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1.
Indian J Ophthalmol ; 72(10): 1488-1494, 2024 Oct 01.
Article de Anglais | MEDLINE | ID: mdl-39331440

RÉSUMÉ

INTRODUCTION: Many countries from South-East Asia reported an epidemic of sino-orbital mucormycosis (SOM), otherwise a rare disease, during the coronavirus disease 2019 pandemic. SOM, a potentially fatal disease, is typically treated with orbital exenteration and systemic antifungals after metabolic stabilization. There is no clear evidence of survival benefit of exenteration in the literature, and thus, there have been attempts at globe conserving treatments like orbital infusion after limited debridement and intraorbital injections with Amphotericin B (IOAB). METHODS: We conducted a prospective comparative interventional study at a tertiary eye care hospital to evaluate treatment outcomes with the use of adjunctive IOAB in cases of SOM with mild to moderate orbital disease. RESULTS: Thirty-six patients of SOM with mild to moderate orbital disease were recruited in the study. In the intervention group, 23/26 (885%) eyes had stable orbital disease at the end of treatment (4-6 weeks). No deterioration in visual acuity was noted as a result of treatment. In 8/26 (30.77%) patients, inflammation was noted as a side effect of IOAB requiring temporary discontinuation of injections. The mean follow-up for cases was 14.2 months (range 12-15 months). 1/23 (4.35%) patients had relapse of orbital disease at 3 months. Twenty-one patients are alive on last follow-up. Of the patients who refused treatment (controls), 2/9 (22.22%) patients relapsed. One of these patients with relapse underwent exenteration, while the other was managed with IOAB. At a follow-up of 14 months (range 12-15 months), eight patients are alive. On evaluating the ocular parameters in salvaged eyes, improvement in extraocular movements was noted in 75-80% cases. The degree of proptosis and resistance to retropulsion did not change significantly. CONCLUSION: In the current study, an improvement in the globe salvage rates was noted in cases of SOM with mild to moderate orbital disease treated with adjunctive IOAB as compared to controls at a mean follow-up of 14 months, although it did not achieve statistical significance. The study supports the inclusion of IOAB in routine management of mild to moderate orbital disease.


Sujet(s)
Amphotéricine B , Antifongiques , Mycoses oculaires , Mucormycose , Maladies de l'orbite , Humains , Mucormycose/diagnostic , Mucormycose/traitement médicamenteux , Mucormycose/thérapie , Mucormycose/épidémiologie , Mâle , Mycoses oculaires/microbiologie , Mycoses oculaires/traitement médicamenteux , Mycoses oculaires/diagnostic , Mycoses oculaires/thérapie , Études prospectives , Femelle , Maladies de l'orbite/microbiologie , Maladies de l'orbite/thérapie , Maladies de l'orbite/diagnostic , Adulte , Adulte d'âge moyen , Antifongiques/usage thérapeutique , Amphotéricine B/usage thérapeutique , COVID-19/épidémiologie , COVID-19/complications , SARS-CoV-2 , Études de suivi , Jeune adulte , Acuité visuelle , Débridement/méthodes , Sujet âgé , Adolescent , Résultat thérapeutique , Orbite
2.
ACS Infect Dis ; 10(9): 3126-3137, 2024 Sep 13.
Article de Anglais | MEDLINE | ID: mdl-39267469

RÉSUMÉ

Fungal endophthalmitis is a chronic inflammatory condition of the eye's posterior segment that can lead to irreversible vision loss. While relatively rare in western countries, its incidence is notably higher in Asia, particularly India. The condition's prevalence is exacerbated by factors such as intravenous drug use, antibiotics, and ocular surgeries. Fungal endophthalmitis can be categorized as endogenous, arising from systemic infection, or exogenous, linked to external sources such as trauma or surgery. The fungal agents responsible vary by region, with Candida species common in the West and Aspergillus and Fusarium species more prevalent in India. Management typically involves vitrectomy and intravitreal antifungal drugs such as amphotericin B and voriconazole, though treatment is often complicated by multidrug resistance and culture-negative cases. Recent proteomic and transcriptomic analyses have highlighted the early and sustained activation of the host immune response during infection involving key inflammatory and oxidative stress-related proteins. Given the potential for excessive inflammation to cause retinal damage, targeted immunotherapies are crucial. Immunomodulation, which aims to balance the immune response, shows promise in preserving vision while effectively combating the infection. Key targets for immunomodulation include pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-17), chemokines (CCL2, CXCL8), Toll-like receptors (TLR2, TLR4), and the complement system. Additionally, modulating the activity of macrophages, neutrophils, regulatory T cells, and Th17 cells, as well as targeting inflammasomes, can help control inflammation. Biologic agents and small molecule inhibitors offer further avenues for precise immune response modulation. This review underscores the importance of a comprehensive understanding of host-pathogen interactions in the development of effective therapies for fungal endophthalmitis.


