Ocular metabolism and distribution of drugs in the rabbit eye: Quantitative assessment after intracameral and intravitreal administrations.

Quantitation of ocular drug metabolism is important, but only sparse data is currently available. Herein, the pharmacokinetics of four drugs, substrates of metabolizing enzymes, was investigated in albino rabbit eyes after intracameral and intravitreal administrations. Acetaminophen, brimonidine, cefuroxime axetil, and sunitinib and their corresponding metabolites were quantitated in the cornea, iris-ciliary body, aqueous humor, lens, vitreous humor, and neural retina with LC-MS/MS analytics. Non-compartmental analysis was employed to estimate the pharmacokinetic parameters of the parent drugs and metabolites. The area under the curve (AUC) values of metabolites were 12-70 times lower than the AUC values of the parent drugs in the tissues with the highest enzymatic activity. The ester prodrug cefuroxime axetil was an exception because it was efficiently and quantitatively converted to cefuroxime in the ocular tissues. In contrast to the liver, sulfotransferases, aldehyde oxidase, and cytochrome P450 3A activities were low in the eye and they had negligible impact on ocular drug clearance. With the exception of esterase substrates, metabolism seems to be a minor player in ocular pharmacokinetics. However, metabolites might contribute to ocular toxicity, and drug metabolism in various eye tissues should be investigated and understood thoroughly.

Desarrollo y validación de un método de valoración de ketoconazol en comprimidos utilizando infrarrojo medio en modo transmitancia / Development and validation of Ketoconazole assay in tablets by infrared spectrophotometry in transmittance mode

El ketoconazol es un antimicótico utilizado para micosis superficiales y sistémicas cuyas formulaciones en el mercado varían desde cremas tópicas a shampús y comprimidos. En relación a este último, los métodos actuales de valoración del ingrediente farmacéutico activo implican el uso de técnicas de cromatografía líquida de alta performance en las que se requiere el procesamiento previo de las muestras. En conocimiento de esto, y en vistas de implementar mejoras en el sistema de control, se propuso como objetivo del trabajo desarrollar y validar un método de valoración de ketoconazol en comprimidos utilizando espectrofotometría de infrarrojo medio en modo transmitancia. Un procedimiento en el que la ventaja viene dada por la disminución del tiempo de análisis y del costo de la técnica debido a que no requiere separación previa del principio activo de la matriz de excipientes. El sistema analítico consistió en un equipo de infrarrojo medio Perkin Elmer, modelo Spectrum Two, provisto de una celda sellada para líquidos, con ventanas de cloruro de sodio, de 1 mm de paso óptico. La concentración de trabajo fue 1,5 mg por ml, el diclorometano fue el solvente de elección y el rango de número de onda para cuantificar fue 1521 cm-1 - 1498 cm-1. Los ensayos de validación demostraron que la técnica resultó ser lineal, exacta, precisa y específica en el rango de 1,2 mg/ ml a 1,8 mg/ ml.

Ketoconazole is an antifungal medication used for superficial and systemic mycoses whose formulations on the market vary from topical creams to shampoos and tablets. Regarding this matter, the current methodologies for quantify the active pharmaceutical ingredient involve the use of high performance liquid chromatography techniques in which pre-processing of the samples is required. In light of this, and also the need of implementing improvements in the control system, the objective proposed was to develop and validate a ketoconazole quantification method in tablets using medium infrared spectrophotometry in transmittance mode. Some advantages of this procedure are the reduction of analysis time and the cost of the technique due to the fact that it does not require to extract previously the active principle of matrix excipients. The analytical system consisted in a Perkin Elmer medium infrared device, Spectrum Two, equipped with a sealed liquid cell, with sodium chloride windows, 1 mm optical path. The working concentration was 1.5 mg per ml, dichloromethane was the solvent of choice and the wavenumber range to quantify was 1521 cm-1 - 1498 cm-1. The validation tests showed that the technique was linear, accurate, precise and specific in the range of 1.2 mg / ml to 1.8 mg / ml.

