0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Clinicopathologic Reports, Case Reports, and Small Case Series |

Endogenous Scedosporium apiospermum Endophthalmitis FREE

ATul Jain, MD; Peter Egbert, MD; Timothy J. McCulley, MD; Mark S. Blumenkranz, MD; Darius M. Moshfeghi, MD
[+] Author Affiliations

Section Editor: W. Richard Green, MD

More Author Information
Arch Ophthalmol. 2007;125(9):1286-1289. doi:10.1001/archopht.125.9.1286.
Text Size: A A A
Published online

Scedosporium apiospermum is the asexual form of Pseudallescheria boydii, a ubiquitous saprophytic filamentous fungus.1 Neutropenia predisposes patients to infection with this organism.2 Endogenous endophthalmitis from S apiospermum is a rare but grave sequela.3

We present 3 cases of endogenous S apiospermum endophthalmitis and histopathologic findings.

REPORT OF CASES

Case 1

A 59-year-old woman with pre–B-cell acute lymphocytic leukemia developed neutropenia (absolute neutrophil count, <100 cells/mm3) and blurred vision in her left eye. She received intravenous piperacillin sodium–tazobactam sodium, amphotericin B, vancomycin hydrochloride, acyclovir sodium, and sulfamethoxazole-trimethoprim. Her vision deteriorated, and skin lesions appeared on the right arm and left hip. Results of peripheral blood and cutaneous and pulmonary biopsy cultures were negative.

Visual acuity was 20/20 OD and 20/400 OS, with central scotoma and pain in the left eye. There was vitritis with preretinal exudation and surrounding areas of focal retinitis and retinal hemorrhages (Figure 1A). Vitreous aspiration and intravitreal administration of amphotericin B (5 μg/0.05 mL) were performed in conjunction with intravenous voriconazole treatment (6 mg/kg). Four days later, 20 colonies of S apiospermum were identified, sensitive only to voriconazole (minimum inhibitory concentration [MIC], 0.5 μg/mL) and resistant to amphotericin B (MIC, >16 μg/mL), flucytosine (MIC, >64 μg/mL), and itraconazole (MIC, 2 μg/mL). The patient received 2 subsequent intravitreal injections of voriconazole (100 μg/0.1 mL), a vitrectomy with intravitreal voriconazole (150 μg), and 3 weekly intravitreal injections of voriconazole (100 μg). Cutaneous blood and lung cultures yielded S apiospermum, and voriconazole monotherapy was continued (4 mg/kg intravenously twice daily in the hospital and then 200 mg orally twice daily at home). Initial and repeated vitreous voriconazole levels (Fungus Testing Laboratory, University of Texas, San Antonio) were evaluated by high-performance liquid chromatography and exceeded the MIC (Table). The patient's visual acuity progressed to no light perception with eye pain, and she chose to undergo enucleation. Only the initial ocular culture had positive findings; results of all subsequent cultures were negative.

Place holder to copy figure label and caption
Figure 1.

Clinical and histologic photographs from patient 1. A, Fundus photograph of the left eye showing dense vitritis, vitreous abscess, and yellow-white fungus–containing plaque obscuring the view of the optic nerve and macula. B, Retinal necrosis over the optic nerve and macula as well as scleral thickening caused by fungal infection. Note the normal retina superiorly with retinal necrosis and inflammatory infiltrate inferiorly (hematoxylin-eosin, original magnification ×10). C, View through plaque showing large, branching, septate fungi (Scedosporium apiospermum) (Gomori methenamine-silver stain, original magnification ×20). D, High-power view of C, demonstrating morphologically normal S apiospermum fungi throughout (original magnification ×40).

Graphic Jump Location
Table Graphic Jump LocationTable. Intraocular Voriconazole Concentrations

Limited exenteration was performed because of gross scleral extension. Histopathologic examination demonstrated a disorganized and necrotic retina with inflammatory infiltrate and scleral thickening (Figure 1B). Morphologically normal-appearing S apiospermum organisms were identified (Figure 1C and D). The patient died 6 months later of overwhelming sepsis.

