Fungal Endophthalmitis 

Updated: Sep 20, 2018
Author: Lihteh Wu, MD; Chief Editor: Hampton Roy, Sr, MD 

Overview

Background

Fungi are eukaryotic organisms that are ubiquitous in nature. The following 3 classes of fungi are important ocular pathogens: molds, yeasts, and diphasic fungi. Molds, also known as filamentous fungi, are multicellular organisms that form a tangled mass known as the mycelium. From this mass, filamentous projections, known as hyphae, branch out. The hyphae may be septate or nonseptate. Septate hyphae have true divisions, subdividing them into several cells, while nonseptate hyphae have no true divisions. Common septate filamentous fungi are Aspergillus, Fusarium, Cephalosporium, Paecilomyces, and Penicillium species. The nonseptate filamentous fungi include the Mucor species.

Yeasts are unicellular organisms that may develop pseudohyphae. Candida and Cryptococcus are the important ocular pathogens. The diphasic fungi exist in 2 forms, yeast and mold. Important ocular pathogens include Histoplasma, Blastomyces, and Coccidioides.

Endophthalmitis refers to intraocular inflammation involving the vitreous and anterior chamber of the eye. In most cases, endophthalmitis results from an infectious organism. Fungal endophthalmitis can be divided into the less common endogenous infections and the more common exogenous infections.

Endogenous fungal endophthalmitis represents intraocular dissemination of a systemic fungal infection. Among the different fungal species, Candida species is the most common cause of infection, followed by Aspergillus species.[1] Risk factors include immunosuppression, intravenous drug abuse, bacterial sepsis, prolonged hyperalimentation, systemic antibiotics, corticosteroid therapy, recent abdominal surgery, malignancy, alcoholism, diabetes mellitus, trauma, and hemodialysis.[2, 3, 4]

Exogenous infections usually are secondary to trauma or surgery. A variety of fungi, including Paecilomyces, Acremonium, and Sporothrix species, has been associated with endophthalmitis following intraocular surgery or trauma. Fungal endophthalmitis is a rare complication after cataract surgery. The most common causative fungal pathogens implicated in fungal endophthalmitis after cataract surgery include Candida species and molds such as Aspergillus and Fusarium species.[5] There have been recent outbreaks of fungal endophthalmitis associated with contaminated compounded brilliant blue G and triamcinolone.[6]

Pathophysiology

Candidal endophthalmitis

Even though Candida albicans is by far the most common cause of endogenous endophthalmitis,[7] other non– C albicans species, in particular C tropicalis, have also been implicated in intraocular infections[8] . The most common risk factors are those that predispose to candidemia (eg, a prior history of gastrointestinal surgery, hyperalimentation, and diabetes mellitus).[9]

Surprisingly, immunosuppression alone does not significantly increase the risk of Candida entering the bloodstream (eg, candidal chorioretinitis is an uncommon ophthalmic condition in AIDS patients). Furthermore, Candida endophthalmitis can occur after abdominal surgery or in diabetic patients without granulocytopenia. Rao and Hidayat have suggested that Candida overgrowth in the gastrointestinal tract and the increased availability of glucose seen in diabetic patients promote the growth of Candida.[9] The intravitreal concentration of glucose is higher in diabetic patients when compared with nondiabetic patients, which may explain Candida' s predilection for the vitreous.[10]

C albicans is by far the most common cause of endogenous endophthalmitis. They are commensal organisms that reside in the human body and are found normally in the female genital tract, the gastrointestinal tract, and the respiratory tract.

These fungi are kept in check by the host's normal immune response. When a breakdown in the host's immune system occurs, fungi may spread throughout the body. Many organs, including the eye, can be affected by this spread of fungi through the bloodstream. However, immunosuppression alone does not increase significantly the risk of fungi entering the bloodstream. For instance, candidal chorioretinitis is an uncommon ophthalmic condition in AIDS patients. Neutrophils are apparently important in the first-line defense against candidal organisms. Infection probably starts in the choroid and spreads to the retina and vitreous.

