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1.
Eye Contact Lens ; 45(5): 301-305, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31442212

RESUMO

PURPOSE: To compare the infectious contact lens-related corneal ulcer (CLRU) and non-CLRU cases at Saint Louis University. METHODS: Retrospective review of corneal ulcer cases identified by search of the ophthalmology and microbiology department databases between 1999 and 2016. RESULTS: Six hundred seventy-seven cases of corneal ulcers were identified, of which 46% were CLRU. CLRU cases were seen more commonly in younger patients (P<0.001) and women (P=0.03) than non-CLRU cases. Many of the infections were vision-threatening as defined by central/paracentral location (73% CLRU and 71% non-CLRU [P=0.60]) and large size of ulcer >2 mm in 36% CLRU and 51% non-CLRU (P=0.002). Causative pathogen in cultured CLRU was predominately Pseudomonas species (44%, P<0.001 vs. the non-CLRU group), other gram-negative (6%), gram-positive (33%), fungi (13%), and Acanthamoeba (5%). Comparatively, cultured non-CLRU was predominately gram-positive (64%, P<0.001 vs. the CLRU group), gram-negative (26%), and fungi (11%). The combined oxacillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus isolates were 35% and 34%, respectively. Despite the progressive increase in the number of corneal ulcers seen, the annual trend for any one particular organism for either CLRU cases or non-CLRU cases did not change significantly. CONCLUSIONS: Most of the cases were non-CLRU. CLRU was disproportionately associated with Pseudomonas species and non-CLRU with Staphylococcal species. Fungal infections were predominately caused by filamentous organisms in both groups. Acanthamoeba keratitis was exclusively associated with CL use.


Assuntos
Ceratite por Acanthamoeba/parasitologia , Lentes de Contato/microbiologia , Lentes de Contato/parasitologia , Úlcera da Córnea/microbiologia , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Parasitárias/parasitologia , Centros Médicos Acadêmicos , Ceratite por Acanthamoeba/diagnóstico , Ceratite por Acanthamoeba/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Antiprotozoários/uso terapêutico , Criança , Pré-Escolar , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/tratamento farmacológico , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Parasitárias/diagnóstico , Infecções Oculares Parasitárias/tratamento farmacológico , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
2.
Cornea ; 38(10): 1309-1313, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31306283

RESUMO

PURPOSE: To determine whether combinations of commonly used antiamoebic agents display synergy in their ability to kill Acanthamoeba cysts in vitro. METHODS: Synergy testing was performed with a microdilution checkerboard assay on 10 clinical Acanthamoeba keratitis isolates collected at the Proctor Foundation from 2008 to 2012. Each isolate was exposed to pairwise combinations of chlorhexidine, propamidine, and voriconazole. The minimum cysticidal concentration (MCC) for each drug pair was estimated for each isolate, and the summed fractional cysticidal concentration (ΣFCC) was calculated for each drug combination in the checkerboard, with synergy defined as a lack of growth at a ΣFCC ≤ 0.5 and antagonism as growth at a ΣFCC > 4. RESULTS: Chlorhexidine and propamidine were cysticidal, with median MCCs of 12.5 (range 1.5-50) and 11.7 (range 0.2-250), respectively. Voriconazole was not cysticidal, with a median MCC of >10,000 µg/mL. The combination of chlorhexidine and propamidine did not markedly change the cysticidal activity compared with either drug alone. By contrast, voriconazole antagonized the cysticidal activity of both chlorhexidine and propamidine, with Acanthamoeba growth observed at antagonistic ΣFCCs in 27 of 49 (55.1%, 95% confidence interval 35.7%-78.6%) checkerboard combinations of voriconazole and chlorhexidine and in 58 of 147 (39.5%, 95% confidence interval 14.3%-50.3%) combinations of voriconazole and propamidine. CONCLUSIONS: In an in vitro assay, voriconazole reduced the cysticidal activity of 2 commonly used antiamoebic drugs. Although the in vivo drug interactions could be different, these observations may be useful in cases of nonhealing Acanthamoeba keratitis being treated with combination therapies that include voriconazole.