Case 2

A 37-year-old woman with pre–B-cell acute lymphocytic leukemia developed pain and redness in her left eye. She had profound neutropenia and systemic sepsis with pulmonary nodules. Visual acuity was 20/20 OD and 20/25 OS with conjunctival injection, chemosis, and decreased abduction in the left eye; the results of the remainder of the anterior and posterior examination were normal in both eyes. Magnetic resonance imaging showed nonspecific temporal, orbital soft-tissue enhancement. Intravenous vancomycin, imipenem, piperacillin sodium–tazobactam sodium, and liposomal amphotericin B treatment resulted in resolution of her ocular symptoms. Results of repeated magnetic resonance imaging were normal.

Fevers and sepsis persisted. Intravenous voriconazole (4 mg/kg twice daily) and azithromycin were added. Four days later the patient developed dull pain in the left eye with decreased vision (visual acuity, 20/100). Examination showed conjunctival injection, vitritis, a yellow-white preretinal mass over the temporal macula, and a flocculent whitish vitreous mass in the inferotemporal macula. The papillomacular bundle demonstrated similarly colored yellow-white infiltrates with surrounding intraretinal hemorrhages.

The patient underwent vitreous aspiration and injection with vancomycin (1 mg/0.1 mL), ceftazidime sodium (2 mg/0.1 mL), and amphotericin B (5 μg/0.05 mL), followed by vitrectomy and injection of vancomycin (1 mg), ceftazidime sodium (2 mg), and voriconazole (100 μg). Four days later, vitreous cultures identified 4 colonies of S apiospermum sensitive only to voriconazole (MIC, 0.25 μg/mL) and resistant to amphotericin B (MIC, >16 μg/mL) and caspofungin acetate (MIC, 8.0 μg/mL). Initial and repeated vitreous voriconazole levels exceeded the MIC (Table).

The patient developed inferior rhegmatogenous retinal detachment, repaired with scleral buckle, vitrectomy, and silicone oil. Her retina attached and her endophthalmitis stabilized, but the patient died shortly thereafter of multiorgan system failure. Numerous blood and intraoperative vitreous culture results were negative.

Autopsy was performed. Gross examination showed a vitreous abscess, intraretinal fungal plaque, retinal necrosis, and proliferative vitreoretinopathy (Figure 2A). Retinal disorganization (Figure 2B) and fungal invasion (Figure 2C) were extensive. Lung specimens showed diffuse infiltration by multiple fungal organisms consistent with S apiospermum (Figure 2D).

Place holder to copy figure label and caption
Figure 2.

Ophthalmic and lung histopathologic photographs from patient 2. A, Gross photograph of the left eye showing a vitreous abscess with a 10 × 8-mm yellow-white fungal plaque covering the optic nerve and macula, retinal necrosis, and proliferative vitreoretinopathy. Note the cut edge of the scleral buckle in the upper left of the figure. B, View through plaque showing retinal necrosis and disorganization caused by fungal invasion (hematoxylin-eosin, original magnification ×10). C, View through plaque showing large, branching, septate fungi (Gomori methenamine-silver stain, original magnification ×20). D, Lung tissue demonstrating numerous, morphologically normal–appearing, large, branching, septate fungi (hematoxylin-eosin, original magnification ×40).

Graphic Jump Location
Case 3

A 21-year-old woman with Wegener granulomatosis treated with prednisone and cyclophosphamide developed fever, myalgias, malaise, and headache with stiff neck. Magnetic resonance images demonstrated diffuse meningeal enhancement, and cerebrospinal fluid demonstrated 4+ white blood cells without organisms. Results of blood and cerebrospinal fluid cultures were negative. The patient reported subjective vision loss for 1 week and developed bilateral vitreous infiltration despite treatment with intravenous amphotericin B, fluconazole, ganciclovir, and broad-spectrum antibiotics.

