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Rhodotorula infection in a corneal graft following penetrating keratoplasty
CASE REPORTS
Rhodotorula infection in a corneal graft following penetrating keratoplasty Ahmed M. Bawazeer,* MD, FRCSC; William G. Hodge,t MD, PhD, FRCSC
C
orneal graft infection is a well-known complication of penetrating keratoplasty (PKP). The reported incidence after corneal transplantation ranges from 1.8% 1 to 11.9%. 2 Bacterial infection is the leading cause of infectious keratitis following keratoplasty. Other, less common causes include fungi, viruses and Acanthamoeba. 3 Candida species are considered the commonest cause of fungal corneal graft infection. 4 Other causes less frequently described in the literature include Aspergillus, Cryptococcus and Penicillium species. 4•5 Because of the geographic differences in the etiology of mycotic infections after keratoplasty, the actual incidence and the type of fungal keratitis following PKP differ according to the climate and the geographic location. We describe a 63-year-old woman with a rare corneal graft infection caused by a red yeast fungal pathogen known as Rhodotorula. CASE REPORT
A 63-year-old woman was referred to the cornea service with a 3-day history of decreased vision in her
*Assistant Professor of Ophthalmology, Department of Ophthalmology, Faculty of Medicine and Allied Sciences, King Abdulaziz University, Jeddah, Saudi Arabia tAssociate Professor of Ophthalmology, Department of Ophthalmology, University of Ottawa Eye Institute, Ottawa, Ont. Originally received Apr. 15, 2002 Accepted for publication Dec. 2, 2002 Reprint requests to: Dr. William G. Hodge, University of Ottawa Eye Institute, 501 Smyth Rd., Ottawa ON KIH 8L6; fax (613) 737-8836; [email protected] This article has been peer-reviewed. Can J Ophthalmol 2003;38:225-7
Rhodotorula keratitis-Bawazeer et al
right eye with pain, redness, tearing and discharge. She had a past ocular history of acute angle-closure glaucoma 10 years earlier in the same eye, and lensinduced uveitis with bullous keratopathy 1 year earlier, which was managed with PKP and open-sky cataract extraction with intraocular lens implantation. One month before presentation she had experienced an acute episode of corneal graft rejection. The patient was healthy, with no history of systemic illness. Her medications included 1% prednisolone acetate instilled four times daily, 0.5% timolol instilled twice daily and 2% dorzolamide instilled twice daily, all onto the right eye. Ocular examination showed a visual acuity of hand motion in the right eye and 20/40 in the left eye. The right pupil was mid-dilated, and the left pupil was reactive to light, with no relative afferent pupillary defect. Ocular motility was within normal limits. Slit-lamp examination of the right cornea showed mild bullous changes with a 2-mm corneal epithelial defect and a deep stromal infiltrate at 10 o'clock, and 4+ cells and 4+ flare in the anterior chamber with no hypopyon. The posterior chamber intraocular lens was in good position. The left eye showed a 2+ nuclear sclerotic cataract; the remainder of the anterior segment examination was within normal limits. The fundus view was limited in the right eye and within normal limits in the left. The intraocular pressure was 15 mm Hg bilaterally. Ocular ultrasound examination showed mild vitreous opacity and posterior vitreous detachment, with no clinical evidence of posterior uveitis or endophthalmitis. An infectious corneal ulcer was diagnosed. Corneal scrapings were obtained, and therapy was started with 0.3% ofloxacin (administered to the right eye every 2 hours), with her other medications being continued. The corneal scrapings grew a-hemolytic streptococci consistent with Streptococcus pneumoniae when cultured. Therapy with cefazolin (50 mg/mL instilled hourly) was started, and ofloxacin therapy
225
Rhodotorula keratitis-Bawazeer et al was stopped. Over 3 weeks there was complete resolution of the ulcer, and topical cefazolin therapy was stopped. One month later the patient returned with a history of pain, redness and tearing in her right eye. A corneal epithelial defect was noted at 9 o'clock, with no signs of infection. Therapy was started with 0.3% ofloxacin (instilled four times daily), and a bandage contact lens was placed on the eye. Prednisolone acetate therapy was continued four times daily. The corneal epithelial defect increased in size, and 2 weeks later a large infiltrate with numerous deep satellite infiltrates and diffuse corneal edema developed between 6 and 9 o'clock (Figs. 1 and 2). The infiltrate did not originate from a suture. Ofloxacin therapy was stopped so that corneal scrapings could be