In vitro and in vivo susceptibility of Candida keratitis to topical polyenes

Area of Science:

• Ophthalmology
• Mycology
• Pharmacology

Background:

• Ocular fungal infections, particularly Candida albicans keratitis, pose a significant threat to vision.
• Topical antifungal agents are crucial for managing stromal keratitis.
• Understanding the in vitro and in vivo efficacy of antifungals like amphotericin B and natamycin is vital for treatment selection.

Purpose of the Study:

• To evaluate the susceptibility of Candida albicans to topical amphotericin B and natamycin in a rabbit model of stromal keratitis.
• To compare the in vivo efficacy with in vitro minimal inhibitory concentrations (MICs).
• To assess the dosing requirements and potential discrepancies between in vitro and in vivo activity.

Main Methods:

• A rabbit model of delayed-onset Candida albicans stromal keratitis was established.
• Ten strains of Candida albicans were tested for susceptibility to amphotericin B and natamycin using tube dilution (MIC).
• In vivo efficacy was assessed after a 24-hour delay in treatment initiation, followed by 5 days of topical drug administration.

Main Results:

• Amphotericin B demonstrated consistent susceptibility classification between in vitro MICs and in vivo response, with a clear dose-response relationship.
• Natamycin's MICs misclassified two strains, and therapeutic efficacy in vivo required administration every 30 minutes, highlighting a higher dosing need compared to amphotericin B.

Conclusions:

• Topical amphotericin B shows reliable in vitro-in vivo correlation for Candida albicans stromal keratitis treatment in this model.
• Natamycin's efficacy is highly dependent on frequent administration, and its in vitro susceptibility testing may not fully predict in vivo outcomes.
• These findings support amphotericin B as a potentially more predictable topical treatment for invasive Candida keratitis.