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1.
ACS Infect Dis ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990785

RESUMO

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.

2.
J Am Vet Med Assoc ; : 1-9, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38991540

RESUMO

Equine fungal keratitis represents a substantial portion of keratitis cases in horses, with fungal involvement identified in approximately half of all infectious keratitis cases. Despite its prevalence, more comprehensive retrospective analyses are needed to better understand this condition. Outcomes vary, with approximately two-thirds of cases achieving complete healing with retained vision, although enucleation is often necessary. Predominant pathogens include Aspergillus and Fusarium, with yeast reported in a minority of cases. Resistance to common antifungal agents among filamentous fungi poses a significant challenge. Advances in diagnostics, including repeat culture and antifungal susceptibility testing, as well as the incorporation of PCR technology, hold promise for improving detection and guiding treatment decisions. Newer antifungals, combination therapies, and innovative modalities such as photodynamic therapy offer hope for improved outcomes. Continued research efforts are essential to further elucidate the epidemiology, pathogenesis, and optimal management strategies for this condition.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38957959

RESUMO

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.

4.
Diagn Microbiol Infect Dis ; 110(1): 116369, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38909427

RESUMO

A 32-year-old contact lens-wearing man with recent travel history to the Caribbean was referred for a corneal infiltrate in the left eye that worsened following 1-week of steroid-antibiotic therapy. Corneal cultures were obtained and sent to our facility's clinical microbiology laboratory for analysis. Same-day in vivo confocal microscopy revealed fungal elements. Nucleic acid sequencing performed on the isolated determined it to be a member of the entomopathogenic genus Metarhizium. Over the course of 3 months, the patient's corneal infiltrate ultimately resolved following topical natamycin 5 % therapy. This is the first reported case to have originated in the Caribbean and to utilize in vivo confocal microscopy to aid diagnosis. Our case also supports previous reports of success with natamycin therapy in treatment of Metarhizium sp. keratitis.

5.
ACS Infect Dis ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900967

RESUMO

Fungal keratitis (FK) is a severe corneal condition caused by pathogenic fungi and is associated with the virulence of fungi and an excessive tissue inflammatory response. Progranulin (PGRN), functioning as a multifunctional growth factor, exerts a pivotal influence on the regulation of inflammation and autophagy. The aim of our research was to analyze the role of PGRN in Aspergillus fumigatus (A. fumigatus) keratitis. We found that PGRN expression was increased in the mouse cornea with A. fumigatus keratitis. In our experiments, corneas of mice with FK were treated with 100 ng/mL of PGRN. In vitro, RAW 264.7 cells were treated with 10 ng/mL of PGRN before A. fumigatus stimulation. The findings suggested that PGRN effectively alleviated corneal edema and decreased the expression of pro-inflammatory cytokines in mice. In stimulated RAW 264.7 cells, PGRN treatment suppressed the expression of pro-inflammatory cytokines IL-6 and TNF-α but promoted the expression of the anti-inflammatory cytokines IL-10. PGRN treatment significantly upregulated the expression of autophagy-related proteins LC3, Beclin-1, and Atg-7. 3-Methyladenine (3-MA, autophagy inhibitor) reversed the regulation of inflammatory cytokines by PGRN. In addition, our study demonstrated that PGRN also enhanced phagocytosis in RAW 264.7 cells. In summary, PGRN attenuated the inflammatory response of A. fumigatus keratitis by increasing autophagy and enhanced the phagocytic activity of RAW 264.7 cells. This showed that PGRN had a protective effect on A. fumigatus keratitis.

6.
ACS Infect Dis ; 10(7): 2356-2380, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38847789

RESUMO

Fungal keratitis (FK) is a severe ocular condition resulting from corneal infection that is prevalent in tropical countries, particularly in developing regions of Asia and Africa. Factors like corneal lens misuse, inappropriate steroid use, and diagnostic challenges have provoked the epidemic. FK causes significant vision impairment, scarring, and ocular deformities. Accurate pathological diagnosis is crucial for effective therapeutic intervention. Topical antifungal therapy with surface healing medications proves effective in preventing fungal-borne ulcers. Managing FK requires a comprehensive understanding of fungal pathogenesis, guiding formulation strategies and preventive measures to curb global ocular blindness. This review provides in-depth insights into FK, covering etiology, epidemiology, pathogenesis, therapeutic interventions, antifungal resistance, limitations, prevention, and future perspectives on ocular surface disease management.