Seguimiento e impacto de la divulgación de cinco alertas sanitarias de medicamentos en f1Colombia / Monitoring and impact of the disclosure of five health alerts for drugs in Colombia

RESUMEN Objetivo Realizar la notificación y verificar el seguimiento de cinco alertas sanitarias de medicamentos a un grupo de prestadores de salud en Colombia. Métodos Estudio cuasi-experimental, prospectivo, antes y después, sin grupo control, mediante una intervención en médicos prescriptores de ketoconazol, metoclopramida, nimesulida, diacereina, ranelato de estroncio. Se tomó como población universo a los afiliados al régimen contributivo del Sistema de Salud Colombiano en 13 entidades promotoras de salud (EPS) de Colombia. Se identificaron los pacientes que recibían mensualmente estos medicamentos previamente a la alerta. Se realizó una intervención educativa y posteriormente se midió la proporción de cambio en la dispensación. Resultados Se realizaron en total unas 26 actividades diferentes a 500 médicos prescriptores. De un total de 4 121 954 de personas se identificaron 13 979 pacientes mensuales en 2013 que recibían alguno de los cinco medicamentos y se observó una reducción en 1 470 sujetos al mes (-10,5%) para 2014. El medicamento con el que se consiguió la mayor reducción fue ketoconazol (-31,1% de casos), seguido de ranelato de estroncio (-30,3%) y metoclopramida (-8,6%). Para nimesulida (+0,7%) y diacereina (+16,4%) no se obtuvieron resultados favorables. Conclusiones Se mantienen prescripciones potencialmente riesgosas en pacientes de Colombia. Con intervenciones basadas en farmacovigilancia posterior al reporte de alertas por agencias reguladoras sanitarias, se puede disminuir la proporción de pacientes que utilizan estos medicamentos.(AU)

ABSTRACT Objective Make the notification and monitoring compliance with five health drug alerts to a group of health care providers in Colombia. Methods Quasi-experimental, prospective, before-after study, without control group, by intervening in physician prescribers of ketoconazole, metoclopramide, nimesulide, diacerein, strontium ranelate. The affiliated population of the contributory system of the Colombian Health System was taken as the universe population sample from 13 health promoting entities (EPS) of Colombia. Patients receiving monthly these drugs prior to the alert were identified. An educational intervention was performed and then the rate of change in the dispensation was measured. Results About 26 different activities were conducted on 500 prescribers. Out of a total of 4 121 954 people, 13 979 patients were identified monthly in 2013, who received some of the five medications. Likewise, a reduction in 1,470 subjects per month (-10.5%) for 2014 was observed. The drug which achieved the greatest reduction was ketoconazole (-31.1% of cases), followed by strontium ranelate (-30.3%) and metoclopramide (-8.6%). For nimesulide (+ 0.7%) and diacerein (+ 16.4%) no favorable results were obtained. Conclusions Patients with potentially risky prescriptions remain in Colombia; educational pharmacovigilance interventions made after the report alerts given by drug regulatory agencies may decrease the proportion of patients using these drugs.(AU)

Incidence and Antifungal Susceptibility of Candida Albicans Infections.

INTRODUCTION: Candida albicans is the most common inhabitant of the skin, mouth, vagina and gastro intestinal tract of human beings. One of the major reasons for the increase in Candida infection is the development of its resistant strains due to drugs used in the treatment of candidiasis. MATERIALS AND METHODS We studied 4027 samples collected from patients in various wards of the Emergency County Hospital Craiova, Romania between 2014-2015. The specimens were: pharyngeal exsudates, sputum, tracheal secretions, skin secretions, stools, ear secretions, urine, vaginal secretions. All the specimens were transported to the microbiology laboratory and cultured within 3 to 4 h of collection. Among the 4027 samples, 652 showed culture characteristics similar to Candida albicans.The samples were inoculated under sterile conditions using Sabouraud culture media, a medium designed to inhibit bacterial growth and allow the development of fungi. Antifungal Susceptibility Testing was performed by disc diffusion according to CLSI 2014 guidelines using: clotrimazole, ketoconazole, miconazole, econazole, amphotericine B, fluorocytozine, nistatin. RESULTS AND DISCUSSION In our study group the urocultures and dermatological products have a high infection rate, between 100% to 70%, in contrast, we find evidence of secretion ear (3.13%) and the throat swab (9.33%). Various resistant levels were detected against antifungal drugs but, complete resistance to 5 - Fluorocitozina (100%), and the organisms showed highly sensitive to Cotrimazol si Ketoconazol (100%). In the case of Miconazol 256 (39, 26%), Econazol, 215 (32,98%), Amphotericinei B, 230(35,28%). Nystatin 329 (50,46%). CONCLUSIONSElucidating these mechanisms may provide new foundations for antifungal chemotherapy and can present an exciting challenge for the future investigations. Candida albicans infections are present and diverse clinical pathology.

