Natamicina versus voriconazol para queratitis fúngica / Natamycin versus voriconazole for fungal keratitis

INTRODUCCIÓN: La queratitis infecciosa de origen fúngico afecta principalmente a personas de países tropicales y subtropicales, y constituye una importante causa de ceguera prevenible. Los antifúngicos tópicos, en particular la natamicina y el voriconazol, se consideran efectivos, pero no está claro cuál de ellos constituye la mejor alternativa de tratamiento. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos tres revisiones sistemáticas que en conjunto incluyeron tres estudios primarios, todos correspondientes a ensayos aleatorizados. Concluimos que natamicina probablemente se asocia a mejor agudeza visual tras la infección, y que previene la perforación corneal y/o la necesidad de realizar queratoplastia terapéutica en comparación a voriconazol en queratitis fúngica.

INTRODUCTION: Infectious keratitis of fungal origin mainly affects people in tropical and subtropical countries, and is an important cause of preventable blindness. Topical antifungals, particularly natamycin and voriconazole, are considered effective, but it is not clear which one is the best treatment alternative. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified three systematic reviews including three studies overall,all of which were randomized trials. We concluded natamycin probably is associated with better visual acuity after infection, and it prevents corneal perforation and/or need to perform therapeutic keratoplasty compared to voriconazole in fungal keratitis.

Bilateral fungal keratitis with ring infiltrates: a rare scenario.

A 12-year-old boy presented to the emergency department with chief complaints of pain, redness, discharge and diminution of vision in both eyes over the previous 20 days. There was no history of preceding trauma, contact lens use, any eye drop usage or ocular surgery. Systemic history was not significant. Presenting uncorrected visual acuity in his right eye was counting fingers at 1 m and 20/200 in the left eye, with accurate projection of rays in both eyes. Slit lamp biomicroscopy showed the presence of bilateral diffuse conjunctival congestion, corneal ring infiltrates and epithelial defect with corneal oedema. Potassium hydroxide wet mount showed the presence of septate fungal hyphae. The patient was treated with topical 5% natamycin and 1% voriconazole over a period of 6 weeks. Best-corrected visual acuity was 20/600 in the right eye and 20/20 in the left eye at 6-month follow-up.

[Prolonged topical natamycin 5 % therapy before and after keratoplasty for Fusarium keratitis]. / Prolongierte topische Natamycin 5 %-Therapie vor und nach Keratoplastik bei Fusarium-Keratitis.

CASE REPORT: A 69-year-old female patient presented with a therapy-resistant corneal ulcer due to contact lenses, which had been present in the left eye for 1 month. The best corrected visual acuity at the first visit was 0.2. Keratitis with a central corneal ulcer was found. A corneal curettage was performed followed by inpatient therapy with antibiotic eye drops. The first PCR result was negative and the microbiological culture was sterile after 48 h. The clinical findings improved during the hospital stay. There was a decrease in the size of the corneal ulcer and an increase of best corrected visual acuity up to 0.4 so that the patient was discharged. COURSE: After 8 weeks the patient presented again with a painful eye and visual decline to 0.1. The left eye showed a fulminant keratitis with corneal abscess so that a second course of therapy was initiated. The PCR of the second corneal curettage was positive for Fusarium. Antifungal therapy with natamycin 5 % eye drops (via the international pharmacy) and systemic antifungal therapy with voriconazole (2 × 200 mg) were initiated. Due to personal circumstances the patient rejected corneal transplantation, therefore, local and systemic antifungal outpatient treatment was continued for another 2 months until keratoplasty à chaud of the left eye could be performed. At this time there was a clear reduction of inflammation but a descemetocele developed. The patient was treated with local and systemic antifungal therapy (under control of liver and kindney parameters in blood) for 3 months postoperatively in addition to administration of local and systemic steroids. DIAGNOSTICS: In cases of therapy-resistant keratitis, a Fusarium keratitis should always be considered. Corneal curettage ahead of therapy is very important. THERAPY: Natamycin 5 % eye drops are the first choice of topical antifungal medication in cases of Fusarium keratitis. Even though intensive local and systemic therapy are performed, patients often require corneal transplantation. Due to a high rate of recurrence a longer local and systemic antifungal therapy is required. CONCLUSION: In the case described here, there was a clear corneal graft without Fusarium recurrence 1 year after surgery and it is presumed the prolonged antifungal therapy before and after surgery was an important factor for this clinical outcome.

