biology, National JALMA Institute for Leprosy and Other Mycobacterial Diseases (Indian Council of Medical Research), PO Box 1101, Dr M. Miyazaki Marg, Tajganj, Agra 282001, India.
Journal of Antimicrobial Chemotherapy (Impact Factor: 5.44). 08/2007; 60(1):152-5. DOI: 10.1093/jac/dkm117
Source: PubMed

ABSTRACT To test susceptibilities of Mycobacterium tuberculosis (MTB) isolates to ethambutol by the Löwenstein-Jensen (LJ) proportion method and resazurin microtitre assay (REMA) and to evaluate REMA for the determination of ethambutol MICs for MTB and Mycobacterium avium isolates.
A total of 50 MTB and 20 M. avium isolates were tested to determine the MICs of ethambutol by REMA and agar dilution method. MTB isolates were also tested by the LJ proportion method.
REMA provided ethambutol susceptibility results for all the isolates within 8-9 days. For MTB isolates, REMA showed 96.7% sensitivity, 100.0% specificity and 98.0% accuracy when LJ proportion results were taken as 'gold standard'. For both MTB and M. avium isolates, the MICs determined by REMA were lower than those determined in agar medium, indicating that MIC values determined by REMA are closer to the actual MICs for the isolates.
REMA can be used as a rapid and inexpensive method for mycobacterial drug susceptibility testing against ethambutol. In comparison with the agar method, the MICs determined by REMA can more accurately be correlated with achievable plasma concentrations of antimycobacterial agents.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The emergence of drug resistant-tuberculosis and other pathogenic diseases over the past decades, constitutes a serious threat to human health worldwide. According to a 2012 report by the World Health Organization (WHO), South Africa, China, India and Russia are the countries with the highest prevalence of Multi-Drug Resistant tuberculosis (MDR-tuberculosis) as they represented 60% of the total. Several reports have documented antimycobacterial properties of Terminalia species but only a few species from this genus have been explored for their antimycobacterial constituents. The crude extracts of Terminalia phanerophlebia showed good antimicrobial activities in our previous study against two Mycobacterium as swell as two other bacterial strains responsible for opportunistic infections related to respiratory ailments. This paper studies the isolation of compounds responsible for such activities.
    Journal of Ethnopharmacology 09/2014; 156. DOI:10.1016/j.jep.2014.09.003 · 2.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Based on the anti-mycobacterial activity of various acid hydrazides, a series of substituted 3-hydrazinyl-3-oxo-propanamides has been designed. The target compounds have been synthesized from diethylmalonate using substituted amines and hydrazine hydrate in ethanol. Computational studies and anti-tubercular activity screenings were undertaken to test their inhibitory effect on protein kinase PknB from Mycobacterium tuberculosis. Binding poses of the compounds were energetically favorable and showed good interactions with active site residues. Designed molecules obey the Lipinski's rule of 5 and gave moderate to good drug likeness score. Among the sixteen compounds (1-16) taken for in silico and in vitro studies, 3 compounds (11, 12 and 15) have shown good binding energies along with exhibiting good anti-tubercular activity and thus may be considered as a good inhibitors of PknB.
    Bioorganic & Medicinal Chemistry Letters 11/2014; 24(22). DOI:10.1016/j.bmcl.2014.09.080 · 2.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cyclohex-3-enyl(5-phenyl-4H-1,2,4-triazol-3-yl)methanol (MSDRT 12) is a novel triazole-based antitubercular compound with two chiral centers. To evaluate the enantiospecific antitubercular activity, the four stereoisomers were isolated using preparative chiral chromatography and the individual stereoisomers were evaluated using the resazurin microtiter assay method (REMA) and a microbroth dilution technique against the Mycobacterium tuberculosis H37Rv strain. Isomer III of MSDRT 12 was found to be the most potent with a minimum inhibitory concentration (MIC) of 0.78 μg/mL, Isomer II had a MIC of 12.5 μg/mL, and isomers I and IV showed no activity. The diastereomeric mixture of MSDRT 12 showed a MIC of 3.125 μg/mL and isoniazid, used as the standard drug, showed a MIC of 0.4 μg/mL. This confirms the necessity of screening individual enantiomers for their pharmacological activity early in the discovery phase to identify the most potent isomer for further development efforts.
    Scientia Pharmaceutica 03/2014; 82(1):87-97. DOI:10.3797/scipharm.1308-15

Full-text (3 Sources)

Available from
May 21, 2014