Exogenous Fungal Endophthalmitis: An Analysis of Isolates and Susceptibilities to Antifungal Agents Over a 20-Year Period (1990–2010)




Purpose


To describe the isolates and susceptibilities to antifungal agents for patients with culture-proven exogenous fungal endophthalmitis.


Design


Noncomparative case series.


Methods


The clinical records of all patients treated for culture-proven exogenous fungal endophthalmitis at a university referral center from 1990 to 2010 were reviewed. Specimens initially used for diagnosis were recovered from the microbiology department and then underwent antifungal sensitivity analysis.


Results


The antifungal susceptibilities of 47 fungal isolates from culture-positive fungal endophthalmitis are reported. Included are 14 isolates from yeast and 33 from mold. The mean (±standard deviation) minimum inhibitory concetrations (MICs) for amphotericin B (2.6 ± 3.5 μg/mL), fluconazole (36.9 ± 30.7 μg/mL), and voriconazole (1.9 ± 2.9 μg/mL) are reported. Presumed susceptibility to oral fluconazole, intravenous amphotericin B, intravitreal amphotericin B, oral voriconazole, and intravitreal voriconazole occurred in 34.8%–43.5%, 0–8.3%, 68.8%, 69.8%, and 100% of isolates, respectively.


Conclusions


Based on this laboratory study of isolates from exogenous fungal endophthalmitis, intravitreal voriconazole appears to provide the broadest spectrum of antifungal coverage and, as such, may be considered for empiric therapy of endophthalmitis caused by yeast or mold.


While fungal infections of the eye (in the form of keratitis) were initially reported as early as 1879, exogenous fungal endophthalmitis was first described 23 years later. The disease stems from 1 of 3 inciting factors: postoperative infections, penetrating ocular trauma, and intraocular extension of ocular surface infections. Each precipitating mechanism of inoculation accounts for roughly one third of exogenous fungal endophthalmitis cases, though keratitis may account for a slightly higher proportion. Clinical outcomes are generally poor, with eventual evisceration or enucleation not uncommon (24%–78%), particularly in posttraumatic cases.


Unlike endogenous fungal endophthalmitis, the vast majority of fungi identified in exogenous cases are molds (87%). Successful treatment of exogenous fungal endophthalmitis is therefore particularly challenging owing to these species of causative molds being relatively virulent and because there is often a lag time from inciting event to endophthalmitis (generally weeks to months ), which can delay the correct diagnosis. A final obstacle in treatment is that appropriate antifungal therapy remains largely undefined in this class of patients. The current study includes a series of patients diagnosed at a university medical center with culture-proven exogenous fungal endophthalmitis and reports both causative fungi and susceptibility to antifungal agents.


Methods


The institutional review board at the University of Miami approved this noncomparative case series (ID# 20100943) and waived informed consent approval for this retrospective study. Compliance with the Health Insurance Portability and Accountability Act and adherence to the Declaration of Helsinki and all federal and state laws in the United States were maintained during all aspects of this research.


The microbiologic and clinical records of all patients treated for culture-proven fungal endophthalmitis (n = 151) between January 1, 1990, and June 30, 2010 were reviewed. Methods for fungal isolate culture and identification have been described previously. Cases of definite endogenous fungal endophthalmitis (n = 66) were excluded. Of the remaining 85 cases, 58 had fungal isolates that were recovered from the microbiology department’s storage freezers (−80 C). Seven of the remaining 27 exogenous cases had prior antifungal susceptibilities already established (via sending samples out to the Fungus Testing Laboratory in San Antonio, Texas) and recorded in the medical record.


The 58 fungal isolates were each plated on Sabouraud agar and incubated at 35 C for 72 hours. Plates were examined daily for detection of fungal regrowth. Colonies suggestive of fungal regrowth were evaluated by Giemsa, calcofluor white, and slide culture to detect microscopic morphologic features and characteristic conidiation. Of these, 41 isolates demonstrated regrowth and were then sent to the Fungus Testing Laboratory (San Antonio, Texas) for identification and susceptibility testing.


