1887

Abstract

The shortage of drugs active against meticillin-resistant (MRSA) is a growing clinical problem. studies indicate that the phenothiazine thioridazine (TZ) might enhance the activity of the β-lactam antibiotic dicloxacillin (DCX) to a level where MRSA is killed, but experiments in simple animal models have not been performed. In the present study, we introduced infected by as an model to test the effect of TZ as a helper drug in combination with DCX. Because TZ is an anthelmintic, initial experiments were carried out to define the thresholds of toxicity, determined by larval development, and induction of stress-response markers. No measurable effects were seen at concentrations of less than 64 mg TZ l. Seven different MRSA strains were tested for pathogenicity against , and the most virulent strain (ATCC 33591) was selected for further analyses. In a final experiment, full-grown were exposed to the test strain for 3 days and subsequently treated with 8 mg DCX l and 8 mg TZ l for 2 days. This resulted in a 14-fold reduction in the intestinal MRSA load as compared with untreated controls. Each drug alone resulted in a two- to threefold reduction in MRSA load. In conclusion, can be used as a simple model to test synergy between DCX and TZ against MRSA. The previously demonstrated synergy can be reproduced .

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2014-09-01
2019-11-22
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