Objectives: Resistance to antibiotics is a life-threatening danger with more severe impacts on fragilized populations like cystic fibrosis (CF) patients 1. Squalamine and AminoSterol Derivatives (ASDs) have demonstrated interesting antimicrobial activities against several bacterial and fungal reference strains 2, 3. However, when it comes to resistant clinical strains the challenge is evidently more difficult. Methods: Antimicrobial activities of squalamine (1) and a synthesized aminosterol (2) against multidrug-resistant bacterial and fungal clinical strains were investigated. 135 bacterial isolates were recovered from sputa of CF patients and 70 fungal strains composed of 50 filamentous fungi isolated from sputa of patients with respiratory disorders (including CF) and 20 non-filamentous bloodstream isolates. Results: In the case of Gram-negative bacteria, MICs ranged from 2 to 128 mg/L. Mucoidity of P.aeruginosa strains and resistance to colistin correlated significantly with high MIC values. In contrast, compounds 1-2 appeared very active against various Gram-positive bacteria with highest MIC value of 4 mg/L. Concerning the antifungal activity, compound 2 appeared more active than squalamine against tested fungal strains as reflected by MIC values (1-4 mg/L vs. 8-32 mg/L, respectively). Conclusions: In spite of correlating with colistin in activity against Gram-negative bacteria, tested compounds demonstrated surprising higher antibacterial effect against Gram-positive isolates naturally resistant to colistin indicating probably the presence of different mechanism of action against both group of bacteria. On the other hand, the antifungal activity was notably enhanced by modifying the aminosterol structure. Taken together, our results indicate that ASDs possess a broad antimicrobial spectrum against various bacterial and fungal clinical strains. 1. Govan JR, Nelson JW. J R Soc Med 1993; 86 Suppl 20: 11-8. 2. Salmi C, Brunel JM. Expert Opin Investig Drugs 2007; 16: 1143-57. 3. Brunel JM, Salmi C, Loncle C, et al. Curr Cancer Drug Targets 2005; 5: 267-72.
Full conference title:
19th European Congress of Clinical Microbiology and Infectious Diseases
- ECCMID 19th (2009)