Assuntos
Ceratite por Acanthamoeba/tratamento farmacológico , Acanthamoeba/isolamento & purificação , Amebicidas/farmacologia , Infecções Oculares Parasitárias/tratamento farmacológico , Voriconazol/farmacologia , Acanthamoeba/efeitos dos fármacos , Ceratite por Acanthamoeba/diagnóstico , Ceratite por Acanthamoeba/parasitologia , Animais , Antifúngicos/farmacologia , Sinergismo Farmacológico , Infecções Oculares Parasitárias/parasitologia , Humanos , Testes de Sensibilidade Parasitária
3.
Cornea ; 38(7): 914-917, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31170106

RESUMO

PURPOSE: Acanthamoeba keratitis is a rare, vision-threatening disease. Commercially available antiamoebics are poorly cysticidal and highly toxic, and therapeutic keratoplasties can be complicated by recurrence or graft failure. We aimed to discuss the use of oral miltefosine for treatment of recalcitrant Acanthamoeba keratitis. METHODS: A 44-year-old contact lens wearer presented with a 2-week history of red painful eye and decreasing vision. After poorly responding to topical corticosteroid on the presumptive diagnosis of anterior uveitis, she developed radial keratoneuritis. Corneal scraping was positive for Acanthamoeba. No clinical response to treatment was observed with topical chlorhexidine 0.02%, polyhexamethylene biguanide 0.02%, and oral voriconazole. She then underwent 2 therapeutic keratoplasties with prompt recurrence of the disease in the keratoplasty graft. RESULTS: Oral miltefosine was added to the treatment. She underwent a third penetrating keratoplasty 8 months later. The excised button was negative for amoeba. She continued miltefosine for 3 more months. No recurrence was observed after 30 months. CONCLUSIONS: This case shows resolution of recalcitrant Acanthamoeba keratitis with oral miltefosine in an immunocompetent patient. Further clinical evidence would be needed to possibly incorporate this medication in the antiamoebic armamentarium.


Assuntos
Ceratite por Acanthamoeba/tratamento farmacológico , Antiprotozoários/administração & dosagem , Fosforilcolina/análogos & derivados , Administração Oral , Adulto , Quimioterapia Adjuvante , Lentes de Contato Hidrofílicas/efeitos adversos , Feminino , Humanos , Ceratoplastia Penetrante , Fosforilcolina/administração & dosagem , Resultado do Tratamento
4.
Parasitol Res ; 118(6): 1953-1961, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31069536

RESUMO

The genus Acanthamoeba can cause Acanthamoeba keratitis (AK) and granulomatous amoebic encephalitis (GAE). The treatment of these illnesses is hampered by the existence of a resistance stage that many times causes infection relapses. In an attempt to add new agents to our chemotherapeutic arsenal against acanthamebiasis, two Acanthamoeba isolates were treated in vitro with newly synthesized biguanide dendrimers. Trophozoite viability analysis and ultrastructural studies showed that dendrimers prevent encystment by lysing the cellular membrane of the amoeba. Moreover, one of the dendrimers showed low toxicity when tested on mammalian cell cultures, which suggest that it might be eventually used as an amoebicidal drug or as a disinfection compound in contact lens solutions.


Assuntos
Ceratite por Acanthamoeba/tratamento farmacológico , Acanthamoeba/efeitos dos fármacos , Amebicidas/farmacologia , Biguanidas/farmacologia , Clorexidina/análogos & derivados , Dendrímeros/farmacologia , Encefalite/tratamento farmacológico , Acanthamoeba/classificação , Acanthamoeba/isolamento & purificação , Animais , Linhagem Celular Tumoral , Clorexidina/farmacologia , Soluções para Lentes de Contato , Encefalite/parasitologia , Células HeLa , Humanos , Trofozoítos/efeitos dos fármacos
5.
Parasitol Res ; 118(8): 2443-2454, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31144032

RESUMO

Acanthamoeba keratitis (AK) is a devastating, painful corneal infection, which may lead to loss of vision. The development of resistance and failure of the currently used drugs represent a therapeutic predicament. Thus, novel therapies with lethal effects on resistant Acanthamoeba are necessary to combat AK. In the present study, the curative effect of Nigella sativa aqueous extract (N. sativa) and chitosan nanoparticles (nCs) and both agents combined were assessed in experimentally induced AK. All inoculated corneas developed varying grades of AK. The study medications were applied on the 5th day postinoculation and were evaluated by clinical examination of the cornea and cultivation of corneal scraps. On the 10th day posttreatment, a 100% cure of AK was obtained with nCs (100 µg/ml) in grades 1 and 2 of corneal opacity as well as with N. sativa 60 mg/ml-nCs 100 µg/ml in grades 1, 2, and 3 of corneal opacity, highlighting a possible synergistic effect. On the 15th day posttreatment, a 100% cure was reached with N. sativa aqueous extract (60 mg/ml). Moreover, on the 20th day posttreatment, N. sativa (30 mg/ml) provided a cure rate of 87.5%, while nCs (50 µg/ml) as well as N. sativa 30 mg/ml-nCs 50 µg/ml yielded a cure rate of 75%; the lowest percentage of cure (25%) was obtained with chlorhexidine (0.02%), showing a non-significant difference compared to the parasite control. The clinical outcomes were in agreement with the results of corneal scrap cultivation. The results of the present study demonstrate the effectiveness of N. sativa aqueous extract and nCs (singly or combined) when used against AK, and these agents show potential for the development of new, effective, and safe therapeutic alternatives.


