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Endophthalmitis Caused by Non-albicans Species of Candida Nirmal Joshi and Bruce H. Hamory

From the Division of Infectious Diseases and Epidemiology, Department of Medicine, The Milton S. Hershey Medical Center, University Hospital, The Pennsylvania State University, Hershey, Pennsylvania

While endophthalmitis due to Candida albieans is commonly seen in clinical practice, nonalbieans species of Candida (NAC) are rarely reported to cause this condition. The English-language literature from 1965 through 1989 was reviewed for cases of endophthalmitis due to NAC. Clinical details of six well-documented cases and one unpublished case are presented here. Large studies

Endophthalmitis caused by yeasts of the genus Candida may follow infections of other sites exogenously introduced by trauma [1] or surgery [2, 3] or introduced by hematogenous dissemination from an endogenous focus. Endophthalmitis poses a threat to vision by causing vitreoretinal abscesses with retinal necrosis, vitreous organization, and traction retinal detachment. In post-mortem series disseminated candidiasis is recognized at necropsy in r'V78 % of patients with apparent hematogenous ocular involvement [4]; moreover, r'V50% of the cases of disseminated candidiasis that are recognized postmortem are diagnosed before death [5]. Thus hematogenous candidal endophthalmitis is an important antemortem marker for disseminated candidiasis. While endophthalmitisdue to Candida albicans is commonly described, there are few reported cases due to non-albicans species of Candida (NAC). These species are acquiring increasing importance as more cases of infection in humans are recognized [6-16]. Of special concern are immunocompromised patients with hematologic malignancies, in whom cases of NAC fungemia have, in some series, outnumbered those of C. albicans fungemia [17]. Diagnosis of disseminated candidiasis caused by NAC may be especially difficult because of a relative lack of serologic tests. Treatment for NAC infections may also by complicated by the relative resistance of these species to standard antifungal agents.

Received 7 March 1990; revised 25 May 1990. Reprints and correspondence: Dr. Nirmal Joshi, Division of Infectious Diseases and Epidemiology, Department of Medicine, The Milton S. Hershey Medical Center, P. O. Box 850, Hershey, Pennsylvania 17033. Reviews of Infectious Diseases 1991;13:281-7 © 1991 by The University of Chicago. All rights reserved. 0162-0886/91/1302-0012$02.00

We reviewed the English-language literature from 1965 through 1989 for cases of endophthalmitis caused by NAC. In this article we discuss the clinical features, pathology, predisposing factors, diagnosis, and treatment of these cases.

Mycology The species of Candida other than C. albicans that are encountered in human disease include Candida tropicalis, Candida parapsilosis, Candida krusei, Candida stellatoidea, Candida guilliermondii, Candida lusitaniae, Candida glabrata, Candida pseudotropicalis, and Candida rugosa [6-16]. Even though all species of Candida will grow on the usual laboratory media, Sabouraud agar with antibiotics is recommended for direct isolation. Cycloheximide, an antibiotic used to selectively inhibit saprophytic fungi, does not affect the growth of most NAC but may inhibit some strains of C. tropicalis, C. krusei, and C. parapsilosis. All Candida species grow best at room temperature. Pasty yeastlike colonies appear within 24-48 hours; colonies of C. albicans and those of NAC do not differ from each other in appearance. NAC in general, however, are rapidly distinguished from C. albicans by their failure to produce germ tubes following a 2-hour period of incubation in serum; the exceptions are occasional strains of C. stellatoidea and C. tropicalis. Further speciation is based on the results of incubation in cornmeal agar (c. albicans forms chlamydoconidia) and of carbohydrate fermentation and assimilation studies [18, 19]. Identification and speciation of yeasts by conventional methods may require as long as 2-4 weeks. A number of commercial kits capable of rapid identification of yeasts are now available. These include the API 20C (Analytab Products, Plainview, NY), the BBL Minitek yeast system (BBL Microbiology Systems, Cockeysville, MD), and the Uni-Yeast-Tec

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of nosocomial fungemia are also summarized to emphasize the growing contribution of NAC to the total number of infections in humans, especially immunocompromised patients. The infrequency of ocular involvement in NAC infection is supported by studies in experimental animals that demonstrate a lower incidence ofNAC endophthalmitis than of C. albieans endophthalmitis in the presence of disseminated infection. Since endophthalmitis in the absence of exogenous infection suggests disseminated candidal infection and since most NAC strains are relatively resistant to amphotericin B, it is important to recognize and appropriately treat endophthalmitis due to NAC.

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Joshi and Hamory

282

Table 1. Contribution of NAC to the total number of cases of nosocomial fungemia. Reference (year)

Total no. of cases

22 (1989) 17 (1985) 23 (1983) 24 (1981) 25 (1974)

135 200 65 136 70

No. (%) of cases with indicated etiology

C. albicans 69 89 35 53 28

(51) (44) (54) (39) (40)

NAC

Other

63 (47) 103 (52) 29 (45) 76 (56) 21 (30)

3 (2) 8 (4) 1 (1) 7 (5) 21 (30)

(Flow Laboratories, McLean, VA). Fairly reliable results may be obtained with these systems in 3-7 days [20].

