Screening of Several Anti-Infectives for in Vitro Activity against Mycobacterium smegmatis
- 1 Mercer University School of Pharmacy, Atlanta, GA, USA
- 2 University of Ghana School of Pharmacy, Legon, Ghana
- 3 University of Ghana School of Pharmacy, Legon, Ghana
- 4 University of Ghana School of Pharmacy, Legon, Ghana
- 5 University of Ghana School of Pharmacy, Legon, Ghana
- 6 University of Ghana School of Pharmacy, Legon, Ghana
- 7 University of Ghana School of Pharmacy, Legon, Ghana
- 8 University of Ghana School of Pharmacy, Legon, Ghana
- 9 University of Ghana School of Pharmacy, Legon, Ghana
Abstract
Aim: To evaluate in vitro the effectiveness of several anti-infective agents alone or in combination against Mycobacterium smegmatis. Method: A convenient stratified sampling method was used to obtain selected anti-infective agents. For individual drug samples, Minimum Inhibitory Concentrations (MIC) were obtained using the agar-well plate diffusion technique. Fractional Inhibitory Concentration Indices (FICI) were calculated for drug combinations using their MIC as obtained from the broth dilution method. Results: Of the thirty (30) anti-infective agents analyzed, ten (10) had MIC equivalent to or better than rifampicin (reference TB drug). Seven (7) drugs had MIC higher than rifampicin, while twelve (12) showed no growth inhibition of M. smegmatis. Analysis of the effect of drug combinations on M. smegmatis indicated that four (4) combinations, including rifampicin/ethambutol showed synergism. One (1) was additive, two (2) were indifferent and one (1) combination showed antagonism. Conclusion: Notable in the results obtained was the high effectiveness of the carbapenems in inhibiting the growth of M. smegmatis. Carbapenems, though not indicated for TB treatment, has a potential of playing a significant role in the treatment of tuberculosis. Also the drug combinations which showed synergism, especially those that involved the macrolide antibiotics, should further be investigated. These results have to be confirmed by in vivo clinical studies to define their roles in tuberculosis treatment.
- North, R.J. and Jung, Y.-J. (2004) Immunity to Tuberculosis. Annual Review of Immunology, 22, 599-623.http://dx.doi.org/10.1146/annurev.immunol.22.012703.104635 http://www.ncbi.nlm.nih.gov/pubmed/15032590
- Ducati, R.G., et al. (2006) The Resumption of Consumption—A Review on Tuberculosis. Memórias do Instituto Oswaldo Cruz, 101, 697-714. http://dx.doi.org/10.1590/S0074-02762006000700001 http://www.ncbi.nlm.nih.gov/pubmed/17160276
- Russell, D.G., et al. (2009) Foamy Macrophages and the Progression of the Human Tuberculosis Granuloma. Nature Immunology, 10, 943-948. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2759071&tool=pmcentrez&rendertype=abstract
- Zignol, M., et al. (2006) Global Incidence of Multidrug-Resistant Tuberculosis. The Journal of Infectious Diseases, 194, 479-485. http://dx.doi.org/10.1086/505877 http://www.ncbi.nlm.nih.gov/pubmed/16845631
- Sareen, D., et al. (2003) Mycothiol Is Essential for Growth of Mycobacterium tuberculosis Erdman. Journal of Bacteriology, 185, 6736-6740. http://dx.doi.org/10.1128/JB.185.22.6736-6740.2003 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=262099&tool=pmcentrez&rendertype=ab stract
- Parish, T. and Stoker, N.G. (2001) Mycobacterium tuberculosis Protocols. Humana Press, Clifton. http://link.springer.com/10.1385/1592591477
- Shiloh, M.U. and Champion, P.A.D. (2010) To Catch a Killer. What Can Mycobacterial Models Teach Us about Mycobacterium tuberculosis Pathogenesis? Current Opinion in Microbiology, 13, 86-92. http://dx.doi.org/10.1016/j.mib.2009.11.006 http://www.sciencedirect.com/science/article/pii/S1369527409001775
- Barry, C.E., et al. (2009) The Spectrum of Latent Tuberculosis: Rethinking the Biology and Intervention Strategies. Nature Reviews Microbiology, 7, 845-855. http://dx.doi.org/10.1038/nrmicro2236
- Altaf, M., et al. (2010) Evaluation of the Mycobacterium smegmatis and BCG Models for the Discovery of Mycobacterium tuberculosis Inhibitors. Tuberculosis (Edinburgh, Scotland), 90, 333-337. http://dx.doi.org/10.1016/j.tube.2010.09.002 http://www.sciencedirect.com/science/article/pii/S1472979210001034
- EUCAST of ESCMID (2000) EUCAST Definitive Document Terminology Relating to Methods for the Determination of Susceptibility of Bacteria to Antimicrobial Agents. Clinical Microbiology and Infection, 6, 503-508.
- Orhan, G., et al. (2005) Synergy Tests by E Test and Checkerboard Methods of Antimicrobial Combinations against Brucella melitensis. Journal of Clinical Microbiology, 43, 140-143. http://dx.doi.org/10.1128/JCM.43.1.140-143.2005 http://jcm.asm.org/content/43/1/140.full#ref-3