Mixed bacterial-fungal infection following total hip arthroplasty: A case report / 中华创伤杂志(英文版)

Prosthetic infection is one of the severe postoperative complications of arthroplasty. Mixed bacterial-fungal prosthetic infection is rare but can be disastrous. This case was a 76-year-old female suffered from prosthetic infection following total hip replacement due to femoral neck fracture and underwent multiple debridements. The culture of periprosthetic tissue was bacteriologically sterile following the first debridement, while the Staphylococcus hominis was identified in the second debridement in the previous hospitalization where fungal infection had not been considered. Thus the pathogen spectrum of anti-infection therapy failed to contain fungus. Ultimately, the culture result of our sampled periprosthetic tissue during the third debridement was Candida albicans without bacterium in our hospital. The fungal prosthetic infection was successfully treated by a two-stage revision with antifungal drugs. Accurate diagnosis and standardized treatment is the key to the therapy of infection after hip arthroplasty, especially for mixed bacterial-fungal prosthetic infection.

Identificación fúngica en pacientes quemados. Un estudio retrospectivo y factores de riesgo / Fungal identification in burn patients. A retrospective study and risk factors

Resumen Se realizó un estudio retrospectivo de las infecciones fúngicas atendidas en un centro de quemados de alta complejidad situado en Buenos Aires, entre 2011 y 2014, mediante el análisis de las histo rias clínicas (n = 36). Las edades de los pacientes estuvieron entre 18 y 87 años, y 23 (63.9%) fueron mujeres. La extensión de la superficie corporal afectada más prevalente varió entre 30 y 50% (p = 0.03), y entre 71% y 100% en pacientes de menor edad, relacionándose con intentos de femicidio. En el 69.4% la profundidad de la quemadura fue grado 4, y en el 50% de los casos se observaron lesiones por inhalación, con una alta mortali dad (p = 0.04). El Candida score resultó de 3 en el 77.7% de los casos. Se usaron vías centrales y ventilación mecánica. Todos los pacientes recibieron tratamiento antibiótico y en 33 (91.7%) antifúngicos. La escisión qui rúrgica de la quemadura se practicó en 33 (91.7%) y los autoinjertos de piel en 29 (80.6%). La infección fúngica se desarrolló en una media de 21.4 días del ingreso en UCI. Se estudiaron 52 muestras de levaduras que se aislaron de urocultivo (42.3%), hemocultivo (26.9%), biopsia cutánea (9.6%), punta de catéter (15.4%) y aspirado traqueal (5.8%). Por cultivo microbiológico y métodos moleculares se identificaron a Candida albicans (53.8%), C. tropicalis (23.1%), C. parapsilosis sensu stricto (13.5%), C. krusei (5.8%), C. glabrata (1.9%) y C. dubliniensis (1.9%). Las infecciones fúngicas representan severas complicaciones en quemados con factores de riesgo.

Abstract A retrospective analysis of fungal infections was carried out in a health-care burn center between 2011 and 2014 using the patients' medical records (n = 36). Patients ranged from 18 to 87 years of age, with 23 (63.9%) being women. The most prevalent widespread total body surface area affected (TBSA) was 30-50% (p = 0.03), and 71-100% in younger patients, mainly associated with femicide. Fourth degree burns were revealed in 69.4% of the patients while in 50%, inhalation injuries were observed to represent a higher mortality rate (p = 0.04). The Candida score was 3 in 77.7% of cases respectively. Central venous catheter and mechanical ventilation were used. All patients received antibiotic treatment and 91.7% antifungal treatment. Surgical excision of the burn was performed in 33 (91.7%) patients, and skin autografting in 29 (80.6%). The median of the fungal infection devel oped was 21.4 days after admission to the ICU. The specimens analyzed involved 52 yeast samples isolated from different cultures: urine (42.3%), blood (26.9%), skin biopsy (9.6%), catheter tip (15.4%) and tracheal aspirate (5.8%). The use of microbiological culture and molecular methods allowed for the identification of Candida albicans (53.8%), C. tropicalis (23.1%), C. parapsilosis sensu stricto (13.5%), C. krusei (5.8%), C. glabrata (1.9%) and C. dubliniensis (1.9%). Fungal infections observed in skin burns lead to severe complications in at-risk patients.