Fungal scleral keratitis caused by Phomopsis phoenicicola.

We report a case of scleral keratitis caused by Phomopsis phoenicicola. Pterygium surgery was a predisposing factor, and the patient was treated with natamycin and fluconazole eye drops and oral fluconazole. The fungus was identified by sequencing of the internal transcribed spacer (ITS) region of the fungal ribosomal DNA (rDNA) locus and confirmed on the basis of its typical pycnidia and conidia.

Practice patterns in the management of fungal corneal ulcers.

PURPOSE: The purpose of this study was to determine the practice patterns of ophthalmologists in the management of fungal corneal ulcers. METHODS: In December 2007, a survey of 13 questions addressing the actual and preferred treatment of fungal ulcers was sent to the kera-net e-mail listserv facilitated by the Cornea Society. RESULTS: Ninety-two respondents from North America, South America, Asia, Europe, and Australia participated by completing the electronic questionnaire. Natamycin was the most commonly used topical treatment for ulcers caused by filamentous fungi (96%) followed by amphotericin (75%) and voriconazole (63%). However, voriconazole was most often listed as the preferred topical treatment in an ideal world (79%) compared with 55% for natamycin. Approximately half of the respondents use combination topical therapy (56%) and the remainder monotherapy. The majority of respondents rescrape the epithelium at some time during the course of treatment, but the frequency of rescraping varied among the different topical treatments. The most common reasons cited for not using their preferred treatment were cost and a desire for further evidence to support preferred treatment. CONCLUSION: There appears to be significant variation in the management of fungal corneal ulcers. Although natamycin was the most commonly used treatment for ulcers caused by filamentous fungi, voriconazole was the most preferred as the ideal treatment. These results highlight the need for more evidence regarding the efficacy of the newer topical antifungals.

Fungal keratitis: changing pathogens and risk factors.

PURPOSE: To describe changes in demographics and pathogens for fungal keratitis cases diagnosed at the Massachusetts Eye and Ear Infirmary. METHODS: Patient demographics, clinical and laboratory findings, treatment and outcomes of 46 cases of culture-proven fungal keratitis diagnosed from January 2004 through November 2007 were compared with 23 cases of fungal keratitis previously collected over a similar period from January 1999 through November 2002. RESULTS: During 2004-2007, the rate of fungal keratitis was 1.0 cases per month, an increase from the baseline rate of 0.5 cases per month during 1999-2002. The proportion of cases caused by filamentous fungi increased from 30% (1999-2002) to 65% (2004-2007) (P = 0.01). Soft contact lens wear accounted for 41% of fungal keratitis cases in 2004-2007, as compared with 17% in 1999-2002. The majority of patients (70%) received oral antifungal treatment in addition to topical amphotericin B and natamycin. Seventeen patients (40%) required therapeutic keratoplasty. Patients with a history of corneal transplant had the highest rate of therapeutic keratoplasties (67%) and had the poorest visual outcome (40% counting fingers or less). In the contact lens group, 94% of patients maintained vision of at least 20/40 and only 12% required surgery to control the infection. CONCLUSIONS: There has been an increase in fungal keratitis in the Boston area and a change in the causative pathogens and risk factors for infection. Filamentous fungi now account for the majority of fungal keratitis cases, whereas yeasts were the predominant pathogen in the past. Soft contact lens wear is currently the most common risk factor for development of fungal keratitis.