Sujet(s)
Antifongiques , Endophtalmie , Mycoses oculaires , Endophtalmie/microbiologie , Endophtalmie/traitement médicamenteux , Humains , Mycoses oculaires/traitement médicamenteux , Mycoses oculaires/microbiologie , Antifongiques/usage thérapeutique , Antifongiques/pharmacologie , Cytokines/métabolisme , Animaux
3.
Trials ; 25(1): 566, 2024 Aug 28.
Article de Anglais | MEDLINE | ID: mdl-39192339

RÉSUMÉ

BACKGROUND: Infectious keratitis secondary to fungus or acanthamoeba often has a poor outcome despite receiving the best available medical therapy. In vitro rose bengal photodynamic therapy (RB-PDT) appears to be effective against fungal and acanthamoeba isolates (Atalay HT et al., Curr Eye Res 43:1322-5, 2018, Arboleda A et al. Am J Ophthalmol 158:64-70, 2014). In one published series, RB-PDT reduced the need for therapeutic penetrating keratoplasty in severe bacterial, fungal, and acanthamoeba keratitis not responsive to medical therapy. METHODS: This international, randomized, sham and placebo controlled 2-arm clinical trial randomizes patients with smear positive fungal and acanthamoeba and smear negative corneal ulcers in a 1:1 fashion to one of two treatment arms: 1) topical antimicrobial plus sham RB-PDT or 2) topical antimicrobial plus RB-PDT. DISCUSSION: We anticipate that RB-PDT will improve best spectacle-corrected visual acuity and also reduce complications such as corneal perforation and the need for therapeutic penetrating keratoplasty. This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Our results will be disseminated via ClinicalTrials.gov website, meetings, and journal publications. Our data will also be available upon reasonable request. TRIAL REGISTRATION: NCT, NCT05110001 , Registered on November 5, 2021.


Sujet(s)
Kératite à Acanthamoeba , Mycoses oculaires , Photothérapie dynamique , Essais contrôlés randomisés comme sujet , Rose de Bengale , Humains , Rose de Bengale/usage thérapeutique , Photothérapie dynamique/méthodes , Kératite à Acanthamoeba/traitement médicamenteux , Kératite à Acanthamoeba/diagnostic , Mycoses oculaires/microbiologie , Mycoses oculaires/traitement médicamenteux , Méthode en double aveugle , Résultat thérapeutique , Acuité visuelle , Photosensibilisants/usage thérapeutique , Études multicentriques comme sujet , Green Light
4.
Cornea ; 43(9): 1065-1071, 2024 Sep 01.
Article de Anglais | MEDLINE | ID: mdl-39102310

RÉSUMÉ

ABSTRACT: Keratomycosis is a serious corneal infection associated with high ocular morbidity that can lead to severe vision loss. It is estimated to affect more than 1 million patients annually, most commonly occurring in tropical climates, and represents a growing threat to patients worldwide. Despite aggressive medical management, fungal infections have a higher rate of perforation requiring surgical intervention compared with other infectious etiologies. Early diagnosis and appropriate treatment are keys to preserving vision and saving patients' eyes.Timely diagnosis of fungal keratitis helps minimize corneal damage and scarring and increases the likelihood of a favorable outcome. Studies have shown that correct identification of fungal infections is often delayed up to 2 to 3 weeks after initial presentation. This leads to incorrect or ineffective treatment for many patients. Diagnostic techniques explored in this study include corneal scrapings with staining and culture, visualization with in vivo confocal microscopy, molecular diagnostic techniques including polymerase chain reaction, and recently developed omics-based technologies.Treatment of fungal keratitis begins with topical antifungals. Medical management has been proven to be effective, but with limitations including poor drug penetration and low bioavailability. Cases that do not respond to topical therapy require more invasive and novel treatments to control the infection. We review the clinical trials that have shaped current practice patterns, with focus on the efficacy of topical natamycin as the primary therapy for filamentous fungal keratitis. We explore additional management strategies such as localized intrastromal and intracameral injections of antifungal medications, photodynamic therapy, and surgical intervention.


Sujet(s)
Antifongiques , Mycoses oculaires , Kératite , Humains , Mycoses oculaires/diagnostic , Mycoses oculaires/microbiologie , Mycoses oculaires/traitement médicamenteux , Mycoses oculaires/thérapie , Antifongiques/usage thérapeutique , Kératite/diagnostic , Kératite/microbiologie , Kératite/traitement médicamenteux , Microscopie confocale
5.
Mycopathologia ; 189(5): 74, 2024 Aug 07.
Article de Anglais | MEDLINE | ID: mdl-39107598