Assuntos
Ceratite por Acanthamoeba/tratamento farmacológico , Antiprotozoários/administração & dosagem , Nigella sativa/química , Extratos Vegetais/administração & dosagem , Acanthamoeba/efeitos dos fármacos , Acanthamoeba/fisiologia , Ceratite por Acanthamoeba/parasitologia , Adulto , Animais , Antiprotozoários/química , Quitosana/química , Quitosana/farmacologia , Quitosana/uso terapêutico , Clorexidina/farmacologia , Córnea/parasitologia , Feminino , Humanos , Masculino , Nanopartículas/química , Extratos Vegetais/química , Ratos , Resultado do Tratamento
6.
Parasitol Res ; 118(7): 2295-2304, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31093751

RESUMO

Acanthamoeba castellanii belonging to the T4 genotype is an opportunistic pathogen which is associated with blinding eye keratitis and rare but fatal central nervous system infection. A. castellanii pose serious challenges in antimicrobial chemotherapy due to its ability to convert into resistant, hardy shell-protected cyst form that leads to infection recurrence. The fatty acid composition of A. castellanii trophozoites is known to be most abundant in oleic acid which chemically is an unsaturated cis-9-Octadecanoic acid and naturally found in animal and vegetable fats and oils. This study was designed to evaluate antiacanthamoebic effects of oleic acid against trophozoites, cysts as well as parasite-mediated host cell cytotoxicity. Moreover, oleic acid-conjugated silver nanoparticles (AgNPs) were also synthesized and tested against A. castellanii. Oleic acid-AgNPs were synthesized by chemical reduction method and characterized by ultraviolet-visible spectrophotometry, atomic force microscopy, dynamic light scattering analysis, and Fourier transform infrared spectroscopy. Viability, growth inhibition, encystation, and excystation assays were performed with 10 and 5 µM concentration of oleic acid alone and oleic acid-conjugated AgNPs. Bioassays revealed that oleic acid alone and oleic acid-conjugated AgNPs exhibited significant antiamoebic properties, whereas nanoparticle conjugation further enhanced the efficacy of oleic acid. Phenotype differentiation assays also showed significant inhibition of encystation and excystation at 5 µM. Furthermore, oleic acid and oleic acid-conjugated AgNPs also inhibited amoebae-mediated host cell cytotoxicity as determined by lactate dehydrogenase release. These findings for the first time suggest that oleic acid-conjugated AgNPs exhibit antiacanthamoebic activity that hold potential for therapeutic applications against A. castellanii.


Assuntos
Ceratite por Acanthamoeba/tratamento farmacológico , Acanthamoeba castellanii/efeitos dos fármacos , Amebicidas/farmacologia , Nanopartículas Metálicas/química , Ácido Oleico/farmacologia , Ceratite por Acanthamoeba/parasitologia , Amebicidas/química , Animais , Olho/parasitologia , Humanos , Microscopia de Força Atômica , Ácido Oleico/química , Prata/química , Espectrofotometria Ultravioleta , Trofozoítos/efeitos dos fármacos
7.
Cornea ; 38(8): 1011-1016, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30932935

RESUMO

PURPOSE: N-chlorotaurine (NCT) is an anti-infective belonging to the class of chloramines and an investigative drug for the topical treatment of keratoconjunctivitis. The aim of the present study was to demonstrate its efficacy against Acanthamoeba and Candida in corneas infected ex vivo. METHODS: Corneal buttons from porcine eyes were contaminated with Acanthamoeba castellanii trophozoites or Candida albicans Centraalbureau voor Schimmelcultures 5982 and incubated for 7 and 3 days, respectively. Subsequently, they were treated with 1% NCT for 5 to 120 minutes. After further incubation for 2 days in the absence of NCT in tests with A. castellanii, the buttons were homogenized, and the amoebae grown for a further 5 days before they were counted in a light microscope. For C. albicans, quantitative cultures were performed from corneal homogenates. RESULTS: Incubation of 120 minutes in NCT completely inhibited the regrowth of A. castellanii and reduced the number of C. albicans colony-forming unit counts by 4 log10. In addition, at 60 minutes, significant reductions of both pathogens could be observed. Histology showed penetration of pathogens into the stroma of the corneal buttons. CONCLUSIONS: NCT inactivates A. castellanii and C. albicans in corneal tissue.


