Elisa Rampacci
University of Perugia, Italy
Title: In vitro cytotoxicity and efficacy against Rhodococcus equi of azithromycin plus rifampicin microparticle combinations
Biography
Biography: Elisa Rampacci
Abstract
Statement of the Problem: Rhodococcus equi is the main infectious agent of pneumonia in foals. This bacterium has recently gained attention as a zoonotic pathogen in immuno depressed people. Two-thirds of cases of R. equi infection in humans involved HIV-infected patients. However, 10%–15% of infections occur in immunocompetent hosts. In human medicine, rhodococcosis may be underdiagnosed because of frequent misidentiï¬cation for Mycobacterium tuberculosis. Combination treatment with two or more drugs is recommended both in equine and human infection in order to contrast the antibiotic resistance, especially including antibiotics with intracellular activity. The purpose of this study is to investigate the potential synergistic effect against R. equi of different azithromycin/rifampicin combinations formulated as dry powders and to assess their possible cytotoxicity.
Methodology & Theoretical Orientation: A broth microdilution test was performed to determine the minimum inhibitory concentration against R. equi of spray-dried azithromycin and rifampicin prepared independently and binary combinations of azithromycin and rifampicin developed as dry powders according to the ratios 1:1, 2:1 and 1:2 using mini spray-drying technology. The fractional inhibitory concentration indexes (FICIs) were calculated to describe drug interactions. Additionally, the minimum bactericidal concentration (MBC) was established. The cytotoxicity on BEAS-2B cells of azithromycin and rifampicin individually and in combination was assessed performing the MTT colorimetric assay.
Findings: FICIs calculation has confirmed the favorable additive effect of each antimicrobial combo. Moreover, MBC determination demonstrated the more powerful killing activity of combinations than single compounds. The MTT assay provided encouraging data about the combination application. Indeed, reduction of cellular viability below 50% was not observed neither at the highest concentration tested (100 µg/mL).
Conclusion & Significance: The additive interaction between azithromycin and rifampicin and the more powerful bactericidal activity of spray-dried combinations compared to single compounds may result in an improved therapeutic dosage and prevention of drug-resistant bacterial strains.