RÉSUMÉ

BACKGROUND: Mycotic keratitis (MK) represents a corneal infection, with Fusarium species identified as the leading cause. Fusarium is a genus of filamentous fungi commonly found in soil and plants. While many Fusarium species are harmless, some can cause serious infections in humans and animals, particularly Fusarium keratitis, that can lead to severe ocular infections, prevalent cause of monocular blindness in tropical and subtropical regions of the world. Due to its incidence and importance in ophthalmology, we conducted a systematic analysis of clinical cases to increase our understanding of Fusarium keratitis by gathering clinical and demographic data. METHODS: To conduct an analysis of Fusarium keratitis, we looked through the literature from the databases PubMed, Embase, Lilacs, and Google Scholar and found 99 papers that, between March 1969 and September 2023, corresponded to 163 cases of Fusarium keratitis. RESULTS: Our analysis revealed the Fusarium solani species complex as the predominant isolate, with females disproportionately affected by Fusarium keratitis. Notably, contact lens usage emerged as a significant risk factor, implicated in nearly half of cases. Diagnosis primarily relied on culture, while treatment predominantly involved topical natamycin, amphotericin B, and/or voriconazole. Surprisingly, our findings demonstrated a prevalence of cases originating from the United States, suggesting potential underreporting and underestimation of this mycosis in tropical regions. This shows the imperative for heightened vigilance, particularly in underdeveloped regions with substantial agricultural activity, where Fusarium infections may be more prevalent than currently reported. CONCLUSION: Our study sheds light on the clinical complexities of Fusarium keratitis and emphasizes the need for further research and surveillance to effectively tackle this vision-threatening condition. Furthermore, a timely identification and early initiation of antifungal treatment appear to be as important as the choice of initial treatment itself.


Sujet(s)
Antifongiques , Fusariose , Fusarium , Kératite , Humains , Kératite/microbiologie , Kératite/épidémiologie , Kératite/traitement médicamenteux , Fusarium/isolement et purification , Fusarium/classification , Fusarium/génétique , Fusariose/microbiologie , Fusariose/traitement médicamenteux , Fusariose/épidémiologie , Fusariose/diagnostic , Antifongiques/usage thérapeutique , Antifongiques/pharmacologie , Mycoses oculaires/microbiologie , Mycoses oculaires/épidémiologie , Mycoses oculaires/traitement médicamenteux , Femelle , Voriconazole/usage thérapeutique , Prévalence , Facteurs de risque , Mâle , Adulte , Adulte d'âge moyen , Lentilles de contact/microbiologie , Lentilles de contact/effets indésirables , Amphotéricine B/usage thérapeutique , Natamycine/usage thérapeutique , Sujet âgé , Jeune adulte , Adolescent
6.
BMC Ophthalmol ; 24(1): 332, 2024 Aug 08.
Article de Anglais | MEDLINE | ID: mdl-39118115

RÉSUMÉ

BACKROUD: Keratitis caused by Lasiodiplodia theobromae is rare and typically associated with a poor prognosis. Current literature lacks sufficient evidence on effective management of patients with this condition. CASE PRESENTATION: A 74-year-old former agricultural worker presented with a red right eye, discomfort, and decreased visual acuity, progressing over three days without treatment. Examination revealed type 2 diabetes and a non-perforating, spiculated corneal abscess with a hypopyon in the right eye. Initial treatment included a triple antibiotic therapy and supportive care. Direct mycological examination identified numerous septate mycelial filaments. Antifungal treatment with natamycin and voriconazole, both topically and orally, was initiated. Cultures confirmed Lasiodiplodia theobromae. The patient showed significant improvement. Treatment continued for eight weeks, with a final visual acuity of 20/50 due to a stromal scar. CONCLUSION: An extensive literature review conducted in November 2023, using databases such as PubMed and Google Scholar with the keywords "lasiodiplodia" and "keratitis" yielded no previous cases of this specific condition being managed solely with the combined use of natamycin and voriconazole. This antifungal combination is commonly included in most management protocols for fungal keratitis. Factors such as the use of corticosteroids and delayed diagnosis were noted to adversely affect the prognosis. This case and this systematic review underscores the potential for non-surgical management options in severe fungal keratitis.


Sujet(s)
Antifongiques , Ascomycota , Mycoses oculaires , Humains , Mycoses oculaires/traitement médicamenteux , Mycoses oculaires/microbiologie , Mycoses oculaires/diagnostic , Sujet âgé , Antifongiques/usage thérapeutique , Ascomycota/isolement et purification , Mâle , Kératite/microbiologie , Kératite/traitement médicamenteux , Kératite/diagnostic , Voriconazole/usage thérapeutique , Acuité visuelle/physiologie , Natamycine/usage thérapeutique , Association de médicaments
7.
Eye Contact Lens ; 50(9): 416-417, 2024 Sep 01.
Article de Anglais | MEDLINE | ID: mdl-39028227

RÉSUMÉ

OBJECTIVE: To describe a patient diagnosed with Exophiala jeanselmei keratitis. METHODS: We report a case of a patient who developed infectious keratitis following laser in situ keratomileusis and chronic topical steroid use for approximately six months in both eyes. An atypical infiltrate containing dark pigmentation was noted in the left eye on the initial presentation. During treatment, the infiltrates of the right eye began to exhibit a similar pigmentation. RESULTS: Early treatment with topical antifungals was initiated in the left eye and later in the right eye once culture results returned. Both eyes recovered with good vision after approximately one month. CONCLUSIONS: Patients treated with postoperative topical corticosteroids should be cautioned of potential adverse effects of chronic use and have close follow-up. If infectious keratitis develops, particularly after two weeks, then atypical organisms, such as fungi, should be considered. In addition, our case highlights the significance of recognizing and associating dark-pigmentation with fungal etiologies.


