RESUMEN
Fungal keratitis is the foremost cause of corneal infections worldwide, of which Fusariumspp. is the common etiological agent that causes loss of vision and warrants surgical intervention. An increase in resistance to the available drugs along with severe side effects of the existing antifungals demands for new effective antimycotics. Here, we demonstrate that antimicrobial peptide S100A12 directly binds to the phospholipids of the fungal membrane, disrupts the structural integrity, and induces generation of reactive oxygen species in fungus. In addition, it inhibits biofilm formation by Fusariumspp. and exhibits antifungal property against Fusariumspp. both in vitro and in vivo. Taken together, our results delve into specific effect of S100A12 against Fusariumspp. with an aim to investigate new antifungal compounds to combat fungal keratitis.
Asunto(s)
Antifúngicos , Biopelículas , Membrana Celular , Fusarium , Proteína S100A12 , Antifúngicos/metabolismo , Antifúngicos/farmacología , Biopelículas/efectos de los fármacos , Infecciones Fúngicas del Ojo/microbiología , Fusarium/efectos de los fármacos , Queratitis/microbiología , Proteína S100A12/metabolismo , Proteína S100A12/farmacología , Humanos , Membrana Celular/efectos de los fármacos , Fosfolípidos/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
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.
Asunto(s)
Úlcera de la Córnea , Infecciones Fúngicas del Ojo , Queratitis , Animales , Ratones , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Queratitis/tratamiento farmacológico , Queratitis/microbiología , Úlcera de la Córnea/tratamiento farmacológico , Úlcera de la Córnea/microbiología , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/microbiología , Córnea/microbiologíaRESUMEN
PURPOSE: Fusarium keratitis is a severe infection of the anterior eye, frequently leading to keratoplasty or surgical removal of the affected eye. A major risk factor for infection is the use of contact lenses. Inadequate hygiene precautions and mold-growth permissive storage fluids are important risk factors for fungal keratitis. The aim of this study was to comparatively analyze contact lens storage fluids disinfection efficacy against Fusarium species. METHODS: Eleven commercially available storage fluids were tested. The storage fluids were classified according to their active ingredients myristamidopropyldimethylamine (Aldox), polyhexanide and hydrogen peroxide. Efficacy was tested against isolates belonging to the Fusarium solani and Fusarium oxysporum species complexes as the most common agents of mould keratitis. Tests were carried out based on DIN EN ISO 14729. RESULTS: All Aldox and hydrogen peroxide (H2O2) based fluids were effective against Fusarium spp., while the majority of polyhexanide based storage fluids showed only limited or no antifungal effects. Efficacy of polyhexanide could be restored by the addition of the pH-regulating agent tromethamine - an additive component in one commercially available product. CONCLUSIONS: In summary, the use of Aldox- or hydrogen peroxide-based storage fluids may reduce the risk of Fusarium keratitis, while polyhexanide-based agents largely lack efficacy against Fusarium.
Asunto(s)
Biguanidas , Lentes de Contacto , Infecciones Fúngicas del Ojo , Fusarium , Queratitis , Propilaminas , Antifúngicos/farmacología , Peróxido de Hidrógeno/farmacología , Queratitis/prevención & control , Queratitis/microbiología , Lentes de Contacto/microbiología , Infecciones Fúngicas del Ojo/microbiologíaRESUMEN
Fungal keratitis (FK) is a refractory keratitis caused by excessive inflammation and fungal damage. Excessive inflammation can lead to tissue damage and corneal opacity, resulting in a poor prognosis for FK. Oxymatrine (OMT) is a natural alkaloid, which has rich pharmacological effects, such as antioxidant and anti-inflammation. However, its antifungal activity and the mechanism of action in FK have not been elucidated. This study confirmed that OMT suppressed Aspergillus fumigatus growth, biofilm formation, the integrity of fungal cell and conidial adherence. OMT not only effectively reduced corneal fungal load but also inflammation responses. OMT lessened the recruitment of neutrophils and macrophages in FK. In addition, OMT up-regulated the expression of Nrf2 and down-regulated the expression of IL-18, IL-1ß, caspase-1, NLRP3 and GSDMD. Pre-treatment with Nrf2 inhibitor up-regulated the expression of IL-1ß, IL-18, caspase-1, NLRP3 and GSDMD supressed by OMT. In conclusion, OMT has efficient anti-inflammatory and antifungal effects by suppressing fungal activity and restricting pyroptosis via Nrf2 pathway. OMT is considered as a potential option for the treatment of FK.