Patients who are at risk include patients with longstanding indwelling catheters; persons who use intravenous drugs; postpartum women; premature infants; patients undergoing hyperalimentation; patients with a history of recent abdominal surgery; and patients with debilitating diseases, such as diabetes mellitus, postorgan transplantation, or malignancies.

Aspergillus endophthalmitis

Of the more than 200 species of Aspergillus, A flavus and A fumigatus are the most common pathogenic organisms in humans. They are ubiquitous organisms found in soil, decaying matter, water, and organic debris. Its conidia, the asexual spores of aspergilli organisms are airborne, so inhalation is an important route of entry into the human body. When conidia enter the terminal alveoli of the lung, they may be engulfed by mononuclear phagocytes. If conidia are not destroyed by this first line of defense, they germinate and extend mycelial structures that are associated with tissue invasion. Neutrophils constitute the second line of defense and kill the mycelia.

In patients who are at risk, such as those patients with chronic pulmonary diseases or those patients with orthotopic liver transplants, renal transplants, leukemia and other hematologic disorders, Goodpasture syndrome, alcoholism, prematurity, and bone marrow transplants, disseminated aspergillosis may result. The most common predisposing factors include intravenous drug abuse, prior cardiac surgery, and organ transplant recipient. The common denominator in these patients appears to be granulocytopenia.[9] The fungus usually gains access to the eye as it spreads from the lungs to the choroid.

Cryptococcal endophthalmitis

Pigeons play an important role in the pathogenesis of cryptococcosis. Cryptococci spores can survive up to 2 years in pigeon droppings. Spores gain access to the human body through inhalation. From the lungs, the fungus is disseminated hematogenously and preferentially affects the central nervous system. It is the most common cause of fungal meningitis. Cryptococci organisms reach the eye through either direct extension from the optic nerve sheath or hematogenously from a distant focus. The choroid is probably the first site of ocular infection.

Coccidioides endophthalmitis

Coccidioides endophthalmitis results from the inhalation of Coccidioides immitis arthroconidia, which are found in the dust of endemic areas. Agricultural workers and constructions crews are at risk. In most patients, the inhalation of the spores leads to a self-limited respiratory disease. In few patients who are reexposed to the fungus, a chronic respiratory disease ensues. Hematogenous dissemination to the eye can occur.

Epidemiology

Frequency

United States

Compared to previous decades, the incidence of endogenous endophthalmitis appears to have increased in the past few decades. This may be secondary to an increase in intravenous drug use; the advent of chemotherapy for cancer patients; and the increased ability to care for more debilitated patients with hyperalimentation, indwelling catheters, and potent antibiotics.

Prospective studies of hospitalized patients with candidemia reveal that 9-37% of patients developed candidal endophthalmitis. In studies where prompt treatment of a systemic fungal infection is instituted, only 3-9% patients developed endogenous fungal endophthalmitis. A prospective cohort study that enrolled 125 inpatients with positive fungal blood culture results showed a 5.6% rate of chorioretinitis and 1.6% rate of endophthalmitis.[11] Despite modern antifungal therapy, fungal chorioretinitis and endophthalmitis continue to occur in patients with positive fungal culture results.

International

In countries with temperate climates, endophthalmitis usually results from an infectious organism such as bacteria. Fungal endophthalmitis remains a relatively rare condition.[12] However, in countries with tropical climates, fungal endophthalmitis is not an infrequent finding. In India, fungi were isolated in 22% of culture-proven endophthalmitis.[13]

Because it is commensal in the human body, Candida species are found throughout the world. Cryptococci and aspergilli also are present worldwide and found in both urban settings and rural settings.

C immitis is endemic in the southwestern United States (the San Joaquin Valley) and Northern Mexico. It also has been reported in Honduras, Venezuela, and Colombia.