Sujet(s)
Antifongiques , Exophiala , Mycoses oculaires , Kératite , Kératomileusis in situ avec laser excimère , Adulte , Humains , Antifongiques/usage thérapeutique , Ulcère de la cornée/microbiologie , Ulcère de la cornée/traitement médicamenteux , Ulcère de la cornée/diagnostic , Ulcère de la cornée/étiologie , Exophiala/isolement et purification , Mycoses oculaires/microbiologie , Mycoses oculaires/traitement médicamenteux , Mycoses oculaires/diagnostic , Glucocorticoïdes/usage thérapeutique , Glucocorticoïdes/administration et posologie , Kératite/microbiologie , Kératite/diagnostic , Kératite/traitement médicamenteux , Kératite/étiologie , Kératomileusis in situ avec laser excimère/effets indésirables , Phaeohyphomycose/microbiologie , Phaeohyphomycose/diagnostic , Phaeohyphomycose/traitement médicamenteux
8.
Ann Clin Microbiol Antimicrob ; 23(1): 64, 2024 Jul 18.
Article de Anglais | MEDLINE | ID: mdl-39026348

RÉSUMÉ

BACKGROUND: Infectious keratitis, a significant contributor to blindness, with fungal keratitis accounting for nearly half of cases, poses a formidable diagnostic and therapeutic challenge due to its delayed clinical presentation, prolonged culture times, and the limited availability of effective antifungal medications. Furthermore, infections caused by rare fungal strains warrant equal attention in the management of this condition. CASE PRESENTATION: A case of fungal keratitis was presented, where corneal scraping material culture yielded pink colonies. Lactophenol cotton blue staining revealed distinctive spore formation consistent with the Fusarium species. Further analysis using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) identified the causative agent as Fusarium proliferatum. However, definitive diagnosis of Pseudonectria foliicola infection was confirmed through ITS sequencing. The patient's recovery was achieved with a combination therapy of voriconazole eye drops and itraconazole systemic treatment. CONCLUSION: Pseudonectria foliicola is a plant pathogenic bacterium that has never been reported in human infections before. Therefore, ophthalmologists should consider Pseudonectria foliicola as a possible cause of fungal keratitis, as early identification and timely treatment can help improve vision in most eyes.


Sujet(s)
Antifongiques , Mycoses oculaires , Fusarium , Kératite , Voriconazole , Humains , Kératite/microbiologie , Kératite/traitement médicamenteux , Kératite/diagnostic , Antifongiques/usage thérapeutique , Mycoses oculaires/microbiologie , Mycoses oculaires/traitement médicamenteux , Mycoses oculaires/diagnostic , Voriconazole/usage thérapeutique , Fusarium/isolement et purification , Fusarium/effets des médicaments et des substances chimiques , Fusarium/pathogénicité , Spectrométrie de masse MALDI , Itraconazole/usage thérapeutique , Fusariose/traitement médicamenteux , Fusariose/microbiologie , Fusariose/diagnostic , Mâle , Cornée/microbiologie , Cornée/anatomopathologie , Femelle , Adulte d'âge moyen
9.
Int J Pharm ; 662: 124505, 2024 Sep 05.
Article de Anglais | MEDLINE | ID: mdl-39059520

RÉSUMÉ

Keratitis is a corneal infection caused by various bacteria and fungi. Eye drop treatment of keratitis involves significant challenges due to difficulties in administration, inefficiencies in therapeutic dosage, and frequency of drug applications. All these are troublesome and result in unsuccessful treatment, high cost, time loss, development of drug resistance by microorganisms, and a massive burden on human health and the healthcare system. Most of the antibacterial and antifungal medications are non-water-soluble and/or include toxic drug formulations. Here, the aim was to develop drug-loaded contact lenses with therapeutic dosage formulations and extended drug release capability as an alternative to eye drops, by employing supercritical carbon dioxide (ScCO2) as a drug impregnation solvent to overcome inefficient ophthalmic drug use. ScCO2, known as a green solvent, has very low viscosity which provides high mass transfer power and could enhance drug penetration into contact lenses much better with respect to drug loading using other solvents. Here, moxifloxacin (MOX) antibiotic and amphotericin B (AMB) antifungal medicines were separately loaded into commercially available silicone hydrogel contact lenses through 1) drug adsorption from the aqueous solutions and 2) impregnation techniques via ScCO2 and their efficacies were compared. Drug impregnation parameters, i.e., 8-25 MPa pressure, 310-320 K temperature, 2-16-hour impregnation times, and the presence of ethanol as polar co-solvent were investigated for the optimization of the ScCO2 drug impregnation process. The highest drug loading and long-term release kinetic from the contact lenses were obtained at 25 MPa and 313 K with 2.5 h impregnation time by using 1 % ethanol (by volume). Furthermore, antibacterial/antifungal activities of the MOX- and AMB-impregnated contact lenses were effective against in vitro Pseudomonas aeruginosa (ATCC 10145) bacteria and Fusarium solani (ATCC 36031) fungus for up to one week. Consequently, the ScCO2 method can be effectively used to impregnate commercial contact lenses with drugs, and these can then be safely used for the treatment of keratitis. This offers a sustainable delivery system at effective dosage formulations with complete bacterial/fungal inhibition and termination, making it viable for real animal/human applications.