Asunto(s)
Aspergilosis , Úlcera de la Córnea , Infecciones Fúngicas del Ojo , Queratitis , Matrinas , Animales , Ratones , Aspergillus fumigatus/fisiología , Proteína con Dominio Pirina 3 de la Familia NLR , Interleucina-18 , Aspergilosis/tratamiento farmacológico , Aspergilosis/metabolismo , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Piroptosis , Factor 2 Relacionado con NF-E2 , Queratitis/microbiología , Inflamación , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/metabolismo , Caspasa 1/metabolismo , Ratones Endogámicos C57BLRESUMEN
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.
Asunto(s)
Aspergilosis , Aspergillus fumigatus , Autofagia , Cinamatos , Depsidos , Infecciones Fúngicas del Ojo , Macrófagos , Especies Reactivas de Oxígeno , Ácido Rosmarínico , Depsidos/farmacología , Animales , Autofagia/efectos de los fármacos , Ratones , Aspergilosis/tratamiento farmacológico , Aspergilosis/microbiología , Aspergilosis/metabolismo , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/microbiología , Cinamatos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Queratitis/microbiología , Queratitis/tratamiento farmacológico , Queratitis/metabolismo , Modelos Animales de Enfermedad , Células RAW 264.7 , Citocinas/metabolismo , Fagocitosis/efectos de los fármacosRESUMEN
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.
Asunto(s)
Antifúngicos , Aspergilosis , Aspergillus fumigatus , Queratitis , Aspergillus fumigatus/efectos de los fármacos , Animales , Queratitis/microbiología , Queratitis/tratamiento farmacológico , Ratones , Aspergilosis/tratamiento farmacológico , Aspergilosis/microbiología , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Modelos Animales de Enfermedad , Materiales Biocompatibles , Plaquetas/efectos de los fármacos , Natamicina/farmacología , Natamicina/administración & dosificación , Natamicina/uso terapéutico , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/microbiología , Córnea/microbiología , Córnea/patología , Córnea/efectos de los fármacosRESUMEN
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.
Asunto(s)
Antifúngicos , Infecciones Fúngicas del Ojo , Fusarium , Queratitis , Voriconazol , Humanos , Queratitis/microbiología , Queratitis/tratamiento farmacológico , Queratitis/diagnóstico , Antifúngicos/uso terapéutico , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/diagnóstico , Voriconazol/uso terapéutico , Fusarium/aislamiento & purificación , Fusarium/efectos de los fármacos , Fusarium/patogenicidad , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Itraconazol/uso terapéutico , Fusariosis/tratamiento farmacológico , Fusariosis/microbiología , Fusariosis/diagnóstico , Masculino , Córnea/microbiología , Córnea/patología , Femenino , Persona de Mediana EdadRESUMEN
INTRODUCTION: Antimicrobial resistance in microbial keratitis has not been previously explored in Alexandria. We aim to recommend effective therapies through identification of etiological agents, determination of antimicrobial susceptibilities, and comparing outcomes of empiric topical antimicrobials. METHODS: In this 2022 prospective cohort conducted in Alexandria Main University Hospital cornea clinic, antimicrobial susceptibilities of isolated microorganisms from corneal scrapings were detected and antibiograms were developed. Bacterial (BK), fungal (FK), or mixed fungal/bacterial keratitis (MFBK) patients on empiric regimens were compared for ulcer healing, time-to-epithelialization, best-corrected visual acuity, interventions, and complications. RESULTS: The prevalent microorganisms in 93 positive-cultures were coagulase-negative staphylococci (CoNS, 30.1%), Pseudomonas aeruginosa (14%), and Aspergillus spp. (12.9%). CoNS were susceptible to vancomycin (VAN, 100%) and moxifloxacin (MOX, 90.9%). Gram-negative bacteria showed more susceptibility to gatifloxacin (90.9%) than MOX (57.1%), and to gentamicin (GEN, 44.4%) than ceftazidime (CAZ, 11.8%). Methicillin-resistance reached 23.9% among Gram-positive bacteria. Fungi exhibited 10% resistance to voriconazole (VRC). Percentages of healed ulcers in 49 BK patients using GEN + VAN, CAZ + VAN and MOX were 85.7%, 44.4%, and 64.5%, respectively (p = 0.259). Their median time-to-epithelialization reached 21, 30, and 30 days, respectively (log-rank p = 0.020). In 51 FK patients, more ulcers (88.9%) healed with natamycin (NT) + VRC combination compared to VRC (39.1%) or NT (52.6%) (p = 0.036). Their median time-to-epithelialization was 65, 60, and 22 days, respectively (log-rank p < 0.001). The VRC group required more interventions (60.9%) than NT + VRC-treated group (11.1%) (p = 0.018). In 23 MFBK patients, none healed using NT + CAZ + VAN, while 50% healed using VRC + CAZ + VAN (p = 0.052). Regimens had comparable visual outcomes and complications. CONCLUSION: Based on the higher detected susceptibility, we recommend empiric MOX in suspected Gram-positive BK, gatifloxacin in Gram-negative BK, and GEN + VAN in severe BK. Due to better outcomes, we recommend NT + VRC in severe FK. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05655689. Registered December 19, 2022- Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05655689?cond=NCT05655689.&draw=2&rank=1.
