Open-Label Study of Absorption and Clearance of 1% Voriconazole Eye Drops.

Twenty participants undergoing elective cataract surgery received 1% voriconazole eye drops (1 drop per eye) either 20, 40, 60, or 80 min before surgery. Median voriconazole concentrations of 1.9 to 3.2 mg/liter in aqueous humor samples were attained over the first 80 min, which were higher than in vitro MIC90 values for typical fungi that cause keratitis.

Penetration of topically administered 0.5-percent caspofungin eye drops into human aqueous humor.

Ten participants attending elective anterior segment eye surgery received 0.5% caspofungin eye drops either 1 drop hourly for 4 h or 1 drop an hour before surgery. The eye drops were generally well tolerated. In the absence of inflammation or corneal abrasion, topical caspofungin does not achieve clinically relevant concentrations.

Rapid and sensitive liquid chromatography/mass spectrometry assay for caspofungin in human aqueous humor.

A rapid, precise, and sensitive liquid chromatography/mass spectrometry (LC/MS) method to quantify the caspofungin concentration in human aqueous humor was developed and validated. Sample preparation involved simple dilution of aqueous humor samples with acetonitrile. Azithromycin was the internal standard. Good linearity over 10 to 5,000 ng/ml was observed. The lower limit of quantification was 10 ng/ml. The intra- and interday accuracies (percent bias) were within 11%, while the intra- and interday precisions were within 6%.

Prospective open-label study of the administration of two-percent voriconazole eye drops.

Thirteen human subjects scheduled for elective anterior segment eye surgery received hourly 2% voriconazole eye drops 4 hours presurgery. No side effects were reported. Significantly, the voriconazole concentration in the aqueous humor of the eye was similar to that reported for the 1% voriconazole solution, suggestive of concentration-independent absorption.

Successful salvage treatment of Scedosporium apiospermum keratitis with topical voriconazole after failure of natamycin.

OBJECTIVE: To report successful management of Scedosporium apiospermum (previously known as Monosporium apiospermum) keratitis with topical voriconazole as monotherapy. CASE SUMMARY: A 54-year-old previously well woman presented to the emergency department with a painful, injected right eye. There was no history of trauma or use of contact lenses. On examination, the right eye was estimated to have visual acuity of hand movement. Slit lamp examination detected a 2.5 x 3.5 mm dense, central corneal infiltrate with overlying epithelial defect. The eye had mild corneal edema with anterior chamber inflammation. Microbiology testing revealed S. apiospermum as the primary pathogen. Hourly administration of topical natamycin 5% resulted in initial improvement in visual acuity to 20/50, with reduction in the size of the central infiltrate. However, 1 month later, the eye infection relapsed, with recurrence of epithelial defect (3.1 x 3.1 mm) and decline in visual acuity to 20/100. Antifungal therapy was switched to topical voriconazole 1%, administered every 2 hours. Vision improved to 20/30 within 5 days, and the central defect had completely re-epithelialized within 1 week. DISCUSSION: Treatment of S. apiospermum keratitis remains inadequate. A high natamycin minimum inhibitory concentration is necessary to treat S. apiospermum infection, which may explain the persistence of central infiltration despite ongoing therapy. The combined use of topical and oral voriconazole for the treatment of S. apiospermum keratitis has been reported. However, this is the first report of a successful clinical experience using topical voriconazole without oral therapy to manage S. apiospermum keratitis. This eliminates some disadvantages associated with oral voriconazole such as high cost, potential significant toxicity, and drug interactions. CONCLUSIONS: The voriconazole 1% eye drop used alone is a promising, cost-effective, safe option for managing fungal keratitis, even that caused by S. apiospermum. It may have a larger role to play than simply that of adjunctive therapy.

Successful use of topical voriconazole 1% alone as first-line antifungal therapy against Candida albicans keratitis.

OBJECTIVE: To report the successful use of topical voriconazole 1% given alone as primary therapy against a case of Candida albicans keratitis. CASE SUMMARY: A 48-year-old previously well man presented to the emergency department with pain and foreign body sensation in the left eye following exposure to dust while driving a forklift. He wore weekly disposable soft contact lenses. Anterior stromal scar and dense infiltrate were detected in the left eye. The anterior chamber remained deep, with flare and copious white cells. Intraocular pressure was 12 mm Hg and visual acuity was 20/200. The epithelial defect persisted, with progressive thinning despite topical fluorometholone and ofloxacin 0.3% therapy for 2 days. Microbiology testing revealed C. albicans as the affecting pathogen. Hourly administration of voriconazole 1% eye drops was initiated as antifungal therapy. The corneal infiltrate began to resolve and the epithelial defect decreased in size within 2 days. Visual acuity improved to 20/120. After 4 days of voriconazole use, the epithelial defect was completely healed and visual acuity was 20/30 in the affected eye. No fungi were isolated from a second eye scrape. DISCUSSION: Topical voriconazole as salvage monotherapy to manage fungal keratitis has been previously reported. It can be argued, however, that the primary therapy has facilitated the positive response to subsequent topical voriconazole. To date, there has been no solid evidence to suggest that topical voriconazole is effective when used as primary therapy. The current report provides evidence of topical voriconazole demonstrating clinical success when used as first-line therapy to treat C. albicans keratitis. The use of topical voriconazole can reduce the costs, toxicity, and drug interactions associated with common antifungal therapies. CONCLUSIONS: Topical voriconazole 1% eye drops administered alone demonstrated success as first-line therapy against the most common fungal keratitis, C. albicans keratitis.

