BritishJournalofOphthalmology, 1992,76,367-368 367

CASE REPORTS Br J Ophthalmol: first published as 10.1136/bjo.76.6.367 on 1 June 1992. Downloaded from

Treatment failure in a case of fungal keratitis caused by Pseudallescheria boydii

Philip A Bloom, D A H Laidlaw, D L Easty, D W Warnock

Abstract Twelve hours postoperatively there was a A case is presented ofPseudallescheria boydii marked fibrinous anterior uveitis and the donor fungal keratitis in an agricultural welder. Treat- corneal button was thickened and hazy. Over the ment with azole antifungal drugs (miconazole next 2 days the graft cleared but the hypopyon and itraconazole) and with penetrating kerato- reformed, so 0-1% dexamethasone drops four plasty was unsuccessful in eradicating the times a day were added. The fibrinous reaction infection, and eventualiy the eye was evis- progressed with lifting of the graft, and the cerated. dexamethasone was increased to 2 hourly. This failed to halt the progression to endophthalmitis (Fig 2). Case report Serum concentrations ofitraconazole were low A 57-year-old man presented with a painful red (0 2 mg/l at 4-5 hours), so the dose was increased eye. Ten days previously he had been welding in to 200 mg twice a day. The results of sensitivity a pig slurry tank while wearing a face mask, but testing of the Bristol corneal isolate became recalled no injury. An ulcer noted on the right available 4 days postoperatively. These showed cornea initially was thought to be herpetic and that the organism was sensitive to miconazole treated with 3% acyclovir ointment. Three days (minimum inhibitory concentration [MIC]= later 0 1% dexamethasone drops four times a day 0.5 mg/l), but resistant to amphotericin B were added. One week later the ulcer had greatly (MIC= 5 mg/l) and itraconazole (MIC >50 mg/l). extended and topical steroids were stopped. Miconazole 600 mg intravenously three times Microscopy following extensive lamellar a day was therefore recommenced. This was later corneal debridement (biopsy) showed massive increased to 1200 mg three times daily in com-

fungal infection. The organism was later identi- bination with hourly topical miconazole 1% http://bjo.bmj.com/ fied as Pseudallescheria. boydii, but sensitivity and two further subconjunctival injections of tests were not performed on this isolate. Treat- miconazole. ment was instituted with 1% miconazole drops The endophthalmitis did not respond, how- hourly and itraconazole 200 mg once a day orally, ever, and the patient became depressed and and a subconjunctival injection of miconazole nauseated from systemic treatment. Because 0 5 ml of 10 mg/ml was given. The ulcer did not clinical success was deemed unlikely, the patient

improve, so 1 week later further corneal requested evisceration, which was performed on September 26, 2021 by guest. Protected copyright. debridement was performed and the subcon- 8 weeks after the original infection. Pseud- junctival miconazole was repeated. Systemic allescheria boydii was isolated from evisceration antifungal treatment was changed to miconazole specimens of cornea and anterior chamber fibrin 600 mg three times a day intravenously, but the but not from lens or vitreous. ulcer continued to enlarge. Ten days later the patient was transferred to Bristol Eye Hospital. On admission the cornea was hazy and Discussion thickened with a deep central ulcer and marked Fungal keratitis is most prevalent in agricultural stromal infiltrate (Fig 1). The anterior chamber workers in the rural populations of tropical was deep with an intense fibrinous exudate and a areas, following traumatic implantation offungal 2-5 mm hypopyon. Following deterioration, an spores from soil or plant matter into the corneal Bristol Eye Hospital, 8 mm eccentric right penetrating keratoplasty stroma. Lower Maudlin Street, and clearout of the anterior chamber exudate Pseudallescheria boydii (previously Petriel- PBAiBloom were performed 3 days after transfer (5 weeks lidium boydii, Allescheria boydii, Monosporium D A H Laidlaw after presentation). Pseudallescheria boydii was apiospermum) is a ubiquitous fungus that has D L Easty isolated from excised cornea and anterior been isolated from soil, polluted water, and Regional Mycology chamber fibrin, but there was no bacterial sewage. It has been reported to cause keratitis, Laboratory, Department growth from these specimens. Microscopy endophthalmitis, mycetoma, pneumonia, of Microbiology, Bristol showed fungus up to the corneal resection osteomyelitis, arthritis, sinusitis, endocarditis, Royal Infirmary, Maudlin meningitis, and brain abscess.' In immuno- Street, Bristol BS2 8HW margi. D W Warnock Because of the patient's clinical deterioration suppressed patients infection may result in fatal Correspondence to: before surgery, postoperative antifungal treat- disseminated pseudallescherosis. Philip A Bloom, FRCS Ed, ment was changed from miconazole to itra- There have been at least 14 reported cases of FCOphth. conazole, initially 200 mg once a day orally. P boydii keratitis2 but none treated with itra- Accepted for publication 14 November 1991 Topical 1% miconazole was continued. conazole, a recently introduced orally adminis- 368 Bloom, Laidlaw, Easty, Warnock Br J Ophthalmol: first published as 10.1136/bjo.76.6.367 on 1 June 1992. Downloaded from

Figure I Corneal ulcer with hypopyon, due to Figure 2 Reformed hypopyon after penetrating keratoplasty Pseudallescheria boydii. for Pseudallescheria boydii keratitis. A stitch abscess can be seen superiorly.