Assuntos
Antifúngicos , Infecções Oculares Fúngicas , Ceratite , Humanos , Ceratite/diagnóstico , Ceratite/epidemiologia , Ceratite/microbiologia , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/epidemiologia , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Fúngicas/tratamento farmacológico , Antifúngicos/uso terapêutico , Farmacorresistência Fúngica
7.
Pak J Med Sci ; 40(5): 974-978, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827873

RESUMO

Objectives: To investigate the clinical efficacy of cyclosporin (CYSP) and natamycin (NAT) as a combination therapy in patients with fungal keratitis. Methods: This is a retrospective study. A total of 64 patients (64 eyes) with fungal keratitis treated by Baoding No.1 Central Hospital between December 2018 and May 2022 according to their treatment methods were divided into a monotherapy (MT) group receiving NAT eye drops solely and a combination therapy (CT) group given CYSP eye drops in addition to the exact treatment provided for the MT group. The clinical responses, visual acuity changes, severity of eye symptoms, and adverse reactions were compared between the two groups. Results: At two and four weeks post-treatment, the CT group had an overall response rate (ORR) significantly higher than that of the MT group (P< 0.05, respectively); both groups showed improved visual acuity and eye symptoms compared with the pre-treatment condition, and these improvements were more pronounced in the CT group (P < 0.05, respectively). Compared with the MT group, the CT group experienced a significantly shorter duration of eye symptoms (P < 0.05). The adverse reaction rate(ARR) was 9.38% in the CT group and 6.25% in the MT group, and the difference was not significant (P > 0.05). Conclusion: Using CYSP and NAT as a combination therapy for fungal keratitis can substantially heighten the therapeutic effects, promote visual acuity recovery, and induce rapid remission of eye symptoms without increasing the risk of adverse reactions.

8.
Exp Eye Res ; 244: 109944, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38797260

RESUMO

Fungal keratitis (FK) is an infectious keratopathy can cause serious damage to vision. Its severity is related to the virulence of fungus and response of inflammatory. Rosmarinic acid (RA) extracted from Rosmarinus officinalis exhibits antioxidant, anti-inflammatory and anti-viral properties. The aim of this study was to investigate the effect of RA on macrophage autophagy and its therapeutic effect on FK. In this study, we demonstrated that RA reduced expression of proinflammatory cytokine, lessened the recruitment of inflammatory cells in FK. The relative contents of autophagy markers, such as LC3 and Beclin-1, were significantly up-regulated in RAW 264.7 cells and FK. In addition, RA restored mitochondrial membrane potential (MMP) of macrophage to normal level. RA not only reduced the production of intracellular reactive oxygen species (ROS) but also mitochondria ROS (mtROS) in macrophage. At the same time, RA induced macrophage to M2 phenotype and down-regulated the mRNA expression of IL-6, IL-1ß, TNF-α. All the above effects could be offset by the autophagy inhibitor 3-Methyladenine (3-MA). Besides, RA promote phagocytosis of RAW 264.7 cells and inhibits spore germination, biofilm formation and conidial adherence, suggesting a potential therapeutic role for RA in FK.


Assuntos
Aspergilose , Aspergillus fumigatus , Autofagia , Cinamatos , Depsídeos , Infecções Oculares Fúngicas , Macrófagos , Espécies Reativas de Oxigênio , Ácido Rosmarínico , Depsídeos/farmacologia , Animais , Autofagia/efeitos dos fármacos , Camundongos , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Aspergilose/metabolismo , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Fúngicas/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/microbiologia , Cinamatos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Ceratite/microbiologia , Ceratite/tratamento farmacológico , Ceratite/metabolismo , Modelos Animais de Doenças , Células RAW 264.7 , Citocinas/metabolismo , Fagocitose/efeitos dos fármacos
9.
Redox Biol ; 73: 103206, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38796864