Efficacy of Posaconazole for Primary Prophylaxis in the Induction Therapy of Childhood Acute Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of posaconazole in the primary prevention of invasive fungal disease (IFD) in the induction therapy of childhood acute lymphoblastic leukemia (ALL).@*METHODS@#From August 2018 to November 2020, 144 pediatric patients with ALL treated in Department of Pediatrics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University were selected, 88 cases received fluconazole as IFD prophylaxis (fluconazole prophylaxis group), 56 cases received posaconazole as IFD prophylaxis (posaconazole prophylaxis group). The incidence of IFD and treatment-related adverse reactions between the two groups were compared, and the safety of posaconazole was evaluated.@*RESULTS@#The incidence of IFD in the fluconazole prophylaxis group was 20.4% (18/88), and in the posaconazole prophylaxis group was 7.1% (4/56). The incidence of IFD between the two groups was statistically significant different(P=0.030). There was no serious adverse reactions in the two groups. The incidence of mild adverse reactions in the posaconazole prophylaxis group (23.2%) was lower than that in the fluconazole prophylaxis group(39.8%), and the difference was statistically significant (P=0.039). There were 12 cases died in the fluconazole prophylaxis group and 4 in the posaconazole prophylaxis group, while no significant difference in the overall survival rate between the two groups (P=0.281).@*CONCLUSION@#The effect of posaconazole in the primary prophylaxis of IFD is better and incidence of adverse reactions is lower than fluconazole. Posaconazole can be tolerated, and expected to become the first-line primary prophylaxis drug for IFD during the induction remission therapy of childhood ALL.

Infection in Children with Acute Myeloid Leukemia in the Intensive Chemotherapy Period / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics of infection in children with acute myeloid leukemia (AML) after high intensive chemotherapy， so as to provide reference for prevention and control of infection.@*METHODS@#56 children diagnosed as acute myeloid leukemia in our hospital from January 2016 to August 2019 were enrolled and retrospectively analyzed, the infection rate, pathogens of disease and common location of infection during the induction and consolidation period were analyzed.@*RESULTS@#The total infection rate of the patients was 93.4%－96.4%, the average of serious infection rate was 16.0%(11.3%－19.6%), and the infection related mortality was 10.7%. Fever of unknown cause was the main reason of infection, while blood flow infections were the most common in severe infection, which were mainly caused by Gramnegative bacteria. The rate of fungal infection was 35.7% during chemotherapy.@*CONCLUSION@#Children with AML shows a high incidence of infection in each stage of chemotherapy. The serious illness caused by blood flow infection and take antifungal drugs to reduce the occurrence of fungal infection in AML patients should be paid attention.

Infección rino-sinusal por Exserohilum rostratum en un niño con leucemia mieloide aguda / Sinus infection caused by Exserohilum rostratum in a pediatric patient with acute myeloid leukemia

Resumen Los episodios de neutropenia febril son cuadros graves, que requieren un estudio etiológico exhaustivo y un inicio rápido de antimicrobianos. Dentro de los posibles microorganismos causales se encuentran los de origen fúngico, los que, dependiendo de su grado de invasión tisular, pueden llegar a presentar una alta mortalidad. Presentamos el caso de un niño con una leucemia mieloide aguda, que tras su quimioterapia de inducción, presentó un episodio de neutropenia febril, con una infección rino-sinusal por Exserohilum rostratum, hongo filamentoso que raramente se asocia a cuadros patológicos. Se inició rápidamente terapia antifúngica, lo cual, asociado a un aseo quirúrgico precoz, lograron una respuesta clínica favorable, sin complicaciones. Luego del seguimiento, y tras recibir profilaxis secundaria durante los episodios de neutropenia, no ha vuelto a presentar nuevas lesiones ni compromiso rino-sinusal.