obtained for culture, and the frequency of administration of prednisolone acetate was reduced to once per day. The bandage contact lens was removed. Therapy was started with cefazolin (50 mg/mL every 2 hours) and tobramycin (14 mg/mL every 2 hours), and the same glaucoma medications were continued. We felt that a new bacterial infection was likely but that a fungal or other atypical form of keratitis was possible. The corneal culture results were negative. The corneal ulcer progressed slowly over 2 weeks, with the development of a fibrinous membrane over the endothelial surface of the cornea. Therapy with both cefazolin and tobramycin was stopped, and corneal scrapings were once again obtained to rule out viral , fungal or atypical mycobacterial infection. No pathogen was identified. Because of the relentless progression of the keratitis, the patient's discomfort and our impression that the entire infiltrate needed to be
Fig. 2-Higher-power view.
removed, PKP with a 9-mm donor graft was performed in lieu of corneal biopsy, and the cornea was submitted for microbiologic examination. Because culture of previous scrapings had given negative results, the growth of atypical organisms is difficult, and the "gold standard" for diagnosis in such cases is microbiology, the entire specimen was sent for microbiologic study, and no smears or pathological stains were performed. On the second postoperative day a heavy yeast growth on Sabouraud dextrose agar without cycloheximide consistent with Rhodotorula species was isolated from the cornea. Therapy was started with 0.15 % amphotericin B, administered four times daily. The patient had an unremarkable postoperative course, and amphotericin B therapy was stopped after 2 weeks, with no evidence of fungal recurrence in the graft. The patient' s visual acuity improved to 20/400, with a clear corneal transplant. The patient was followed regularly in our clinic for 6 months, without any evidence of recurrence. Thereafter, she moved out of the country and was lost to follow-up. COMMENTS
Fig. 1-Large deep infiltrate, corneal edema and satellite lesion in corneal transplant recipient with Rhodotoru/a infection.
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CAN J OPHTHALMOL-VOL. 38, NO. 3, 2003
Rhodotorula is a yeast with a basidiomycetous affinity that produces mucoid colonies with red or yellow carotinoid pigment. It is frequently isolated from the air, fruit juice, dairy products, soil and water.5 In humans, it has been isolated from the skin, urine, stool and upper respiratory tract. 6 In rare situations, typically in immunocompromised patients, this organism can be infectious to humans, in the form of septicemia,? endocarditis,8 peritonitis, 9 meningitis 10 and ventriculitis. 11
Rhodotorula keratitis-Bawazeer et al
Ocular infection with this yeast is extremely rare. Romano and colleagues 12 isolated Rhodotorula from only 1 of 304 healthy eyes examined, and the yeast was isolated from 3 eyes of 313 patients with chronic conjunctivitis, keratoconjunctivitis or keratitis. Rhodotorula has been cultured from contact lens solution13 and donor corneal beds. 14 Other rare forms of ocular infection include keratitis, 15 •16 chronic dacryocystits 17 and chronic endophthalmitis.18 Rhodotorula infection following lamellar keratoplasty or PKP is extremely rare. Panda and associates19 reported a case of infection with this organism in the corneal interface following lamellar keratoplasty. The patient was treated with 0.15% amphotericin eye drops and donor button removal. In our case the corneal graft infection occurred 1 year after the initial PKP procedure while the patient was receiving longterm topical steroid therapy and had an abnormal corneal epithelial surface. There are many risk factors associated with fungal keratitis following keratoplasty, including long-term topical steroid therapy, persistent epithelial defect and the possibility of graft contamination. 4 Our patient's presentation was suggestive of typical fungal keratitis. In addition to the risk factors mentioned in the previous paragraph, she had pain, deep infiltrates and satellite lesions, and progression despite topical antibacterial therapy. However, there was nothing specific to suggest Rhodotorula species as opposed to any other type of fungus. Like most yeast pathogens, Rhodotorula is sensitive to amphotericin B and fluorocytosine. In advanced cases, however, corneal transplantation may be indicated to eradicate the infection, as was necessary in our case. The ideal method of treatment of this and other fungal ulcers, including the possible benefit of systemic therapy as well as the method of prophylactic therapy after keratoplasty, is currently not known.