Members of the genus Candida are not normal inhabitants of the soil but are isolated regularly from the human gastrointestinal tract and skin. C. albicans is recovered from the gastrointestinal tract of 20%-40% of healthy individuals [19]. C. guilliermondii, C. parapsilosis, C. krusei, and C. tropicalis may also be found in the gastrointestinal tract, although in lower concentrations [21]. Selected large series of cases of nosocomial fungemia are summarized in table 1 [17,22-25]. As shown, 30%-56% of fungemia cases in this setting are caused by NAC. Rates of NAC fungemia may exceed those of C. albicans fungemia among immunocompromised patients with cancer [24]. None

Table 2. Proportion of candidal fungemic episodes resulting in endophthalmitis. No. (%) of patients with infection as reported in indicated reference no. (year) Organism, type of infection

26 (1989): n = 32

27 (1987)*: n = 48

28 (1982): n = 38

29 (1979)t: n = 85

Total: n = 203

C. albicans Fungemia Endophthalmitis C. tropicalis Fungemia Endophthalmitis

17 (53) 6 (35) 1 (3) 0(... )

28 (58) 1 (4)

27 (71) 10 (37)

12 (25) 1 (8)

5 (13) I (20)

44 (52) 9 (20)

116 (57) 26 (22)

11 (13) 0(... )

29 (14) 2 (7)

3 (8) 0( ... )

3 (3) 0(...)

20 (10) I (4)

C. parapsilosis Fungemia Endophthalmitis C. glabrata Fungemia Endophthalmitis Other Fungemia Endophthalmitis

7 (22) I (14)

o (...)

7 (15)

0( ... ) 0( ... )

o (...)

2 (5) 0( ... )

5 (6) 2 (5)

10 (5) 2 (20)

7 (22):1: 2 (29)

1 (2)§ 0( ... )

I (3)11 0(... )

5 (6)§ 0( ... )

14 (7) 2 (14)

3 (6)

* Three patients had two different yeast species isolated from blood. t Noncandidal fungemias were reported but are not shown in the table. t Episodes were caused by C. lusitaniae. § Episodes were caused by Candida species. II Episodes were caused by C. krusei.

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Epidemiology

of the referenced studies specifically reported examination of the ocular fundus. Table 2 [26-29] summarizes those series offungemia cases in which evidence for endophthalmitis was specifically sought ante-mortem. Brooks [26] reported endophthalmitis in six (35 %) of 17 episodes of C. albicans fungemia and in only three (20%) of 15 episodes of NAC fungemia. In the study reported by Harvey and Myers [27], the overall prevalence of endophthalmitis was low, with only two of 48 patients developing the complication; C. albicans and NAC were responsible for one case each. Parke et al. [28] reported the development of endophthalmitis in 10 (37 %) of 27 episodes of C. albicans fungemia and in one (9 %) of 11 episodes of NAC fungemia. Klein and Watanakunakom [29] demonstrated endophthalmitis in nine (20 %) of 44 patients with C. albicans fungemia and in two (8 %) of 24 patients with NAC fungemia (both of the latter due to C. glabrata). In these four series the contribution ofNAC cases to all fungemia episodes ranged from 29% to 47%. Endophthalmitis associated with NAC fungemia has been reported most frequently for C. tropicalis and C. glabrata. The frequency of ocular involvement in fungemic patients and in those with disseminated fungal infection has also been estimated by postmortem examination. Necropsy findings for 133 such patients at the Johns Hopkins Hospital were reviewed by McDonnell et al. [30]. About 10% of these patients had ocular involvement. In contrast to findings from clinical studies, disseminated C. tropicalis infection was associated with a higher rate of endophthalmitis than was C. albicans

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283

NAC Endophthalmitis

infection. Of 22 patients with C. tropicalis infection, live (22.7%) had ocular lesions demonstrable at postmortem examinations; of 48 patients with C. albicans infection, only three (6.3%) had ocular lesions post-mortem.

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Tbe three mctorsmost consistentlyreported in patients with NAC endophthalmitis (table 3) are use of prolonged or multiple systemic antibiotics, abdominal surgery, and hyperalimentation. It is of interest that the most common agent of fungal endocarditis in intravenous drug addiets is C. parapsilosis [38]. Nevertheless, no case of fungal endophthalmitis due to this organism has been reported in this population. No cases of endophthalmitisdue to NAC havebeen diagnosed ante-mortemin patientswith cancer despitethe common presence of these organisms in the bloodstream. There are three possibleexplanations for this observation. First, a rabbit model of endophthalmitis demonstrates that neutropenia interferes with the formation of ocular lesionsin candidalendophthalmitis since the lesions are composed predominantly of infiammatory exudate surrounding a fewyeasts. Second, NAChave

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Endophthalmitis caused by non-albicans species of Candida.

While endophthalmitis due to Candida albicans is commonly seen in clinical practice, non-albicans species of Candida (NAC) are rarely reported to caus...
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