Asunto(s)
Bacterias , Infecciones Bacterianas del Ojo , Infecciones Fúngicas del Ojo , Hongos , Pruebas de Sensibilidad Microbiana , Humanos , Estudios Prospectivos , Masculino , Egipto/epidemiología , Femenino , Infecciones Bacterianas del Ojo/microbiología , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Infecciones Bacterianas del Ojo/diagnóstico , Infecciones Bacterianas del Ojo/epidemiología , Bacterias/aislamiento & purificación , Persona de Mediana Edad , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/diagnóstico , Adulto , Hongos/aislamiento & purificación , Antibacterianos/uso terapéutico , Queratitis/microbiología , Queratitis/tratamiento farmacológico , Queratitis/diagnóstico , Estudios de Seguimiento , Resultado del Tratamiento , Agudeza Visual , Adulto Joven , Córnea/microbiologíaRESUMEN
PURPOSE: To explore the clinical value of ß-D-glucan (BDG) testing and metagenomic next-generation sequencing (mNGS) for detecting the pathogens of fungal endophthalmitis (FE). METHODS: This study included 32 cases (32 eyes) with FE and 20 cases (20 eyes) with intraocular inflammation caused by other etiologies. All patients underwent extraction of aqueous humor or vitreous fluid samples for BDG testing and mNGS. The diagnostic performance and total clinical concordance rate of BDG testing and mNGS for FE were evaluated and calculated based on the results of the clinical diagnosis. RESULTS: Among the clinically diagnosed FE, the positivity rates of BDG testing and mNGS (90.63%) were both significantly higher ( P < 0.001) than that of microbial cultures (53.13%). There was 100% consistency in pathogen identification using mNGS and culture identification for culture-positive cases. The area under the curve was 0.927 for BDG testing and 0.853 for mNGS. When the two tests were combined, sensitivity (93.75%), specificity (100.00%), and total clinical concordance rate (96.15%) were all improved, compared with the single tests. CONCLUSION: The positive rates of BDG test and mNGS were markedly higher than those of cultures in FE identification. The combination of these two tests showed improved performance when compared with individual tests.
Asunto(s)
Humor Acuoso , Endoftalmitis , Infecciones Fúngicas del Ojo , Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Cuerpo Vítreo , beta-Glucanos , Humanos , Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Fúngicas del Ojo/microbiología , Endoftalmitis/diagnóstico , Endoftalmitis/microbiología , Masculino , Persona de Mediana Edad , Femenino , Humor Acuoso/microbiología , beta-Glucanos/análisis , Cuerpo Vítreo/microbiología , Anciano , Metagenómica/métodos , Adulto , Estudios Retrospectivos , Hongos/aislamiento & purificación , Hongos/genética , ADN de Hongos/análisis , Proteoglicanos , Anciano de 80 o más AñosRESUMEN
PURPOSE: To evaluate the utility of galactomannan testing of intraocular fluid in the diagnosis of Aspergillus endophthalmitis (AE). METHODS: This retrospective study enrolled three groups of patients, including those with 17 eyes with AE; 20 eyes with intraocular infection of bacteria, viruses, or other fungi; and 19 eyes with cataract. Intraocular fluid from all these patients was collected for galactomannan testing. In addition, the receiver operating characteristic curves and diagnostic significance were analyzed. RESULTS: The mean optical density index (ODI) of galactomannan was 5.77 ± 1.73 in the AE group, which was significantly higher than that in the non- Aspergillus intraocular infection group (0.19 ± 0.11, P < 0.001) and the negative control group (0.29 ± 0.27, P < 0.001). The area under the receiver operating characteristic curve (area under the curve) was 1.00 (95% confidence interval, 1.00-1.00; P < 0.001) in the AE group and the other two groups. At a cutoff optical density index of 1.88, the sensitivity and specificity were 100.0% and 100.0%, respectively, and the Youden index reached its highest value of 1.00. CONCLUSION: Galactomannan testing of intraocular fluid indicated good sensitivity and specificity for the diagnosis of AE, thereby promising a rapid diagnostic modality for AE.
