eMedicine Specialties > Ophthalmology > Infectious Disease
Endophthalmitis, Fungal: Treatment & Medication
Updated: Jul 24, 2007
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
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
- 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.
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.
Medication
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
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.
Adult
5-10 µg intravitreally; levels remain above MIC for 11 d following injection in a nonvitrectomized eye compared to 2 d in vitrectomized eyes
Pediatric
Not established
Antineoplastic agents may enhance the potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; risk of renal toxicity is increased with cyclosporine
Documented hypersensitivity
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Monitor renal function, serum electrolytes (eg, magnesium, potassium), liver function, CBC, and hemoglobin concentrations; resume the therapy at the lowest level (eg, 0.25 mg/kg) when the therapy is interrupted for more than 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in neutropenic patients receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion); fever and chills are not uncommon after first few administrations of drug; rare acute reactions may include hypotension, bronchospasm, arrhythmias, and shock
Imidazoles
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.
Adult
400 mg PO loading dose, followed by 200 mg PO qd
Pediatric
12 mg/kg loading dose, followed by 6 mg/kg/d; total dose should not exceed 600 mg/d
Levels may increase with hydrochlorothiazides; fluconazole levels may decrease with chronic coadministration of rifampin; coadministration of fluconazole may decrease phenytoin concentrations; may increase concentrations of theophylline, tolbutamide, glyburide, and glipizide; effects of anticoagulants may increase with fluconazole coadministration; increases in cyclosporine concentrations may occur when administered concurrently
Documented hypersensitivity
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Adjust dose for renal insufficiency; monitor closely if rashes develop, and discontinue drug if lesions progress; may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including death), with underlying medical conditions (eg, AIDS, malignancy) and while taking multiple concomitant medications; breastfeeding; convenience and efficacy of single dose regimen for treatment of vaginal yeast infections should be weighed against difficulties resulting from higher incidence of adverse reactions reported with oral fluconazole versus intravaginal agents
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.
Adult
200 mg PO qd/bid
Pediatric
<2 years: Not recommended
>2 years: 3.3-6.6 mg/kg/d
Isoniazid may decrease bioavailability of ketoconazole; coadministration decreases effects of either rifampin or ketoconazole; may increase effect of anticoagulants; may increase toxicity of corticosteroids and cyclosporine (cyclosporine dosage can be adjusted); may decrease theophylline levels
Documented hypersensitivity; fungal meningitis
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Hepatotoxicity may occur; may reversibly decrease corticosteroid serum levels (adverse effects avoided with dose of 200-400 mg/d); administer antacid, anticholinergics, or H2-blockers at least 2 h after taking ketoconazole
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.
Adult
200 mg PO tid loading dose, followed by 200-400 mg PO qd
Pediatric
Not established
Antacids may reduce absorption of itraconazole; edema may occur with coadministration of calcium channel blockers (eg, amlodipine, nifedipine); hypoglycemia may occur with sulfonylureas; may increase tacrolimus and cyclosporine plasma concentrations when high doses are used; rhabdomyolysis may occur with coadministration of HMG-CoA reductase inhibitors (lovastatin or simvastatin); coadministration with cisapride can cause cardiac rhythm abnormalities and death; may increase digoxin levels; coadministration may increase plasma levels of midazolam or triazolam; phenytoin and rifampin may reduce itraconazole levels (phenytoin metabolism may be altered)
Documented hypersensitivity; coadministration with cisapride may cause adverse cardiovascular effects (possibly death)
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in hepatic insufficiencies
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.
Adult
600-3600 mg/d divided tid
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
If sensitivity or chemical irritation occurs, discontinue use; use only externally; avoid contact with eyes
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.
Adult
Loading dose: 6 mg/kg IV q12h infused over 2 h for 2 doses
Maintenance: 4 mg/kg IV q12h infused over 2 h and switch to 200 mg PO q12h when able to tolerate; may increase to 300 mg PO q12h if inadequate response
<40 kg: Average maintenance dose is 100 mg PO q12h (may increase to 150 mg PO q12h)
Up to 25 µg/mL (final vitreous concentration) of voriconazole has been reported to cause no retinal toxicity in rats
Pediatric
<12 years: Not established
>12 years: Limited data exist, administer as in adults
CYP450 2C19 (highest affinity), 2C9, and 3A4 (minor) substrate and inhibitor; CYP450 inducers (eg, rifampin) have shown to decrease steady state peak plasma levels by up to 93%; may increase serum levels of drugs metabolized by CYP450 2C19 or 2C9, of which some are contraindicated (eg, sirolimus, pimozide, quinidine, cisapride, ergot alkaloids), other may need more frequent monitoring (eg, cyclosporine, tacrolimus, warfarin, HMG CoA inhibitors, benzodiazepines, calcium channel blockers)
Documented hypersensitivity; CrCl <50 mL/min if administering IV (due to decreased excretion of IV vehicle); coadministration with rifampin, rifabutin, carbamazepine, barbiturates, sirolimus, pimozide, quinidine, cisapride, ergot alkaloids
Pregnancy
D - Unsafe in pregnancy
Precautions
Decrease maintenance dose in hepatic dysfunction; common adverse effects include visual disturbances, fever, rash, vomiting, nausea, diarrhea, headache, sepsis, peripheral edema, abdominal pain, rash (including Stevens-Johnson syndrome and phototoxicity), and respiratory disorder; rare cases of severe hepatotoxicity reported; administer PO dosage form 1 h ac or pc
Corticosteroids
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.
Adult
400 µg intravitreally
Pediatric
Not established
None reported
Documented hypersensitivity; active bacterial, viral, or fungal infection
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
If retina is detached and needs intraocular tamponade with either silicone oil or perfluorocarbon gases, adjust dose to prevent retinal toxicity
Chemotherapeutic agents
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.
Adult
50-150 mg/kg/d q6h
Pediatric
Not established
Amphotericin B may increase toxicity of flucytosine; cytosine may inactivate flucytosine
Documented hypersensitivity
Pregnancy
D - Unsafe in pregnancy
Precautions
Caution in bone marrow suppression; adjust dose in renal impairment
Echinocandins
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.
Adult
70 mg IV over 1 h on day 1; 50 mg IV qd thereafter
Pediatric
Not established
Coadministration with cyclosporine may increase risk of hepatotoxicity; carbamazepine, nelfinavir, efavirenz, or dexamethasone may decrease levels of caspofungin; caspofungin may decrease levels of tacrolimus
Documented hypersensitivity
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in moderate hepatic dysfunction (decrease dose); may exacerbate preexisting renal dysfunction or myelosuppression
More on Endophthalmitis, Fungal |
| Overview: Endophthalmitis, Fungal |
| Differential Diagnoses & Workup: Endophthalmitis, Fungal |
 Treatment & Medication: Endophthalmitis, Fungal |
| Follow-up: Endophthalmitis, Fungal |
| References |
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Further Reading
Keywords
fungal endophthalmitis, fungi, fungal infection, intraocular inflammation, intraocular surgery, eye trauma, vitreous, anterior chamber, candidal endophthalmitis, Candida endophthalmitis, Candida albicans, C albicans, Aspergillus endophthalmitis, Coccidioides endophthalmitis, Cryptococcus endophthalmitis, Blastomyces, Sporothrix, Paecilomyces, Acremonium, endogenous endophthalmitis, exogenous infections
