Micafungin vs Amphotericin B in the Treatment of Experimental Aspergillosis Endophthalmitis

Abstract

Abstract: : Purpose: To evaluate the efficacy, intravitreally and intravenously (IV), of a new antifungal micafungin (MF) vs traditional amphotericin B (AB) in the treatment of Aspergillus fumigatus endophthalmitis in rabbit eyes. Methods: 6 groups of 5 New Zealand rabbits (n=30) were studied: 2 control and 4 treatment groups, in an IACUC–approved protocol. Experimental endophthalmitis was induced OD in all animals by intravitreal inoculation with 0.06 ml of Aspergillus fumigatus suspension (1x10⁶ CFU/ml), confirmed by indirect ophthalmoscopy. Fellow eyes (OS) were uninfected controls. Twelve hr after infection, one control group received 0.06 ml 0.9% saline intravitreally OU, and corresponding treatment groups received equal volumes of either 150µg MF or 75 µg AB, OU. Intravitreal treatments were all single doses. The second control group received IV saline twice daily, and corresponding treatment groups received either MF 2 mg/kg or AB 1 mg/kg body wt IV, twice daily. Pretreatment baseline ERGs and serial ERGs were recorded OU 24 & 72 hrs after inoculation, and at 96hrs if the ERG amplitude was maintained. Animals were sacrificed 8 days post treatment, or earlier if the ERG b–wave amplitude was reduced below 30% of baseline. Drug concentration in samples of aqueous and vitreous was measured by HPLC. Results:By 72 hrs, the mean ERG b–wave amplitude in both saline control groups had fallen below the 30% criterion, and the animals were sacrificed. In the single–dose intravitreal AB treated group, single animals were sacrificed at 48 and 72 hr. Three maintained ERG function through day 8 (P=0.007). All five MF–treated eyes maintained ERG through day 5, 3 through day 7, and 1 through day 8 (P=0.002). Among the bid IV treatment group, all animals receiving AB were sacrificed by 72 hrs, while two of those receiving MF maintained ERG function through day 7, and one through day 8. Microbiological analysis of vitreous samples had conidia in all 30 OD. Interestingly, HPLC demonstrated MF in the infected OD of all 5 animals receiving intravitreal MF, but in only 1 uninfected OS. Conclusions:Both MF and AB exhibited antifungal activity, preserving retinal function (ERG amplitude). MF appears to be very effective for several days after a single intravitreal injection, and was the only effective therapy via chronic IV administration. We hypothesize that the persistence of intravitreal MF in infected eyes may relate to its known incorporation into fungal cell walls, while in normal uninfected eyes it is eliminated more rapidly.

Keywords: antibiotics/antifungals/antiparasitics • endophthalmitis • fungal disease