Postoperative Fungal Keratitis Managed by Anterior Chamber Washout and Intracameral Amphotericin-B: A Report of Two Cases

ABSTRACT Fungal keratitis is a common but severe eye infection in tropical and subtropical areas of the world. In regions with a temperate climate, the frequency of infection is rising in patients with contact lenses and following trauma. Early and adequate therapy is important to prevent disease progression and loss of vision. The management of Fusarium keratitis is complex, and the optimal treatment is not well defined. We investigated the in vitro activity of chlorhexidine and seven antifungal agents against a well-characterized collection of Fusarium isolates recovered from patients with Fusarium keratitis. The fungus culture collection of the Center of Expertise in Mycology Radboudumc/CWZ was searched for Fusarium isolates that were cultured from cornea scrapings, ocular biopsy specimens, eye swabs, and contact lens fluid containers from patients with suspected keratitis. The Fusarium isolates that were cultured from patients with confirmed keratitis were all identified using conventional and molecular techniques. Antifungal susceptibility testing was performed according to the EUCAST broth microdilution reference method. The antifungal agents tested included amphotericin B, voriconazole, posaconazole, miconazole, natamycin, 5-fluorocytosine, and caspofungin. In addition, the activity of chlorhexidine was determined. The fungal culture collection contained 98 Fusarium isolates of confirmed fungal keratitis cases from 83 Dutch patients and 15 Tanzanian patients. The isolates were collected between 2007 and 2017. Fusarium oxysporum (n = 24, 24.5%) was the most frequently isolated species followed by Fusarium solani sensu stricto (n = 18, 18.4%) and Fusarium petroliphilum (n = 11, 11.2%). Amphotericin B showed the most favorable in vitro inhibition of Fusarium species followed by natamycin, voriconazole, and chlorhexidine, while 5-fluorocytosine, posaconazole, miconazole, and caspofungin showed no relevant inhibiting effect. However, chlorhexidine showed fungicidal activity against 90% of F. oxysporum strains and 100% of the F. solani strains. Our study supports the clinical efficacy of chlorhexidine and therefore warrants its further clinical evaluation for primary therapy of fungal keratitis, particularly in low and middle income countries where fungal keratitis is much more frequent and, currently, antifungal eye drops are often unavailable.

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Effectiveness of Posaconazole in Recalcitrant Fungal Keratitis Resistant to Conventional Antifungal Drugs

Case Reports in Ophthalmological Medicine ◽

10.1155/2014/701653 ◽

2014 ◽

Vol 2014 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

A. Altun ◽

S. A. Kurna ◽

T. Sengor ◽

G. Altun ◽

O. O. Olcaysu ◽

...

Keyword(s):

Amphotericin B ◽

Corneal Ulcer ◽

Ocular Trauma ◽

Fungal Keratitis ◽

Antifungal Drugs ◽

Effective Treatment Option ◽

Clinical Appearance ◽

Hand Motion ◽

Corrected Visual Acuity ◽

History Of

Purpose. To present the success of posaconazole in two cases with recalcitrant fugal keratitis that were resistant to conventional antifungal drugs.Method. We presented two cases that were treated with posaconazole after the failure of fluconazole or voriconazole, amphotericin B, and natamycin therapy. Case 1 was a 62-year-old man with a history of ocular trauma. He had been using topical fluorometholone and tobramycin. His best corrected visual acuity (BCVA) was hand motion. He had 5.0 × 4.5 mm area of deep corneal ulcer with stromal infiltration. Case 2 was a 14-year-old contact lens user. He had been using topical moxifloxacin, tobramycin, and cyclopentolate. His BCVA was 20/200. He had a 4.0 × 3.0 mm area of pericentral corneal ulcer with deep corneal stromal infiltration and 2 mm hypopyon.Results. Both patients initially received systemic and topical fluconazole or voriconazole and amphotericin B and topical natamycin that were all ineffective. But the response of posaconazole was significant. After posaconazole, progressive improvement was seen in clinical appearance. BCVA improved to 20/100 in case 1 and 20/40 in case 2.Conclusion. Posaconazole might be an effective treatment option for recalcitrant fusarium keratitis and/or endophthalmitis resistant to conventional antifungal drugs.

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Features of antifungal therapy during long-lasting infectious process: a clinical case of fungal keratitis and profile of antifungal sensitivity based on assessing biofilm formation

Russian Journal of Infection and Immunity ◽

10.15789/2220-7619-foa-1495 ◽

2021 ◽

Vol 11 (4) ◽

pp. 789-797

Author(s):

R. I. Valieva ◽

S. A. Lisovskaya ◽

K. A. Mayanskaya ◽

D. V. Samigullin ◽

G. Sh. Isaeva

Keyword(s):