Asunto(s)
Aspergilosis , Endoftalmitis , Infecciones Fúngicas del Ojo , Galactosa , Mananos , Curva ROC , Humanos , Mananos/análisis , Endoftalmitis/diagnóstico , Endoftalmitis/microbiología , Galactosa/análogos & derivados , Estudios Retrospectivos , Masculino , Femenino , Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Fúngicas del Ojo/microbiología , Persona de Mediana Edad , Anciano , Aspergilosis/diagnóstico , Aspergilosis/microbiología , Aspergilosis/metabolismo , Adulto , Aspergillus/aislamiento & purificación , Humor Acuoso/metabolismo , Humor Acuoso/microbiología , Anciano de 80 o más Años , Sensibilidad y Especificidad , Cuerpo Vítreo/microbiología , Cuerpo Vítreo/metabolismo , Biomarcadores/metabolismoRESUMEN
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.
Asunto(s)
Antifúngicos , Ascomicetos , Infecciones Fúngicas del Ojo , Humanos , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/diagnóstico , Anciano , Antifúngicos/uso terapéutico , Ascomicetos/aislamiento & purificación , Masculino , Queratitis/microbiología , Queratitis/tratamiento farmacológico , Queratitis/diagnóstico , Voriconazol/uso terapéutico , Agudeza Visual/fisiología , Natamicina/uso terapéutico , Quimioterapia CombinadaRESUMEN
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.
Asunto(s)
Antifúngicos , Infecciones Fúngicas del Ojo , Fusariosis , Fusarium , Queratitis , Pruebas de Sensibilidad Microbiana , Humanos , Brasil/epidemiología , Fusarium/genética , Fusarium/efectos de los fármacos , Fusarium/aislamiento & purificación , Fusarium/clasificación , Masculino , Femenino , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Adulto , Queratitis/microbiología , Queratitis/epidemiología , Queratitis/tratamiento farmacológico , Persona de Mediana Edad , Fusariosis/microbiología , Fusariosis/epidemiología , Fusariosis/tratamiento farmacológico , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/epidemiología , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Anciano , Adulto Joven , Adolescente , Clima Tropical , Anciano de 80 o más Años , Anfotericina B/farmacología , Anfotericina B/uso terapéuticoRESUMEN
BACKGROUND: To assess the long-term incidence and risk factors for post-keratoplasty infectious keratitis (IK), associated ocular pathogens, and antibiotic resistance profiles. METHODS: Cohort study including 2553 consecutive penetrating, endothelial, and anterior lamellar keratoplasties performed between 1992 and 2020. Medical and microbiological records of patients clinically diagnosed with IK were retrospectively reviewed. MAIN OUTCOME MEASURES: cumulative incidence of IK, infectious agent species, and antibiotics resistance profiles. RESULTS: The average follow-up time after transplantation was 112 ± 96 months. Eighty-nine IK episodes were recorded; microbiological tests were positive in 55/89 (62%). The cumulated incidence of postoperative IK was 5.50%/10.25% at 10/20 years. The occurrence of at least one episode of IK after transplantation was associated with lower graft survival in the long term (p < 0.0001). Rejection risk (adjusted Hazard Ratio, 2.29) and postoperative epithelial complications (HR, 3.44) were significantly and independently associated with a higher incidence of postoperative IK. Infectious agents included 41 bacteria, 10 HSV, 6 fungi, and 1 Acanthamoeba. The rate of antibiotic resistance was 0% for vancomycin, 13% for fluoroquinolones, 20% for rifamycin, 59% for aminoglycosides, and 73% for ticarcillin. In 41% of cases, patients were under prophylactic topical antibiotics before the infectious episode. Topical antibiotics were significantly associated with increased resistance to penicillin, carbapenems, and aminoglycosides. CONCLUSION: IK (mainly bacterial) is a frequent complication of corneal transplantation in the long term. Vancomycin and fluoroquinolones can be considered as first-line treatments. Prolonged postoperative antibiotic preventive treatment is not advisable as it may increase antibiotic resistance.