4.
5.
6. 7.
8.
9.
10. 11.
12.
13.
14.
15.
16. 17.
18.
REFERENCES
19. 1. Lamensdorf M, Wilson LA, Waring GO, Cavanagh D. Microbial keratitis after penetrating keratoplasty [abstract]. Ophthalmology 1982;89(Suppl): 124. 2. Al-Hazzaa SAF, Tabbara KF. Bacterial keratitis after penetrating keratoplasty. Ophthalmology 1988;95(11): 1504-8. 3. Parrish CM, Head WS, O'Day DM, Rowlett W. Acan-
thamoeba keratitis following keratoplasty without other identifiable risk factors. Arch Ophthalmol 1991; 109(4): 471. Fong LP, Ormerod LD, Kenyon KR, Foster CS. Microbial keratitis complicating penetrating keratoplasty. Ophthalmology 1988;95(9): 1269-75. Harris DJ Jr, Stulting RD, Waring GO III, Wilson LA. Late bacterial and fungal keratitis after corneal transplantation: spectrum of pathogens, graft survival, and visual prognosis. Ophthalmology 1988;95(10): 1450-7. Kwon-Chung KJ, Bennett JE. Medical mycology. Philadelphia: Lea & Febiger; 1992. p. 770-2. Anaissie E, Bodey GP, Kantarjian H, Ro J, Vartivarian SE, Hopfer R, et al. New spectrum of fungal infections in patients with cancer. Rev Infect Dis 1989;11(3):369-78. Naveh Y, Friedman A, Merzbach D, Hashman N. Endocarditis caused by Rhodotorula successfully treated with 5-fluorocytosine. Br Heart J 1975;37(1):101-4. Eisenberg ES, Alpert BE, Weiss RA, Mittman N, Soeiro R. Rhodotorula rubra peritonitis in patients undergoing continuous ambulatory peritoneal dialysis. Am J Med 1983;75(2):349-52. Pore RS, Chen J. Meningitis caused by Rhodotorula. Sabouraudia 1976;14(3):331-5. Donald FE, Sharp JF, Firth JL, Crowly JL, Ispahani P. Rhodotorula rubra ventriculitis. J Infect 1988;16(2): 187-91. Romano A, Segal E, Stein R, Eylan E. Yeast in banal external ocular inflammations. Ophthalmologica 1975; 170(1):13-21. van Setten GB, Tervo T, Tarkkanen A. [Acute keratitis and contamination of contact lens care systems with Bacillus cereus.] Klin Monatsbl Augenheilkd 1989; 195(1): 28-31. Dixon DM, Graham CR Jr, Shaffer RM, Tarantino P. Fungal flora from diabetic and non-diabetic human donor corneas. Cornea 1984-85;3(4):281-4. Guerra R, Cavallini GM, Longanesi L, Casolari C, Bertoli G, Rivasi F, et al. Rhodotorula glutinis keratitis. Int Ophthalmoll992;16(3):187-90. Fran'
Key words: keratitis, Rhodotorula species, penetrating keratoplasty
CAN
J OPHTHALMOL-VOL. 38, NO.3, 2003
227
Rhodotorula infection in a corneal graft following penetrating keratoplasty Ahmed M. Bawazeer,* MD, FRCSC; William G. Hodge,t MD, PhD, FRCSC
C
orneal graft infection is a well-known complication of penetrating keratoplasty (PKP). The reported incidence after corneal transplantation ranges from 1.8% 1 to 11.9%. 2 Bacterial infection is the leading cause of infectious keratitis following keratoplasty. Other, less common causes include fungi, viruses and Acanthamoeba. 3 Candida species are considered the commonest cause of fungal corneal graft infection. 4 Other causes less frequently described in the literature include Aspergillus, Cryptococcus and Penicillium species. 4•5 Because of the geographic differences in the etiology of mycotic infections after keratoplasty, the actual incidence and the type of fungal keratitis following PKP differ according to the climate and the geographic location. We describe a 63-year-old woman with a rare corneal graft infection caused by a red yeast fungal pathogen known as Rhodotorula. CASE REPORT
A 63-year-old woman was referred to the cornea service with a 3-day history of decreased vision in her
*Assistant Professor of Ophthalmology, Department of Ophthalmology, Faculty of Medicine and Allied Sciences, King Abdulaziz University, Jeddah, Saudi Arabia tAssociate Professor of Ophthalmology, Department of Ophthalmology, University of Ottawa Eye Institute, Ottawa, Ont. Originally received Apr. 15, 2002 Accepted for publication Dec. 2, 2002 Reprint requests to: Dr. William G. Hodge, University of Ottawa Eye Institute, 501 Smyth Rd., Ottawa ON KIH 8L6; fax (613) 737-8836; [email protected] This article has been peer-reviewed. Can J Ophthalmol 2003;38:225-7