RESUMO

Fungal keratitis is a severely vision-threatening corneal infection, where the prognosis depends on both fungal virulence and host immune defense. Inappropriate host responses can induce substantial inflammatory damage to the cornea. Therefore, in the treatment of fungal keratitis, it is important to concurrently regulate the immune response while efforts are made to eliminate the pathogen. Ebselen is a widely studied organo-selenium compound and has been demonstrated to have antifungal, antibacterial, anti-inflammatory, and oxidative stress-regulatory properties. The effectiveness of ebselen for the treatment of fungal keratitis remains unknown. In this study, ebselen was demonstrated to produce a marked inhibitory effect on Aspergillus fumigatus (A. fumigatus), including spore germination inhibition, mycelial growth reduction, and fungal biofilm disruption. The antifungal activity of ebselen was related to the cell membrane damage caused by thioredoxin (Trx) system inhibition-mediated oxidative stress. On the contrary, ebselen enhanced the antioxidation of Trx system in mammalian cells. Further, ebselen was proven to suppress the expressions of inflammatory mediators (IL-1ß, IL-6, TNF-α, COX-2, iNOS, and CCL2) and reduce the production of oxidative stress-associated indicators (ROS, NO, and MDA) in fungi-stimulated RAW264.7 cells. In addition, ebselen regulated PI3K/Akt/Nrf2 and p38 MAPK signaling pathways, which contributed to the improvement of inflammation and oxidative stress. Finally, we verified the therapeutic effect of ebselen on mouse fungal keratitis. Ebselen improved the prognosis and reduced the fungal burden in mouse corneas. Expressions of inflammatory mediators, as well as the infiltration of macrophages and neutrophils in the cornea were also obviously decreased by ebselen. In summary, ebselen exerted therapeutic effects by reducing fungal load and protecting host tissues in fungal keratitis, making it a promising treatment for fungal infections.


Assuntos
Anti-Inflamatórios , Antifúngicos , Azóis , Isoindóis , Ceratite , Compostos Organosselênicos , Estresse Oxidativo , Compostos Organosselênicos/farmacologia , Compostos Organosselênicos/uso terapêutico , Animais , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Azóis/farmacologia , Azóis/uso terapêutico , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Células RAW 264.7 , Antioxidantes/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Fúngicas/metabolismo , Modelos Animais de Doenças
10.
Pharm Nanotechnol ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38797907

RESUMO

Keratomycosis, also termed fungal keratitis (FK), is an invasive eye condition for which there is a lack of available effective treatment due to pharmacological shortages and vital ocular obstacles. This severe corneal infection typically suppurates and eventually ulcerates, ultimately causing blindness or decreased vision. According to epidemiological studies, FK is more common in warm, humid places with an agricultural economy. The use of nanoemulsion carriers for ocular fungal infection has been promoting better treatment and patient compliance. The persistent fungal infection like FK, affecting particularly the stroma heralds complications thereby posing difficulty in diagnosis and treatment. To help treat refractory cases and improve outcomes, recently targeted drug delivery techniques and novel antifungal drugs shall be explored. A delay in diagnosis may cause corneal fungal infections to have irreversible consequences, which cannot be avoided. However, infections can develop into ocular perforation even after receiving intense care. The commonly used chemotherapy for FK is based on topical (natamycin 5% is typically first-line therapy) and systemic administration of azole drugs. To address the problems related to better treatment, various nanoemulsion carriers were discussed. Novel drug delivery systems based on nanoemulsions are a viable therapeutic option for treating keratomycosis and may be a candidate method for overcoming obstacles in the treatment of many other ocular illnesses when combined with different hydrophobic medicines. With a brief explanation of the pathogenesis, this article seeks to give readers a thorough analysis of current trends, various treatment choices, and care strategies for fungal keratitis.

