Repurposing FDA-approved drugs to combat drug-resistant Acinetobacter baumannii.
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.


METHODS
In this study, we screened 1040 FDA-approved drugs against drug-susceptible A. baumannii ATCC 17978 and drug-resistant A. baumannii BAA-1605.


CONCLUSIONS
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.


CONCLUSIONS
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.
Chopra
Sidharth
S
Center for Infectious Disease and Biodefense Research, SRI International, Menlo Park, CA, USA.
Torres-Ortiz
Maria
M
Hokama
Leslie
L
Madrid
Peter
P
Tanga
Mary
M
Mortelmans
Kristien
K
Kodukula
Krishna
K
Galande
Amit K
AK
D000151:Acinetobacter Infections / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003428:Cross Infection / Q000382:microbiology*; D017277:Drug Approval; D055808:Drug Discovery / Q000379:methods*; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D014449:Tyrothricin / Q000494:pharmacology*; D014481:United States; D014486:United States Food and Drug Administration
D000900:Anti-Bacterial Agents; D014449:Tyrothricin