Rhodotorula keratitis-Bawazeer et al
right eye with pain, redness, tearing and discharge. She had a past ocular history of acute angle-closure glaucoma 10 years earlier in the same eye, and lensinduced uveitis with bullous keratopathy 1 year earlier, which was managed with PKP and open-sky cataract extraction with intraocular lens implantation. One month before presentation she had experienced an acute episode of corneal graft rejection. The patient was healthy, with no history of systemic illness. Her medications included 1% prednisolone acetate instilled four times daily, 0.5% timolol instilled twice daily and 2% dorzolamide instilled twice daily, all onto the right eye. Ocular examination showed a visual acuity of hand motion in the right eye and 20/40 in the left eye. The right pupil was mid-dilated, and the left pupil was reactive to light, with no relative afferent pupillary defect. Ocular motility was within normal limits. Slit-lamp examination of the right cornea showed mild bullous changes with a 2-mm corneal epithelial defect and a deep stromal infiltrate at 10 o'clock, and 4+ cells and 4+ flare in the anterior chamber with no hypopyon. The posterior chamber intraocular lens was in good position. The left eye showed a 2+ nuclear sclerotic cataract; the remainder of the anterior segment examination was within normal limits. The fundus view was limited in the right eye and within normal limits in the left. The intraocular pressure was 15 mm Hg bilaterally. Ocular ultrasound examination showed mild vitreous opacity and posterior vitreous detachment, with no clinical evidence of posterior uveitis or endophthalmitis. An infectious corneal ulcer was diagnosed. Corneal scrapings were obtained, and therapy was started with 0.3% ofloxacin (administered to the right eye every 2 hours), with her other medications being continued. The corneal scrapings grew a-hemolytic streptococci consistent with Streptococcus pneumoniae when cultured. Therapy with cefazolin (50 mg/mL instilled hourly) was started, and ofloxacin therapy
225
Rhodotorula keratitis-Bawazeer et al was stopped. Over 3 weeks there was complete resolution of the ulcer, and topical cefazolin therapy was stopped. One month later the patient returned with a history of pain, redness and tearing in her right eye. A corneal epithelial defect was noted at 9 o'clock, with no signs of infection. Therapy was started with 0.3% ofloxacin (instilled four times daily), and a bandage contact lens was placed on the eye. Prednisolone acetate therapy was continued four times daily. The corneal epithelial defect increased in size, and 2 weeks later a large infiltrate with numerous deep satellite infiltrates and diffuse corneal edema developed between 6 and 9 o'clock (Figs. 1 and 2). The infiltrate did not originate from a suture. Ofloxacin therapy was stopped so that corneal scrapings could be obtained for culture, and the frequency of administration of prednisolone acetate was reduced to once per day. The bandage contact lens was removed. Therapy was started with cefazolin (50 mg/mL every 2 hours) and tobramycin (14 mg/mL every 2 hours), and the same glaucoma medications were continued. We felt that a new bacterial infection was likely but that a fungal or other atypical form of keratitis was possible. The corneal culture results were negative. The corneal ulcer progressed slowly over 2 weeks, with the development of a fibrinous membrane over the endothelial surface of the cornea. Therapy with both cefazolin and tobramycin was stopped, and corneal scrapings were once again obtained to rule out viral , fungal or atypical mycobacterial infection. No pathogen was identified. Because of the relentless progression of the keratitis, the patient's discomfort and our impression that the entire infiltrate needed to be