Assuntos
Ceratite por Acanthamoeba/tratamento farmacológico , Anti-Infecciosos/uso terapêutico , Candidíase/tratamento farmacológico , Córnea/microbiologia , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Parasitárias/tratamento farmacológico , Taurina/análogos & derivados , Ceratite por Acanthamoeba/microbiologia , Acanthamoeba castellanii/isolamento & purificação , Acanthamoeba castellanii/fisiologia , Animais , Candida albicans/isolamento & purificação , Candida albicans/fisiologia , Candidíase/microbiologia , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Parasitárias/microbiologia , Modelos Biológicos , Suínos , Taurina/uso terapêutico
8.
Am J Ophthalmol ; 201: 31-36, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30721687

RESUMO

PURPOSE: To ascertain the incidence of Acanthamoeba keratitis and the coexistence of Acanthamoeba and fungi in microbial keratitis. DESIGN: Prospective cross-sectional study. METHODS: Patients presenting with stromal keratitis were additionally tested for Acanthamoeba irrespective of the clinical diagnosis. Culture positivity was the gold standard. RESULTS: Of the 401 cases included in the study, 40 were positive for Acanthamoeba (10%); of these 40, 16 were positive for both Acanthamoeba and fungi (4.5% of the study group was Acanthamoeba and fungal keratitis positive); 5 were positive for Acanthamoeba and bacteria; and 2 had triple infection with Acanthamoeba, fungi, and bacteria. Ring infiltrates and stromal edema are frequently associated with Acanthamoeba keratitis, as well as in Acanthamoeba coinfections. Ring infiltrates in particular were more frequently seen in the Acanthamoeba and fungal keratitis group (8/16) and they were often yellowish with hyphate edges (vs ring infiltrates only, which are seen in the patients with Acanthamoeba alone). Only 2 patients were contact lens wearers: however, they presented with history of trauma. CONCLUSIONS: Acanthamoeba coinfections are much more frequent and are not restricted to contact lens users. Anticipating coinfections is necessary for establishing a diagnosis as well as for appropriate and timely therapeutic interventions.


Assuntos
Ceratite por Acanthamoeba/epidemiologia , Coinfecção/epidemiologia , Úlcera da Córnea/epidemiologia , Úlcera da Córnea/parasitologia , Infecções Oculares Fúngicas/epidemiologia , Infecções Oculares Parasitárias/epidemiologia , Acanthamoeba/isolamento & purificação , Ceratite por Acanthamoeba/diagnóstico , Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/microbiologia , Adolescente , Adulto , Antibacterianos/uso terapêutico , Antiprotozoários/uso terapêutico , Bactérias/isolamento & purificação , Coinfecção/diagnóstico , Coinfecção/tratamento farmacológico , Coinfecção/microbiologia , Lentes de Contato/microbiologia , Lentes de Contato/parasitologia , Substância Própria/microbiologia , Substância Própria/parasitologia , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/microbiologia , Estudos Transversais , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/epidemiologia , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Parasitárias/diagnóstico , Infecções Oculares Parasitárias/tratamento farmacológico , Infecções Oculares Parasitárias/microbiologia , Feminino , Fungos/isolamento & purificação , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
9.
Cornea ; 38(4): 463-468, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30640249

RESUMO

PURPOSE: Acanthamoeba keratitis (AK) is a severe vision-threatening ocular infection that is frequently a diagnostic challenge. Treatment course is lengthy and often not fully effective. Contact lens wear has been recognized as the prime risk factor for AK. In vivo confocal microscopy (IVCM) is a noninvasive imaging modality that allows direct visualization of potential causative pathogens in real time with an established utility in the diagnosis of AK. In this study, we aim to assess the utility of IVCM in monitoring disease progression in contact lens wearers with culture-confirmed keratitis. METHODS: Fourteen eyes from 11 patients with culture-confirmed AK were included in this retrospective study. IVCM was performed during the patient's initial visit and all follow-up visits. All available confocal sequences were reviewed and graded in a masked fashion. Density of Acanthamoeba cyst infiltration and changes in the cyst density as a percentage of baseline cyst density measured at each patient's initial visit were calculated. A univariate regression analysis was performed to assess the association between treatment and changes in cyst density per month of treatment. RESULTS: Acanthamoeba cysts were identified by IVCM in all of these culture-confirmed cases of keratitis. Mean cyst density in the central cornea at presentation was 99 ± 64.9 cells per square millimeter (range, 38-255/mm). Cyst density in our study population significantly decreased by approximately 5.3% with each month of antiamebic treatment (P = 0.001; R = 0.41). CONCLUSIONS: Reduction in Acanthamoeba cyst density with treatment can be monitored by IVCM, which in turn can be used clinically in prognostication and disease monitoring of AK.