Visual acuity was 20/30 OD and 20/70 OS. Fundus examination demonstrated 1+ to 2+ vitritis with prominent infiltrates extending from the optic discs bilaterally, obscuring the central macula in the left eye. The patient received bilateral intravitreal injections of amphotericin B (5 μg/0.05 mL) and a vitrectomy in the left eye, followed by weekly intravitreal itraconazole (5 μg/0.05 mL) injections during the next month. Vitreous cultures isolated S apiospermum, sensitive to itraconazole (MIC, 0.5 μg/mL) but resistant to amphotericin B (>16 μg/mL) and miconazole nitrate (>4 μg/mL). At no point was any visual recovery observed.

An unrelenting neurologic deterioration paralleled the visual status. Despite intrathecal injections of itraconazole, the patient became progressively lethargic and died shortly thereafter.

COMMENT

We describe 3 patients with endogenous S apiospermum endophthalmitis involving 4 eyes that lost substantial vision despite early diagnosis and appropriate therapy. Disseminated S apiospermum has mortality exceeding 90%, consistent with the deaths noted in all 3 affected patients in this report.4

Most S apiospermum organisms are sensitive only to itraconazole and voriconazole.5 Voriconazole achieves therapeutic vitreous levels after systemic administration.6 Vitreous concentrations up to 25 μg/mL were safely tolerated in rats,7 and doses of 200 μg/mL are safely tolerated in humans.8 To our knowledge, ocular voriconazole levels have not previously been documented in S apiospermum endophthalmitis. Herein, both aqueous and vitreous voriconazole levels exceeded the MIC after systemic therapy and exceeded the MIC by 10-fold after intravitreal injections. Despite this, normal-appearing fungi were identified on histopathologic examination.

Vitreous culture secured the systemic diagnosis, highlighting the role of ophthalmologic evaluation in immunocompromised patients. Resistance to amphotericin B is increasing, and voriconazole might be a reasonable first-line alternative against most fungi and molds with the exception of Zygomycetes.9

ARTICLE INFORMATION

Correspondence: Dr Moshfeghi, 1225 Crane St, Menlo Park, CA 94025 (dariusm@stanford.edu).

Financial Disclosure: None reported.

REFERENCES

McGuire  TWBullock  JDBullock  JD  JrElder  BLFunkhouser  JW Fungal endophthalmitis: an experimental study with a review of 17 human ocular cases. Arch Ophthalmol 1991;109 (9) 1289- 1296
PubMed Link to Article
McKelvie  PAWong  EYChow  LPHall  AJ Scedosporium endophthalmitis: two fatal disseminated cases of Scedosporium infection presenting with endophthalmitis. Clin Experiment Ophthalmol 2001;29 (5) 330- 334
PubMed Link to Article
Figueroa  MSFortun  JClement  ADe Arevalo  BF Endogenous endophthalmitis caused by Scedosporium apiospermum treated with voriconazole. Retina 2004;24 (2) 319- 320
PubMed Link to Article
Maertens  JLagrou  KDeweerdt  H  et al.  Disseminated infection by Scedosporium prolificans: an emerging fatality among haematology patients: case report and review. Ann Hematol 2000;79 (6) 340- 344
PubMed Link to Article
Larocco  A  JrBarron  JB Endogenous Scedosporium apiospermum endophthalmitis. Retina 2005;25 (8) 1090- 1093
PubMed Link to Article
Breit  SMHariprasad  SMMieler  WFShah  GKMills  MDGrand  MG Management of endogenous fungal endophthalmitis with voriconazole and caspofungin. Am J Ophthalmol 2005;139 (1) 135- 140
PubMed Link to Article
Gao  HPennesi  MEShah  K  et al.  Intravitreal voriconazole: an electroretinographic and histopathologic study [published correction appears in Arch Ophthalmol. 2005;123(1):130]. Arch Ophthalmol 2004;122 (11) 1687- 1692
PubMed Link to Article
Scott  IUCruz-Villegas  VFlynn  HW  JrMiller  D Delayed-onset, bleb-associated endophthalmitis caused by Lecythophora mutabilisAm J Ophthalmol 2004;137 (3) 583- 585
PubMed Link to Article
Johnson  LBKauffman  CA Voriconazole: a new triazole antifungal agent. Clin Infect Dis 2003;36 (5) 630- 637
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Clinical and histologic photographs from patient 1. A, Fundus photograph of the left eye showing dense vitritis, vitreous abscess, and yellow-white fungus–containing plaque obscuring the view of the optic nerve and macula. B, Retinal necrosis over the optic nerve and macula as well as scleral thickening caused by fungal infection. Note the normal retina superiorly with retinal necrosis and inflammatory infiltrate inferiorly (hematoxylin-eosin, original magnification ×10). C, View through plaque showing large, branching, septate fungi (Scedosporium apiospermum) (Gomori methenamine-silver stain, original magnification ×20). D, High-power view of C, demonstrating morphologically normal S apiospermum fungi throughout (original magnification ×40).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Ophthalmic and lung histopathologic photographs from patient 2. A, Gross photograph of the left eye showing a vitreous abscess with a 10 × 8-mm yellow-white fungal plaque covering the optic nerve and macula, retinal necrosis, and proliferative vitreoretinopathy. Note the cut edge of the scleral buckle in the upper left of the figure. B, View through plaque showing retinal necrosis and disorganization caused by fungal invasion (hematoxylin-eosin, original magnification ×10). C, View through plaque showing large, branching, septate fungi (Gomori methenamine-silver stain, original magnification ×20). D, Lung tissue demonstrating numerous, morphologically normal–appearing, large, branching, septate fungi (hematoxylin-eosin, original magnification ×40).

