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Exogenous Endophthalmitis Caused by Amphotericin B–Resistant Paecilomyces lilacinus: Treatment Options and Visual Outcomes
Arch Ophthalmol. 2001;119:916-919.
INTRODUCTION
Paecilomyces lilacinus, an uncommon cause of exogenous endophthalmitis, presents a challenging management problem since the organism is usually resistant to amphotericin B, the most commonly employed intravitreal antifungal, and natamycin, a frequently employed topical antifungal. The organism is sensitive to miconazole nitrate, ketoconazole, and, in some cases, fluconazole. We report 4 cases of endophthalmitis caused by P lilacinus and discuss treatment options.
Report of Cases
Case 1
A 37-year-old man with hand motion vision in the left eye underwent penetrating keratoplasty, extracapsular cataract extraction, and posterior chamber intraocular lens implantation in the left eye 4 years after a bilateral ammonia chemical injury that resulted in persistent keratitis and corneal thinning. One day postkeratoplasty, he underwent wound leak repair. Examination 3 weeks later demonstrated a best-corrected visual acuity of 2/200 OS and a white flocculent mass on the cornea extending into the anterior chamber (Figure 1). After aqueous and vitreous specimens demonstrated filamentous fungi (Figure 2), a total of 4 amphotericin B injections (5-10 µg/0.1 mL) were administered (3 into the anterior chamber and 1 into the vitreous). Due to enlargement of the flocculent mass the patient underwent partial iridectomy, removal of the mass, and a fifth anterior chamber injection of amphotericin B. Nine days later, because of worsening pain and decreased vision to bare light perception, the patient underwent enucleation. Five days later, intraocular cultures had grown P lilacinus (Figure 3) resistant to amphotericin B, fluconazole, and itraconazole, but sensitive to ketoconazole and miconazole.
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Figure 1. A 37-year-old man with endophthalmitis associated with a penetrating keratoplasty and subsequent wound leak. Examination demonstrates a visual acuity of 2/200 OS and a white flocculent mass on the cornea and extending into the anterior chamber. Intraocular cultures grew Paecilomyces lilacinus.
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Figure 2. Paecilomyces lilacinus growth on Sabouraud agar stained with Evans blue (aqueous specimen).
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Figure 3. Lactophenol blue preparation showing typical microscopic conidia and hyphae of Paecilomyces lilacinus.
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Case 2
A 68-year-old woman with a history of leukemia had a perforated corneal ulcer at the graft-host junction of a penetrating keratoplasty performed in the left eye 10 days prior for sterile corneal ulceration associated with rheumatoid arthritis. Visual acuity was light perception and the anterior chamber contained white flocculent inflammatory material. An anterior chamber tap was performed and the patient received an injection of amphotericin B and topical amphotericin B and oral fluconazole. Owing to progressive thinning of the graft-host junction, a tectonic graft was performed. On the day of surgery, P lilacinus was identified from an anterior chamber culture that had been obtained 1 week earlier, and the patient received topical, subconjunctival, and intravitreal miconazole. Subsequent antifungal sensitivities demonstrated that the organism was resistant to amphotericin B, fluconazole, and itraconazole, but sensitive to ketoconazole and miconazole. The patient progressively improved and at 6 months after treatment her visual acuity stabilized at 20/400 OS.
Case 3
A 48-year-old woman who had undergone penetrating keratoplasty in the right eye for a P lilacinus corneal ulcer 3 weeks earlier had a visual acuity of 20/400 OD and a white flocculent mass on the iris. The patient underwent pars plana vitrectomy, lensectomy, excision of the iris mass, and intravitreal injection of fluconazole (10 µg/0.1 mL). Intraocular cultures grew P lilacinus. The patient progressively improved and at 4 months after treatment her vision stabilized at 20/50 OD. Subsequent antifungal sensitivities demonstrated that the organism was resistant to amphotericin B and itraconazole, but sensitive to fluconazole, ketoconazole, and miconazole.
Case 4
A 23-year-old man had a visual acuity of 2/200 OS on initial examination. He had undergone scleral laceration repair and traumatic cataract removal in the left eye 3 months prior and secondary anterior chamber intraocular lens (IOL) implantation 1 month previously. White flocculent material was present in the anterior chamber, in the vitreous, and on the IOL. The patient was treated with pars plana vitrectomy and intravitreal ceftazidime (2.25 mg/0.1 mL), vancomycin hydrochloride (1.0 mg/0.1 mL), amphotericin B (5 µg/0.1 mL), and dexamethasone sodium phosphate (0.4 mg/0.1 mL). Aqueous and vitreous smears showed filamentous fungi. One week postoperatively, vision had improved to 20/400 OS. Two weeks postoperatively, the patient had increasing pain and worsening vision. Examination revealed recurrence of a white flocculent mass on the iris. Intravitreal amphotericin B (7.5 µg/0.1 mL) was administered. Two days later, antifungal sensitivities demonstrated that the organism was resistant to amphotericin B, fluconazole, and itraconazole, but sensitive to ketoconazole and miconazole. Due to progressive inflammation and worsening vision to light perception, the patient underwent pars plana vitrectomy, anterior chamber IOL removal, and an intravitreal miconazole injection (50 µg/0.1 mL). Because the eye became hypotonic and painful postoperatively, enucleation was performed.