Sujet(s)
Amphotéricine B , Antibactériens , Antifongiques , Dioxyde de carbone , Kératite , Moxifloxacine , Dioxyde de carbone/composition chimique , Kératite/traitement médicamenteux , Kératite/microbiologie , Antibactériens/composition chimique , Antibactériens/administration et posologie , Antibactériens/pharmacologie , Antifongiques/composition chimique , Antifongiques/administration et posologie , Moxifloxacine/administration et posologie , Moxifloxacine/composition chimique , Moxifloxacine/pharmacologie , Amphotéricine B/administration et posologie , Amphotéricine B/composition chimique , Amphotéricine B/pharmacologie , Libération de médicament , Lentilles de contact/microbiologie , Fusarium/effets des médicaments et des substances chimiques , Humains , Hydrogels/composition chimique , Systèmes de délivrance de médicaments , Solvants/composition chimique , Mycoses oculaires/traitement médicamenteux , Mycoses oculaires/microbiologie
10.
Indian J Ophthalmol ; 72(8): 1130-1135, 2024 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-39078956

RÉSUMÉ

PURPOSE: To study the risk factors, clinical features, and treatment outcomes of patients with culture-negative keratitis (CNK). METHODS: A retrospective data review of 933 patients with CNK was performed from January 2018 to December 2020. The variables such as the history of injury, visual acuity, slit-lamp findings with measurements of size and depth of ulcer, microbiological evaluation, duct patency, blood glucose levels, and treatment were considered, and clinical outcome was analyzed. RESULTS: Of the 933 patients with CNK, 763 (81.8%) were medically managed, with a mean treatment duration of 2.08 ± 1.7 weeks. Among them, 622 (66.7%) were both smear and culture-negative, and 311 (33.3%) showed only smear positivity. Smear-positive patients showed a positive correlation with the history of injury. A higher incidence of fungal growth on repeat culture was observed. Surgical interventions were done only in 18.2% of the patients; the rest were treated with topical medications alone. CONCLUSION: High clinical suspicion, differentiation of causative organisms based on clinical findings, and initiating empirical therapy with broad-spectrum antibiotics and antifungals improve the ultimate prognosis in patients with CNK, even though a standard protocol for empirical medical treatment may differ among institutions and surgeons based on their clinical experience and geographical variations.


Sujet(s)
Antibactériens , Infections bactériennes de l'oeil , Mycoses oculaires , Acuité visuelle , Humains , Études rétrospectives , Femelle , Mâle , Infections bactériennes de l'oeil/microbiologie , Infections bactériennes de l'oeil/diagnostic , Infections bactériennes de l'oeil/traitement médicamenteux , Adulte d'âge moyen , Acuité visuelle/physiologie , Adulte , Mycoses oculaires/microbiologie , Mycoses oculaires/diagnostic , Mycoses oculaires/traitement médicamenteux , Mycoses oculaires/thérapie , Antibactériens/usage thérapeutique , Bactéries/isolement et purification , Antifongiques/usage thérapeutique , Kératite/microbiologie , Kératite/diagnostic , Kératite/traitement médicamenteux , Facteurs de risque , Études de suivi , Champignons/isolement et purification , Cornée/microbiologie , Cornée/anatomopathologie , Sujet âgé
11.
Surg Infect (Larchmt) ; 25(7): 550-552, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-38957959

RÉSUMÉ

Objective: The purpose of this study was to report a case of herpes simplex virus-1 (HSV-1) keratitis misdiagnosed as fungal keratitis due to its clinical presentation being similar to that of fungal keratitis, ultimately diagnosed by NGS. Patients and Methods: A 59-year-old male presented with reduced vision in the right eye, combined with a history of trauma with vegetative matter. The corneal ulcer was accompanied with feathery infiltration, satellite lesion, and endothelial plaques. In vivo confocal microscopy (IVCM) showed hyper-reflective linear, thin, and branching interlocking structures. Fungal keratitis was diagnosed. Voriconazole 100 mg orally daily, topical tobramycin and 1% voriconazole were initiated empirically right away. The condition was aggravated and penetrating keratoplasty was performed. Anterior segment optical coherence tomography (AS-OCT) demonstrated the presence of plaques with a clear boundary between plaques and endothelium, resembling the AS-OCT images observed in cases of viral keratitis. Next-generation sequencing (NGS) further detected HSV-1 deoxyribonucleic acid, and no fungal component was found. Antifungal agents were discontinued and antiviral treatments were added. Results: We successfully treated a patient with HSV-1 keratitis who was misdiagnosed due to clinical features and IVCM findings similar to fungal keratitis. The patient's infection was controlled. At 2 years after surgery, the cornea recovered well. Conclusions: HSV-1 keratitis with atypical clinical presentation can be easily misdiagnosed. This case report emphasizes the importance of NGS in diagnosing the pathogens of keratitis.


