Evaluation of Amlodipine and Imipramine Efficacy to Treat Infection by Biofilm-Producing and Antimicrobial-Resistant

Antimicrobial-resistant is a growing threat to human health for which alternative therapeutic options are needed. In this study, we aimed to evaluate the efficacy of amlodipine (AML) and imipramine (IMI) to treat infection in the larval model by targeting efflux and biofilms, which are relevant contributors to antimicrobial resistance and virulence in . In-house reared were used in virulence assays to determine the infective dose of two strains differing in the expression of (gene encoding the native NorA efflux pump). Toxicology assays were conducted to determine the drugs' LD for . Drug efficacy assays were performed to evaluate the potential of amlodipine, imipramine and the control drugs ciprofloxacin (CIP) and enalapril (ENA) to clear infection in . Survival analysis defined the infective dose as 1 × 10 CFU/larva for both strains. High LD values were determined (CIP: >1000 mg/kg; AML: >640 mg/kg; IMI: 1141 mg/kg; ENA: >1280 mg/kg), revealing a high tolerance of to these drugs. AML at 15 mg/kg and IMI at 100 mg/kg increased the larvae survival by 20% ( = 0.04) and 11% ( = 0.11), respectively, also positively affecting health score indexes. In agreement with the literature, ciprofloxacin at >100 mg/kg promoted larvae survival by >73%. Amlodipine and imipramine show mild potential as new therapeutic options for managing infections but are promising as new lead molecules. This study also reinforces as a sustainable, reliable model for drug evaluation.