tered broad-spectrum triazole compound. In Suspected mycotic keratitis, or mycotic only five of these 14 cases was treatment success- keratitis in which the organism or its sensitivities ful, the remainder requiring evisceration. have not yet been identified, should be treated Although many isolates of P boydii are resistant empirically with a combination of antifungal to amphotericin B,3 several cases ofkeratitis have agents. The broadest such 'best guess' combina- been successfully treated with this drug alone, or tion treatment should probably include topical in combination with nystatin or natamycin. miconazole or econazole, subconjunctival Although many strains ofP boydii are sensitive miconazole, and either oral itraconazole or intra- to miconazole,37 there have been no published venous miconazole. reports of Pseudallescheria keratitis successfully In any case of atypical or indolent keratitis the treated with this drug. The reasons for the failure possibility of fungal infection should be borne in ofhigh dose miconazole treatment in this case are mind, and steroids should be used with great unclear, but the administration of topical corti- caution, if at all. costeroids and lack of drug penetration to the infection site may have contributed. We thank Mrs G Bennerson for the photographs. Only three cases of endophthalmitis due to P boydii have been previously reported, none 1 Warnock DW, Johnson EM. Clinical manifestations and associated with keratitis. In one case of endoph- management of hyalohyphomycosis, phaeohyphomycosis and other uncommon forms of fungal infection in the thalmitis following cataract extraction8 the compromised patient. In: Warnock DW, Richardson MD, patient recovered after 3 months of topical treat- eds. Fungal infection in the compromised patient. 2nd ed. http://bjo.bmj.com/ Chichester: Wiley, 1991: 247-310. ment with amphotericin B, 4 mg/ml 2 hourly. 2 Rippon JW. Medical mycology. The pathogenic fungi and the Treatment success may have been due to the pathogenic actinomycetes. 3rd ed. Philadelphia: Saunders, 1988. anterior location of this infection. In a second 3 Lutwick LI, Galgiani JN, Johnson RH, Stevens DA. Visceral case3 the infection was haematogenous in origin fungal infections due to Petriellidium boydii (Allescheria boydii). In vitro drug sensitivity studies. AmJf Med 1976; 61: in a woman receiving corticosteroid treatment 632-40. for lupus nephritis. Parenteral therapy with 4 Gordon MA, Vallotton WW, Groffead GS. Corneal sclerosis.

A case of keratomycosis treated successfully with nystatin on September 26, 2021 by guest. Protected copyright. miconazole was unsuccessful despite the fact that and amphotericin B. Arch Ophthalmol 1959; 62: 758-63. the drug was detected in the vitreous. The third 5 Matsuzaki 0. Ocular infection with a fungus from rice leaf. JpnJr Med Mycol 1969; 10: 239. case9 occurred in a 15-year-old patient who 6 Zapater RC, Albesi EJ. Corneal monosporiosis. Ophthalmo- developed aspiration pneumonia and died logica 1979; 178: 142-7. 7 Galgiani JN, Stevens DA, Graybill JR, Stevens DL, Tillinghast despite niconazole therapy. AJ, Levin HB. Pseudallescheria boydii infections treated with The treatment of mycotic keratitis remains a ketoconazole: clinical evaluation of seven patients and in vitro susceptibility results. Chest 1984; 86: 219-24. difficult problem, because none of the available 8 Glassman MI, Henkind P, Alture-Werber E. Monosporium antifungal drugs is ideal. Natamycin has been apiospermum endophthalmitis. Am J Ophthalmol 1973; 76: 821-4. used successfully to treat filamentous fungal 9 Meadow WL, Tipple MA, Rippon JW. Endophthalmitis infections, but its tissue penetration is limited caused by Petriellidium boydii. Am j Dis Child 1981; 135: 378-80. and it is ineffective subconjunctivally.'°0" 10 Jones DB. Initial therapy of suspected microbial corneal Nystatin and amphotericin B have been even less ulcers. II. Specific antibiotic therapy based on corneal scrapings. Surv Ophthalmol 1979; 24: 97. successful than natamycin, and both are irritat- 11 Forster RK. Fungal diseases. In: Smolin G, Thoft RA, eds. ing to the involved tissue. ' Of the topical The cornea: scientific foundations and clinical practice. Boston: Little, Brown, 1983: 168-77. imidazoles, econazole has the broadest 12 Jones BR, Clayton YM, Oji EO. Recognition and chemo- spectrum'2 and has been used successfully to therapy ofoculomycosis. Postgrad MedJ3 1979; 55: 625-8. 13 Foster CS. Miconazole therapy for keratomycosis. treat mycotic keratitis due to Aspergillus spp and AmJ Ophthalmol 1981; 91: 622-9. Fusarium spp. Miconazole has been used success- 14 Ishibashi Y, Matsumoto Y, Takei K. The effects ofintravenous miconazole on fungal keratitis. Am J Ophthalmol 1984; 98: fully in treating mycotic keratitis both topically'3 433-7. and intravenously. 14 Itraconazole has been shown 15 Thomas PA, Abraham DJ, Kalavathy CM, Rajasekaran J. Oral itraconazole therapy for mycotic keratitis. Mycoses to be useful treating some cases ofsevere keratitis 1988; 31: 271-9. due to Aspergillus spp,'5 but it has proved less 16 Ragge NK, Dean Hart JC, Easty DL, Tyers AG. A case of fungal keratitis caused by Scopulariopsis brevicaulis: treat- successful in eradicating infections caused by ment with antifungal agents and penetrating keratoplasty. Fusarium spp and other filamentous fungi. I5 16 BrJ7 Ophthalmol 1990; 74: 561-2.