O7-4 Screening of FDA approved Drugs to treat Brucellosis

Abstract

Treatment of Brucellosis in humans for six to eight weeks with a combination of doxycycline plus an aminoglycoside and/or rifampicin has been shown to be effective in the majority of cases. But they’re a small percentage (2 to 5%) of such treated cases has been shown to relapse; relapse rates were higher with two week regimen irrespective of combination of therapeutics. Therefore, there is a need for novel therapeutics that can effectively treat brucellosis with no cases of relapse. There is no cost-effective treatment of Brucellosis in food-producing animals. Drug repurposing is an efficient way of generating novel clinical opportunities for already existing drugs with the advantage of an economical accelerated drug development timeline with reduced costs. In the current study, we screened the MedChemExpress library consisting of FDA- approved drugs and additional clinical molecules against Brucella abortus. Out of the 2,591 drugs, 87 drugs were identified that did inhibit B. abortus at a concentration of 8 μM or less. The minimum inhibitory concentration (MIC) of the eleven drugs identified in the initial screening were tested against B. abortus using commercially certified concentrations of drug set. We found that Auranofin, Cinacalcet and Setraplatin are the most potent non-antibiotic drugs, identified in the MIC assay. They were further evaluated against two clinically important species i.e., B. suis and B. melitensis. The MIC values were similar and in the range of 0.06-4 μg/ml. Synergistic activity with approved antibiotics doxycycline and gentamicin against Brucella.