Efficacy and Safety of Voriconazole as an Additive in Optisol GS

Ritterband, David C.; Shah, Mahendra; Meskin, Seth W.; Seedor, John A.; Koplin, Richard S.; Perez, Wilma; Yang, Renee; Huang, Dan; Dahl, Patricia

doi:10.1097/ico.0b013e31802d82e8

Cited by 53 publications

(44 citation statements)

References 37 publications

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“…In addition, far fewer cases of fungal endophthalmitis have been reported in the literature after organ culture storage compared with after hypothermic storage. 6,7 Our results are in contradiction to a previous study by Ritterband and colleagues, 11 which found a significant reduction in the rate of positive fungal donor rim cultures with voriconazole-supplemented Optisol-GS compared with Optisol-GS alone (0 vs 7 of 533 positive rim cultures; P = .02). However, there were important differences in methods between the previous study and this study.…”

Section: Corneal Safety Resultscontrasting

confidence: 85%

“…10 The organ culture medium commonly used in Europe contains the antifungal amphotericin B. 6 A previous US study 11 examined voriconazole as an additive to Optisol-GS and found that there was a significant reduction in the rate of positive fungal donor rim cultures with voriconazole-supplemented Optisol-GS compared with Optisol-GS alone. The aim of the present study was to assess the efficacy and safety of voriconazole and amphotericin B in reducing C albicans and C glabrata contamination of Optisol-GS under normal storage conditions.…”

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confidence: 97%

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Efficacy and Safety of Antifungal Additives in Optisol-GS Corneal Storage Medium

et al. 2014

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IMPORTANCE Optisol-GS, the most common corneal storage medium in the United States, contains antibacterial but no antifungal supplementation. Most postkeratoplasty endophthalmitis and keratitis cases are now of a fungal origin.OBJECTIVE To assess the efficacy and safety of voriconazole and amphotericin B in reducing Candida species contamination of Optisol-GS under normal storage conditions. DESIGN, SETTING, AND PARTICIPANTSIn vitro laboratory study using 15 pairs of research-grade donor corneas and 20-mL vials of Optisol-GS.INTERVENTIONS Twenty vials of Optisol-GS were supplemented with either voriconazole at 1×, 10×, 25×, or 50× minimum inhibitory concentration (MIC) or amphotericin B at 0.25×, 0.5×, 1×, or 10× MIC. Known concentrations of Candida albicans and Candida glabrata were each added to a set of vials. Safety studies were performed by separating 15 pairs of donor corneas into unsupplemented Optisol-GS or Optisol-GS plus an antifungal.MAIN OUTCOMES AND MEASURES Efficacy outcomes were viable fungal colony counts determined from samples taken on days 2, 7, and 14 immediately after removal from refrigeration and after warming to room temperature for 2 hours. Safety outcomes included percentage of intact epithelium and endothelial cell density on days 0, 7, and 14, as well as percentage of nonviable endothelial cells by vital dye staining on day 14.RESULTS Growth of C albicans and C glabrata was observed in all voriconazole-supplemented vials. In contrast, there was no growth of either organism in amphotericin B-supplemented vials, except at 0.25× and 0.5× MIC on day 2, when viable counts of C glabrata were reduced by 99% and 96%, respectively. Compared with paired controls, with the exception of Optisol-GS plus amphotericin B at 10× MIC, donor corneas in supplemented Optisol-GS appeared to have no difference in endothelial cell density reduction, percentage of intact epithelium, or percentage of nonviable endothelial cells. CONCLUSIONS AND RELEVANCEThe addition of amphotericin B to Optisol-GS may significantly improve activity against contamination with Candida species, the primary cause of fungal infection after corneal transplantation. This study found significant endothelial toxic effects at the maximal concentration of amphotericin B.