Abstract The episodes of febrile neutropenia are severe cases that require an exhaustive etiological study and a quick start of antimicrobial agents. Within the possible microorganisms, fungal origins are also found, and depending on its tissue invasion, they can reach a high mortality rate. A case of a pediatric patient who suffered from acute myeloid leukemia is reported, and after his induction chemotherapy, the patient showed an episode of febrile neutropenia, which matches a rhinosinusal infection caused by Exserohilum rostratum, a filamentous fungi that is uncommonly associated with pathological cases. An antifungal therapy and an early surgical treatment were started, which lead to a positive response, without complications to the patient. After the monitoring and receiving secondary prophylaxis during the episodes of neutropenia, the patient hasn't presented new injuries nor rhinosinusal damage.

Histoplasmosis: epidemiología, diagnóstico y terapéutica / Histoplasmosis: epidemiology, diagnosis and therapy

La histoplasmosis es una enfermedad granulomatosa, producida por hongos dimorfos del género Histoplasma. Se observa en casi todos los países del mundo. En América Latina, en Venezuela, Colombia, Brasil, Argentina, Ecuador, Perú, Paraguay y Uruguay, entre otros. Datos epidemiológicos recienteshanmostrado un aumento de histoplasmosis en Venezuela y otros países.Los clínicos no están conscientes de su importancia en nuestro medio. Objetivo: Dar a conocer la situación actual de esta enfermedad en el Area Metropolitana de Caracas y en otras áreas endémicas, con la intención de crear la inquietud de investigar su incidencia y otras características relevantes en el resto del país. Métodos: Se analizaron las características de todos los pacientes con diagnóstico de certeza de histoplasmosis registrados y realizados por la Sección de Micología Médica ­Dr. Dante Borelli‖ del Instituto de Medicina Tropical de la UCV, referidos de los diferentes hospitales del Distrito Capital y otros estados del país, con énfasis en los datos epidemiológicos, manifestaciones clínicas, diagnóstico, tratamiento y evolución entre 1994 y 2012. Resultados: se encontraron 553 pacientes. La mayoría estaban entre los 20 y 49 años, relacionado con un alto número de pacientes con VIH/SIDA. Hubo más casos en hombres que en mujeres en todos los grupos etarios, menos en los pacientes mayores de 60 años, posiblemente debido a la disminución de los estrógenos, que son protectores en la mujer. Casi todos los pacientes con VIH/SIDA mostraron la forma diseminada, solo uno presentó una forma pulmonar. De los pacientes VIH negativos, 54,62% presentaron infección diseminada y 44,47%, formas pulmonares. 93 de los de enfermedad diseminada tenían estados de inmunocompromiso. El examen directo fue el método más fácil y eficaz para diagnosticar la histoplasmosis. La anfotericina B (AMB) fue el tratamiento para la histoplasmosis en pacientes con o sin SIDA, que requirieron hospitalización, seguido por itraconazol (ITC). Esta droga se utilizó en pacientes que no se encontraban severamente enfermos o con afectación del sistema nervioso central. Conclusiones: histoplasmosis se encuentra en aumento en nuestro país. Se observa con más frecuencia en pacientes con SIDA, inmunosuprimidos y pacientes que han recibido un inóculo abundante. El examen directo con coloraciones especiales es el método de mayor rendimiento para el diagnóstico. Este debe ser realizado por personal con experiencia.Es conveniente utilizar diferentes técnicas para aumentar la probabilidad de obtener un diagnóstico correcto. AMB e ITC son los tratamientos de elección. Los médicos deben estar alertas de los signos y síntomas, correlacionándolos con los antecedentes epidemiológicos, para evitar el retraso del diagnóstico y mejorar la evolución de los pacientes.