Assuntos
Ceratite por Acanthamoeba/diagnóstico por imagem , Ceratite por Acanthamoeba/tratamento farmacológico , Acanthamoeba/citologia , Antiprotozoários/uso terapêutico , Técnicas de Diagnóstico Oftalmológico , Microscopia Confocal , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Lentes de Contato/efeitos adversos , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
10.
Curr Med Chem ; 26(30): 5711-5726, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29745319

RESUMO

BACKGROUND: First discovered in the early 1970s, Acanthamoeba keratitis has remained a major eye infection and presents a significant threat to the public health, especially in developing countries. The aim is to present a timely review of our current understanding of the advances made in this field in a comprehensible manner and includes novel concepts and provides clear directions for immediate research priorities. METHODS: We undertook a search of bibliographic databases for peer-reviewed research literature and also summarized our published results in this field. RESULTS: The present review focuses on novel diagnostic and therapeutic strategies in details which can provide access to management and treatment of Acanthamoeba keratitis. This coupled with the recently available genome sequence information together with high throughput genomics technology and innovative approaches should stimulate interest in the rational design of preventative and therapeutic measures. Current treatment of Acanthamoeba keratitis is problematic and often leads to infection recurrence. Better understanding of diagnosis, pathogenesis, pathophysiology and therapeutic regimens, would lead to novel strategies in treatment and prophylaxis.


Assuntos
Ceratite por Acanthamoeba , Ceratite por Acanthamoeba/diagnóstico , Ceratite por Acanthamoeba/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Humanos
12.
Exp Parasitol ; 196: 22-27, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30472333

RESUMO

Acanthamoeba keratitis (AK) is a sight-threatening corneal infection. The early symptoms include redness, pain, photophobia and intense tearing. Chronic infection usually progresses to stromal inflammation, ring ulcers, corneal opacification and hypopyon. Here we document an AK case in a high myopic 38-year-old woman from Mexico City, with a history of wearing contact lenses while swimming. Corneal scrapes cultures were positive only for amoebae, consequently a treatment including netilmicin 0.3% and oral itraconazole 100 mg/12 h was prescribed. The infection was resolved after 8 months, leaving a slight leucoma outside the visual axis, with a visual acuity of 20/150. In the laboratory, the amoebic isolate was axenized in PYG medium, with an optimal growth at 30 °C, and was identified morphologically as Acanthamoeba polyphaga according to the taxonomic criteria of Page (1988) and placed in the T4 group by genotyping. The virulence of this strain (40%) was determined by intranasal inoculation of 1 × 106/20 µl trophozoites in BALB/c mice recovering from brain, proving their invasion ability and by the interaction with monolayers of epithelial cells of the established MDCK line of canine kidney origin (1:2 ratio of interaction), at 1, 3, 6, 8 and 24 h; trophozoites migrated to cell junctions inducing few lytic zones. In addition to the biological characterization, in vitro drug sensitivity tests were performed using chlorhexidine, itraconazole, netilmicin and voriconazole. Results revealed that voriconazole was the most effective compound. A. polyphaga remains as one of the most frequently isolated species producing AK. The treatment of AK case using netilmicin and oral itraconazole solved the disease, but the healing process was wide-ranging (8 months). The use of voriconazole and chlorhexidine may be an alternative treatment of future AK cases in Mexico.


Assuntos
Ceratite por Acanthamoeba/parasitologia , Acanthamoeba/efeitos dos fármacos , Anti-Infecciosos/administração & dosagem , Acanthamoeba/isolamento & purificação , Ceratite por Acanthamoeba/tratamento farmacológico , Adulto , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Antifúngicos/administração & dosagem , Antifúngicos/farmacologia , Clorexidina/farmacologia , Lentes de Contato/efeitos adversos , Lentes de Contato/parasitologia , Cães , Feminino , Humanos , Concentração Inibidora 50 , Itraconazol/administração & dosagem , Itraconazol/farmacologia , Células Madin Darby de Rim Canino , México , Camundongos , Camundongos Endogâmicos BALB C , Midriáticos/administração & dosagem , Netilmicina/administração & dosagem , Netilmicina/farmacologia , Testes de Sensibilidade Parasitária , Fenilefrina/administração & dosagem , Tropicamida/administração & dosagem , Voriconazol/farmacologia
13.
Int J Pharm ; 556: 330-337, 2019 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-30553004