Race

No racial predisposition has been observed.

Sex

A male preponderance is reported for endogenous fungal endophthalmitis.

Age

With regard to endogenous fungal endophthalmitis, there are 2 incidence peaks: one in patients younger than 1 year, and the other in middle-aged patients.

Prognosis

The prognosis of fungal endophthalmitis depends on the virulence of the organism, the extent of intraocular involvement, and the timing and mode of interventions.

Infections secondary to molds have a worse outcome than those due to yeasts.[3]

Prompt therapy following early diagnosis helps to reduce significant visual loss in all forms of fungal endophthalmitis.

The visual outcome of Aspergillus endophthalmitis usually is poor because of the preferred macular involvement by the fungus.

In cases of candidal endophthalmitis, prognostic factors include baseline visual acuity and location of the lesions. Early vitrectomy reduces the risk of retinal detachment.[14]

The prognosis following fungal endophthalmitis depends on the virulence of the organism, the extent of intraocular involvement, and the timing and mode of interventions.

A retrospective study of 17 eyes in 9 patients diagnosed with endogenous C albicans and C tropicalis fungal endophthalmitis showed that early ophthalmic consultation, better initial visual acuity, and use of effective systemic antifungal treatment might lead to relatively good visual outcomes in these patients. A final visual acuity of 20/200 or more was achieved in 69.2% of the eyes in this study.[15] In contrast, in a Chines series of 32 eyes, a poor visual outcome was seen, particularly if the presenting visual acuity was less than counting fingers or molds were involved.[16]

 

Presentation

History

Risk factors for Candida ​endophthalmitis

The most common risk factor for the development of endogenous Candida endophthalmitis is intravenous drug abuse.

Other risk factors include patients with long-standing indwelling catheters;[17] postpartum women; premature infants; patients undergoing hyperalimentation; patients with a history of recent abdominal surgery; patients who have undergone genitourinary procedures;[18] and patients with debilitating diseases, such as diabetes mellitus, post–organ transplantation, or malignancies.

Risk factors for Aspergillus endophthalmitis

Patients with a history of renal transplantation who are receiving corticosteroids, leukemia and other hematological disorders, Goodpasture syndrome, alcoholism, and prematurity.

The most common predisposing factor is intravenous drug abuse.

Notably, chest x-ray film findings are normal in up to 20% of patients with invasive pulmonary aspergillosis.

Aspergillus endogenous endophthalmitis tends to present more acutely than Candida endophthalmitis and to progress more rapidly.

Aspergillus endocarditis is often found together with Aspergillus endophthalmitis; therefore, a thorough cardiac workup is necessary.

Risk factors for Cryptococcus endophthalmitis

Patients who are known to be at risk of developing this condition are those with lymphoproliferative diseases, collagen vascular diseases, sarcoidosis, tuberculosis, diabetes mellitus, Cushing syndrome, or AIDS; those who are pregnant or abuse drugs; and those who have had organ transplants.

A few cases of cryptococcosis have been reported in individuals with no known risk factors or immune deficiencies.

Since the arthroconidia of C immitis are found in the dust of endemic areas, agricultural workers and construction crews are at risk of acquiring the infection.

Symptoms

Symptoms include the following:

  • Visual loss may be present; however, several studies have shown that visual acuity is not a useful factor in assessing the presence of endogenous fungal endophthalmitis in patients who are at risk.

  • In addition, patients may be asymptomatic if the lesion is in the peripheral retina or if the patient is moribund.

  • Red eye

  • Photophobia

  • Pain

  • Floaters

  • Scotoma

Physical

Candida endophthalmitis

Candida chorioretinitis typically presents as several, small, creamy white, circumscribed chorioretinal lesions with overlying vitreous inflammation.

In certain cases, these chorioretinal lesions may be surrounded by hemorrhage, giving them the appearance of a white-centered hemorrhage (Roth spot).

In the area of the lesion, the retinal vessels may be sheathed.