Histoplasmosis is a granulomatous disease, caused by dimorphic fungi from the genus Histoplasma. It is described worldwide.In Latin America, Venezuela, Colombia, Brasil, Argentina, Ecuador, Perú, Paraguay and Uruguay among others are affected. Recent epidemiological data have shown an increase of histoplasmosis in Venezuela and other countries. Clinicians are nor aware of the importance of this mycosis. Objective: analyze the current situation of this disease in the Caracas Metropolitan Area and other endemic areas, with intention to create awareness of its incidence and other relevant characteristics in our country. Methods: characteristics of the patients with diagnosis of histoplasmosis, performed and registered at the Sección de Micología Médica ­Dr. Dante Borelli‖, Instituto de Medicina Tropical, UCV, referred from different hospitals at Distrito Capital and other states of the country, with emphasis on epidemiological data, clinical manifestations, diagnosis, treatment and outcome, between 1994 and 2012 are analized. Results: 553 patients were found. Most of them were between 20 and 49 years old, possibly due to a high number of HIV/AIDS patients. There were more male than female patients in all age groups, except in 60 years and older, possibly due to the lack of estrogenic hormones, which protect women from infection. All HIV/AIDS patients but one, presented with a disseminated form of the disease, and one, a pulmonary form. Of the HIV negative patients, 54,62% showed disseminated infection and 44,47%, pulmonary presentation. 93 of the disseminated infection patients had immunocompromising conditions. Direct examination was the easiest and most efficacious diagnostic method. Amphotericin B (AMB) was the drug of choice for the treatment of hospitalized patients, followed by Itraconazole (ITC). This was the preferred treatment for mild to moderate disease or non CNS infection. Conclusions: Histoplasmosis is rising in our country. It is more frequent in HIV/AIDS patients and immune suppression. It is also seen in patients who have inhaled a large inoculum. Direct examination with special stains is the diagnostic method with better results. It must be performed by experienced personnel in fungal diagnosis. The use of different techniques is recommended to improve early and correct diagnosis. AMB and ITC are drugs of choice for the treatment of histoplasmosis. Clinicians should be aware of suggestive symptoms and signs, correlating them with epidemiological data, to avoid diagnostic delay and improve the outcome of the patients.

Drug susceptibility in emerging fungal infections: tests with fluconazole, itraconazole, and amphotericin B

Abstract: The number of new cases of emerging fungal infections has increased considerably in recent years, mainly due to the large number of immunocompromised individuals. The objective of this study was to evaluate the susceptibility of emerging fungi to fluconazole, itraconazole and amphotericin B by disk diffusion method. In 2015, 82 emerging fungi were evaluated in IPB-LACEN/RS and 13 (15.8%) were resistant: 10/52 were from superficial mycoses and 3/30 from systemic mycoses. The data from the study point to the need for permanent vigilance regarding the careful evaluation in the prescription and clinical and laboratory follow-up of patients affected by fungal infections.

Efectos adversos de anfotericina B desoxicolato en neonatos del Hospital Nacional de Itauguá / Adverse effects of amphotericin B deoxycholate in neonates of the National Hospital of Itauguá

Introducción En las últimas décadas, el agente de elección para el tratamiento de la mayoría de las micosis sistémicas ha sido la anfotericina B que, a pesar de los efectos tóxicos, sigue teniendo un papel importante en el tratamiento de las infecciones micóticas. Objetivo Determinar los efectos adversos asociados al empleo de anfotericina B en neonatos del Servicio de Neonatología del Hospital Nacional de Itauguá, en el periodo 2013 - 2015. Materiales y métodos Estudio de serie de casos, retrospectivo, de recién nacidos con tratamiento con anfotericina B. Resultados: Entre 28 recién nacidos tratados con anfotericina B, hubo mayor prevalencia en el sexo masculino. Con respecto a la edad más de la mitad de los recién nacidos fueron pre-término en el grupo estudiado. Hubo predominio de bajo peso al nacer (32,14%). Los factores de riesgo arrojaron que 53,5% no contaba con antecedentes de sepsis. La edad media de inicio de anfotericina fue 19±9 días, más de la mitad de los neonatos utilizó dosis progresiva de 0,5 mg/kp/día a 1 mg/kp/día, en 24 hs.El 96,4% recibió infusión de anfotericina B de 4 horas, 1 caso requirió 6 horas. Entre los efectos secundarios, 35,7% de los pacientes presentó anemia, el disturbio hidroelectrolítico más frecuente fue la hipokalemia, entre los signos se destacaron la taquicardia e hipotensión. Conclusiones Los efectos secundarios más llamativos encontrados durante el tratamiento con anfotericina B fueron la anemia, alteraciones de Sodio y Potasio

