Notes on Amphotericin B for Aspergillus Conjunctivitis and Mass
Clin Microbiol Rev. 2003 Oct; 16(4): 730–797.
PMCID: PMC207127
PMID: 14557297
Current Perspectives on Ophthalmic Mycoses
Fungi may infect the cornea, orbit and other ocular structures. Species of Fusarium, Aspergillus, Candida, dematiaceous fungi, and Scedosporium predominate. Diagnosis is aided by recognition of typical clinical features and by direct microscopic detection of fungi in scrapes, biopsy specimens, and other samples. Culture confirms the diagnosis. Histopathological, immunohistochemical, or DNA-based tests may also be needed. Pathogenesis involves agent (invasiveness, toxigenicity) and host factors. Specific antifungal therapy is instituted as soon as the diagnosis is made. Amphotericin B by various routes is the mainstay of treatment for life-threatening and severe ophthalmic mycoses. Topical natamycin is usually the first choice for filamentous fungal keratitis, and topical amphotericin B is the first choice for yeast keratitis. Increasingly, the triazoles itraconazole and fluconazole are being evaluated as therapeutic options in ophthalmic mycoses. Medical therapy alone does not usually suffice for invasive fungal orbital infections, scleritis, and keratitis due to Fusarium spp., Lasiodiplodia theobromae, and Pythium insidiosum. Surgical debridement is essential in orbital infections, while various surgical procedures may be required for other infections not responding to medical therapy. Corticosteroids are contraindicated in most ophthalmic mycoses; therefore, other methods are being sought to control inflammatory tissue damage. Fungal infections following ophthalmic surgical procedures, in patients with AIDS, and due to use of various ocular biomaterials are unique subsets of ophthalmic mycoses. Future research needs to focus on the development of rapid, species-specific diagnostic aids, broad-spectrum fungicidal compounds that are active by various routes, and therapeutic modalities which curtail the harmful effects of fungus- and host tissue-derived factors.
Notes:
Intravenous administration frequently associated with renal tubular damage, due to use of deoxycholate as vehicle (187) Subconjunctival injection causes marked tissue necrosis at the site of injection (269)
Topical application of concern >5.0 mg/ml may cause ocular irritation (solutions of 1.5-3.0 mg/ml are better tolerated) Not commercially available as topical ophthalmic preparation; needs to be reconstituted from powder or intravenous preparation Poor intraocular penetration after intravenous administration
In a previous paper:
Aspergillus niger keratitis. The patient was initially treated with topical amphotericin B, which was not effective. When the patient was switched to a combination of oral and topical voriconazole, the infection improved rapidly and resolved after five weeks.
But would recommend using topical first, especially if no systemic symptoms, such as coughing, fever.
| 2 (396) | 1. Suggestive clinical features 2. DM, growth in ≥2 culture media (A. fumigatus, A. flavus) | Topical 2% ketoconazole | Keratitis resolved in both patients after 17 days therapy | Both patients apparently had only superficial keratitis |
| 22 (309) | 1. Suggestive clinical features 2. DM, growth in ≥2 culture media (A. fumigatus in 7, A. flavus in 11, Aspergillus spp. in 4) | Oral ketoconazole (600 mg/day) in 10 patients Oral ketoconazole and topical 1% ketoconazole in 12 patients Response to therapy in 7 patients (5 with superficial keratitis, 2 with deep lesions); no response in 5 (all had deep lesions) | Lesions resolved in 5 of 10 patients (3 of 8 with A. flavus, 2 of 2 with A. fumigatus). Lesions resolved in 7 of 12 patients (1 of 3 with A. flavus, 3 of 5 with A. fumigatus, 3 of 4 with Aspergillus spp.) Overall, PKP necessary in 10 patients (7 of 11 with A. flavus, 2 of 7 with A. fumigatus, 1 of 4 with Aspergillus spp.) | Nonrandomised, noncomparative case series; ketoconazole used due to nonavailability of natamycin at the time of study |
| 11 (385) | 1. Suggestive clinical features 2. DM, growth in ≥2 culture media (A. flavus, A. fumigatus) | Topical 0.15% amphotericin B | Lesions resolved in 3 patients (all 3 had keratitis with deep lesions); no response in 8 patients (2 with superficial keratitis, 6 with deep lesions); PKP done | Nonrandomized, noncomparative case series; amphotericin B used due to nonavailability of natamycin at the time of study |
| 15 (390) | 1. Suggestive clinical features 2. DM, growth in ≥2 culture media (A. flavus in 10, A. fumigatus in 5) | Oral itraconazole (200 mg/day); response in 10 patients (9 with A. flavus keratitis, 1 with A. fumigatus keratitis) | Lesions resolved in 10 patients (6 with superficial keratitis, 4 with deep lesions); No response in 5 patients (all with deep lesions); PKP done in all 5 patients | Nonrandomized, noncomparative case series; itraconazole used due to nonavailability of natamycin at the time of study |
| 1 (68) | HPE, culture (A. fischerianus) | No response to oral ketoconazole | Evisceration | |
| 1 (142) | HPE, culture (A. fumigatus) | No response to topical amphotericin B and oral itraconazole; PKP done | Lesions resolved after PKP | Keratitis following radial keratotomy |
| 1 (148) | 1. Suggestive clinical features 2. DM, culture (A. fumigatus) | No response to fluconazole (systemic, topical), miconazole, flucytosine, natamycin | Lesions resolved after amphotericin B treatment (topical 2% ointment, intravenous) | No mention of severity of keratitis |
| 1 (134) | DM, culture (A. fumigatus) | Natamycin | Lesions resolved | No mention of severity of keratitis |
| 1 (361) | DM, culture (A. flavus) | No response to natamycin, oral ketoconazole; PKP done | Lesions resolved after PKP | Keratitis after LASIK |
| 1 (203) | HPE, culture of biopsy material (A. fumigatus) | No response to antibacterials; perforation after biopsy (sealed with glue and sutures); antifungals used | Infiltrate resolved after medical therapy; perforation required other measures | Keratitis after LASIK |
| 1 (362) | DM, culture (A. fumigatus) | Natamycin | Lesions resolved | Superficial keratitis, hence resolved |
| 1 (327) | Culture (A. fumigatus) | Natamycin, topical 0.1% amphotericin B | Lesions resolved | Polymicrobial keratitis after LASIK |
| 3 (183) | DM and culture of corneal scrapes and aqueous aspirates (A. flavus from all 3 patients) | Partial response to initial natamycin, topical amphotericin B, and oral itraconazole in all 3 patients | Lesions completely resolved in all 3 patients after intracameral administration of amphotericin B (7.5 μg/0.1 ml and 10 μg/0.1 ml) | Partial response of corneal infiltrate to topical and oral antifungals; complete resolution of hypopyon probably aided by removal of aqueous prior to intracameral injection of amphotericin B |