Sidharth Chopra, Maria Torres-Ortiz, Leslie Hokama, Peter Madrid, Mary Tanga, Kristien Mortelmans, Krishna Kodukula, Amit K. Galande, Repurposing FDA-approved drugs to combat drug-resistant Acinetobacter baumannii, Journal of Antimicrobial Chemotherapy, Volume 65, Issue 12, December 2010, Pages 2598–2601, https://doi.org/10.1093/jac/dkq353
Abstract
Objective
The rising occurrence of drug-resistant pathogens accentuates the need to identify novel antibiotics. We wanted to identify new scaffolds for drug discovery by repurposing FDA-approved drugs against Acinetobacter baumannii, an emerging Gram-negative nosocomial drug-resistant pathogen.
Materials and methods
In this study, we screened 1040 FDA-approved drugs against drug-susceptible A. baumannii ATCC 17978 and drug-resistant A. baumannii BAA-1605.
Results and discussion
Twenty compounds exhibited significant antimicrobial activity (MIC ≤8 mg/L) against ATCC 17978 while only five compounds showed such activity against BAA-1605. Among the most notable results, tyrothricin, a bactericidal antibiotic typically active only against Gram-positive bacteria, exhibited equipotent activity against both strains.
Conclusion
The paucity of identified compounds active against drug-resistant A. baumannii exemplifies its ability to resist antimicrobials as well as the resilience of drug-resistant Gram-negative pathogens. Repurposing of approved drugs is a viable alternative to de novo drug discovery and development.
Keywords: Gram-negative infections, cyclic peptides, tyrothricin