Penetration of 1% voriconazole eye drops into human vitreous humour: a prospective, open-label study.

PURPOSE: Although there have been reports describing the use of 1% voriconazole eye drops in the treatment of fungal infections, little is known about the penetration of voriconazole eye drops into the vitreous humour. The aim of this study was to elucidate if topical application of 1% voriconazole eye drops could reach therapeutic levels in the vitreous humour. METHODS: A prospective, open-label trial involving 10 participants selected from patients scheduled to undergo elective, posterior segment surgery. Participants received 1% voriconazole solution, preserved with 0.01% benzalkonium chloride, hourly for four doses or four times a day for 3 days. Vitreous humour was obtained at the start of surgery and analysed using a validated high-performance liquid chromatography assay. RESULTS: The minimum and maximum voriconazole concentration after hourly dosing (n = 5) was 0.1 and 1.1 microg/mL, respectively, whereas the median was 0.3 microg/mL. Samples were taken between 0.8 and 5.4 h after the last dose, with the median at 1.2 h. Almost all voriconazole concentrations from the four times a day group (n = 5) were below the limit of quantification. CONCLUSIONS: One per cent voriconazole eye drops are able to penetrate into human vitreous humour. Adequate concentration for treatment of sensitive Candida species can be achieved upon hourly administration.

Audit of the use of antimicrobial prophylaxis in nasal surgery at a specialist Australian hospital.

BACKGROUND: In 2002-03 a retrospective audit of the use of surgical antimicrobial prophylaxis (AMP) for elective nasal surgery was undertaken at the Royal Victorian Eye and Ear Hospital (RVEEH). The RVEEH is a publicly funded teaching hospital that provides specialist eye, nose and throat medicine in Victoria, Australia. The aim of the audit was to determine the extent to which the use of antimicrobial prophylaxis in the hospital was consistent with Australian and international evidence-based guidelines and if there was a need for the hospital to develop internal guidelines for the use of AMP. METHODS: The histories of 500 consecutive patients who had undergone nasal surgery within the study period of August 2001 and July 2002 were examined. The data collected from these histories included information such as the patients' age, gender, diagnosis, surgical procedure performed, antimicrobial agents used, and the length of follow up and a range of factors shown in previous studies to increase the risk of surgical site infection. RESULTS: A total of 306 (72.86%) patients were found to have received antimicrobial agents either prior to admission, during admission or on discharge. Only 24 patients (5.71%) were administered antimicrobials immediately prior to surgery and at no other time. CONCLUSIONS: The findings of this study support the need for further research to examine the appropriateness of the use of AMP at the RVEEH and the need for internal guidelines for its use.

Stability of extemporaneously prepared voriconazole ophthalmic solution.

PURPOSE: The stability of extemporaneously prepared voriconazole ophthalmic solution was studied. METHODS: Voriconazole solutions (2% and 1%) were reconstituted from the i.v. formulation. After thorough mixing, 3-mL samples of each of the resulting 2% and 1% solutions were filtered into eyedroppers. Three samples for both solutions were analyzed in triplicate at each time point. The 2% voriconazole ophthalmic solutions were stored at 2-8 degrees C, 25 degrees C, and 40 degrees C. The 1% voriconazole eye drops were stored at 2-8 degrees C. The 2% voriconazole solution samples were analyzed at time 0 and at weeks 1, 2, 4, 8, 16, and 32. The 1% solution samples were analyzed at time 0 and at weeks 6 and 14. Stability was measured using high-performance liquid chromatographic analysis. RESULTS: The 2% voriconazole ophthalmic solution demonstrated excellent stability at 2-8 degrees C and 25 degrees C for up to 16 weeks. The voriconazole solution displayed no significant change in pH at all time intervals. No change in visual appearance or clarity was observed in the 2% voriconazole eye drops at any point of the study for all study temperatures. Voriconazole 1% solution was stable at 2-8 degrees C for up to 14 weeks. CONCLUSION: Voriconazole 2% (20 mg/mL) solution preserved with 0.01% benzalkonium chloride prepared as alternative antifungal eye drops was stable for 16 weeks when stored at 2-8 degrees C and 25 degrees C and for 8 weeks when stored at 40 degrees C, while voriconazole 1% solution was stable at 2-8 degrees C for up to 14 weeks.