Introduction In recent decades, the agent of choice for the treatment of most systemic mycoses has been amphotericin B which, despite the toxic effects, continues to play an important role in the treatment of fungal infections. Objective To determine the adverse effects associated with the use of amphotericin B in neonates of the Neonatology Service of the National Hospital of Itauguá, in the period 2013 - 2015. Materials and methods: retrospective case series study of newborns treated with amphotericin B. Results Among 28 newborns treated with amphotericin B, there was a higher prevalence in males. With regard to age, more than half of the newborns were pre-term in the group studied. There was a predominance of low birth weight (32.14%). The risk factors showed that 53.5% did not have a history of sepsis. The mean age of onset of amphotericin was 19 ± 9 days, more than half of the infants used progressive dose from 0.5 mg / kp / day to 1 mg / kp / day, in 24 hours. 96.4% received infusion of amphotericin B for 4 hours, 1 case required 6 hours. Among the side effects, 35.7% of the patients presented anemia, the most frequent water and electrolyte disturbance was hypokalemia, among the signs were tachycardia and hypotension. Conclusions The most striking side effects found during treatment with amphotericin B were anemia, Sodium and Potassium alterations.

Non-viral microbial keratitis in adults: clinical and laboratory aspects

Abstract This study compares patients with and without non-viral microbial keratitis in relation to sociodemographic variables, clinical aspects, and involved causative agent. Clinical aspects, etiology and therapeutic procedures were assessed in patients with and without keratitis that were diagnosed in an Eye Care Center in Campo Grande, MS, Brazil. Patients were divided into two groups: (a) cases: 64 patients with non-viral microbial keratitis diagnosed at biomicroscopy; and (b) controls: 47 patients with other eye disorders that were not keratitis. Labor activity related to agriculture, cattle raising, and contact lens use were all linked to keratitis occurrence (p < 0.005). In patients with keratitis, the most common symptoms were pain and photophobia, and the most frequently used medicines were fourth-generation fluoroquinolones (34.4%), amphotericin B (31.3%), and natamycin (28.1%). Microbial keratitis evolved to corneal perforation in 15.6% of cases; transplant was indicated in 10.9% of cases. Regarding the etiology of this condition, 23 (42.2%) keratitis cases were caused by bacteria (Pseudomonas aeruginosa, 12.5%), 17 (39.1%) by fungi (Fusarium spp., 14.1% and Aspergillus spp., 4.7%), and 4 (6.3%) by Acanthamoeba. Patients with keratitis present with a poorer prognosis. Rapid identification of the etiologic agent is indispensable and depends on appropriate ophthalmological collection and microbiological techniques.

Infección pulmonar por Arthrographis kalrae en un paciente con enfermedad granulomatosa crónica / Pulmonary infection by Arthrographis kalrae in patient with chronic granulomatous disease

Antecedentes: Arthrographis kalrae es un hongo hialino de crecimiento lento que, en su desarrollo, forma artroconidios. Es un patógeno oportunista que causa infecciones en personas inmunocomprometidas e inmunocompetentes, y ha sido aislado muy raramente en muestras clínicas de seres humanos. Caso clínico: Se describe el caso de un paciente con inmunodeficiencia primaria y afectación pulmonar con evolución tórpida. Presentó compromiso de ambos pulmones a pesar del tratamiento antibiótico y antifúngico instaurado. Durante su seguimiento, se realizaron múltiples biopsias pulmonares y se aisló A. kalrae en el cultivo de tejido pulmonar. Recibió tratamiento con posaconazol, con buena respuesta y remisión de las lesiones. Conclusión: Este es el primer caso reportado de infección pulmonar por A. kalrae en un paciente pediátrico con enfermedad granulomatosa crónica en Argentina.