The vitreous opacities resemble fluffy balls, and they may be linked to each other by strands giving them the so-called string of pearls appearance.

If the infection is not suspected and the disease advances, epiretinal membranes may develop, leading to vitreoretinal traction and retinal detachment.

As the lesions heal with treatment, chorioretinal scarring evolves in the areas of prior inflammation.

Choroidal neovascular membranes may develop at the site of these scars.

Two thirds of patients have bilateral disease, and more than one half of patients have vitreous involvement.

Iridocyclitis often is present, and a hypopyon also may be present.

Infection of the iris and ciliary body is rare.

Aspergillus endophthalmitis

In Aspergillus endophthalmitis, an iridocyclitis with or without a hypopyon may be present; yellow subretinal and retinal infiltrates that preferentially affect the macula are observed.

Inflammatory cells within the infiltrate may layer secondary to gravity, thereby creating a pseudohypopyon.

As the disease progresses, the vitreous becomes severely involved, concealing all fundus details. With time, the macular lesions scar.

In addition, Aspergillus species have a propensity for vascular invasion, leading to thrombosis and necrosis.

If the fungus invades the choroidal vessels, an exudative retinal detachment may result.

When the retinal vessels become involved, retinal necrosis may occur.

Cryptococcus endophthalmitis

Cryptococcus neoformans usually presents intraocularly as a multifocal chorioretinitis characterized by discrete yellow-white lesions of different sizes.

Retinal vessels may be sheathed, and a vitritis of variable intensity may develop.

Retinal necrosis accompanied by retinal hemorrhage and exudative retinal detachments also have been known to occur.

If the central nervous system is involved, papilledema is present.

A mild inflammatory reaction is present in the anterior segment.

If treatment is not instituted, iris neovascularization and cataract may result.

Coccidioides endophthalmitis

Ocular coccidioidomycosis is an uncommon finding in patients with disseminated disease.

Usually, a severe granulomatous iridocyclitis characterized by mutton-fat keratic precipitates is present.

Multifocal choroiditis, typified by several, scattered, discrete, yellow-white lesions measuring less than the disc diameter in size, is observed.

Occasionally, vascular sheathing, vitreous haze, serous retinal detachment, and retinal hemorrhage also may be seen.

Causes

C albicans is by far the most common cause of endogenous fungal endophthalmitis.

Other organisms that can cause fungal endophthalmitis include the following:

  • Aspergillus species

  • Cryptococcus neoformans

  • Coccidioides immitis

Complications

See the list below:

  • Choroidal neovascularization at the site of chorioretinal scars
  • Epiretinal membranes
  • Tractional retinal detachment
 

DDx

 

Workup

Laboratory Studies

The diagnosis of endogenous fungal endophthalmitis should be considered in patients who present with vitritis accompanied by a chorioretinal focus in the clinical setting of a recent or current debilitating illness. Clinical suspicion plays an important role in identifying patients who may have fungal endophthalmitis.

A presumptive diagnosis of fungal endophthalmitis can be made if the fungus is isolated from anywhere in the body and the typical intraocular findings are present.

Blood cultures, urine cultures, sputum cultures, and cerebrospinal fluid (CSF) cultures should be obtained in patients suspected of endogenous endophthalmitis. In addition, direct examination of fungi with Giemsa, Gomori-methenamine-silver (GMS), and periodic-acid Schiff (PAS) stains should be obtained.

Culture of the fungus confirms the diagnosis. However, the fungus may not always be detected, even clinically, in certain cases or in cases where the fungus has grown from another site. Fungal cultures can be positive in 44-70% of patients diagnosed clinically. Vitrectomy samples are more sensitive for fungal cultures than vitreous needle biopsies.

Part of the delay in making a diagnosis is because many laboratory isolates are considered contaminants by laboratory personnel. Laboratory personnel should be told to consider all fungal growth as significant and to report these findings. In addition, the culture must be kept at the laboratory for at least 4-6 weeks to ensure that slow-growing or fastidious fungal organisms are not missed.