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Section: Corneal Safety Resultscontrasting

confidence: 85%

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confidence: 97%

Efficacy and Safety of Antifungal Additives in Optisol-GS Corneal Storage Medium

et al. 2014

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“…The antimicrobial agents tested in this study are active against all of these pathogens, and the concentrations used have been proven to be nontoxic for the corneal endothelium. 9,[16][17][18] Three different types of decay were identified: exponential-indicating a first-order chemical reaction, linearindicating a zero-order chemical reaction, and a 1-step decay. During the exponential decay (penicillin G and possibly amphotericin B, and streptomycin), indicating a first-order chemical reaction, a constant percentage of penicillin G is consumed per time unit.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, Ritterband et al 18 found a significant reduction in fungal contaminations in corneas stored in Optisol with voriconazole added. However, there were significant differences between both studies.…”

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confidence: 94%

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Time Course of Antibiotic and Antifungal Concentrations in Corneal Organ Culture

Seiler

Tschopp

Zimmerli

et al. 2016

Cornea

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Purpose: Contamination with bacteria and/or fungi is a serious complication in organ-cultured corneas. Hence, antibiotic and antifungal agents are added to the culture medium. The concentration of different antimicrobial and antifungal additives to the media over time has so far not been investigated in detail and is the aim of this study.Methods: Nine human fresh corneoscleral discs were stored in corneal culture medium consisting of 2% fetal bovine serum and minimal essential medium. In addition, the culture medium contained 1200 mg/mL penicillin G, 25 mg/mL amphotericin B, 120 mg/mL streptomycin, and 100 mg/mL voriconazole. The concentration of amphotericin B used was 10 times higher than in clinical routine to facilitate its detection. The cultures were kept at 37°C for 28 days. At days 0, 7, 14, 21, and 28, samples of the culture medium were harvested for analysis of antimicrobial concentrations by liquid chromatography and electrospray ionization tandem mass spectrometry.Results: During corneal storage, the concentration of all antibiotics and antifungal agents declined significantly. By day 28, penicillin G was reduced to 14% of the original concentration. Amphotericin B and streptomycin retained approximately 60% of the original concentration to the end of the experiment and voriconazole maintained stable concentrations after an initial decline to approximately 80% at 7 days.Conclusions: Throughout the entire storage period, the concentrations of penicillin G, streptomycin, and voriconazole exceeded the minimum inhibitory concentrations of all common contaminants, obviating the need for a change of the medium for antimicrobial reasons. Based on the minimum inhibitory concentrations and our findings, the initial concentration of amphotericin B should be raised to 5 mg/mL. Warm preservation at 31 to 37°C is more commonly used in European eye banks: corneas can be stored up to 4 weeks in organ culture medium consisting of minimum essential medium with the addition of 2% fetal bovine serum.2-6 Antibiotics and antifungal agents are added to the organ culture media to kill contaminants and to avoid iatrogenic infections at transplantation. Despite this prophylaxis, severe complications like endophthalmitis can still occur. 7,8 Little is known about the decay characteristics and efficacy over time of antimicrobial agents kept at body temperature. Therefore, we studied the concentration of the most commonly used antimicrobial and antifungal additives over time under the standard conditions established at the local eye bank at the Department of Ophthalmology, University Hospital in Bern. METHODS Sample PreparationNine human corneoscleral discs unsuitable for transplantation were excised under sterile conditions from intact globes not later than 6 hours post mortem and stored each in a corneal culture medium consisting of 2% fetal bovine serum and minimal essential medium (Sigma Aldrich, St Louis, MO) following the standard protocol of the eye bank of the University Hospital of Bern. The culture medium contained 1...

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Trypan Blue Vital Dye Staining vs TUNEL Technique to Detect Corneal Endothelium Toxic Effects—Reply

2014

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Efficacy and Safety of Voriconazole as an Additive in Optisol GS

Abstract: Voriconazole seems to be safe as a fortifying agent for cornea storage medium. It significantly reduces the rate of positive fungal rim cultures and shows no signs of endothelial cytotoxicity as viewed by EM and by a bioassay of trypan blue and alizarin red.

Cited by 53 publications

References 37 publications

Efficacy and Safety of Antifungal Additives in Optisol-GS Corneal Storage Medium

Efficacy and Safety of Antifungal Additives in Optisol-GS Corneal Storage Medium

Time Course of Antibiotic and Antifungal Concentrations in Corneal Organ Culture

Trypan Blue Vital Dye Staining vs TUNEL Technique to Detect Corneal Endothelium Toxic Effects—Reply

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