Abstract
Purpose::
S. aureus is a leading cause of bacterial keratitis. The disease is characterised by destruction of the cornea by bacterial exoproteins and host associated factors. Neutrophils are recruited to the site of infection leading to inflammation and loss of visual acuity and blindness. Furanones are compounds that have shown to be antibacterial and to change the immune response to bacterial infection. These compounds offer a new improved treatment option for this disease.
Methods::
Corneas of A/J mice were scarcified, and 0.6% acetyl cysteine applied to the eyes to disrupt the tear film. Ten microlitres of 4.0 x 108 cfu was applied to mice corneas. Mice were treated topically with furanone alone or in combination with 0.3% ciprofloxacin for 10 -15 h post infection. Mice were examined by slit lamp at 16 h post infection and the corneas harvested for enumeration of bacterial and PMN numbers.
Results::
In the ciprofloxacin sensitive S. aureus keratitis mouse model furanone combined with ciprofloxacin treatment significantly reduced the pathology compared to ciprofloxacin treatment alone. A significant decrease in PMN numbers was also observed following furanone combined with ciprofloxacin treatment compared to ciprofloxacin alone.In a ciprofloxacin resistant S. aureus keratitis mouse model furanone combined with ciprofloxacin treatment reduced cfu recovered by up to 98 % compared to ciprofloxacin alone. Additionally treatment of furanone in combination with ciprofloxacin reduced PMN recruitment to the cornea compared to ciprofloxacin alone.
Conclusions::
Furanone in combination with ciprofloxacin was able to exert an effect on clinical severity, cfu recovery and PMN recruitment to the cornea in a S. aureus keratitis model. A greater effect of the furanone/ciprofloxacin combination was observed in treating ciprofloxacin resistant S. aureus keratitis infections. Furanones have potential for use clinically to treat antibiotic resistant infections.
Keywords: antibiotics/antifungals/antiparasitics • keratitis • immunomodulation/immunoregulation