Asunto(s)
Trasplante de Córnea , Infecciones Bacterianas del Ojo , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Infecciones Bacterianas del Ojo/epidemiología , Infecciones Bacterianas del Ojo/microbiología , Infecciones Bacterianas del Ojo/etiología , Incidencia , Factores de Riesgo , Estudios de Seguimiento , Adulto , Trasplante de Córnea/efectos adversos , Úlcera de la Córnea/microbiología , Úlcera de la Córnea/epidemiología , Úlcera de la Córnea/tratamiento farmacológico , Antibacterianos/uso terapéutico , Supervivencia de Injerto , Infecciones Fúngicas del Ojo/epidemiología , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Fúngicas del Ojo/etiología , Anciano , Complicaciones Posoperatorias/epidemiología , Queratitis/epidemiología , Queratitis/etiología , Queratitis/microbiología , Queratitis/tratamiento farmacológico , Queratitis/diagnóstico , Bacterias/aislamiento & purificaciónRESUMEN
PURPOSE: To examine the microbiological profile of cases of culture-positive fungal keratitis presenting to a tertiary eye care center in eastern India. METHODS: Microbiology records of all culture-positive microbial keratitis patients presenting to L V Prasad Eye Institute, Bhubaneswar, between January 2020 and December 2021, were retrospectively reviewed. Collected data included smear results of culture-positive fungal or mixed infections, the species isolated, and the time taken for organisms to grow in each media. RESULTS: Fungal keratitis formed 36% of all culture-positive microbial keratitis, whereas mixed infections (fungi and other organisms) formed 8.5%. The most common fungal species isolated was Fusarium spp. (25.8%). The most common bacteria involved in mixed infection with fungi was Staphylococcus spp. (54.8%). The positivity of potassium hydroxide+calcofluor white stain in detecting fungal filaments was 89.0% and that of Gram stain was 76.1%. Culture-positive cases of fungal keratitis showed most frequent growth on potato-dextrose agar (77.6%). A similar pattern was observed in culture-positive mixed infections (Sabouraud dextrose agar [SDA]: 84%). Most frequent growth of bacteria in mixed infections was seen in thioglycolate broth (54.7%). The shortest time to achieve significant fungal growth was observed in blood agar (BA) and chocolate agar (CA) (2.2/2.3 days, and 1.8/2 days for fungal keratitis and mixed infections, respectively). Filamentous hyaline fungi took the shortest time to achieve significant growth (2.8 days), whereas yeast forms took the longest (5 days). CONCLUSION: This study highlights the importance of combined use of both solid and liquid culture media, especially potato dextrose agar (PDA)/SDA and CA, to arrive at a definitive diagnosis of fungal keratitis and possible bacterial co-infection, which forms a significant proportion of cases with fungal keratitis. In resource-poor laboratories, two culture media, either SDA or PDA, along with BA, may be plated to detect mixed infections. Examination of stained smears of corneal samples provides an inexpensive method of rapid diagnosis of fungal keratitis when culture media is not available.
Asunto(s)
Infecciones Fúngicas del Ojo , Hongos , Queratitis , Humanos , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/diagnóstico , Estudios Retrospectivos , Hongos/aislamiento & purificación , Queratitis/microbiología , Queratitis/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Adulto , India , Bacterias/aislamiento & purificación , AncianoRESUMEN
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.