Amphotericin B ◽

Biofilm Formation ◽

Clinical Case ◽

Antifungal Agents ◽

Fungal Keratitis ◽

Laser Scanning Microscopy ◽

Clinical Strain ◽

Mycelial Fungi ◽

Infectious Process ◽

Test Culture

Among infectious diseases, opportunistic mycoses hold a special place. There has been accumulating a lot of evidence regarding the clinical and epidemiological aspects of infection caused by Fusarium spp., which global incidence rate among microbial keratitis ranges from 2 to 40% depending on the geographical location of the country. Colonizing mucous membranes, fungi can exist not only in the form of plankton, but form biofilms after surface attachment, which leads to elevated resistance to multiple antifungal agents. Here we describe a clinical case of fungal keratitis due to Fusarium solani by determining profile of the antifungal sensitivity for isolated fungal strains, by taking into account their potential for biofilm formation. We used an F. solani culture isolated from the patient as well as F. solani test culture obtained from the Russian National Collection of Microorganisms. While determining the sensitivity of fungal planktonic cultures to antifungal agents from the azole group (fluconazole, voriconazole), amphotericin B and terbinafine, it was revealed that antimycotics amphotericin B and voriconazole exerted a marked antifungal activity against clinical isolate, whereas the plankton F. solani test culture was more sensitive to all groups of antifungal agents. Due to a long-lasting progressive course of the infectious process and the high biofilm-forming ability of the clinical strain F. solani, the activity of antifungal agents on biofilm cells was modeled and examined in vitro. It was shown that regarding to the fungal biofilms, value of the minimally inhibitory concentration exceeded those for planktonic cultures by 100-fold. The mechanisms of action for antifungal agents on vital parameters of fungal cell structures were analyzed by using confocal laser scanning microscopy after staining samples with propidium iodide and acridine orange for 15 min to detect changes between intact and damaged cell surface. It was found that within the biofilm fungal cells preserved viability even after exposure to high concentrations of antifungals. In addition, despite the fungicidal drug activity at substantial concentrations acting on the biofilm cell membrane, the cell nuclei remained viable. Owing to the presence ot the mechanism of resistance in mycelial fungi shown in the study, it is necessary to take into account and investigate characteristics of biofilms in terms of drug sensitivity that will allow to optimize a choice of antimicrobial therapy.

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Topical corneal targeted sustained release amphotericin B liposomal formulation for the treatment of fungal keratitis and its PK-PD evaluation

Journal of Drug Delivery Science and Technology ◽

10.1016/j.jddst.2020.101944 ◽

2020 ◽

Vol 60 ◽

pp. 101944

Author(s):

Anjali Mishra ◽

Mehdiya Bano ◽

Amol Chhatrapati Bisen ◽

Sarvesh Verma ◽

Sachin Nashik Sanap ◽

...

Keyword(s):

Sustained Release ◽

Amphotericin B ◽

Fungal Keratitis ◽

Liposomal Formulation

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Development of amphotericin B nanosuspensions for fungal keratitis therapy: effect of self-assembled γ-cyclodextrin

Journal of Pharmaceutical Investigation ◽

10.1007/s40005-020-00474-z ◽

2020 ◽

Vol 50 (5) ◽

pp. 513-525 ◽

Cited By ~ 1

Author(s):

Phatsawee Jansook ◽

Phyo Darli Maw ◽

Hay Man Saung Hnin Soe ◽

Ravinsinee Chuangchunsong ◽

Kitisak Saiborisuth ◽

...

Keyword(s):

Amphotericin B ◽

Fungal Keratitis ◽

Therapy Effect ◽

Self Assembled

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A Combination of Intrastromal and Intracameral Injections of Amphotericin B in the Treatment of Severe Fungal Keratitis

Journal of Ophthalmology ◽

10.1155/2016/3436415 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Jianzhang Hu ◽

Jingjin Zhang ◽

Yanling Li ◽

Xiaoli Han ◽

Weidong Zheng ◽

...

Keyword(s):

Amphotericin B ◽

Conventional Therapy ◽

Clinical Evidence ◽

Surgical Intervention ◽

Fungal Keratitis ◽

Medical Treatments ◽

Clinical Appearance ◽

Corneal Ulcers ◽

Corneal Damage ◽

Medical University

Purpose. To evaluate the efficacy of a combination of intrastromal and intracameral injections of amphotericin B in the treatment of severe recalcitrant fungal keratitis.Methods. Patients with severe fungal keratitis who were resistant to conventional antifungal medical treatments and needed potential surgical intervention were recruited at the First Affiliated Hospital of Fujian Medical University between January 2012 and July 2013. The patients were treated with a combination of intrastromal and intracameral injections of amphotericin B (25 μg/mL and 50 μg/mL, resp.). Selectively repeated injections were performed as necessary. The efficacy, complications, and outcome were evaluated.Results. Nine patients (9 eyes) were involved in this study. All 9 cases responded favorably, and the clinical appearance of serious corneal damage and intraocular extension was resolved after the treatment. Four eyes required only 1 injection, and 5 eyes required repeated injections. Seven corneal ulcers healed with leucoma, and 2 healed with adherent leucoma. All of our cases had a marked increase in the anterior chamber reaction and pain immediately after the injection. There was no obvious clinical evidence of corneal or lenticular toxicity in any patient.Conclusions. A combination of intrastromal and intracameral injections of amphotericin B may be safe and effective for the treatment of severe fungal keratitis that is resistant to conventional therapy.

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