Fig. 2-Higher-power view.
removed, PKP with a 9-mm donor graft was performed in lieu of corneal biopsy, and the cornea was submitted for microbiologic examination. Because culture of previous scrapings had given negative results, the growth of atypical organisms is difficult, and the "gold standard" for diagnosis in such cases is microbiology, the entire specimen was sent for microbiologic study, and no smears or pathological stains were performed. On the second postoperative day a heavy yeast growth on Sabouraud dextrose agar without cycloheximide consistent with Rhodotorula species was isolated from the cornea. Therapy was started with 0.15 % amphotericin B, administered four times daily. The patient had an unremarkable postoperative course, and amphotericin B therapy was stopped after 2 weeks, with no evidence of fungal recurrence in the graft. The patient' s visual acuity improved to 20/400, with a clear corneal transplant. The patient was followed regularly in our clinic for 6 months, without any evidence of recurrence. Thereafter, she moved out of the country and was lost to follow-up. COMMENTS
Fig. 1-Large deep infiltrate, corneal edema and satellite lesion in corneal transplant recipient with Rhodotoru/a infection.
226
CAN J OPHTHALMOL-VOL. 38, NO. 3, 2003
Rhodotorula is a yeast with a basidiomycetous affinity that produces mucoid colonies with red or yellow carotinoid pigment. It is frequently isolated from the air, fruit juice, dairy products, soil and water.5 In humans, it has been isolated from the skin, urine, stool and upper respiratory tract. 6 In rare situations, typically in immunocompromised patients, this organism can be infectious to humans, in the form of septicemia,? endocarditis,8 peritonitis, 9 meningitis 10 and ventriculitis. 11
Rhodotorula keratitis-Bawazeer et al
Ocular infection with this yeast is extremely rare. Romano and colleagues 12 isolated Rhodotorula from only 1 of 304 healthy eyes examined, and the yeast was isolated from 3 eyes of 313 patients with chronic conjunctivitis, keratoconjunctivitis or keratitis. Rhodotorula has been cultured from contact lens solution13 and donor corneal beds. 14 Other rare forms of ocular infection include keratitis, 15 •16 chronic dacryocystits 17 and chronic endophthalmitis.18 Rhodotorula infection following lamellar keratoplasty or PKP is extremely rare. Panda and associates19 reported a case of infection with this organism in the corneal interface following lamellar keratoplasty. The patient was treated with 0.15% amphotericin eye drops and donor button removal. In our case the corneal graft infection occurred 1 year after the initial PKP procedure while the patient was receiving longterm topical steroid therapy and had an abnormal corneal epithelial surface. There are many risk factors associated with fungal keratitis following keratoplasty, including long-term topical steroid therapy, persistent epithelial defect and the possibility of graft contamination. 4 Our patient's presentation was suggestive of typical fungal keratitis. In addition to the risk factors mentioned in the previous paragraph, she had pain, deep infiltrates and satellite lesions, and progression despite topical antibacterial therapy. However, there was nothing specific to suggest Rhodotorula species as opposed to any other type of fungus. Like most yeast pathogens, Rhodotorula is sensitive to amphotericin B and fluorocytosine. In advanced cases, however, corneal transplantation may be indicated to eradicate the infection, as was necessary in our case. The ideal method of treatment of this and other fungal ulcers, including the possible benefit of systemic therapy as well as the method of prophylactic therapy after keratoplasty, is currently not known.
