Abstract
Purpose :
The oomycete Pythium insidiosum has been recognized as a significant cause of infectious keratitis in humans. Challenge in managing this infection lies not only in its misdiagnosis as fungus due to structural similarity but also in lack of availability of antimicrobial agents directed against it. Recent, in vitro studies have shown certain class of antibacterial agents to have potential inhibitory effect against this organism. We studied efficacy and safety of three antibiotics (Linezolid-LZ, Azithromycin-AZ, Tigecycline-TG) in the treatment of experimentally induced Pythium keratitis in New Zealand rabbits.
Methods :
Standard inoculum of P. insidiosum zoospores was injected intra corneally in right eye (left eye received saline) of 38 New Zealand White rabbits (19 male, 19 female) to induce keratitis. Both eyes were subjected to topical application of one of the three antibiotics under study (3 study groups of 12 rabbits each) from 3rd day onwards except for 2 control rabbits. Each group received either Linezolid 0.2 %, Azithromycin 1 % or Tigecycline 1% as eye drops every hour daily for 3 weeks (7 applications per day). Additionally, half of rabbits in each group received 1 additional intra corneal injection of the respective antibiotic solution (50 microliters) after 4 days of starting eye drops. Clinical scoring of both eyes using slit lamp was done at pre-specified intervals and cornea were harvested and preserved in 10% neutral buffered formalin for histopathology.
Results :
Corneal ulcer developed in all right eyes. Fulminant corneal infection developed in control rabbits (without drugs), which were enucleated after 10 days of infection. Although not statistically significant, the median clinical scores were reduced posttreatment in all groups. Reduction in clinical score was highest in LZ group as compared to AZ and TG groups (Median of 3 vs 1 and 1.5). Eyes receiving intrastromal antibiotics showed statistically significant reduction in clinical score (from 9 to 6, p 0.049). While no/minimal adverse effect of LZ (topical and intracorneal) was seen in control cornea, 66-100% of rabbits showed reaction to topical and intracorneal AZ and TG.
Conclusions :
Linezolid emerges as an antibiotic with superior efficacy and safety compared to azithromycin and tigecycline in the treatment of P. insidiosum keratitis in rabbits and can be considered for trial in human disease.
This is a 2020 ARVO Annual Meeting abstract.