Assessment of the outcomes of the treatment of Cushing's disease in the hospitals of Castilla-La Mancha.

OBJECTIVE: Treatment of Cushing's disease poses interesting dilemmas in clinical practice. The aim of our study was to analyze the outcomes of the different treatments, the control and recurrence rates, and the complications derived from them. MATERIAL AND METHODS: Data were collected from the clinical records of 22 patients over 18 years of age (86.4% women). They had been diagnosed with Cushing's disease between 2000 and 2012, and were monitored at Complejo Hospitalario Universitario-Albacete, Hospital Virgen de la Salud-Toledo Hospital General Universitario de Ciudad Real, Hospital Virgen de la Luz-Cuenca, Hospital Nuestra Señora del Prado-Talavera de la Reina, and Complejo Hospitalario la Mancha Centro-Alcázar de San Juan. RESULTS: Surgery was the treatment of choice in all patients. Biochemical cure was achieved in 72.2% of patients. Nine patients developed in the early postoperative period diabetes insipidus, which became in 2 patients only. Surprisingly, 3 patients with normal postoperative neurohypophyseal function later developed permanent diabetes insipidus. New hormone deficiencies occurred in 7 patients. Seventeen patients received ketoconazole before surgery (5 of them after surgery also), and 70% of them achieved normal urinary free cortisol levels. Three patients also received radiotherapy, and all of them were cured after a median follow-up of 85.5 months; they developed no tumors or other complications. CONCLUSIONS: Our study reports the outcomes of management of Cushing's disease in non-reference centers for this disease, possibly giving a realistic picture of standard clinical practice for the condition in Spain.

Susceptibilidad in vitro de candida spp: aisladas de la cavidad oral de pacientes VIH/Sida a itraconazol, clotrimazol y ketoconazol / In vitro susceptibility of candida ssp: isolated fromthe oral cavity of HIV/AIDS patientes to itraconazole, clotrimazole and ketoconazole

La candidiasis orofaríngea (COF) permanece como una de las principales infecciones oportunistas en pacientes infectados con el virus de la inmunodeficiencia humana (VIH) y con el síndrome de inmunodeficiencia adquirida (sida), y aunque su incidencia ha disminuido con la introducción de la terapia antirretroviral de alta eficacia, continúa siendo una afección característica en estos pacientes. En el presente trabajo se realizó un estudio de susceptibilidad in vitro mediante la metodología del CLSI, frente a itraconazol, ketoconazol y clotrimazol de 144 aislamientos clínicos de Candida, aisladas de la cavidad oral de pacientes infectados con el VIH/sida con cuadros clínicos de COF. La identificación de los aislamientos demostró que más del 90% pertenecían a Candida albicans. Al determinar el patrón general de susceptibilidad frente a los azoles estudiados mediante el método de microdilución en caldo del documento M27-A2 del Clinical and Laboratory Standard Institute, C. albicans exhibió valores de concentración mínima inhibitoria (CMI) en un rango de 0,01 a 8µg/mL para el itraconazol y el ketoconazol y de 0,01 a 2 g/mL para el clotrimazol. Sólo el 2,1 % de los aislamientos mostró franca resistencia frente al itraconazol, en tanto que el 3,5 % quedó clasificado dentro de la categoría “susceptible dosis-dependiente” para este triazol. La mayoría de los aislamientos de C. albicans mostraron valores de CMI frente al ketoconazol y al clotrimazol menores a 0.06 g/mL, siendo de un 96,9% (129 aislamientos) y de un 97,7% (129 aislamientos), respectivamente. El clotrimazol tuvo una mejor actividadin vitro comparado con los restantes azoles frente a los aislamientos estudiados. Candida spp. Mostró una elevada sensibilidad in vitro a los azoles estudiados. Se hace necesario continuar realizando estudios epidemiológicos para determinar los patrones de susceptibilidad y tasas de resistencias frente a los agentes...