RESUMO

Poor bioavailability and low residence time limit the efficiency of conventional biguanide-based eye drops against Acanthamoeba keratitis. The aim of this work was to formulate an original anti-amoebic thermoreversible ocular gel combining biguanide and metalloproteases inhibitor - chelating agent. Chlorhexidine digluconate (CHX)-ethylenediaminetetraacetic acid disodium salt (Na2EDTA) were compounded in poloxamer 407 saline solution. 0.02% CHX - 0.1% Na2EDTA loaded thermosensitive ocular gel exhibited appropriate pH (5.73 ±â€¯0.06), iso-osmolality (314 ±â€¯5 mOsm/kg), viscosity (ranged between 15 and 25 mPa.s) and thermal gelation (26.5 °C and 33 °C) properties. Bioadhesion of gel was successfully tested onto isolated bovine eyes as well as the assessment of CHX penetration into the cornea. Intracorneal CHX concentration was found greater than trophozoite minimum amoebicidal concentration and minimal cysticidal concentration after 15-min and 2-h ocular exposure, respectively, while any CHX permeation through the cornea was detected (<51 ng/cm2/h). Improvement of CHX ocular bioavailability was attributed to probable solubilization of tear film lipid layer by poloxamer. In vitro efficiency of CHX-Na2EDTA ocular gel was confirmed from the drastic reduction of trophozoite and cyst survival (to 25% and 2%, respectively), confirming the potential of the multicomponent pharmaceutical material strategy for the treatment of Acanthamoeba keratitis.


Assuntos
Ceratite por Acanthamoeba/tratamento farmacológico , Amebicidas/administração & dosagem , Clorexidina/análogos & derivados , Ácido Edético/administração & dosagem , Administração Oftálmica , Amebicidas/farmacocinética , Amebicidas/farmacologia , Animais , Disponibilidade Biológica , Bovinos , Quelantes/administração & dosagem , Quelantes/farmacocinética , Quelantes/farmacologia , Química Farmacêutica/métodos , Clorexidina/administração & dosagem , Clorexidina/farmacocinética , Clorexidina/farmacologia , Córnea/metabolismo , Combinação de Medicamentos , Ácido Edético/farmacocinética , Ácido Edético/farmacologia , Géis , Concentração Osmolar , Temperatura Ambiente , Trofozoítos/efeitos dos fármacos , Viscosidade
15.
BMJ Case Rep ; 11(1)2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30567163

RESUMO

The oomycete Pythium and the protozoan Acanthamoeba can cause fulminant and recalcitrant keratitis, respectively. These infections are not only sight-threatening but can also threaten the structural integrity of the eye. A high index of suspicion is required to identify Pythium keratitis given its uncommon occurrence. Acanthamoeba keratitis is most commonly associated with contact lens wear. However, its coexistence with Pythium has not been reported. We present the successful management of a case of contact lens-related keratitis, coinfected with Pythium and Acanthamoeba.


Assuntos
Ceratite por Acanthamoeba/diagnóstico , Lentes de Contato , Pitiose/diagnóstico , Ceratite por Acanthamoeba/complicações , Ceratite por Acanthamoeba/tratamento farmacológico , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Azitromicina/administração & dosagem , Azitromicina/uso terapêutico , Diagnóstico Diferencial , Humanos , Injeções Intraoculares , Masculino , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/uso terapêutico , Pitiose/complicações , Pitiose/tratamento farmacológico , Voriconazol/administração & dosagem , Voriconazol/uso terapêutico , Adulto Jovem
16.
Ann Agric Environ Med ; 25(4): 725-731, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30586959

RESUMO

INTRODUCTION: Free-living amoebae, ubiquitous in outer environments, in predisposing circumstances may exist as parasites, infectious agents of Acanthamoeba keratitis. In recent decades, the vision-threatening corneal infection is a growing human health threat worldwide, including Poland. The applied therapy is often ineffective due to diagnostic mistakes, various pathogenicity of Acanthamoeba strains and high resistance of cysts to drugs; many agents with possible anti-amoebic activity are still being tested. In the presented study, selected chemicals are investigated in terms of their in vitro effect on corneal and environmental Acanthamoeba strains. MATERIAL AND METHODS: Samples of a corneal isolate from a patient with severe Acanthamoeba keratitis,of assessed on the basis of genotype associations of 18S rRNA and the type strain, Acanthamoeba castellanii Neff cultivated in bacteria-free condition, were exposed to povidone iodine, chlorhexidine digluconate or toyocamycin. In vitro population dynamics of the strains were monitored and compared to those of control cultures. RESULTS: All chemicals showed anti-amoebic effects with different degrees of effectiveness. Significant differences were observed in the in vitro population dynamics, and the morpho-physiological status of A. castellanii Neff T4 and corneal strains determined as A. polyphaga T4 genotype, exposed to povidone iodine or toyocamycin, in comparison with chlorhexidine taken as reference. CONCLUSIONS: Time-dependent amoebstatic in vitro effects were demonstrated for all agents, in particular, the results of assays with povidone iodine are promising. No significant stimulation of encystation appeared; however, as cysticidal efficacy of chemicals is expected, complementary research is needed on different Acanthamoeba strains with modified agent concentrations and method application.