11.
Microorganisms ; 12(5)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38792749

RESUMO

This study aims to report the efficacy of a combined intrastromal injection in optimizing the outcome of severe mycotic keratitis. Herein, we report a case series of 20 consecutive patients with positive fungal cultures not responding to topical antifungal treatment. Patients received cycles of intrastromal injections of voriconazole (50 µg/0.1 mL) and amphotericin B (2.5 µg/0.1 mL); all patients continued their topical antifungal therapy. The organisms isolated were Fusarium (n = 5), Aspergillus (n = 4), Candida (n = 4), Rhodotorula (n = 2), Penicillium (n = 2), Alternaria (n = 1), Bipolaris (n = 1), and Curvularia (n = 1). The size of the infiltrate varied from 6.5 to 1.5 mm. At presentation, the best corrected visual acuity (BCVA, namely, the best visual acuity achieved with glasses, if needed) was less than 20/400 in all patients, improving to better than 20/400 in eleven patients. Seven patients required surgical intervention; four of them underwent penetrating keratoplasty (PK) à chaud one month after the first intrastromal injection. Patients who underwent surgery achieved a BCVA of 20/40 or better. Combined intrastromal injections before therapeutic penetrating keratoplasty (TPK) effectively reduced ulcer size and graft diameter, preventing infection recurrence. Our results highlight the efficacy of combined intrastromal injections in optimizing outcomes for severe mycotic keratitis undergoing TPK.

12.
Mycoses ; 67(5): e13728, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38695201

RESUMO

BACKGROUND: Fungal keratitis is a severe eye infection that can result in blindness and visual impairment, particularly in developing countries. Fusarium spp. are the primary causative agents of this condition. Diagnosis of Fusarium keratitis (FK) is challenging, and delayed treatment can lead to serious complications. However, there is limited epidemiological data on FK, especially in tropical areas. OBJECTIVES: This study aimed to describe the clinical, laboratorial and epidemiological characteristics of FK in a tropical semi-arid region of Brazil. PATIENTS/METHODS: Adult patients with laboratory-confirmed FK diagnosed between October 2019 and March 2022 were evaluated. Fusarium isolates were characterized at molecular level and evaluated regarding antifungal susceptibility. RESULTS: A total of 226 clinical samples from patients suspected of keratitis were evaluated; fungal growth was detected in 50 samples (22.12%); out of which 42 were suggestive of Fusarium spp. (84%). Molecular analysis of a randomly selected set of 27 isolates identified F. solani species complex (n = 14); F. fujikuroi sensu lato (n = 6) and F. dimerum sensu lato (n = 7); a total of 10 haplotypes were identified among the strains. All but one Fusarium strains were inhibited by amphotericin B, natamycin and fluconazole. Most patients were male (71.42%; 30 out of 42), aged from 27 to 73 years old. Trauma was the most important risk factor for FK (40.47%; 17 out of 42). Patients were treated with antifungals, corticoids and antibiotics; keratoplasty and eye enucleation were also performed. CONCLUSIONS: The study provided insights into the characteristics of FK in tropical regions and emphasized the importance of enhanced surveillance and management strategies.


Assuntos
Antifúngicos , Infecções Oculares Fúngicas , Fusariose , Fusarium , Ceratite , Testes de Sensibilidade Microbiana , Humanos , Brasil/epidemiologia , Fusarium/genética , Fusarium/efeitos dos fármacos , Fusarium/isolamento & purificação , Fusarium/classificação , Masculino , Feminino , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Adulto , Ceratite/microbiologia , Ceratite/epidemiologia , Ceratite/tratamento farmacológico , Pessoa de Meia-Idade , Fusariose/microbiologia , Fusariose/epidemiologia , Fusariose/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Fúngicas/epidemiologia , Infecções Oculares Fúngicas/tratamento farmacológico , Idoso , Adulto Jovem , Adolescente , Clima Tropical , Idoso de 80 Anos ou mais , Anfotericina B/farmacologia , Anfotericina B/uso terapêutico
13.
Appl Microbiol Biotechnol ; 108(1): 291, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592509