A useful, recently introduced diagnostic tool for fungal endophthalmitis is the polymerase chain reaction (PCR). The main advantages of PCR over conventional fungal cultures are the higher sensitivity and the rapid results obtained with PCR. Although PCR does not replace conventional mycologic methods, it helps to make an early differentiation between bacterial endophthalmitis and fungal endophthalmitis.

Where available, DNA microarray analysis may be useful for obtaining a rapid diagnosis.[19]

Candida species grow well on Sabouraud media without cycloheximide. The colonies are white and pasty. PCR has been used successfully to identify Candida species from an intraocular sample.

Aspergilli species are observed best with GMS or PAS stains. Culture is the most reliable means of identification. The fungus grows readily in Sabouraud and Czapek solutions. Aspergilli cultures are initially flat, white, and filamentous. Within 48 hours, conidia are produced with a concomitant change in pigmentation. Blood cultures are often negative for aspergilli organisms.

Cryptococci also grow well in Sabouraud agar. Cryptococci may be identified by India ink. C immitis can be diagnosed using a 10% KOH mount and identifying endospores that contain spherules.

Imaging Studies

Fluorescein angiography: The chorioretinal lesions appear hypofluorescent in the early phases of the study; leakage occurs in the later phases.

Procedures

Anterior chamber tap

Anterior chamber (AC) specimens are unreliable in the diagnosis of Candida species.

Coccidioidomycosis has been diagnosed in a handful of cases by analyzing the AC taps.

Pars plana vitrectomy

Pars plana vitrectomy is important in obtaining undiluted specimens for culture and sensitivity. Primary 23-gauge vitrectomy can be used to confirm the diagnosis of endogenous fungal endophthalmitis. A retrospective analysis of 19 eyes in 15 patients demonstrated that 23-gauge vitrectomy confirmed diagnosis in 75% of the eyes (12 of 16). Candida was found to be a causative agent in 62.5% and Aspergillus in 12.5% of the eyes. Retinal detachment was the most common complication (42% of eyes).[20]

Vitreous samples should be concentrated either by centrifugation or by millipore filtration.

If C neoformans is suspected, the sample should be stained with mucicarmine and undergo membrane filtration cytology.

Histologic Findings

Candida endophthalmitis: Candida organisms can be seen as budding yeasts with pseudohyphae within the lesions. The lesions contain few organisms, but they are surrounded by an intense granulomatous and suppurative inflammatory reaction.

Aspergillus endophthalmitis: Identification of branching septate hyphae in the choroid, retina, and vitreous characterizes Aspergillus endophthalmitis. Vessel thrombosis characterized by perivasculitis and necrotizing vasculitis often is observed in the retina and the choroid. Acute and chronic inflammatory cells are present in the anterior chamber and the vitreous.

Cryptococcus endophthalmitis: Cryptococci organisms usually are found in the choroid. They also have been identified in the retina, subretinal space, vitreous, and optic nerve. Typically, a diffuse or focal granulomatous inflammatory reaction that leads to a noncaseating necrosis is elicited. However, the number of inflammatory cells involved is much less than the expected given inflammatory reaction.

Coccidioides endophthalmitis: C immitis has been isolated from the limbus, iris, ciliary body, retina, choroid, and optic nerve. Typically, a granulomatous inflammatory reaction is present.

 

Treatment

Medical Care

In vitro, minimum inhibitory concentration (MIC) data do not always correlate with in vivo MIC values. Therefore, these should only be used as a guideline.

The following drugs are used in treating of fungal endophthalmitis:

  • Amphotericin B

  • Fluconazole

  • Ketoconazole

  • Miconazole

  • Flucytosine

  • Itraconazole

  • Caspofungin

Systemic amphotericin has been the treatment of choice because of its broad-spectrum coverage; however, the penetration of the vitreous cavity is poor. Doses of 5- to 10-mg intravitreal amphotericin have been used. Retinal toxicity has been reported in animal models at these doses. Fluconazole and flucytosine have good intraocular penetration, but Candida species show high resistance to flucytosine.