Graphic Jump Location

Tables

Table Graphic Jump LocationTable. Intraocular Voriconazole Concentrations

References

McGuire  TWBullock  JDBullock  JD  JrElder  BLFunkhouser  JW Fungal endophthalmitis: an experimental study with a review of 17 human ocular cases. Arch Ophthalmol 1991;109 (9) 1289- 1296
PubMed Link to Article
McKelvie  PAWong  EYChow  LPHall  AJ Scedosporium endophthalmitis: two fatal disseminated cases of Scedosporium infection presenting with endophthalmitis. Clin Experiment Ophthalmol 2001;29 (5) 330- 334
PubMed Link to Article
Figueroa  MSFortun  JClement  ADe Arevalo  BF Endogenous endophthalmitis caused by Scedosporium apiospermum treated with voriconazole. Retina 2004;24 (2) 319- 320
PubMed Link to Article
Maertens  JLagrou  KDeweerdt  H  et al.  Disseminated infection by Scedosporium prolificans: an emerging fatality among haematology patients: case report and review. Ann Hematol 2000;79 (6) 340- 344
PubMed Link to Article
Larocco  A  JrBarron  JB Endogenous Scedosporium apiospermum endophthalmitis. Retina 2005;25 (8) 1090- 1093
PubMed Link to Article
Breit  SMHariprasad  SMMieler  WFShah  GKMills  MDGrand  MG Management of endogenous fungal endophthalmitis with voriconazole and caspofungin. Am J Ophthalmol 2005;139 (1) 135- 140
PubMed Link to Article
Gao  HPennesi  MEShah  K  et al.  Intravitreal voriconazole: an electroretinographic and histopathologic study [published correction appears in Arch Ophthalmol. 2005;123(1):130]. Arch Ophthalmol 2004;122 (11) 1687- 1692
PubMed Link to Article
Scott  IUCruz-Villegas  VFlynn  HW  JrMiller  D Delayed-onset, bleb-associated endophthalmitis caused by Lecythophora mutabilisAm J Ophthalmol 2004;137 (3) 583- 585
PubMed Link to Article
Johnson  LBKauffman  CA Voriconazole: a new triazole antifungal agent. Clin Infect Dis 2003;36 (5) 630- 637
PubMed Link to Article

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

636 Views
11 Citations
×

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
Jobs