Sujet(s)
Erreurs de diagnostic , Herpèsvirus humain de type 1 , Séquençage nucléotidique à haut débit , Kératite herpétique , Humains , Mâle , Adulte d'âge moyen , Herpèsvirus humain de type 1/isolement et purification , Herpèsvirus humain de type 1/génétique , Séquençage nucléotidique à haut débit/méthodes , Kératite herpétique/diagnostic , Kératite herpétique/traitement médicamenteux , Kératite/diagnostic , Kératite/microbiologie , Kératite/virologie , Kératite/traitement médicamenteux , Mycoses oculaires/diagnostic , Mycoses oculaires/traitement médicamenteux , Antifongiques/usage thérapeutique , Antiviraux/usage thérapeutique
12.
Adv Ther ; 41(8): 3316-3327, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38958844

RÉSUMÉ

INTRODUCTION: This research aims to describe clinical findings, epidemiology and treatment outcomes in patients with filamentous fungi keratitis of a tertiary centre in Germany over a 7-year period and to compare the efficacy of different antifungal treatments and the effect of additive topical steroids. METHODS: This retrospective study included 25 eyes of 23 patients from October 2013 to December 2020 with cultural isolates of filamentous fungi and corresponding keratitis. Best-corrected visual acuity (BCVA), clinical signs, symptoms, risk factors and outcome were extracted from medical records. RESULTS: Improvement of BVCA was noted in 68% of eyes. Mean BCVA of the study population increased from 0.75 logMAR [median 0.40, standard deviation (SD) 0.82, range 0-2.3] to 0.48 logMAR (median 0.10, SD 0.88, range - 0.1 to 3). The most commonly used antifungal topical treatment was a combination of natamycin 5% and voriconazole 2% (44% of eyes), followed by voriconazole 2% in 36% of cases. An antiinflammatory topical steroid was applied in 52%. In 16% of the eyes, penetrating keratoplasty (pKP) was performed. CONCLUSION: Diagnosis of filamentous fungi keratitis is often difficult or delayed. Outcomes can be poor even with intensive treatment because of high resistance to common antifungals. Access to natamycin 5% seems to lead to favourable outcomes in filamentous fungi keratitis.


Sujet(s)
Antifongiques , Mycoses oculaires , Kératite , Humains , Études rétrospectives , Femelle , Mâle , Antifongiques/usage thérapeutique , Adulte d'âge moyen , Mycoses oculaires/traitement médicamenteux , Mycoses oculaires/microbiologie , Kératite/microbiologie , Kératite/traitement médicamenteux , Sujet âgé , Adulte , Voriconazole/usage thérapeutique , Sujet âgé de 80 ans ou plus , Acuité visuelle , Résultat thérapeutique , Natamycine/usage thérapeutique , Kératoplastie transfixiante
13.
ACS Infect Dis ; 10(8): 2991-2998, 2024 Aug 09.
Article de Anglais | MEDLINE | ID: mdl-39083647

RÉSUMÉ

Purpose: to explore the anti-inflammatory effects of a nanobody (Nb) specific to ß-glucan on fungal keratitis (FK). Methods: in order to verify the therapeutic and anti-inflammatory efficacy of Nb in FK, the severity of inflammation was assessed with inflammatory scores, hematoxylin-eosin (HE) staining, and myeloperoxidase (MPO) assays. In corneas of mice of FK model and human corneal epithelial cells stimulated by fungal hyphae, real-time reverse transcriptase polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay were used to detect the expression levels of inflammatory cytokines and pattern recognition receptors (PRRs). In vivo, macrophages and neutrophils infiltration in the cornea stroma was detected by immunofluorescence (IFS) staining. Results: In murine models infected with Aspergillus fumigatus (A. fumigatus), Nb treatment could reduce the inflammatory scores. HE staining and MPO results showed Nb significantly alleviated corneal edema and reduced inflammatory cell infiltration 3 days post-infection. In addition, the expression levels of LOX-1 and Dectin-1 were significantly decreased in the Nb group in vivo. The expression of chemokines CCL2 and CXCL2 also decreased in the Nb group. Compared with the PBS group, the number of macrophages and neutrophils in the Nb group was significantly decreased, which was shown in IFS results. Moreover, Nb attenuated the expression of Dectin-1, LOX-1, and inflammatory mediators, including IL-6 and IL-8 in vitro. Conclusion: our study showed that Nb could alleviate FK by downregulating the expression of PRRs and inflammatory factors as well as reducing the infiltration of macrophages and neutrophils.


