Drug repurposing is a viable approach to expediting the tedious conventional drug discovery process, given rapidly increasing bacterial resistance. In this context, we have repurposed pyrvinium pamoate (PP) for its antibacterial activity against . US FDA-approved non-antibiotics were screened against clinically relevant bacterial pathogens to identify antibacterials. The hits were further evaluated utilizing a variety of preclinical parameters, following which efficacy was estimated in isolation and in combination in a murine neutropenic thigh infection model. The screening identified PP exhibiting potent activity against along with concentration-dependent killing. PP also showed a post-antibiotic effect of >22 h and significantly eradicated preformed biofilms and intracellular at 1× and 5× MIC, respectively. PP synergized with levofloxacin both and , resulting in ∼1.5 and ∼0.5 log CFU/g reduction against susceptible and resistant infections, respectively, as compared with untreated control. Pyrvinium potentiates levofloxacin against levofloxacin-resistant
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| http://dx.doi.org/10.2217/fmb-2022-0159 | DOI Listing |
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