Comment
Endophthalmitis caused by P lilacinus has generally been associated with poor visual outcome, probably due at least in part to the organism's resistance to the most commonly used intravitreal antifungal agent, amphotericin B. In a series of 13 cases of P lilacinus endophthalmitis following implantation of contaminated IOLs, 8 eyes were enucleated, 2 had a final vision of no light perception, and 1 had light perception.1 Retention of useful vision (20/80 and 20/25) in the remaining 2 eyes was attributed to early removal of the IOL and inflammatory material in one case and prompt use of intraocular miconazole in the other.1 In another series of patients with postoperative P lilacinus endophthalmitis, enucleation was performed in 2 of the 3 cases; the salvaged eye was treated with miconazole early in the course of the disease.2 In a case report of successful treatment of P lilacinus endophthalmitis following cataract extraction, treatment consisted of early vitrectomy, multiple intravitreal injections of amphotericin B and miconazole, intravenous miconazole, and later, oral ketoconazole.3 The IOL was removed 6 weeks after initiation of therapy and found to contain P lilacinus. Visual acuity 8 months after cataract extraction was 20/20 with aphakic correction.
Current management of P lilacinus is challenging because of the organism's resistance to amphotericin B, natamycin, and, in some cases, fluconazole.4-5 In addition, miconazole and ketoconazole, agents to which P lilacinus is sensitive, are not generally included in the initial management of suspected fungal endophthalmitis. Further, the sensitivity profile of P lilacinus differs significantly from that of Paecilomyces variotii, and although intraocular cultures may permit identification of the Paecilomyces genus within several days, it may take up to 2 weeks to identify the specific Paecilomyces species. Therefore, initial antifungal treatment should ideally cover both species. To date, miconazole is the only known medication to which P lilacinus and P variotii are consistently sensitive. Miconazole is currently available in powder form, which can be used to prepare topical and intravitreal preparations.
In a patient with suspected exogenous Paecilomyces endophthalmitis, if miconazole is not readily available, a combination of intravitreal amphotericin B and oral ketoconazole seems to be the best management option since P variotii is sensitive to amphotericin B and P lilacinus is sensitive to ketoconazole. While intravitreal amphotericin B is readily available from most pharmacies, ketoconazole is available only in an oral preparation. A single intravitreal ketoconazole dose of 540 µg or less (in 0.1 mL of dimethyl sulfoxide) has been shown to be safe in rabbit eyes6 but, to our knowledge, intravitreal ketoconazole use has not been reported in humans. Approximately 10% of P lilacinus organisms are sensitive to fluconazole, which can be prepared in an intravitreal form. Thus, as case 3 demonstrates, treatment with intravitreal fluconazole may be associated with good visual outcomes.
Conflicting data have been reported concerning intravitreal penetration of oral ketoconazole. Malecaze et al7 reported undetectable ketoconazole levels in the vitreous of healthy rabbits and rabbits with chorioretinitis exhibiting little or no vitreitis; 2 of 6 rabbits with severe vitreitis had therapeutic ketoconazole levels following an oral dose of 100 mg. Savani et al8 reported therapeutic intravitreal ketoconazole levels in both inflamed and uninflamed rabbit eyes 4 hours following an 80-mg/kg dose, with the intravitreal concentration being 3 times greater in inflamed eyes. O'Day et al9 reported an intravitreal ketoconazole concentration of 0.71 µg/mL in a patient who took 600-mg of ketoconazole orally 4 times per day for at least 2 weeks prior to therapeutic vitrectomy.
Of the currently available treatment options for exogenous endophthalmitis caused by amphotericin B–resistant P lilacinus, intravitreal miconazole (25 µg/0.1 mL) should be considered if it can be obtained and administered promptly. This intravitreal treatment can be supplemented by oral ketoconazole (200-400 mg 4 times daily). In the absence of miconazole, oral ketoconazole and intravitreal fluconazole may be considered.
AUTHOR INFORMATION
This research was supported in part by Research to Prevent Blindness Inc, New York, NY.
Corresponding author: Ingrid U. Scott, MD, MPH, Bascom Palmer Eye Institute, PO Box 016880, Miami, FL 33101 (e-mail: iscott{at}med.miami.edu).
Ingrid U. Scott, MD, MPH;
Harry W. Flynn, Jr, MD;
Darlene Miller, MS, MPH
Miami, Fla
James W. Speights, MD;
Robert C. Snip, MD
San Antonio, Tex
Roy D. Brod, MD
Hershey, Pa
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