The oropharyngeal candidiasis (OFC) remains as one of the principal opportunistic infections in patients infected with the human immunodeficiency virus (HIV) and with the acquired immunodeficiency syndrome (aids), and although his incidence has declined with the introduction of the highly active anti-retroviral therapy (HAART), remains as a typical complaint in these patients. A study of antifungal in vitro susceptibility testing, following the CLSI methodology, was realized against itraconazole, ketoconazole and clotrimazole of 144 clinical isolations of Candida, isolated from the oral cavity of patients infected with HIV/aids, with clinical pictures of OFC. The isolation’s identification, demonstrated that more than 90% belonged to Candida albicans. The determination of the general pattern of susceptibility, following the document M27-A2 of the Clinical and Laboratory Standard Institute, against to the studied azoles by means of the method of microdilution in liquid medium, show that the majority of C. albicans isolates showed values of MIC against ketoconazole and clotrimazole lower than 0.06 g/mL, representing a 96,9% (129 isolations) and a 97,7% (129 isolations), respectively. C. albicans exhibited the widest range of minimal inhibitory concentration (MIC). Only 2.1% of the isolations showed resistance against to itraconazole, while 3.5 % remained classified in the category “sensible dose - dependent” for this triazole. The majority of the strains showed values of MIC against ketoconazole and clotrimazole below 0.06 g/mL. The clotrimazole had a better in vitro activity compared with the remaining azoles opposite to the isolations. Candida spp. showed a high in vitro sensibility to the azoles studied. It becomes necessary the maintenance of epidemiologic studies for the determination of susceptibility patterns and of resistances rates against to the antifungal agents

Resultados del rratamiento con yodo salicilico y ketoconazol en la pitiriasis versicolor / The results of the treatment of Tinea Versicolor utilisig salicylic iodine and Ketoconazol

El tratamiento de la Pitiriasis Versicólor depende de varios factores como la localización, el tamaño, el número de lesiones y la edad. La vía a utilizar puede ser sistémica o local;se prefiere esta última por tener menos efectos adversos (cremas de tolnaftato, ketoconazol, pinceladas de yodo salicílico, pinceladas de timol y otros). El universo de estudio estuvo integradopor 50 pacientes portadores de Pitiriasis Versicolor diagnosticados por la clínica y el exudado micológico, la mitad de los cuales usó pinceladas de yodo salicílico y la otra mitad crema de ketoconazol durante 3 semanas de forma tópica dos veces al día. El resultado fue similar, con una mayor eficacia de la pincelada de yodo salicílico (92%) sobre la crema de ketoconazol (88 %). El costo por tratamiento fue significativamente menor en los tratados con pinceladas de yodo salicílico ($0.50) que los tratados con crema de ketoconazol ($3.80). Se concluye que debe utilizarse de elección la pincelada de yodo salicílico por ser más barata y efectiva.

The treatment of Tinea Versicólor depend on various factors, such as location of the lesions, size, number and age. The way of the treatment use might be systemic or local, rather preferable is the last one, because of less adverse effects ( Tolnaftate cream, Ketoconazol, Salicylic Iodine brushes , Timol brushes and others) The total of patients was conformed by 50 patients clinically and mycological diagnosed of Tinea Versicólor, 25 of them utilised salicylic iodine brushes in the lesions and the rest, Ketoconazol for 3 weeks, Bid. The results was similar, with higher efficacy on the salicylic iodine brushes (92%) , compared with an 88% of Ketoconazol cream The treatment cost was significantly less in the brushes than with the cream. It is concluded that the choice must be made on the salicylic iodine brushes compared with the Ketoconazol cream.

