Treatment With Voriconazole in 3 Eyes With Resistant Acanthamoeba Keratitis


To report the use of topical voriconazole 1% (Vfend; Pfizer Inc, New York, New York, USA) ophthalmic solution for Acanthamoeba keratitis (AK) resistant to treatment with chlorhexidine (PerioChip; Dexel Pharma Technologies, Jerusalem, Israel).


Retrospective case series.


Three eyes of 2 patients with culture-proven AK were treated at a tertiary care institution, and their charts were reviewed. Topical voriconazole 1% was instituted as second-line treatment for AK unresponsive to standard treatment with chlorhexidine and hexamidine. Treatment with voriconazole 1% was started at 1-hour intervals. Improvement was assessed and defined by absence of clinical signs of active infection and visual improvement.


One patient with unilateral AK and 1 patient with bilateral AK who remained culture-positive for Acanthamoeba despite ongoing treatment with chlorhexidine and hexamidine were treated with voriconazole 1% topical solution as an adjuvant. Both patients were contact lens wearers. Of 3 eyes additionally treated with voriconazole, 2 eyes had clinical resolution of disease. One eye demonstrated recurrent disease after penetrating keratoplasty that resolved after intrastromal injection of voriconazole.


We report the use of topical and intrastromal voriconazole in successfully treating AK in cases of chlorhexidine- and hexamidine-resistant Acanthamoeba. Voriconazole may be a promising adjuvant agent in treating AK.

Acanthamoeba keratitis (AK) is an increasingly prevalent corneal disease of infectious origin caused by an ubiquitous, free-living protozoan. Clinically, AK often presents as a unilateral infection among contact lens wearers, with bilateral involvement found in only 2% to 15% of cases. Diagnosis often is determined by both clinical findings and culture-positive laboratory tests using nonnutrient agar overlaid with E. coli. Delay in diagnosis and treatment can lead to significant loss of vision and may occur when the diagnosis is presumed to be a herpetic infection.

After an increase in cases during the late 1980s and early 1990s associated with contact lens wear among the public, a shift toward better cleansing practices and hygiene resulted in a decreased incidence rate of disease. However, a number of outbreaks since 2004 have made Acanthamoeba infection a national epidemic of significant importance. A recent study by Wilhelmus and associates of AK cases in 1 institution from 1997 through 2007 demonstrated that more than two-thirds of cases had occurred in the previous 4 years.

Treatment generally includes combination therapy to cover pathogenic strains and resistance from Acanthamoeba cysts. A steric biguanide such as polyhexamethylene biguanide (PHMB) or chlorhexidine serves as a cationic surfactant resulting in structural and intracellular damage to trophozoites and cysts. These have been shown to be effective when administered with a diamidine such as hexamidine or propamidine. Although the 2 steric biguanides were shown generally to be equivalent in efficacy as monotherapy, cases of resistance to PHMB were reported approximately 1 decade ago. Neomycin often encounters resistance from cysts, demonstrates a significant hypersensitivity rate, and is no longer used commonly.

As Acanthamoeba infection increases in incidence, new therapies then are required to overcome organisms resistant to common treatment. Here, we report the use of voriconazole (Vfend; Pfizer Inc, New York, New York, USA) as an additional topical and intrastromal treatment against Acanthamoeba resistant to chlorhexidine (PerioChip; Dexel Pharma Technologies, Jerusalem, Israel) and hexamidine combination therapy.


In this retrospective chart review, we examined outcomes for 2 patients with culture-proven AK, one of whom experienced bilateral disease (total of 3 eyes). All patients were treated by 1 ophthalmologist (J.D.G.) at a tertiary care center.

Topical voriconazole 1% (Vfend; Pfizer Inc) was instituted as second-line treatment for AK unresponsive to chlorhexidine and hexamidine and was administered at 1-hour intervals. One patient was also started on oral voriconazole (200 mg twice daily). Treatment with oral voriconazole included baseline and repeat liver function tests and was discontinued if liver enzymes increased significantly. Concentration of voriconazole injection was 25 μg/mL.

Patients were assessed for clinical absence of active infection and visual improvement. Clinical improvement included decreased infiltrates, resolution of hypopyon, neovascularization, and resolved epithelial defect.


Patient 1

A 49-year-old woman was referred to clinic after initial corneal irritation treated with various antibiotics progressed bilaterally over 4 weeks to epithelial and stromal ulceration. During this time, the patient had received a variety of medications without amelioration, including moxifloxacin, prednisone, ciprofloxacin, gentamicin, and fortified cefazolin. She had a history of wearing contact lenses while sleeping and did not report any other medical problems.