Asunto(s)
Antifúngicos , Exophiala , Infecciones Fúngicas del Ojo , Queratitis , Queratomileusis por Láser In Situ , Humanos , Exophiala/aislamiento & purificación , Queratomileusis por Láser In Situ/efectos adversos , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/diagnóstico , Antifúngicos/uso terapéutico , Queratitis/microbiología , Queratitis/diagnóstico , Queratitis/tratamiento farmacológico , Queratitis/etiología , Feohifomicosis/microbiología , Feohifomicosis/diagnóstico , Feohifomicosis/tratamiento farmacológico , Masculino , Femenino , Glucocorticoides/uso terapéutico , Glucocorticoides/administración & dosificación , Adulto , Úlcera de la Córnea/microbiología , Úlcera de la Córnea/tratamiento farmacológico , Úlcera de la Córnea/diagnóstico , Úlcera de la Córnea/etiologíaRESUMEN
BACKGROUND: Fungal keratitis (FK) is a kind of infectious keratopathy with a high rate of blindness worldwide. Deoxynivalenol (DON) has been proven to have multiple toxic effects on humans and animals. OBJECTIVES: The aim of this study was to explore a possible pathogenic role of DON in FK. METHODS: We first made an animal model of FK in New Zealand white rabbits, and then attempted to detect DON in a culture medium in which Fusarium solani had been grown and also in the corneal tissue of the animal model of Fusarium solani keratitis. Next, a model of DON damage in human corneal epithelial cells (HCECs) was constructed to evaluate effects of DON on the activity, migration ability, cell cycle, and apoptosis in the HCECs. Then, putative the toxic damaging effects of DON on rabbit corneal epithelial cells and the impact of the repair cycle were studied. The expression levels of inflammatory factors in the corneas of the animal model and in the model of DON-damaged HCECs were measured. RESULTS: The Fusarium solani strain used in this study appeared to have the potential to produce DON, since DON was detected in the corneal tissue of rabbits which had been inoculated with this Fusarium solani strain. DON was found to alter the morphology of HCECs, to reduce the activity and to inhibit the proliferation and migration of HCECs. DON also induced the apoptosis and S-phase arrest of HCECs. In addition, DON was found to damage rabbit corneal epithelial cells, to prolong the corneal epithelial regeneration cycle, and to be associated with the upregulated expression of inflammatory factors in HCECs and rabbit corneas. CONCLUSIONS: DON appears to have a toxic damaging effect on HCECs in FK, and to induce the expression of inflammatory factors, leading to the exacerbation of keratitis and the formation of new blood vessels. Future studies will explore the possibility of developing a test to detect DON in ophthalmic settings to aid the rapid diagnosis of FK, and to develop DON neutralizers and adsorbents which have the potential to improve keratocyte status, inhibit apoptosis, and alleviate inflammation, therein providing new thinking for therapy of clinical FK.
Asunto(s)
Úlcera de la Córnea , Infecciones Fúngicas del Ojo , Fusarium , Queratitis , Tricotecenos , Humanos , Conejos , Animales , Queratitis/microbiología , Células EpitelialesRESUMEN
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.
Asunto(s)
Antifúngicos , Fusariosis , Fusarium , Queratitis , Humanos , Queratitis/microbiología , Queratitis/epidemiología , Queratitis/tratamiento farmacológico , Fusarium/aislamiento & purificación , Fusarium/clasificación , Fusarium/genética , Fusariosis/microbiología , Fusariosis/tratamiento farmacológico , Fusariosis/epidemiología , Fusariosis/diagnóstico , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/epidemiología , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Femenino , Voriconazol/uso terapéutico , Prevalencia , Factores de Riesgo , Masculino , Adulto , Persona de Mediana Edad , Lentes de Contacto/microbiología , Lentes de Contacto/efectos adversos , Anfotericina B/uso terapéutico , Natamicina/uso terapéutico , Anciano , Adulto Joven , AdolescenteRESUMEN
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.