Resultados del tratamiento con yodo salicilico y ketoconazol en la Pitiriasis vesicolor / The results of the treatment of Tinea Versicolor utilisig salicylic iodine and Ketoconazol

El tratamiento de la Pitiriasis Versicólor depende de varios factores como la localización, el tamaño, el número de lesiones y la edad. La vía a utilizar puede ser sistémica o local;se prefiere esta última por tener menos efectos adversos (cremas de tolnaftato, ketoconazol, pinceladas de yodo salicílico, pinceladas de timol y otros).El universo de estudio estuvo integradopor 50 pacientes portadores de Pitiriasis Versicolor diagnosticados por la clínica y el exudado micológico, la mitad de los cuales usó pinceladas de yodo salicílico y la otra mitad crema de ketoconazol durante 3 semanas de forma tópica dos veces al día.El resultado fue similar, con una mayor eficacia de la pincelada de yodo salicílico (92 por ciento) sobre la crema de ketoconazol (88 por ciento).El costo por tratamiento fue significativamente menor en los tratados con pinceladas de yodo salicílico (0.50) que los tratados con crema de ketoconazol (3.80).Se concluye que debe utilizarse de elección la pincelada de yodo salicílico por ser más barata y efectiva(AU)

The treatment of Tinea Versicólor depend on various factors, such as location of the lesions, size, number and age. The way of the treatment use might be systemic or local, rather preferable is the last one, because of less adverse effects ( Tolnaftate cream, Ketoconazol, Salicylic Iodine brushes , Timol brushes and others)The total of patients was conformed by 50 patients clinically and mycological diagnosed of Tinea Versicólor, 25 of them utilised salicylic iodine brushes in the lesions and the rest, Ketoconazol for 3 weeks, Bid.The results was similar, with higher efficacy on the salicylic iodine brushes (92 percent) , compared with an 88 percent of Ketoconazol creamThe treatment cost was significantly less in the brushes than with the cream.It is concluded that the choice must be made on the salicylic iodine brushes compared with the Ketoconazol cream(AU)

Effect of hypercortisolism control on high blood pressure in Cushing's syndrome / Efecto del control del hipercortisolismo sobre la hipertensión arterial en el síndrome de Cushing

Many hypertensive patients affected by endogenous Cushing's syndrome (CS) persist with high blood pressure (HBP) despite good control of cortisol excess. We assessed the effect of preoperative ketoconazole administration and of definitive treatment of CS on arterial hypertension and analysed the factors involved in the persistence of hypertension. We assessed retrospectively 71 patients with CS and HBP (60 women, 11 men; 50 pituitary, 21 adrenal) successfully treated by surgery and/or radiotherapy; 19 of them received ketoconazole (KNZ) before surgery. After treatment, patients were divided into those with persistent high blood pressure (PHBP) and those with normal blood pressure (NBP). As possible predictive factors for PHBP we analysed age, duration and family history of HBP, pre-treatment 24 hour urinary free cortisol (24h-UFC) and body mass index (BMI). HBP normalized in 53 out of 71 patients (74.6%), regardless of the origin of Cushing's syndrome. PHBP patients were older (p=0.003), had longer duration (p=0.007) and higher systolic blood pressure before treatment (p=0.046) than NBP patients. Thirteen out of 19 patients (68.4%) treated with ketoconazole, normalized their hypertension and remained normotensive after successful surgery. Five patients became normotensive only after surgery. In conclusion: a) blood pressure levels normalized in most patients after remission of CS; b) ketoconazole was effective for the control of HBP, and seems to be a good indicator of post-surgical outcome, and c) higher age at presentation, longer duration of hypertension and higher systolic blood pressure figures before treatment negatively influence normalization of blood pressure after resolution of Cushing's syndrome.