Sujet(s)
Anti-inflammatoires , Aspergillus fumigatus , Modèles animaux de maladie humaine , Kératite , Anticorps à domaine unique , bêta-Glucanes , Animaux , Kératite/traitement médicamenteux , Kératite/microbiologie , Souris , bêta-Glucanes/pharmacologie , Anti-inflammatoires/pharmacologie , Humains , Anticorps à domaine unique/pharmacologie , Paroi cellulaire/composition chimique , Aspergillose/traitement médicamenteux , Aspergillose/microbiologie , Aspergillose/immunologie , Cornée/effets des médicaments et des substances chimiques , Cytokines/métabolisme , Macrophages/effets des médicaments et des substances chimiques , Mycoses oculaires/traitement médicamenteux , Mycoses oculaires/microbiologie , Granulocytes neutrophiles/effets des médicaments et des substances chimiques , Granulocytes neutrophiles/immunologie
14.
Arch Microbiol ; 206(8): 358, 2024 Jul 20.
Article de Anglais | MEDLINE | ID: mdl-39033220

RÉSUMÉ

Fungal keratitis is a severe corneal infection characterized by suppurative and ulcerative lesions. Aspergillus fumigatus is a common cause of fungal keratitis. Antifungal drugs, such as natamycin, are currently the first-line treatment for fungal keratitis, but their ineffectiveness leads to blindness and perforation. Additionally, the development of fungal resistance makes treating fungal keratitis significantly more challenging. The present study used platelet-derived biomaterial (PDB) to manage A. fumigatus keratitis in the animal model. Freezing and thawing processes were used to prepare PDB, and then A. fumigatus keratitis was induced in the mice. Topical administration of PDB, natamycin, and plasma was performed; quantitative real-time PCR (qPCR) and histopathologic examination (HE) were used to assess the inhibitory effect of the mentioned compounds against fungal keratitis. The qPCR results showed that PDB significantly decreased the count of A. fumigatus compared to the control group (P-value ≤ 5). Natamycin also remarkably reduced the count of fungi in comparison to the untreated animal, but its inhibitory effect was not better than PDB (P-value > 5). The findings of HE also demonstrated that treatment with PDB and natamycin decreased the fungal loads in the corneal tissue. However, plasma did not show a significant inhibitory effect against A. fumigatus. PDB is intrinsically safe and free of any infections or allergic responses; additionally, this compound has a potential role in decreasing the burden of A. fumigatus and treating fungal keratitis. Therefore, scientists should consider PDB an applicable approach to managing fungal keratitis and an alternative to conventional antifungal agents.


Sujet(s)
Antifongiques , Aspergillose , Aspergillus fumigatus , Kératite , Aspergillus fumigatus/effets des médicaments et des substances chimiques , Animaux , Kératite/microbiologie , Kératite/traitement médicamenteux , Souris , Aspergillose/traitement médicamenteux , Aspergillose/microbiologie , Antifongiques/pharmacologie , Antifongiques/usage thérapeutique , Modèles animaux de maladie humaine , Matériaux biocompatibles , Plaquettes/effets des médicaments et des substances chimiques , Natamycine/pharmacologie , Natamycine/administration et posologie , Natamycine/usage thérapeutique , Mycoses oculaires/traitement médicamenteux , Mycoses oculaires/microbiologie , Cornée/microbiologie , Cornée/anatomopathologie , Cornée/effets des médicaments et des substances chimiques
15.
ACS Infect Dis ; 10(8): 2950-2960, 2024 Aug 09.
Article de Anglais | MEDLINE | ID: mdl-38990785

RÉSUMÉ

Fungal keratitis (FK) is a leading cause of preventable blindness and eye loss. The poor antifungal activity, increased drug resistance, limited corneal permeability, and unsatisfactory biosafety of conventional antifungal eye drops are among the majority of the challenges that need to be addressed for currently available antifungal drugs. Herein, this study proposes an effective strategy that employs chitosan-poly(ethylene glycol)-LK13 peptide conjugate (CPL) in the treatment of FK. Nanoassembly CPL can permeate the lipophilic corneal epithelium in the transcellular route, and its hydrophilicity surface is a feature to drive its permeability through hydrophilic stroma. When encountering fungal cell membrane, CPL dissembles and exposes the antimicrobial peptide (LK13) to destroy fungal cell membranes, the minimum inhibitory concentration values of CPL against Fusarium solani (F. solani) are always not to exceed 8 µg peptide/mL before and after drug resistance induction. In a rat model of Fusarium keratitis, CPL demonstrates superior therapeutic efficacy than commercially available natamycin ophthalmic suspension. This study provides more theoretical and experimental supports for the application of CPL in the treatment of FK.


Sujet(s)
Antifongiques , Chitosane , Cornée , Résistance des champignons aux médicaments , Fusarium , Kératite , Tests de sensibilité microbienne , Polyéthylène glycols , Chitosane/composition chimique , Chitosane/pharmacologie , Kératite/traitement médicamenteux , Kératite/microbiologie , Antifongiques/pharmacologie , Antifongiques/composition chimique , Fusarium/effets des médicaments et des substances chimiques , Animaux , Rats , Résistance des champignons aux médicaments/effets des médicaments et des substances chimiques , Polyéthylène glycols/composition chimique , Cornée/effets des médicaments et des substances chimiques , Mycoses oculaires/traitement médicamenteux , Mycoses oculaires/microbiologie , Perméabilité/effets des médicaments et des substances chimiques , Fusariose/traitement médicamenteux , Peptides antimicrobiens/pharmacologie , Peptides antimicrobiens/composition chimique , Natamycine/pharmacologie , Natamycine/administration et posologie , Mâle , Modèles animaux de maladie humaine , Rat Sprague-Dawley
17.
BMJ Open ; 14(7): e082793, 2024 Jul 05.
Article de Anglais | MEDLINE | ID: mdl-38969381