A new systemic treatment is voriconazole; when administered orally or intravenously, it has good intravitreal concentrations. Intravitreal administration of voriconazole also seems safe without evidence of retinal toxicity with concentrations up to 25 mg/mL.

The echinocandins (caspofungin, micafungin, and anidulafungin) are newer agents that exert their antifungal activity by inhibiting D-glucan synthase, an enzyme involved in fungal cell wall synthesis. Because mammalian cells lack a cell wall, it also represents an ideal and specific target for antifungal therapy. Echinocandins exert antifungal activity against Candida and Aspergillus species[21]

In a double-blind multicenter trial of 239 patients, caspofungin was found to be equally as effective as amphotericin B in the treatment of candidemia. Patients were infused with either amphotericin B (0.6–1 mg/kg/d) or caspofungin as a single loading dose of 70 mg with a daily maintenance dose of 50 mg. In this cohort of patients, 7 patients with endophthalmitis were included and the endophthalmitis resolved in all 7 patients. Unfortunately, the authors failed to mention whether or not these 7 patients received caspofungin or amphotericin B. Significantly fewer drug-related adverse events occurred in the caspofungin group than in the amphotericin B group.[22]

Gauthier et al reported a case of Candida endophthalmitis that failed treatment with caspofungin because of its poor penetration into the vitreous cavity.[23] Given its limited vitreal penetration, the role of echinocandins remains to be determined in fungal endophthalmitis.

Surgical Care

The advent of pars plana vitrectomy has improved the treatment results of fungal endophthalmitis.

The advantages of pars plana vitrectomy are that it provides material for culture, removes viable organisms and inflammatory end products from the infected vitreous, and provides intravitreal access to antifungal agents (eg, amphotericin B).

Vitrectomy and intravitreal amphotericin B should be considered in those cases of endogenous fungal endophthalmitis where the disease is progressing despite initial therapy with an appropriate systemic antifungal agent.

As a general rule, moderate-to-severe vitreous involvement requires vitrectomy because most systemic antifungals have poor vitreous penetration.

Endogenous fungal endophthalmitis without evidence of disseminated disease can be treated successfully with vitrectomy and intravitreal amphotericin B.

Given the narrow therapeutic range of amphotericin B, it should not be given in a gas-filled eye.

Some authors have advocated the use of 400 µg of intravitreal dexamethasone as an adjuvant.

Consultations

Because endogenous fungal endophthalmitis is frequently an ocular manifestation of a systemic disease, the patient requires a multidisciplinary approach.

Prevention

Once a positive fungal culture is obtained, the patient should be started on systemic antifungals. At the same time, an ophthalmologic consultation should be obtained. In 2 different studies using this protocol, the incidence of endogenous fungal endophthalmitis was reported to be only 3-9%.

Long-Term Monitoring

Patients should receive follow-up care as needed. Optical coherence tomography (OCT) may assist in the follow-up of patients with fungal endophthalmitis. A small retrospective case series of 12 eyes of 7 patients showed two patterns of posterior segment involvement of fungal endophthalmitis. Fifteen eyes demonstrated chorioretinal infiltration on OCT imaging, whereas 5 eyes showed inner retinal/retinal vascular infiltration without choroidal involvement. The presence of optic nerve edema, epiretinal membranes, and subretinal fluid was also noted. Upon successful treatment, these OCT abnormalities resolved.[24]

Further Inpatient Care

Many patients with fungal endophthalmitis are hospitalized. Patients may require intravenous medications.

Two dilated ophthalmic examinations should still be considered, even in asymptomatic patients with fungemia.[25]

 

Medication

Medication Summary

The best initial therapy for patients with endogenous fungal endophthalmitis has not been established. However, a broad-spectrum systemic antifungal agent, such as amphotericin B or fluconazole, is recommended as first-line therapy.