RESUMO

Melanin is an Aspergillus flavus cell wall component that provides chemical and physical protection to the organism. However, the molecular and biological mechanisms modulating melanin-mediated host-pathogen interaction in A. flavus keratitis are not well understood. This work aimed to compare the morphology, surface proteome profile, and virulence of melanized conidia (MC) and non-melanized conidia (NMC) of A. flavus. Kojic acid treatment inhibited melanin synthesis in A. flavus, and the conidial surface protein profile was significantly different in kojic acid-treated non-melanized conidia. Several cell wall-associated proteins and proteins responsible for oxidative stress, carbohydrate, and chitin metabolic pathways were found only in the formic acid extracts of NMC. Scanning electron microscopy (SEM) analysis showed the conidial surface morphology difference between the NMC and MC, indicating the role of melanin in the structural integrity of the conidial cell wall. The levels of calcofluor white staining efficiency were different, but there was no microscopic morphology difference in lactophenol cotton blue staining between MC and NMC. Evaluation of the virulence of MC and NMC in the Galleria mellonella model showed NMC was less virulent compared to MC. Our findings showed that the integrity of the conidial surface is controlled by the melanin layer. The alteration in the surface protein profile indicated that many surface proteins are masked by the melanin layer, and hence, melanin can modulate the host response by preventing the exposure of fungal proteins to the host immune defense system. The G. mellonella virulence assay also confirmed that the NMC were susceptible to host defense as in other Aspergillus pathogens. KEY POINTS: • l-DOPA melanin production was inhibited in A. flavus isolates by kojic acid, and for the first time, scanning electron microscopy (SEM) analysis revealed morphological differences between MC and NMC of A. flavus strains • Proteome profile of non-melanized conidia showed more conidial surface proteins and these proteins were mainly involved in the virulence, oxidative stress, and metabolism pathways • Non-melanized conidia of A. flavus strains were shown to be less virulent than melanised conidia in an in vivo virulence experiment with the G. melonella model.


Assuntos
Melaninas , Proteínas de Membrana , Aspergillus flavus , Esporos Fúngicos , Proteoma , Virulência
14.
Int J Pharm ; 656: 124118, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38615806

RESUMO

Fungal infections of cornea are important causes of blindness especially in developing nations with tropical climate. However, the challenges associated with current treatments are responsible for poor outcome. Natamycin is the only FDA-approved antifungal drug to treat fungal keratitis, but unfortunately due to its poor water solubility, it is available as suspension. The marketed suspension (5% Natamycin) has rapid precorneal clearance, poor corneal permeability, a higher frequency of administration, and corneal irritation due to undissolved suspended drug particles. In our study, we developed clear and stable natamycin-loaded nanomicelles (1% Natcel) to overcome the above challenges. We demonstrated that 1% Natcel could permeate the cornea better than 5% suspension. The developed 1% Natcel was able to provide sustained release for up to 24 h. Further, it was found to be biocompatible and also improved the mean residence time (MRT) than 5% suspension in tears. Therefore, the developed 1% Natcel could be a potential alternative treatment for fungal keratitis.


Assuntos
Antifúngicos , Córnea , Liberação Controlada de Fármacos , Infecções Oculares Fúngicas , Ceratite , Micelas , Nanopartículas , Natamicina , Natamicina/administração & dosagem , Antifúngicos/administração & dosagem , Antifúngicos/química , Antifúngicos/farmacologia , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Animais , Córnea/microbiologia , Córnea/metabolismo , Córnea/efeitos dos fármacos , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Coelhos , Solubilidade , Preparações de Ação Retardada , Lágrimas/metabolismo
15.
Int Ophthalmol ; 44(1): 205, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38676784