Effect of topical 0.5 percent povidone-iodine compared to 5 percent natamycin in fungal keratitis caused by Fusarium solani in a rabbit model: a pilot study / Efeito tópico de iodo-povidona 0, 5 por cento comparado com natamicina 5 por cento em ceratites fúngicas causadas por Fusarium solani em um modelo animal de coelhos: estudo piloto

PURPOSE: To evaluate the efficacy of topical administration of 0.5 percent povidone-iodine in experimental Fusarium solani keratitis in rabbits. METHODS: Fungal keratitis caused by Fusarium solani was induced in the right eye of 24 New Zealand rabbits. The rabbits were randomly divided into 3 different treatment groups: Group I (povidone-iodine) - treated with topical 0.5 percent povidone-iodine; Group II (natamycin) - treated with topical 5 percent natamycin; and Group III (control) - treated with topical saline solution. In all groups the rabbits were treated for three days and then sacrificed. The corneas were excised, macerated and immersed in 10 mL BHI. Culture samples were plated daily on Sabouraud's agar for 7 days, and the number of colony-forming units (CFU) was counted. The rabbits were clinically evaluated during the treatment period. RESULTS: The povidone-iodine and natamycin groups demonstrated better efficacy than the control group based on the number of rabbits with no colonies growing. However, there were no statistically significant differences between the three groups when the number of CFU was analyzed (p>0.05). CONCLUSIONS: Our study demonstrates important methodological considerations in the use of in vivo animal models for the testing of antifungal agents. Using this sample size and methodology of counting CFU, topical 0.5 percent povidone-iodine demonstrated no benefit in the treatment of experimental Fusarium solani when compared with topical 5 percent natamycin.

OBJETIVO: Avaliar a eficácia do uso tópico de iodo-povidona 0,5 por cento em ceratite experimental por Fusarium solani em coelhos. MÉTODOS: Ceratite fúngica por Fusarium solani foi induzida no olho direito de 24 coelhos da raça New Zealand. Os coelhos foram divididos aleatoriamente em 3 diferentes grupos de tratamento: Grupo I (iodo-povidona) - tratados com iodo-povidona 0,5 por cento; Grupo II (natamicina) - tratados com natamicina 5 por cento; Grupo III (controle) - tratados com solução salina. Os coelhos dos 3 grupos foram tratados por 3 dias e sacrificados em seguida. As córneas foram removidas cirurgicamente, maceradas e incubadas em meio BHI. Semeou-se culturas em placas de ágar Sabouraud, diariamente, durante 7 dias, e contou-se o número de unidades formadoras de colônias (UFC). Os coelhos foram avaliados clinicamente durante o período de tratamento. RESULTADOS: Os grupos iodo-povidona e natamicina demonstraram melhor eficácia do que o grupo controle considerando-se o número de coelhos nos quais não houve crescimento de colônias. Entretanto, não houve diferença estatística significante entre os 3 grupos quando se analizou o número de UFC (p>0,05). CONCLUSÃO: Este estudo demonstrou considerações metodológicas importantes na utilização de modelos animais para o teste de agentes antifúngicos. Usando a metodologia de contar UFC e com este tamanho amostral, administração tópica de iodo-povidona 0,5 por cento não demonstrou benefício do tratamento de ceratite fúngica experimental causada por Fusarium solani quando comparado com a administração tópica de natamicina 5 por cento.

Paecilomyces lilacinus scleritis with secondary keratitis.

PURPOSE: To report a case of Paecilomyces lilacinus scleritis with secondary keratitis after initially diagnosed immune-based scleritis. METHODS: An 82-year-old man was diagnosed with immune-based scleritis and treated with oral cyclophosphamide 50 mg twice daily. However, multiple scleral abscesses and a fibrinoid aqueous reaction developed 3 months later. Infectious scleritis was suspected. The culture from the necrotic sclera grew P. lilacinus. Despite treatment with antimicrobials, the infection progressed to the cornea. The medication included topical natamycin suspension 5% and fluconazole 2 mg/mL hourly, as well as oral itraconazole 100 mg daily. Debridement of the necrotic tissue and intracameral injection with amphotericin-B were performed. RESULTS: The infection resolved 4 months later, although its resolution was accompanied by development of phthisis bulbi, and the visual acuity remained light perception. CONCLUSION: Infection by P. lilacinus can occur in a patient with scleritis. Infectious scleritis is a particular risk in cases involving diabetes mellitus, prior scleritis, previous surgery, and immunosuppression. Early detection of the microorganism and aggressive treatment are necessary to eradicate such an infection; however, the prognosis for vision recovery can remain poor despite treatment.

