Evaluation of a Library of FDA-Approved Drugs for Their Ability To Potentiate Antibiotics against Multidrug-Resistant Gram-Negative Pathogens

Antimicrob Agents Chemother. 2019 Jul 25;63(8):e00769-19. doi: 10.1128/AAC.00769-19. Print 2019 Aug.

Abstract

The Prestwick library was screened for antibacterial activity or "antibiotic resistance breaker" (ARB) potential against four species of Gram-negative pathogens. Discounting known antibacterials, the screen identified very few ARB hits, which were strain/drug specific. These ARB hits included antimetabolites (zidovudine, floxuridine, didanosine, and gemcitabine), anthracyclines (daunorubicin, mitoxantrone, and epirubicin), and psychoactive drugs (gabapentin, fluspirilene, and oxethazaine). These findings suggest that there are few approved drugs that could be directly repositioned as adjunct antibacterials, and these will need robust testing to validate efficacy.

Keywords: antibiotic resistance breakers; antimicrobial combinations; repurposing.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Didanosine / pharmacology
  • Drug Resistance, Multiple, Bacterial
  • Ethanolamines / pharmacology
  • Floxuridine / pharmacology
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / genetics
  • Microbial Sensitivity Tests
  • Mitoxantrone / pharmacology
  • Zidovudine / pharmacology

Substances

  • Anti-Bacterial Agents
  • Ethanolamines
  • Floxuridine
  • Zidovudine
  • Mitoxantrone
  • oxethazaine
  • Didanosine