Visual acuity (VA) on examination was hand movements bilaterally. The right cornea had an epithelial defect measuring 7 mm temporally and 3 mm nasally. The left cornea had a C-shaped ulcer measuring approximately 5 mm, with anterior stromal haze and a small hypopyon. Bacterial, fungal, and Acanthamoeba cultures were ordered. The patient was started on hourly vancomycin (25 mg/mL) and ofloxacin. Acanthamoeba cultures demonstrated positive results bilaterally, organisms were isolated from the contact lens bottle, and the patient was started on 0.02% chlorhexidine and 0.1% hexamidine drops hourly.

After 5 months with little to no improvement, repeat cultures were obtained from both eyes with positive results. The patient then was started on voriconazole, both topical (1% hourly) and oral (200 mg twice daily), and hourly drops of PHMB (0.06%) and propamidine (0.1%). After 7 weeks, the epithelial defect in her left eye had healed and the patient reported that she was able to read once again out of this eye. At this time, oral voriconazole was discontinued because of elevated liver enzyme levels.

After 1 year of treatment with PHMB and voriconazole, during which propamidine was administered for 4 months, disease persisted in the right eye and did not improve. PHMB was discontinued and the patient then was given 0.06% chlorhexidine for 4 months, still without improvement. Bacterial and fungal cultures were obtained and demonstrated negative results. The patient underwent penetrating keratoplasty with intracameral injection of 0.1 ml voriconazole (25 μg/mL). After 1 month, recurrence of disease was noted with cultures and a repeat graft was performed. Intrastromal injections with a total of 0.1 ml voriconazole (25 μg/mL) were administered into the host and newly placed graft, in between each of the 16 interrupted sutures. The eye subsequently remained quiet and cultures after 3 months showed negative results for Acanthamoeba.

Patient 2

A 17-year-old female with no history of previous medical problems sought treatment at the clinic after 2 weeks of pain, tearing, photophobia, and decreased VA in her left eye. During this time, she had been given tobramycin and dexamethasone without clinical benefit, trifluridine with worsening of symptoms, and moxifloxacin and prednisolone 1% with only partial resolution of symptoms. She had a history of contact lens wear for which she used Clear Care solution (CIBA Vision, Duluth, Georgia, USA).

On examination, VA was 20/25+ in the right eye and 20/200 in the left, pinholed to 20/125. Her left eye had 1+ injection and displayed an irregular epithelium with significant corneal perineuritis and subepithelial infiltrates in an early ring configuration. The anterior chamber (AC) demonstrated 1+ cell with trace flare.

Topical chlorhexidine 0.02% and hexamidine 0.1% drops were ordered to be administered hourly. Oral itraconazole 400 mg daily and topical moxifloxacin 4 times daily also were given. Cultures then were obtained, including nonnutrient agar with E. coli overlay, revealing Acanthamoeba organisms.

She continued her regimen which included topical chlorhexidine and hexamidine hourly. Seven weeks after the onset of therapy and with no clinical improvement, cultures were repeated. Despite ongoing therapy, viable Acanthamoeba organisms still were present. At this point, topical voriconazole 1% was added hourly to the regimen, with chlorhexidine and hexamidine administered every 2 hours.

Within 2 weeks, a decrease in the size and intensity of the corneal infiltrate was appreciated with intense corneal vascularization. By 8 weeks, the epithelial defect healed ( Figure ). Doses then were decreased to voriconazole every 2 hours, with chlorhexidine and hexamidine given every 4 hours. Hexamidine, chlorhexidine, and voriconazole were discontinued at weeks 18, 21, and 26 after presentation, respectively. One year after discontinuing treatment, the patient opted to undergo penetrating keratoplasty. Examination of the removed cornea revealed no remaining Acanthamoeba cysts or organisms.


Photographs from Patient 2 showing that Acanthamoeba keratitis resistant to treatment with chlorhexidine and hexamidine improves with administration of voriconazole. (Top) Despite treatment with chlorhexidine, an epithelial defect continued to progress and remained culture-positive after 7 weeks of treatment. (Bottom) Addition of voriconazole resulted in clinical resolution with neovascularization and healing of epithelial defect.

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Jan 17, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Treatment With Voriconazole in 3 Eyes With Resistant Acanthamoeba Keratitis

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