Stock solutions of amphotericin B, fluconazole, and voriconazole were prepared in dimethylsulfoxide (DMSO). Further dilutions were made in RPMI-1640 and the final concentration of DMSO was 1%. The final testing concentrations for each agent ranged from 0.03 to 16 μg/mL for amphotericin B and voriconazole and between 0.125 and 64 μg/mL for fluconazole. Testing was completed with a common lot for each agent. Drug preparations were prepared and antifungal testing was performed according to the recommendations outlined in the Clinical and Laboratory Standards Institute (CLSI) document M38-A2 and M27-A3. Testing parameters include testing in RPMI-1640 with L-glutamine and without bicarbonate. The isolates were incubated at 35 C for 24–48 hours. The minimum inhibitory concentration (MIC) was measured as the lowest concentrations of each azole that resulted in a 50% reduction in turbidity as compared to drug-free growth control wells for yeasts and 100% reduction for molds. For amphotericin B, 100% reduction in turbidity was the endpoint used for all isolates. Of the 41 submitted specimens, 39 isolates demonstrated fungal growth suitable for antifungal testing.




Results


The antifungal susceptibilities of 47 cases are reported ( Table 1 ). Of the frozen specimens, 39 (83.0%) demonstrated regrowth and underwent antifungal susceptibility analysis while the antifungal susceptibilities in 8 additional cases (17.0%) are reported from testing performed at the time of initial diagnosis and treatment (obtained from review of patient medical records).



Table 1

Minimum Inhibitory Concentrations of Fungal Cultures in Exogenous Fungal Endophthalmitis










































































































































































































































































































































































































Case Organism Source Year of Diagnosis Amphotericin B Fluconazole Voriconazole
Yeast
1 Candida albicans AH 1999 0.5 ≤0.125 ≤0.03
2 Candida albicans VH 2003 0.5 0.25 ≤0.03
3 Candida albicans VH 2004 0.5 ≤0.125 ≤0.03
4 Candida albicans AH 2005 0.25 ≤0.125 ≤0.03
5 Candida albicans AH 2005 0.5 0.25 ≤0.03
6 Candida albicans AH 2006 0.5 ≤0.125 ≤0.03
7 Candida albicans VH 2007 0.5 ≤0.125 ≤0.03
8 Candida albicans AH 2008 0.5 ≤0.125 ≤0.03
9 Candida albicans VH 2009 0.125 ≤0.125 ≤0.03
10 Candida albicans VH 2010 0.5 ≤0.125 ≤0.03
11 Candida glabrata AH 2008 0.5 2 ≤0.03
12 Candida parapsilosis VH 2003 1 0.25 ≤0.03
13 Candida parapsilosis VH 2004 0.5 0.25 ≤0.03
14 Candida sp VH 2006 1 2 0.06
Mold
15 Acremonium sp VH 2006 1 16 0.125
16 Acremonium sp AH 2006 1 16 0.06
17 Acremonium sp AH 2006 2 >64 8
18 Aspergillus fumigatus VH 2007 4 >64 0.25
19 Aspergillus fumigatus IOL 2010 2 >64 0.25
20 Aspergillus sp VH 1992 8 >64 0.25
21 Aspergillus terreus VH 2004 4 >64 0.125
22 Aspergillus terreus VH 2004 1 >64 0.25
23 Aspergillus terreus AH 2005 8 >64 0.25
24 Aspergillus terreus VH 2006 4 >64 0.25
25 Aspergillus terreus VH 2006 8 >64 0.25
26 Curvularia sp VH 2007 0.5 16 0.25
27 Curvularia sp VH 2007 4 >64 8
28 Curvularia sp VH 2010 0.5 4 0.06
29 Fusarium oxysporum K 1999 4 >64 4
30 Fusarium oxysporum AH 2000 2 >64 4
31 Fusarium oxysporum K 2005 4 >64 8
32 Fusarium oxysporum VH 2007 1 >64 0.25
33 Fusarium oxysporum AH 2007 4 >64 8
34 Fusarium oxysporum AH 2008 4 >64 8
35 Fusarium sp VH 2006 2 >64 4
36 Fusarium sp K 2006 2 >64 4
37 Fusarium sp AH 2009 2 >64 4
38 Fusarium sp K 2010 4 >64 2
39 Paecilomyces sp VH 2008 >16 64 0.125
Susceptibilities from medical records
40 Acremonium strictum VH 2003 >16 8 0.5
41 Fusarium oxysporum AH 1991 2 ND ND
42 Fusarium oxysporum AH 2000 2 >64 ND
43 Fusarium solani K 1993 0.5 ND ND
44 Fusarium solani AH 2003 1 >64 ND
45 Lecythophoria mutablis VH 2003 >16 >64 8
46 Paecilomyces variotti AH 2005 0.25 >64 8
47 Phialophora verrucosa AH 1996 0.5 32 ND

AH = aqueous humor; IOL = intraocular lens; K = cornea; ND = not done; VH = vitreous humor.


