4.4 Article

In vitro activity of non-antibiotic drugs against Staphylococcus aureus clinical strains

Journal

JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE
Volume 27, Issue -, Pages 167-171

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.jgar.2021.09.003

Keywords

Drug repurposing; Antibiotics; Drug development; Staphylococcus aureus

Funding

  1. NIH Clinical and Translational Science Award [National Center for Advancing Translational Sci-ences] [UL1 TR002645]

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The study found that four non-antibiotic drugs demonstrated varying degrees of in vitro activity against clinical isolates of Staphylococcus aureus, with ebselen showing the most potent effect.
Objectives: We hypothesised that one or more of the non-antibiotic candidates selected for this study would demonstrate antibiotic activity against Staphylococcus aureus. Methods: We determined minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) for non-antibiotic drugs (amlodipine, azelastine, ebselen and sertraline) against five clinical S. aureus isolates and one quality control strain using the Microplate Alamar Blue Assay (MABA). Our research group selected clinical isolates obtained from nasal and wound swab cultures of patients with skin and soft-tissue infections who were seen at primary care clinics in the South Texas Ambulatory Research Network (STARNet). Results: Three of the non-antibiotic drugs had identical MICs for all isolates: amlodipine, 64 mu g/mL; azelastine, 200 mu g/mL; and sertraline, 20 mu g/mL. MICs for ebselen were 0.25 mu g/mL (SA-29213, A1019 and J1019), 0.5 mu g/mL (A32 and B60) and 1 mu g/mL (B72). MBCs for amlodipine, azelastine and sertraline were within one dilution of their MICs, indicating bactericidal activity for all test isolates. Ebselen MBCs were one to two dilutions higher in most isolates, also indicating bactericidal activity for all test isolates. Conclusion: In summary, all four non-antibiotics demonstrated in vitro activity to varying degrees against S. aureus clinical isolates. Ebselen was the most potent of the four non-antibiotics tested. (C) 2021 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.

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