Microbiological profiles of fungal keratitis: a 10-year study at a tertiary referral center.

BACKGROUND: Given the rise in cases of fungal keratitis in recent years, this study was performed to better elucidate the microbiological profile, risk factors, and surgical intervention rates of fungal keratitis at a tertiary referral center in the Southeastern USA. FINDINGS: This is a retrospective case series of fungal keratitis infections treated at Duke University Eye Center from January 1, 1998, to October 6, 2008. Of the 4651 culture-proven corneal ulcers identified, 63 (1.4 %) were positive for fungal keratitis with a total of 69 fungal organisms isolated. The majority of isolates were filamentous species (44 of 69, 64 %), and the most commonly isolated organism was Curvularia (11 of 69, 16 %). Bacterial coinfections were found in 24 of the 63 cases (38 %). The most commonly associated risk factors were contact lens wear (n = 15, 24 %) and prior penetrating keratoplasty (PKP) (n = 15, 24 %). Twenty-three cases (37 %) required surgical intervention. The rate of surgical intervention was highest in patients with prior PKP (7/15, 47 %). CONCLUSIONS: In this study, the leading risk factors for fungal keratitis were contact lens wear and prior PKP. Filamentous species were the most common causative pathogens. A relatively high rate of mixed bacterial-fungal infections was found. Patients with prior PKP were more likely to require surgery than patients without history of keratoplasties.

Polyhexamethylene biguanide and calcineurin inhibitors as novel antifungal treatments for Aspergillus keratitis.

PURPOSE: To establish polyhexamethylene biguanide (PHMB) as an effective treatment for Aspergillus keratitis in a novel murine model. To determine the ability of the calcineurin inhibitors tacrolimus (FK506) and cyclosporine A (CSA) to enhance the activity of PHMB, amphotericin B (AMB), and voriconazole (VCZ) against Aspergillus keratitis. IN VITRO STUDIES: Broth antifungal susceptibility tests were performed with PHMB, AMB, VCZ, and FK506, individually and in combination against Aspergillus fumigatus. Minimum inhibitory concentrations (MIC) and fractional inhibitory concentration index (FICI) values were used to analyze antifungal activity. In vivo studies: A novel murine model was created to establish Aspergillus keratitis. Infected mice were randomly assigned to treatment groups receiving saline, CSA, AMB, VCZ, PHMB, AMB+CSA, VCZ+CSA, or PHMB+CSA. An ophthalmologist blinded to the treatment groups assessed disease severity daily based on a grading scale. The mean end change in disease score was compared between groups. IN VITRO STUDIES: FK506 in combination with PHMB, VCZ, or AMB enhanced fungal growth inhibition. FICI values showed an additive effect between FK506 and PHMB, AMB, or VCZ. PHMB monotherapy eliminated Aspergillus growth starting at 4 µg/mL. In vivo studies: All treatment groups showed a significant improvement in disease score compared to the control group. CSA significantly worsened VCZ activity against Aspergillus keratitis. CONCLUSIONS: PHMB is an effective inhibitor of Aspergillus growth. Further investigation of the role of calcineurin inhibitors in the treatment for Aspergillus keratitis is warranted.