Large antibacterial activity spectrum of aminosterols derivatives towards multidrug-resistant Gram-negative and Gram-positive bacteria from patients with cystic fibrosis
Abstract number: P1127
Objectives: Resistance to antibiotics is a life-threatening danger with more severe impacts on fragilised populations like cystic fibrosis (CF) patients . 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  and a synthesized aminosterol  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 12 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 (14 mg/L vs. 832 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.
|Session name:||19th European Congress of Clinical Microbiology and Infectious Diseases|
|Location:||Helsinki, Finland, 16 - 19 May 2009|
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