Muchos pacientes con síndrome de Cushing (SC) permanecen hipertensos a pesar del control del exceso glucocorticoideo. Investigamos el efecto de la administración de ketoconazol (KNZ) y del tratamiento definitivo del SC sobre la hipertensión arterial (HTA), analizando su relación con diversos factores. Evaluamos 71 pacientes con SC e HTA (60 mujeres, 11 varones; 50 pituitarios, 21 adrenales) exitosamente tratados por cirugía y/o radioterapia; 19 de ellos recibieron KNZ antes de cirugía. Luego del tratamiento, fueron divididos en pacientes con HTA persistente (HTAP) y normal (HTAN). Como posibles factores predictivos de HTAP se analizaron edad, duración, historia familiar de HTA, cortisol libre urinario de 24 hs pre-tratamiento e índice de masa corporal. La HTA normalizó en 53/71 pacientes (74.6%) independientemente del origen del síndrome de Cushing. Los pacientes con HTAP fueron de mayor edad (p=0.003), con mayor duración previa (p=0.007) y valores mayores de presión arterial sistólica antes de tratamiento (p=0.046) que aquellos con HTAN. Trece de 19 pacientes (68.4 %) tratados con ketoconazol normalizaron su tensión arterial y se mantuvieron normotensos luego de cirugía exitosa. Cinco pacientes se tornaron normotensos solo después de cirugía. En conclusión: a) la HTA se normalizó en la mayoría de pacientes luego de remisión del SC, b) el ketoconazol fue efectivo para el control tensional y aparenta ser indicador de la evolución pos-quirúrgica, y c) mayor edad, duración más prolongada de la HTA y valores más altos de presión sistólica influencian negativamente la normalización de la presión arterial luego de resolución del síndrome de Cushing.

Ketoconazole therapy: an efficacious alternative to achieve eucortisolism in patients with Cushing's syndrome

El síndrome de Cushing (SC) es un trastorno grave que requiere frecuentemente tratamiento medicamentoso. Cincuenta y cuatro pacientes (44 mujeres, 10 varones) de 14-63 años de edad con SC, recibieron ketoconazol (KTZ) previo a cirugía (n=27), como complemento luego de cirugía y/o radioterapia (n=16), o como tratamiento primario (n=11). La dosis de mantenimiento fue de 600 (500 - 600) mg/día (mediana-IC95) durante 15 días a 13 años. Los signos clínicos, hepatograma y cortisol libre urinario (CLU) fueron evaluados antes y durante tratamiento con KNZ. El CLU cayó a valores normales o subnormales en 85% de los pacientes, 5 a 150 días luego de iniciar el tratamiento; aún sin normalizar, el CLU disminuyó a 12-48% de los valores pre-tratamiento en el resto de los pacientes acompañándose de mejoría de los signos clínicos. Los efectos colaterales fueron: insuficiencia adrenal (18.5%), toxicidad hepática reversible (11%), "rash" cutáneo (5.5%) e intolerancia gástrica (3.7%); en 11% de los pacientes se observó un fenómeno de "escape". Veinticuatro pacientes (44.4%) fueron tratados por períodos prolongados, de uno a trece años. Este estudio confirma que el KTZ constituye un tratamiento eficaz y generalmente bien tolerado del SC, en particular: a) como preparación para cirugía b) en casos de hipercortisolismo residual luego de cirugía o en espera de resultados de radioterapia, c) como una alternativa razonable en pacientes con SC de origen desconocido y, d) como tratamiento crónico en casos de hipercortisolismo no resuelto luego de fracaso de las terapéuticas habituales.