[Intestinal candidiasis: modern therapeutic tactics].

Bowels candidiasis is an urgent problem not only for gastroenterology but also for other fields of medicine--gynecology, dentistry, phthisiology, surgery, etc. as this disease is directly related with the manifestations of systemic candidiasis in other organs. The diagnostics algorithm includes the detection of a filamentary form (pseudomyceliums) of micromycetes of the Candida genus in the morphological study of a tissue sampling of the bowels mucous coat. The drug of choice for the treatment of bowels candidiasis is Pimafucin (Natamycin) having a local action on the Candida fungi in the intestinal lumen in the absence of any systemic absorption of the drug or any side effects.

The use of 2.5% natamycin, as orally administered drops, in the treatment of fungal infections of the oral cavity in children with chronic blood diseases.

A total of 34 children with oral candidiasis were treated with 2.5% natamycin in the form of orally administered drops; 6-20 drops applied to oral lesions four times daily for up to 8 weeks. A total cure was achieved in 28 (82.3%) cases. No side-effects were observed. This preparation was an effective treatment for Candida albicans infections in children with blood diseases, and was well tolerated.

Pimaricin potentiation of bleomycin activity against murine tumors.

Antitumor activity of bleomycin against Ehrlich ascites carcinoma in mice was examined in the presence and absence of a polyene antibiotic, pimaricin. A single intraperitoneal (ip) injection of bleomycin and pimaricin in combination into tumor-bearing mice on day 1 produced a synergistic life-prolongation effect as compared with that of each agent alone. Accumulation of abdominal ascites was almost completely blocked by bleomycin in combination with the tetraene antibiotic. Frequent ip injection of small doses of bleomycin and pimaricin on day 1 produced a much greater increase in life span than the single ip injection. To obtain effective synergism under these treatment schedules, it appeared that the dose of bleomycin should be reciprocally proportional to the dose of pimaricin.

Oral anticandidal prophylaxis in patients undergoing chemotherapy for acut- leukemia.

Fifty-six untreated patients with acute leukemia (38 acute myelogenous leukemia, 16 acute lymphoblastic leukemia, and 2 blast crisis of chronic granulocytic leukemia) were randomized on admission to one of three groups--one to receive oral anticandidal prophylaxis through the period of remission induction chemotherapy with nystatin, another to receive natamycin, and the third to receive no anticandidal prophylaxis. Neither of the first two groups show any advantage over the last and it is concluded that provided gut sterilization regimes are not employed, prophylactic oral anticandidal treatment is of no value in these patients and should be reserved until there is clinical evidence of infection.

[Therapeutic results achieved through the advantage of a combination of oral metronidazole and vaginal natamycin tablets in urogenital protozoan, trichobacterial and blastomyces infections]. / Therapieerfolge durch den Vorteil einer Kombination von peroralem Metronidazol und Natamycin-Scheidentabletten bei urogenitalen Protozoen-, Trichobakterien- und Sprosspilzinfektionen

Vaginal inflammations caused by Trichomonas, Leptothrix vaginalis or Candida and other less common organisms respectively, were treated very successfully with a combination of metronidazole orally and a natamycin preparation vaginally (Pimafucin vaginal tablets). In women with urogenital Trichomoniasis a cure was obtained in 96,1% of the cases (microbiologically controlled); Candida mycoses of the vagina were cured clinically in 89% of the cases after the first course of treatment and mycologically in 79% of the cases. Of special importance is the rapid and successful elimination of the mixed infection before birth, because this diminishes perinatal morbidity of the fetus. The combination treatment of bilateral, constantly interchanging Candida and Trichomonas infections of the vagina is of importance to both sexes, especially with respect to the elimination of sterility. From the onco-gynecological point of view the combination treatment with metronidazole and natamycin appeared to be of value as it limits the incidence of dyskariosis of the epithelial cells, which occur frequently in cases of inflammation of the vagina or cervix uteri. No teratogenic effect was observed with this combination when applied during pregnancy.