RESUMO

PURPOSE: Microbial keratitis is a sight-threatening condition with a higher incidence in agrarian populations. In countries with a high indigent population, due to financial and other constraints, patients prefer to seek therapy locally rather than travel to advanced centres. The aim of this study is to describe the epidemiology, clinical characteristics, and outcomes of 60 consecutive patients with microbial keratitis managed at a rural centre. METHODS: Descriptive case series. All patients clinically diagnosed with infectious keratitis were included. Corneal scrapings were obtained and microbiological identification was done by Gram stain. Anti-microbial therapy was commenced based on smear findings and the patients were followed up till disease resolution. RESULTS: Sixty eyes of 60 patients were diagnosed with microbial keratitis in the study period. The mean age was 47.43 ± 18.69 years. Male:female ratio was 47:53. Risk factors included ocular trauma in the majority of patients (46/60; 76.7%). Microorganisms were identified on 75.6% of smears, with fungal filaments (65.4%) being the most common. Ulcers were central in over half (32/60; 53.3%), and > 3 mm in diameter in over three-fourths (81.6%) of patients. Forty-four patients (73.3%) achieved treatment success whereas 16/60 (26.6%) required referral to our tertiary-eye care facility for management. The median time to resolution was 14 days (IQR 10-26 days). CONCLUSION: Our series demonstrates the feasibility of microbiology-guided therapy in microbial keratitis by ophthalmologists at the secondary rural eye-care level. Two-thirds of the patients could be successfully managed at the rural centre and only severe cases needed a referral to tertiary centres.


Assuntos
Infecções Oculares Bacterianas , População Rural , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Infecções Oculares Bacterianas/epidemiologia , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/terapia , Idoso , Índia/epidemiologia , População Rural/estatística & dados numéricos , Ceratite/epidemiologia , Ceratite/microbiologia , Ceratite/diagnóstico , Adulto Jovem , Antibacterianos/uso terapêutico , Adolescente , Úlcera da Córnea/microbiologia , Úlcera da Córnea/epidemiologia , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/terapia , Incidência , Infecções Oculares Fúngicas/epidemiologia , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/terapia , Infecções Oculares Fúngicas/tratamento farmacológico , Fatores de Risco , Bactérias/isolamento & purificação
16.
Microorganisms ; 12(4)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38674731

RESUMO

Infectious keratitis is a significant global problem that can lead to corneal blindness and visual impairments. This study aimed to investigate the etiology of infectious bacterial and fungal keratitis, identify the causative pathogens and their antimicrobial resistance patterns, and analyze the risk factors associated with the development of infectious keratitis. The study was observational and retrospective, involving 226 eyes from 223 patients presented at the Ophthalmology Clinic of the County Clinical Emergency Hospital of Craiova, Romania. The inclusion criteria included corneal ulceration/abscess/infiltrate present on slit-lamp examination and positive microbiological sampling for bacteria or fungi. The study found that the most common causes of infectious keratitis were coagulase-negative staphylococci (35.40%), Staphylococcus aureus (11.06%), and Pseudomonas aeruginosa (14.16%). The Gram-positive bacteria showed high resistance rates to penicillin, moderate rates to gentamycin and clindamycin, and low resistance to chinolones. The Gram-negative bacteria were highly resistant to ampicillin and amoxicillin-clavulanic acid, while third-generation cephalosporins, quinolones, and carbapenems were effective. Systemic antibiotics, such as vancomycine, piperacillin-tazobactam, amikacin, and ceftazidime, show promise against keratitis with low resistance rates, whereas carbapenems and topical aminoglycosides had higher resistance, leaving moxifloxacin as a potential topical option for Gram-positive bacteria and Pseudomonas aeruginosa, albeit with resistance concerns for Klebsiella spp. Although fungal keratitis was rare, Fusarium spp. and Candida albicans were the leading fungal pathogens, with incidences of 2.65% and 2.21%, respectively. Candida albicans was broadly susceptible to most antifungals, while Fusarium solani, Curvularia lunata, and Alternaria alternata exhibited resistance to many antifungals. Amphotericin B and caspofungin can be used as systemic antifungals in fungal keratitis. The study also identified risk factors for keratitis such as ocular trauma (65.92%, OR: 2.5), contact lens wear (11.94%, OR: 1.8), and corneal scarring/leukoma (10.17%, OR: 1.6). Keratitis was more frequent in individuals over 60 years old. The findings of this study have implications for the development of effective diagnostic, therapeutic, and preventive strategies for infectious keratitis.