RÉSUMÉ

OBJECTIVES: To investigate the epidemiological characteristics and clinical outcomes of culture-proven bacterial and fungal keratitis at a single tertiary referral centre on Jeju Island, South Korea. DESIGN: A retrospective study design. SETTING: Data from a solitary referral centre on Jeju Island spanning January 2011 to December 2022. PARTICIPANTS: Among the 245 patients clinically diagnosed with infectious microbial keratitis, 110 individuals had culture-positive results. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the identification of causative microbial profiles and epidemiological characteristics, while the secondary outcome was the correlation of these factors with treatment outcomes. RESULTS: Of 245 patients, 110 (44.9%) had culture-positive infectious keratitis, showing 69 bacterial, 32 fungal, 4 superimposed bacterial and 5 cases with coinfection by bacteria and fungus. The most common pathogen was Pseudomonas species in 14.4% of the bacterial keratitis cases, followed by Staphylococcus epidermidis (9%), Staphylococcus aureus (8%) and Moraxella species (7%). The total treatment success rate for bacterial keratitis was 67.5%. The frequency of methicillin-resistant Staphylococcus on Jeju Island did increase during the study period. Fusarium species had the highest incidence at 22.2%, followed by Candida (16.7%) and Colletotrichum species (11.1%). 56.7% of fungal keratitis patients were successfully treated. An initial large corneal lesion (>3 mm) showed a statistically significant association with treatment failure. CONCLUSION: The incidence of Moraxella and Colletotrichum species in our study was higher than that reported in other districts with different climates and environments. The results reported here reflect the unique environmental features of Jeju Island, characterised by high humidity and temperatures.


Sujet(s)
Mycoses oculaires , Kératite , Humains , Études rétrospectives , République de Corée/épidémiologie , Femelle , Mâle , Adulte d'âge moyen , Kératite/épidémiologie , Kératite/microbiologie , Adulte , Sujet âgé , Mycoses oculaires/épidémiologie , Mycoses oculaires/microbiologie , Mycoses oculaires/traitement médicamenteux , Infections bactériennes de l'oeil/épidémiologie , Infections bactériennes de l'oeil/microbiologie , Antibactériens/usage thérapeutique , Incidence , Centres de soins tertiaires/statistiques et données numériques
20.
PLoS Negl Trop Dis ; 18(6): e0012247, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38885283

RÉSUMÉ

BACKGROUND: Fusarium and allied genera (fusarioid) species are common colonizers of roots and aerial plant parts, or act as phytopathogens in forestry and horticultural or grain crops. However, they can also cause a wide range of infections in humans, including onychomycosis, cutaneous and invasive infections. Fusarioid keratitis is characterized by an infection of the cornea with a suppurative and ulcerative appearance, which may cause damage to vision and permanent blindness. The aim of the present study was to investigate the prevalence of fusarioid species, biofilm formation and antifungal susceptibility profiling of clinical isolates recovered from patients with keratitis and dermatomycoses. METHODOLOGY/PRINCIPAL FINDINGS: The study was performed between March, 2012-December, 2022. Demographic, clinical and epidemiological data of patients were also collected. In the present study, most of the patients with keratitis were male (74%), had a median age of 42 years old, worked with plant material or debris and 26% of them reported eye trauma. Regarding dermatomycosis, most of patients were female and exhibited toenail lesions. Forty-seven isolates belonged to the genus Neocosmospora (78.33%), nine to the Fusarium fujikuroi (15%) and four to the Fusarium oxysporum (6.66%) species complexes. Several strains were moderate biofilm producers, specifically among Fusarium annulatum. Most strains showed increased MICs to amphotericin B and ketoconazole and low MICs to itraconazole. MICs ranged from 0.25 to 16 µg/mL for amphotericin B, 0.0625 to >16 µg/mL for ketoconazole and 0.125 to 8 for itraconazole. CONCLUSIONS/SIGNIFICANCE: It is possible to conclude that fusarioid keratitis in Northeastern Brazil is an important and neglected disease, given the high number of cases, increased need for keratoplasty and poor outcome of the disease.


Sujet(s)
Antifongiques , Fusarium , Kératite , Tests de sensibilité microbienne , Humains , Femelle , Mâle , Adulte , Brésil/épidémiologie , Kératite/microbiologie , Kératite/épidémiologie , Études prospectives , Adulte d'âge moyen , Antifongiques/pharmacologie , Fusarium/effets des médicaments et des substances chimiques , Fusarium/isolement et purification , Fusarium/classification , Fusariose/microbiologie , Fusariose/épidémiologie , Fusariose/traitement médicamenteux , Jeune adulte , Mycoses cutanées/épidémiologie , Mycoses cutanées/microbiologie , Mycoses cutanées/traitement médicamenteux , Sujet âgé , Biofilms/effets des médicaments et des substances chimiques , Biofilms/croissance et développement , Prévalence , Adolescent , Mycoses oculaires/microbiologie , Mycoses oculaires/épidémiologie , Mycoses oculaires/traitement médicamenteux
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