Assuntos
Ceratite por Acanthamoeba/parasitologia , Acanthamoeba/efeitos dos fármacos , Antiprotozoários/farmacologia , Clorexidina/análogos & derivados , Povidona-Iodo/farmacologia , Toiocamicina/farmacologia , Acanthamoeba/classificação , Acanthamoeba/genética , Acanthamoeba/isolamento & purificação , Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/epidemiologia , Clorexidina/farmacologia , Genótipo , Humanos , Polônia/epidemiologia
17.
Ann Parasitol ; 64(3): 229-233, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30316219

RESUMO

Small amoebae belonging to the Acanthamoeba genus complete their life cycles in different environmental niches as free-living protists however some of them are facultative parasites that can cause severe disease in humans. The sight-threatening Acanthamoeba keratitis develops in immune-competent persons, mainly in contact lens wearers; it is detected with increasing frequency along with the spread of contact lens use. The high abundance of the amoebae in the environment is important for dispersion and transmission of the infections among humans. Emerging threats for the public health generated by these amoebae is the serious medical problem worldwide. Nonspecific symptoms, similar to those occurring in the other eye diseases, diagnostic mistakes, the delay of an appropriate treatment, an exceptional high resistance of the amoebae to chemicals and drugs result in a prolonged course of the disease and often unsuccessful therapeutic management. Thus, different chemicals are still examined for their potential activity in vitro against various species, strains/isolates of Acanthamoeba. As the prolonged therapy often induces encystation subsequently leading to excystment and recurrences of amoebic keratitis, apart from anti-amoebic activity, cysticidal effect of examined agents is desirable. In the present study, results of our comparative investigations showed that cationic antiseptic chlorhexidine digluconate indicated in vitro anti-amoebic effect on environmental Acanthamoeba castellanii Neff strain and pathogenic corneal Acanthamoeba polyphaga T4 genotype. Amoebostatic effect of the disinfectant was expressed in reduced number of surviving amoebae in comparison to the respective control cultures; simultaneously, despite prolonged incubation with the agent no stimulation of encystation was noted. The corneal strain was more resistant to the tested compound than the Neff strain. The cysticidal efficacy of chemicals is very expected, thus further in vitro studies on pathogenic Acanthamoeba strains with different application chemicals pattern are needed.


Assuntos
Ceratite por Acanthamoeba , Acanthamoeba , Clorexidina , Desinfetantes , Acanthamoeba/efeitos dos fármacos , Ceratite por Acanthamoeba/tratamento farmacológico , Clorexidina/farmacologia , Doenças Transmissíveis Emergentes , Desinfetantes/farmacologia , Humanos , Polônia
18.
Arch. Soc. Esp. Oftalmol ; 93(10): 497-502, oct. 2018. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-175125

RESUMO

Casos clínicos: Presentamos 10 casos de queratitis por Acanthamoeba tratados en nuestro hospital entre 2008 y 2017. Todos eran portadores de lentes de contacto. Como tratamiento todos recibieron una biguanida junto a una diamidina. En 3 casos la infección no superaba el estroma superficial, respondiendo al tratamiento tópico. En 7 alcanzaba el estroma profundo, precisando 6 de ellos una queratoplastia penetrante, 3 «en caliente» por riesgo de perforación o extensión ocular. La agudeza visual mejoró en todos los casos. Conclusión: La profundidad de la infección al diagnóstico aparece como el principal factor de riesgo para necesitar una queratoplastia penetrante


Clinical cases: Cases are presented of 10 patients with Acanthamoeba keratitis treated between 2008 and 2017. All were contact lens wearers. All of them received treatment with a biguanide combined with a diamidine. In 3 cases the infestation did not exceed the superficial stroma, responding to topical treatment. In 7, the infection reached the deep stroma, with 6 of these cases requiring penetrating keratoplasty (PKP), 3 of them therapeutic PKP because of perforation risk or ocular spreading. The visual acuity improved in all the cases. Conclusion: The infestation depth at the time of diagnosis appears to be the main risk factor for requiring a PKP