4.
5.
6. 7.
8.
9.
10. 11.
12.
13.
14.
15.
16. 17.
18.
REFERENCES
19. 1. Lamensdorf M, Wilson LA, Waring GO, Cavanagh D. Microbial keratitis after penetrating keratoplasty [abstract]. Ophthalmology 1982;89(Suppl): 124. 2. Al-Hazzaa SAF, Tabbara KF. Bacterial keratitis after penetrating keratoplasty. Ophthalmology 1988;95(11): 1504-8. 3. Parrish CM, Head WS, O'Day DM, Rowlett W. Acan-
thamoeba keratitis following keratoplasty without other identifiable risk factors. Arch Ophthalmol 1991; 109(4): 471. Fong LP, Ormerod LD, Kenyon KR, Foster CS. Microbial keratitis complicating penetrating keratoplasty. Ophthalmology 1988;95(9): 1269-75. Harris DJ Jr, Stulting RD, Waring GO III, Wilson LA. Late bacterial and fungal keratitis after corneal transplantation: spectrum of pathogens, graft survival, and visual prognosis. Ophthalmology 1988;95(10): 1450-7. Kwon-Chung KJ, Bennett JE. Medical mycology. Philadelphia: Lea & Febiger; 1992. p. 770-2. Anaissie E, Bodey GP, Kantarjian H, Ro J, Vartivarian SE, Hopfer R, et al. New spectrum of fungal infections in patients with cancer. Rev Infect Dis 1989;11(3):369-78. Naveh Y, Friedman A, Merzbach D, Hashman N. Endocarditis caused by Rhodotorula successfully treated with 5-fluorocytosine. Br Heart J 1975;37(1):101-4. Eisenberg ES, Alpert BE, Weiss RA, Mittman N, Soeiro R. Rhodotorula rubra peritonitis in patients undergoing continuous ambulatory peritoneal dialysis. Am J Med 1983;75(2):349-52. Pore RS, Chen J. Meningitis caused by Rhodotorula. Sabouraudia 1976;14(3):331-5. Donald FE, Sharp JF, Firth JL, Crowly JL, Ispahani P. Rhodotorula rubra ventriculitis. J Infect 1988;16(2): 187-91. Romano A, Segal E, Stein R, Eylan E. Yeast in banal external ocular inflammations. Ophthalmologica 1975; 170(1):13-21. van Setten GB, Tervo T, Tarkkanen A. [Acute keratitis and contamination of contact lens care systems with Bacillus cereus.] Klin Monatsbl Augenheilkd 1989; 195(1): 28-31. Dixon DM, Graham CR Jr, Shaffer RM, Tarantino P. Fungal flora from diabetic and non-diabetic human donor corneas. Cornea 1984-85;3(4):281-4. Guerra R, Cavallini GM, Longanesi L, Casolari C, Bertoli G, Rivasi F, et al. Rhodotorula glutinis keratitis. Int Ophthalmoll992;16(3):187-90. Fran'
Key words: keratitis, Rhodotorula species, penetrating keratoplasty
CAN
J OPHTHALMOL-VOL. 38, NO.3, 2003
227