Out of a total of 47 isolates, yeast was present in 14 (29.8%, all owing to species of Candida ) and mold occurred in 33 (70.2%). Fungal cultures were isolated from aqueous humor (18 cases, 38.3%), vitreous humor (23 cases, 48.9%), corneal specimens (5 cases, 10.6%) and intraocular lenses (1 case, 2.1%). The median MICs for amphotericin B, fluconazole, and voriconazole were 1 μg/mL (range, 0.125–16), 64 μg/mL (range, 0.125–64), and 0.25 μg/mL (range, 0.015–8), respectively.




Results


The antifungal susceptibilities of 47 cases are reported ( Table 1 ). Of the frozen specimens, 39 (83.0%) demonstrated regrowth and underwent antifungal susceptibility analysis while the antifungal susceptibilities in 8 additional cases (17.0%) are reported from testing performed at the time of initial diagnosis and treatment (obtained from review of patient medical records).



Table 1

Minimum Inhibitory Concentrations of Fungal Cultures in Exogenous Fungal Endophthalmitis










































































































































































































































































































































































































Case Organism Source Year of Diagnosis Amphotericin B Fluconazole Voriconazole
Yeast
1 Candida albicans AH 1999 0.5 ≤0.125 ≤0.03
2 Candida albicans VH 2003 0.5 0.25 ≤0.03
3 Candida albicans VH 2004 0.5 ≤0.125 ≤0.03
4 Candida albicans AH 2005 0.25 ≤0.125 ≤0.03
5 Candida albicans AH 2005 0.5 0.25 ≤0.03
6 Candida albicans AH 2006 0.5 ≤0.125 ≤0.03
7 Candida albicans VH 2007 0.5 ≤0.125 ≤0.03
8 Candida albicans AH 2008 0.5 ≤0.125 ≤0.03
9 Candida albicans VH 2009 0.125 ≤0.125 ≤0.03
10 Candida albicans VH 2010 0.5 ≤0.125 ≤0.03
11 Candida glabrata AH 2008 0.5 2 ≤0.03
12 Candida parapsilosis VH 2003 1 0.25 ≤0.03
13 Candida parapsilosis VH 2004 0.5 0.25 ≤0.03
14 Candida sp VH 2006 1 2 0.06
Mold
15 Acremonium sp VH 2006 1 16 0.125
16 Acremonium sp AH 2006 1 16 0.06
17 Acremonium sp AH 2006 2 >64 8
18 Aspergillus fumigatus VH 2007 4 >64 0.25
19 Aspergillus fumigatus IOL 2010 2 >64 0.25
20 Aspergillus sp VH 1992 8 >64 0.25
21 Aspergillus terreus VH 2004 4 >64 0.125
22 Aspergillus terreus VH 2004 1 >64 0.25
23 Aspergillus terreus AH 2005 8 >64 0.25
24 Aspergillus terreus VH 2006 4 >64 0.25
25 Aspergillus terreus VH 2006 8 >64 0.25
26 Curvularia sp VH 2007 0.5 16 0.25
27 Curvularia sp VH 2007 4 >64 8
28 Curvularia sp VH 2010 0.5 4 0.06
29 Fusarium oxysporum K 1999 4 >64 4
30 Fusarium oxysporum AH 2000 2 >64 4
31 Fusarium oxysporum K 2005 4 >64 8
32 Fusarium oxysporum VH 2007 1 >64 0.25
33 Fusarium oxysporum AH 2007 4 >64 8
34 Fusarium oxysporum AH 2008 4 >64 8
35 Fusarium sp VH 2006 2 >64 4
36 Fusarium sp K 2006 2 >64 4
37 Fusarium sp AH 2009 2 >64 4
38 Fusarium sp K 2010 4 >64 2
39 Paecilomyces sp VH 2008 >16 64 0.125
Susceptibilities from medical records
40 Acremonium strictum VH 2003 >16 8 0.5
41 Fusarium oxysporum AH 1991 2 ND ND
42 Fusarium oxysporum AH 2000 2 >64 ND
43 Fusarium solani K 1993 0.5 ND ND
44 Fusarium solani AH 2003 1 >64 ND
45 Lecythophoria mutablis VH 2003 >16 >64 8
46 Paecilomyces variotti AH 2005 0.25 >64 8
47 Phialophora verrucosa AH 1996 0.5 32 ND

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Jan 7, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Exogenous Fungal Endophthalmitis: An Analysis of Isolates and Susceptibilities to Antifungal Agents Over a 20-Year Period (1990–2010)

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