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Ceratite por Acanthamoeba/diagnóstico , Ceratite por Acanthamoeba/tratamento farmacológico , Biguanidas/uso terapêutico , Diaminas/uso terapêutico , Infecções Oculares/diagnóstico , Diagnóstico Precoce , Biópsia , Ceratite por Acanthamoeba/parasitologia , Acuidade Visual , Lentes de Contato/parasitologia , Infecções Oculares/tratamento farmacológico , Infecções Oculares/parasitologia
19.
Invest Ophthalmol Vis Sci ; 59(11): 4567-4571, 2018 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-30242357

RESUMO

Purpose: To assess the amoebicidal effect of titanium dioxide (TiO2)/UV-A combination against Acanthamoeba sp trophozoites and cysts. Methods: The amoebicidal effect of the TiO2/UV-A combination was tested on trophozoites and cysts of clinical isolates of Acanthamoeba hatchetti and Acanthamoeba sp genotype T4, obtained from two severe cases of ulcerative keratitis. Samples of cultured Acanthamoeba were transferred to a 96-well plate. We tested the effect of sterile water (blank control), TiO2 alone, UV-A alone, TiO2 and additional UV-A exposure, chlorhexidine 0.02% alone, chlorhexidine 0.02% and TiO2, chlorhexidine and UV-A, chlorhexidine 0.02% and TiO2, and additional UV-A exposure. Cell viability assessment was done using the trypan blue dye exclusion method. Results: The combination of TiO2 with UV-A demonstrated antitrophozoite and anticyst activity (P < 0.05). This in vitro study showed a synergistic effect of the association of chlorhexidine with TiO2 and UV-A on cysts (P < 0.001). Conclusions: Given the in vitro synergistic effectiveness of the association of chlorhexidine with TiO2 and UV-A against cysts, the treatment of Acanthamoeba keratitis could be improved by this new therapeutic approach.


Assuntos
Acanthamoeba/efeitos dos fármacos , Acanthamoeba/efeitos da radiação , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Titânio/farmacologia , Raios Ultravioleta , Ceratite por Acanthamoeba/tratamento farmacológico , Amebicidas , Animais , Humanos , Fatores de Tempo
20.
Acta Biomater ; 80: 48-57, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30267886

RESUMO

There are increasing demands for long-term and controlled corneal drug delivery to treat various ocular diseases. Although biodegradable ocular inserts or contact lenses have been developed, the invasiveness and inefficiency of the approaches still need to be improved. Microneedle (MN) technology can deliver therapeutic molecules to the eye in a minimally invasive manner. However, the current ocular MN technology is limited to either short-term corneal drug delivery or retinal drug delivery by suprachoroidal injection. For long-term and minimally invasive corneal drug delivery, we have developed a detachable biodegradable MN that can be delivered to the inside of the cornea for sustained drug release. The detachable and biodegradable MN is a hybrid MN consisting of a drug-loaded biodegradable tip and a supporting base. The hybrid MN can be applied to the cornea by impact insertion, and it leaves only the drug-loaded biodegradable tip within the corneal tissue so that it can release the drug for a certain period. By concentration-controlled molding, the dimension of drug-loaded MN tips was precisely controlled and their detachability was optimized. The detachable tip and a supporting base were assembled to form a hybrid MN by pressure-assisted transfer molding. We carefully optimized the dimension of the drug-tip, injection dwell time, and insertion depth to achieve effective intracorneal injection of the drug-tip. The detachable hybrid MN was applied to an Acanthamoeba keratitis model wherein a biodegradable drug-tip was successfully delivered to the inside of the mouse cornea in vivo. Follow-up of the MN-treated cases for 7 days confirmed the therapeutic efficacy of the detachable biodegradable MN tips. STATEMENT OF SIGNIFICANCE: For the treatment of infectious diseases in the cornea, such as keratitis, eye drops need to be applied topically every hour for a couple of days. This is extremely uncomfortable, and poor compliance to such tightly scheduled drug administration can result in permanent scar formation in the cornea. In this work, we demonstrate a simple and rapid injection of biodegradable microneedle tips in the corneal tissue wherein the tips can deliver antibacterial drugs for 4 days to treat keratitis. Unlike other patch-style microneedle technologies, this approach allows for insertion depth-controlled and highly localized injection of detachable individual microneedle tips to the diseased tissue for sustained drug delivery. This overcomes the limitations of patch-style microneedles such as short-term drug delivery and unnecessary blockage of tissue.


Assuntos
Córnea/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Microinjeções/métodos , Agulhas , Ceratite por Acanthamoeba/tratamento farmacológico , Animais , Biguanidas/administração & dosagem , Biguanidas/farmacologia , Biguanidas/uso terapêutico , Córnea/parasitologia , Córnea/patologia , Dimetilpolisiloxanos/química , Feminino , Camundongos Endogâmicos C57BL , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Pressão
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