Asunto(s)
Infecciones Bacterianas del Ojo , Población Rural , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Infecciones Bacterianas del Ojo/epidemiología , Infecciones Bacterianas del Ojo/microbiología , Infecciones Bacterianas del Ojo/diagnóstico , Infecciones Bacterianas del Ojo/terapia , Anciano , India/epidemiología , Población Rural/estadística & datos numéricos , Queratitis/epidemiología , Queratitis/microbiología , Queratitis/diagnóstico , Adulto Joven , Antibacterianos/uso terapéutico , Adolescente , Úlcera de la Córnea/microbiología , Úlcera de la Córnea/epidemiología , Úlcera de la Córnea/diagnóstico , Úlcera de la Córnea/tratamiento farmacológico , Úlcera de la Córnea/terapia , Incidencia , Infecciones Fúngicas del Ojo/epidemiología , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Fúngicas del Ojo/terapia , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Factores de Riesgo , Bacterias/aislamiento & purificaciónRESUMEN
PURPOSE: The present study aimed to epidemiologically evaluate patients with infectious keratitis following corneal transplantation. METHODS: This retrospective study analyzed medical records of patients who underwent keratoplasty from March 2014 to March 2022 at a tertiary center. A total of seventy-five patients were evaluated. The data were classified based on culture results, the type of microorganisms involved, treatment requirements, and the type of primary keratoplasty performed. RESULTS: Seventy-five patients were evaluated in this study, with a mean age of 45.9 years (22-95 years). The mean duration between the first surgery and the incidence of infectious keratitis was 1.43 years, and most cases occurred in the first year (56.2%). Bacterial and fungal keratitis in 2.17%, 1.39%, and 1.26% of cases undergoing penetrating keratoplasty (PK), endothelial keratoplasty (EK), and anterior lamellar keratoplasty (ALK) occurred, respectively. Streptococcus viridans (9.3%) and Staphylococcus aureus (6.6%) had the highest prevalence. Across various smear and culture results (gram-positive, gram-negative, fungal, and negative culture), no significant differences were found in endophthalmitis rates (P = 0.797) and the necessity for tectonic grafts (P = 0.790). Similarly, the choice of surgical method (PK, ALK, EK) showed no significant impact on the need for tectonic grafts (P = 0.45) or the rate of endophthalmitis (P = 0.55). CONCLUSIONS: The incidence of keratitis after a corneal graft was 1.7%, with Streptococcus viridans and Staphylococcus aureus the most common microorganisms. The rate of endophthalmitis associated with post-keratoplasty keratitis was 0.053%. There was no correlation between the necessity for a tectonic graft or the incidence of endophthalmitis and the type of microorganisms involved.
Asunto(s)
Trasplante de Córnea , Infecciones Bacterianas del Ojo , Infecciones Fúngicas del Ojo , Queratitis , Centros de Atención Terciaria , Humanos , Estudios Retrospectivos , Persona de Mediana Edad , Femenino , Masculino , Adulto , Anciano , Infecciones Bacterianas del Ojo/epidemiología , Infecciones Bacterianas del Ojo/microbiología , Infecciones Bacterianas del Ojo/etiología , Infecciones Bacterianas del Ojo/diagnóstico , Centros de Atención Terciaria/estadística & datos numéricos , Adulto Joven , Anciano de 80 o más Años , Incidencia , Queratitis/epidemiología , Queratitis/microbiología , Queratitis/diagnóstico , Queratitis/etiología , Trasplante de Córnea/efectos adversos , Infecciones Fúngicas del Ojo/epidemiología , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Fúngicas del Ojo/etiología , Bacterias/aislamiento & purificación , Complicaciones Posoperatorias/epidemiologíaRESUMEN
PURPOSE: Invasive fungal orbital infections (IFOI) may be difficult to differentiate from sinogenic bacterial orbital cellulitis (OC). This study investigates the features differentiating OC from IFOI on magnetic resonance imaging (MRI). METHODS: Retrospective study of adult patients with sinogenic OC and IFOI with pre-intervention MRI. Patients without post-septal involvement, non-sinogenic OC (e.g.: secondary to trauma) and poor-quality scans were excluded. Independent Sample's t test and Fisher's exact test were conducted with p < 0.05 deemed statistically significant. RESULTS: Eleven cases each of OC (Mean age: 41.6 ± 18.4 years-old, Male: 10) and IFOI (Mean age: 65.0 ± 16.6 years-old, Male: 9) between 2006 and 2023. IFOI patients were older, more likely immunocompromised and had a lower mean white-cell count (p value = 0.005, 0.035 and 0.017, respectively). The ethmoid and maxillary sinuses were most commonly involved in both entities. Pre-septal and lacrimal gland involvement were more common in OC (p = 0.001 and 0.008, respectively). Infiltrative OC orbital lesions were poorly demarcated, whilst those in IFOI were expansile/mass-like invading the orbit from the adjacent paranasal sinuses. Specific IFOI features included loss-of-contrast-enhancement (LoCE) of paranasal sinus tissues with orbital extension. Extra-orbital and -sinonasal extension indicative of IFOI included contiguous skull base or pterygopalatine fossa involvement, retro-antral and masticator space stranding and vasculitis. CONCLUSION: This study describes the key MRI features of IFOI including differentiating markers from OC. These specific features, such as LoCE of the paranasal and orbital soft tissues, the location and pattern of contiguous soft-tissue involvement, provide expedient identification of IFOI which necessitate early surgical intervention for microbiological confirmation of an invasive fungal pathology.