Cushing's syndrome (CS) is a serious condition requiring drug management in diverse clinical settings. Fifty four patients (44 females, 10 males) with CS, aged 14-63, received ketoconazole (KTZ) prior to surgery (n= 27), as complementary therapy after surgery and/or radiotherapy (n= 16), or as primary treatment (n= 11). It was given at a 600 (500 - 600) mg/day (median - CI95) maintenance dose for periods ranging from 15 days to 13 years. Clinical signs, hepatic enzymes and urinary free cortisol (UFC) were evaluated before and during KTZ treatment. UFC normalised or decreased to subnormal values in 85% of the patients, in 5 to 150 days after starting treatment; although failing to normalise, UFC decreased to 12-48% of pre-treatment values in the remaining patients. Clinical signs improved throughout. Side effects were adrenal insufficiency (18.5%), reversible hepatic toxicity (11%), allergic skin rash (5.5%) and gastric intolerance (3.7%); in 11% of patients, an "escape phenomenon" was observed. Twenty-four out of the total (44.4%) were treated for prolonged periods, from one up to 13 years. In conclusion, this study confirms that KTZ is an effective and generally well tolerated treatment for CS particularly: a) shortly before surgery, b) because of persistent hypercortisolism after surgery or awaiting the results of radiotherapy, c) as a reasonable option in patients with CS of unknown aetiology and, d) as long-term therapy in any case of unsolved hypercortisolism after failure of current treatments.

Arritmia ventricular maligna tras empleo simultáneo de terfenadina y ketoconazol

Se reportó el caso de una paciente joven que presentó arritmia ventricular maligna tras empleo simultáneo de terfenadina y ketoconazol, con el objetivo de ratificar lo contraproducente de determinadas asociaciones farmacológicas. El cuadro clínico estuvo matizado por las manifestaciones cardiovasculares y las severas alteraciones electrocardiográficas. Se empleó pidolato magnésico por vía oral y monitorización electrocardiográfica continua. No fueron necesarias otras medidas para el tratamiento de la arritmia. La paciente se recuperó en un tiempo relativamente breve de estrecha observación en la Unidad de Cuidados Intensivos, fue dada de alta con una evolución satisfactoria.

The case of a young patient who presented malignant ventricular arrhytmia after having used terfenadine and ketoconazole simultenously was reported aimed at ratifying that certain pharmacological associations may not produce the desired effect. The clinical picture was characterized by cardiovascular manifestations and severe electrocardiographic alterations. Magnesic pidolate was orally administered and the continual electrocardiographic monotiring was used. No other measures were necessary for the treatment of arrhytmia. The patient recovered in a relatively short time of close observation at the Intensive Care Unit. She was discharged after a satisfactory evolution.

The epidemiology of pseudallescheriasis complicating transplantation: Nosocomial and community-acquired infection.

The epidemiology of two cases of pseudallescheriasis in organ transplant patients are described and the disease in that population is reviewed. Disseminated hospital-acquired infection occurred in a liver transplant recipient and was fatal despite therapy with miconazole. A heart transplant recipient developed localized disease following soil contamination of soft tissue trauma which was cured with surgical resection and miconazole therapy. Itraconazole showed in vitro activity against Pseudallescheria boydii and should be evaluated in pseudallescheriasis. P. boydii infections are important complications of transplantation and should be considered in the differential diagnosis of community-acquired as well as nosocomial fungal infections in this population.

In Vitro and in Vivo Activity of Antifungal Agents in Combination with Fleroxacin, a New Quinolone.

The in vitro and in vivo Interaction of fleroxacin with amphotericin B (Amph B), flucytosine (5-FC) and azoles against Candida albicans strains was tested. In vitro the interaction between fleroxacin and various antifungals was not dependent on the incubation time. Fleroxacin neither enhances nor antagonizes the in vitro activity of Amph B at high concentration (50-100 µg/ml). Fleroxacin has a synergistic effect with ketoconazole (KETO), but this is not observed with itraconazole (ITRA) or fluconazole (FLU). In no instance antagonism was observed. The activity of 5-FC was antagonized by fleroxacin being generally reduced by 2-4 dilution steps. In murine candidosis the efficacies of all antifungal drugs were not influenced by addition of 100 mg/kg fleroxacin. Therefore, the effects seen in in vitro tests are most probably not relevant for the clinical use of a combination of fleroxacin with antifungal drugs.