Background: Arthrographis kalrae is a hyaline fungus that grows forming arthroconidia. It is an opportunistic pathogen that causes infections in immunocompromised as in immunocompetent people and has been rarely isolated from human clinical samples. Case report: We describe the case of a male child with primary immunodeficiency who initially presented unilateral pneumonia and progressed to bilateral involvement despite antibiotic, antifungal treatment. A. kalrae was diagnosed by pulmonary biopsy. He received posaconazole with resolution of disease. Conclusions: This is the first case of A. kalrae pulmonary infection in a pediatric patient with chronic granulomatous disease in Argentina.

Is the emergence of fungal resistance to medical triazoles related to their use in the agroecosystems? A mini review

Abstract Triazole fungicides are used broadly for the control of infectious diseases of both humans and plants. The surge in resistance to triazoles among pathogenic populations is an emergent issue both in agriculture and medicine. The non-rational use of fungicides with site-specific modes of action, such as the triazoles, may increase the risk of antifungal resistance development. In the medical field, the surge of resistant fungal isolates has been related to the intensive and recurrent therapeutic use of a limited number of triazoles for the treatment and prophylaxis of many mycoses. Similarities in the mode of action of triazole fungicides used in these two fields may lead to cross-resistance, thus expanding the spectrum of resistance to multiple fungicides and contributing to the perpetuation of resistant strains in the environment. The emergence of fungicide-resistant isolates of human pathogens has been related to the exposure to fungicides used in agroecosystems. Examples include species of cosmopolitan occurrence, such as Fusarium and Aspergillus, which cause diseases in both plants and humans. This review summarizes the information about the most important triazole fungicides that are largely used in human clinical therapy and agriculture. We aim to discuss the issues related to fungicide resistance and the recommended strategies for preventing the emergence of triazole-resistant fungal populations capable of spreading across environments.

Eficacia y seguridad de la caspofungina en pediatría: revisión sistemática y metaanálisis / Efficacy and safety of caspofungin in children: systematic review and meta-analysis

Las infecciones fúngicas invasivas son una importante causa de morbimortalidad en pediatría. La caspofungina es una equinocandina utilizada como alternativa en la prevención y/o tratamiento de ciertas infecciones fúngicas invasivas en niños, aunque con poca evidencia sobre su eficacia y seguridad en comparación con el tratamiento habitual. Objetivos. Evaluar la eficacia y seguridad de la caspofungina comparada con otros antifúngicos en la prevención y/o tratamiento de infecciones fúngicas invasivas en pediatría. Material y métodos. La estrategia de búsqueda inicial tuvo como objetivo identificar estudios controlados aleatorizados de aceptable calidad metodológica (escala de Jadad > 3) mediante la palabra clave "caspofungin" realizados en pacientes de entre los 0 y los 18 años. Resultados. Solo 3 publicaciones cumplieron los criterios de inclusión. De ellas, 2 fueron en población pediátrica y una en neonatal. No se documentó una mayor incidencia de efectos adversos para la caspofungina y su eficacia no se diferenció de otros antifúngicos (RR típico 1,47; IC 95%: 0,78-2,79). Conclusiones. Esta revisión sistemática sugiere que la caspofungina podría considerarse como una alternativa para su indicación en pediatría en la prevención y tratamiento de las infecciones fúngicas invasivas. Sin embargo, dado el pequeño número de publicaciones existentes, se requieren más estudios para alcanzar conclusiones definitivas.