Polyene antibiotics

Class Summary

They are classified based on the number of conjugated double bonds. Fungicidal agents bind to sterols in the cell membrane of susceptible fungi and change the permeability of the cell membrane, leading to leakage of cellular constituents and consequently cell death.

Amphotericin B (Amphocin, Fungizone)

Polyene antibiotic produced by a strain of Streptomyces nodosus; can be fungistatic or fungicidal. Binds to sterols, such as ergosterol, in the fungal cell membrane, causing intracellular components to leak with subsequent fungal cell death. Particularly active against Candida, Cryptococcus, and Aspergillus species.

An infectious disease specialist should be consulted regarding the appropriate protocol and dosage.

Several studies have shown poor intravitreal penetration when given systemically.

Special attention is required when making the dilutions and injecting in gas-filled eyes because it has a narrow therapeutic range and can cause retinal toxicity.

Subconjunctival injections of amphotericin B have no role in fungal ocular infections.

Imidazoles

Class Summary

Bind to the fungal cell membrane and induce permeability changes that alter intracellular electrolyte levels, leading to fungal cell damage. These agents are fungistatic.

Fluconazole (Diflucan)

Fungistatic activity. Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes. Effective against Candida, Cryptococcus, and Aspergillus species. Bioavailability following oral administration is comparable to parenteral administration. Good CSF and intravitreal penetration is achieved after systemic administration.

Ketoconazole (Nizoral)

Fungistatic activity. Imidazole broad-spectrum antifungal agent; inhibits synthesis of ergosterol, causing cellular components to leak, resulting in fungal cell death. Active against Blastomyces dermatitidis, C immitis, and Candida and Fusarium species, and exhibits some activity against Aspergillus species.

Itraconazole (Sporanox)

Fungistatic activity. Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting cytochrome P-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.

Miconazole (Absorbine, Femizol)

Damages fungal cell wall membrane by inhibiting biosynthesis of ergosterol. Membrane permeability is increased, causing nutrients to leak out, resulting in fungal cell death.

The lotion is preferred in intertriginous areas. If the cream is used, apply sparingly to avoid maceration effects.

Administered intravenously due to poor absorption from the gastrointestinal tract.

Used as a second-line drug in the treatment of Candida, Cryptococcus, and Aspergillus species and coccidioidomycosis.

Use in cases that are resistant to treatment with amphotericin B.

Voriconazole (Vfend)

Used for primary treatment of invasive aspergillosis and salvage treatment of Fusarium species or Scedosporium apiospermum infections. A triazole antifungal agent that inhibits fungal cytochrome P-450-mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis.

Corticosteroids

Class Summary

Some have advocated the use of intravitreal dexamethasone as an adjuvant. Inflammation is believed to play a role in the destructive nature of this disease.

Dexamethasone (Ocu-Dex)

For various allergic and inflammatory diseases. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability.

Chemotherapeutic agents

Class Summary

Inhibit cell growth and proliferation.

Flucytosine (Ancobon)

Converted to fluorouracil after penetrating fungal cells. Inhibits RNA and protein synthesis. Active against Candida and Cryptococcus species and generally used in combination with amphotericin B.

A fluorinated pyrimidine that becomes deaminated by susceptible fungi to fluorouracil, which blocks thymidine synthesis.

Effective against Candida and Cryptococcus species and certain strains of Aspergillus species.

Use in combination with another agent because acquired resistance develops frequently when flucytosine is administered alone.

Echinocandins

Class Summary

Inhibit cell wall synthesis.

Caspofungin (Cancidas)

Used to treat refractory invasive aspergillosis. First of a new class of antifungal drugs (glucan synthesis inhibitors). Inhibits synthesis of beta-(1,3)-D-glucan, an essential component of fungal cell wall.