P2174Antimicrobial activity of newly synthesized gold(III) complexes against multidrug-resistant pathogens

05. New antibacterial agents, PK/PD & Stewardship
05a. Mechanisms of action, new compounds, preclinical data & basic pharmacology of antibacterial agents (incl. investigational and non-traditional therapeutics)
C. Ratia 1, M.A. Mateo 2, H. Rodríguez-Solla 2, R.G. Soengas 2, S.M. Soto 1, 3.
1Instituto de Salud Global de Barcelona - Barcelona (Spain), 2Universidad de Oviedo - Oviedo (Spain), 3CIBER Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III - Madrid (Spain)

Background

Drug-resistant bacteria represent one of the most serious threats to global health. The development of antibacterial treatments is stalled and inadequate to address the growing threat of antibiotic resistance. A promising new approach is to explore the antimicrobial properties of transition metal complexes. In this regard, gold(III) metalloantibiotics have raised interest due to their high antibacterial activity against resistant bacteria. We evaluate the effectiveness of a series of gold(III) complexes against MDR clinical isolates.


Methods

Susceptibility of gold(III) complexes was assessed by determining the minimal inhibitory concentration (MIC) by microdilution method following the EUCAST guidelines against MDR clinical isolates of Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Stenotrophomonas maltophilia, Acinetobacter baumannii, and Escherichia coli. ATCC strains were included as controls and reference antibiotics were used to compare the obtained results. Experiments were performed by triplicate.


Results

Nineteen gold(III) complexes with variations in their chemical structures were tested. Susceptibility studies showed high efficacy of 16/19 (84%) of the gold(III) complexes against Gram-positive bacteria (MRSA and S. epidermidis) with MIC values ranging from 0.125 to 2 mg/L. In the case of A. baumannii, the MIC values ranged from 1-4 mg/L of the 8/19 (42%) gold(III) complexes tested. For S. maltophilia, the MICs ranged from 2 to 8 mg/L for the active compounds. For E. coli and P. aeruginosa, the MIC values of the active molecules ranged from 8-32 mg/L. Three gold(III) complexes were not active against Gram-negative bacteria, but all compounds showed activity to at least one of the species under study.


Conclusions

The studied gold(III) complexes display potent antibacterial activity against several Gram-positive and negative resistant bacteria. Their activity against multidrug resistant strains of S. aureus and A. baumannii deserves a special mention since those bacteria are causative of most of the diagnosed nosocomial infections. Considering their antibacterial profile and the high-level resistance to clinical antibiotics of the strains here tested, metalloantibiotics based on gold(III) molecular scaffold can be considered as a potential new family of antibacterial agents.


Conclusions

Case(s) description

Discussion

References

Keyword 1
Antimicrobial resistance (AMR)
Keyword 2
Bacteria and bacterial infections
Keyword 3
Gold(III) complexes

Conflicts of interest


Do you have any conflicts of interest to declare?
No