Evaluation of a nonsteroidal topical cream in a guinea pig model of Malassezia furfur infection.

Malassezia furfur is an important causal factor for seborrheic dermatitis, and topical antifungal therapy is an effective treatment approach. This study assessed the antifungal activity of Promiseb Topical Cream (Promius Pharma, LLC, Bridgewater, NJ), a novel nonsteroidal prescription medical device cream, in the M furfur-infected skin model for guinea pigs. Guinea pigs (N = 28) were divided into 4 groups and infected with M furfur for 7 days. On day 8, the first group of animals was sacrificed. The scrapings of inoculation site on each animal were tested for the presence of the organism, and the skin was excised for quantitation of M furfur. The second group was left untreated. The remaining 2 groups were treated with one of the test agents (Promiseb) and the positive control product (ciclopirox olamine cream, 0.77%; Loprox, Medicis, Scottsdale, AZ) each once daily for 3 days. At the end of treatment, animals were sacrificed and analyzed similarly to the first group. M furfur was recovered from all animals in the first group. Visual signs of infection, such as erythema and edema, were not observed in the infected animals at the end of the study. In the animals treated for 3 days with the test agents, the M furfur counts were reduced to below the limit of quantitation. Both test agents were equally effective in substantially reducing the density of M furfur compared with the untreated control.

Inhibitory effect of REP3123 on toxin and spore formation in Clostridium difficile, and in vivo efficacy in a hamster gastrointestinal infection model.

OBJECTIVES: REP3123 is a fully synthetic methionyl-tRNA synthetase inhibitor in pre-clinical development as a novel agent to treat Clostridium difficile infection (CDI). This novel agent was investigated for its ability to block the production of toxins and spores, and was tested for efficacy in vivo in a hamster model. METHODS: Clostridial toxin levels were determined qualitatively using monoclonal antibodies and by cytotoxicity assays. Spores were detected by staining and by quantitative dilution plating after ethanol treatment. Efficacy of REP3123 was tested in a clindamycin-induced C. difficile hamster gastrointestinal (GI) infection model. RESULTS: REP3123 at concentrations as low as 1 mg/L inhibited de novo toxin production in high cell density, stationary phase cultures of C. difficile. Among comparator agents currently used for CDI therapy, vancomycin required much higher levels of 20 mg/L, and metronidazole had no effect on toxin levels. REP3123 caused a >10-fold reduction of the sporulation rate in vitro. Vancomycin and, in particular, metronidazole appeared to promote the formation of spores. REP3123, at concentrations as low as 0.5 mg/kg, demonstrated efficacy in the hamster model of CDI and was superior to vancomycin in the overall survival of the animals at the end of the study (33 days). CONCLUSIONS: REP3123 inhibited growth of C. difficile, affected the production of toxins and spores and demonstrated superior efficacy compared with vancomycin in the hamster GI infection model. This agent may be a promising candidate for CDI treatment; in particular, the inhibition of toxin production and spore formation may reduce the severity and spread of the disease, respectively.