کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5666800 | 1591737 | 2017 | 9 صفحه PDF | دانلود رایگان |
- Human β-defensin 3 and LL37 were the most active antimicrobial peptides tested.
- Ivacaftor had bactericidal activity against Streptococcus spp. and bacteriostatic activity against Staphylococcus aureus.
- Both LL37 and ivacaftor demonstrated synergy with tobramycin against S. aureus and Streptococcus spp. isolates.
There is a clear need for new antimicrobials to improve current treatment of chronic lung infection in people with cystic fibrosis (CF). This study determined the activities of antimicrobial peptides (AMPs) and ivacaftor, a novel CF transmembrane conductance regulator potentiator, for CF treatment. Antimicrobial activities of AMPs [LL37, human β-defensins (HβD) 1-4 and SLPI] and ivacaftor against clinical respiratory isolates (Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus spp., Achromobacter spp. and Stenotrophomonas maltophilia) were determined using radial diffusion and time-kill assays, respectively. Synergy of LL37 and ivacaftor with tobramycin was determined by time-kill, with in vivo activity of ivacaftor and tobramycin compared using a murine infection model. LL37 and HβD3 were the most active AMPs tested, with MICs ranging from 3.2-ââ¥â200âmg/L and 4.8-ââ¥â200âmg/L, respectively, except for Achromobacter that was resistant. HβD1 and SLPI demonstrated no antimicrobial activity. LL37 demonstrated synergy with tobramycin against 4/5 S. aureus and 2/5 Streptococcus spp. isolates. Ivacaftor demonstrated bactericidal activity against Streptococcus spp. (mean log10 decrease 3.31âCFU/mL) and bacteriostatic activity against S. aureus (mean log10 change 0.13âCFU/mL), but no activity against other genera. Moreover, ivacaftor demonstrated synergy with tobramycin, with mean log10 decreases of 5.72âCFU/mL and 5.53âCFU/mL at 24âh for S. aureus and Streptococcus spp., respectively. Ivacaftor demonstrated immunomodulatory but no antimicrobial activity in a P. aeruginosa in vivo murine infection model. Following further modulation to enhance activity, AMPs and ivacaftor offer real potential as therapeutics to augment antibiotic therapy of respiratory infection in CF.
Journal: International Journal of Antimicrobial Agents - Volume 50, Issue 3, September 2017, Pages 427-435