Abstract
BackgroundWe aimed to demonstrate the contribution of anti-inflammatory and anti-virulence effects of azithromycin (AZM) in ocular surface infection treatment.MethodsStaphylococcus aureus was injected into the corneal stroma of rabbits to induce keratitis. AZM at concentrations of 0.01, 0.1, and 1% was instilled into the eye twice daily. The eyes were examined using a slit lamp and scored. The viable bacteria in the cornea were counted at 48 h post infection. To evaluate the anti-inflammatory efficacy of AZM, S. aureus culture supernatant-induced anterior ocular inflammation in rabbit was examined using a slit lamp and scored. To evaluate the inhibitory effect of AZM on bacterial toxin production, S. aureus was cultured with AZM and hemolytic reaction in the culture supernatant was determined.ResultsIn the bacterial keratitis model, AZM dose-dependently inhibited the increase in the clinical score. The viable bacterial count in the cornea treated with 1% AZM significantly decreased compared with that of the vehicle, whereas bacterial count in 0.01 and 0.1% AZM-treated corneas was similar to that of the vehicle. In the anterior ocular inflammation model, 0.1 and 1% AZM inhibited the increase in the clinical score. AZM inhibited hemolytic reaction at concentrations that did not inhibit bacterial growth.ConclusionsThe results demonstrated that AZM has not only anti-bacterial, but also anti-inflammatory effects, and inhibits bacterial toxin production leading to ocular surface damage in bacterial infection. Thus, the therapeutic effect of AZM against ocular infections is expected to be higher than that which could be assumed if it only had anti-bacterial activity.
Highlights
We aimed to demonstrate the contribution of anti-inflammatory and anti-virulence effects of azithromycin (AZM) in ocular surface infection treatment
We investigated whether AZM exerts anti-inflammatory and anti-virulence effects in addition to anti-bacterial activity in a staphylococcal keratitis model in order to elucidate their contribution in the treatment of ocular infection
After measuring the optical density at 660 nm to evaluate the growth of bacterial cells in the culture solution, bacterial culture supernatant was collected by centrifugation at 1610×g
Summary
We aimed to demonstrate the contribution of anti-inflammatory and anti-virulence effects of azithromycin (AZM) in ocular surface infection treatment. The initial acute inflammatory response against the bacteria is initiated by the innate immune system of the body to eliminate the pathogen and further stimulate adaptive immune responses [1] These processes are important to eradicate the invading pathogens, they have the risk of simultaneously damaging the host tissues. Ocular infectious diseases can cause scarring due to the inflammatory response as describe above, which may not be resolved, and result in blindness or visual impairments [4]. This encourages the use of broad-spectrum bactericidal agents for the treatment of ocular infections without identifying causative pathogens or without testing their susceptibility to anti-microbial agents. Several studies have demonstrated that inhibition of bacterial toxin production could suppress ocular tissue damage [5, 6]
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