17.
Nano Lett ; 24(13): 4044-4053, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38517749

RESUMO

Fungal keratitis (FK) is an infectious eye disease that poses a significant risk of blindness. However, the effectiveness of conventional antifungal drugs is limited due to the intrinsic ocular barrier that impedes drug absorption. There is an urgent need to develop new therapeutic strategies to effectively combat FK. Herein, we synthesized an ultrasmall positively charged carbon dot using a simple stage-melting method. The carbon dot can penetrate the corneal barrier by opening the tight junctions, allowing them to reach the lesion site and effectively kill the fungi. The results both in vitro and in vivo demonstrated that it exhibited good biocompatibility and antifungal activity, significantly improving the therapeutic effect in a mouse model of FK. Therefore, this biophilic ultrasmall size and positive carbon dot, characterized by its ability to penetrate the corneal barrier and its antifungal properties, may offer valuable insights into the design of effective ocular nanomedicines.


Assuntos
Úlcera da Córnea , Infecções Oculares Fúngicas , Ceratite , Animais , Camundongos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/microbiologia , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Córnea/microbiologia
18.
J Control Release ; 368: 483-497, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458571

RESUMO

Fungal keratitis is a refractory eye disease that is prone to causing blindness. Fungal virulence and inflammatory responses are two major factors that accelerate the course of fungal keratitis. However, the current antifungal drugs used for treatment usually possess transient residence time on the ocular surface and low bioavailability deficiencies, which limit their therapeutic efficacy. In this work, natamycin (NATA)-loaded mesoporous zinc oxide (Meso-ZnO) was synthesized for treating Aspergillus fumigatus keratitis with excellent drug-loading and sustained drug release capacities. In addition to being a carrier for drug delivery, Meso-ZnO could restrict fungal growth in a concentration-dependent manner, and the transcriptome analysis of fungal hyphae indicated that it inhibited the mycotoxin biosynthesis, oxidoreductase activity and fungal cell wall formation. Meso-ZnO also promoted cell migration and exhibited anti-inflammatory role during fungal infection by promoting the activation of autophagy. In mouse models of fungal keratitis, Meso-ZnO/NATA greatly reduced corneal fungal survival, alleviated tissue inflammatory damage, and reduced neutrophils accumulation and cytokines expression. This study suggests that Meso-ZnO/NATA can be a novel and effective treatment strategy for fungal keratitis.


Assuntos
Aspergilose , Infecções Oculares Fúngicas , Ceratite , Óxido de Zinco , Animais , Camundongos , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Óxido de Zinco/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Ceratite/tratamento farmacológico , Ceratite/metabolismo , Ceratite/microbiologia , Natamicina/uso terapêutico , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/metabolismo , Infecções Oculares Fúngicas/microbiologia , Sistemas de Liberação de Medicamentos , Camundongos Endogâmicos C57BL
19.
Case Rep Ophthalmol ; 15(1): 273-278, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38549912

RESUMO

Introduction: This case report describes a rare case of fungal keratitis following femtoLASIK. Despite targetted antifungal therapy, this case necessitated an innovative surgical approach to manage an unexpected corneal perforation. Case Presentation: A 35-year-old male presented 3 weeks post-femtoLASIK for myopic astigmatism with discomfort and reduced vision in his right eye. He was diagnosed with fungal keratitis surgery caused by Purpureocillium lilacinum and was treated with a myriad of therapy. Unfortunately, the patient developed corneal perforation during flap lift and flap bed irrigation. An innovative approach involving a tectonic autograft using a viable LASIK flap, followed by prompt penetrating keratoplasty, was utilised. Conclusion: This technique was effective and able to mitigate the progression to an open globe.

20.
Med Mycol Case Rep ; 44: 100644, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38550852

RESUMO

We present two cases with a history of trauma to the cornea and after a few days patients developed symptoms of corneal ulcers with one showing hypopyon as well. Due to strong suspicion of fungal keratitis both cases were treated with topical and intravenously voriconazole. Fungal culture showed white fluffy growth which was identified as Schizophyllum commune by conventional and molecular methods. In both cases surgical intervention was essential. Therapeutic keratoplasty was done in both cases but failed. Unfortunately, both patients lost vision in the affected eyes.

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