Invasive fungal infections are a significant cause of morbidity and mortality in children. Caspofungin is an echinocandin used as an alternative treatment in the prevention and/or treatment of certain invasive fungal infections in children, although compared to the standard treatment there is little evidence on its efficacy and safety. Objectives. To evaluate the efficacy and safety of caspofungin compared with other antifungal drugs for the prevention and/or treatment of invasive fungal infections in children. Material and methods. The objective of the initial search strategy was to identify randomized controlled studies of acceptable methodological quality (Jadad scale >3), through the key word "caspofungin", conducted in patients with an age range from 0 to 18 years old. Results. Only 3 publications met the inclusion criteria. Two of them were studies conducted in children and one in newborn infants. A higher incidence of adverse events was not documented for caspofungin and its efficacy was not different from that of other antifungal drugs (typical RR 1.47; CI 95%: 0.78-2.79). Conclusions. This systematic review suggests that caspofungin could be considered as an alternative drug in children for the prevention and treatment of invasive fungal infections. However, given the small number of existing publications, more studies are required to reach definite conclusions.

Posaconazol (Noxafil®) suspensión y comprimidos no deben utilizarse indistintamente sin realizar un ajuste de dosis / Posaconazole (Noxafil®) suspension and tablets should not be used interchangeably without making a dose adjustment

El posaconazol es un antifúngico de amplio espectro de la familia de los triazólicos que se utiliza en el tratamiento y profilaxis de infecciones micóticas invasivas en pacientes de 13 años de edad o mayores, en las cuales otros tratamientos no han sido eficaces o tolerados. En junio de 2016 la Agencia Europea de Medicamentos y la Agencia Española de Medicamentos y Productos Sanitarios emitieron un alerta donde advierten que debido a diferencias en la frecuencia de dosificación, interacción con los alimentos y en los niveles plasmáticos alcanzados por el medicamento, los comprimidos y la suspensión de posaconazol no son intercambiables. (AU)

Posaconazole is a broad-spectrum triazole family antifungal used in the treatment and prophylaxis of invasive fungal infections in patients 13 years of age or older, in which other treatments have not been effective or tolerated. In June 2016 the European Medicines Agency and the Spanish Agency for Medicines and Health Products issued a warning alerting that because of differences in the frequency of dosing, interactions with food and plasma levels achieved by the drug, tablets and posaconazole suspension are not interchangeable. (AU)

Macelignan inhibits bee pathogenic fungi Ascophaera apis growth through HOG1 pathway

Ascosphaera apis is a bee pathogen that causes bee larvae infection disease, to which treatment is not yet well investigated. The aim of this study was to investigate antifungal susceptibility in vitro against A. apis and to identify a new antifungal agent for this pathogen through minimal inhibitory concentration (MIC) assay and western blot analysis. Macelignan had 1.56 and 3.125 μg/mL MIC against A. apis after 24 and 48 h, respectively, exhibiting the strongest growth inhibition against A. apis among the tested compounds (corosolic acid, dehydrocostus lactone, loganic acid, tracheloside, fangchinoline and emodin-8-O-β-D-glucopyranoside). Furthermore, macelignan showed a narrow-ranged spectrum against various fungal strains without any mammalian cell cytotoxicity. In spite of miconazole having powerful broad-ranged anti-fungal activity including A. apis, it demonstrated strong cytotoxicity. Therefore, even if macelignan alone was effective as an antifungal agent to treat A. apis, combined treatment with miconazole was more useful to overcome toxicity, drug resistance occurrence and cost effectiveness. Finally, HOG1 was revealed as a target molecule of macelignan in the anti-A. apis activity by inhibiting phosphorylation using S. cerevisiae as a model system. Based on our results, macelignan, a food-grade antimicrobial compound, would be an effective antifungal agent against A. apis infection in bees.

Formas lipídicas de anfotericina / Lipid formulations of amphotericin

Amphotericin B deoxycholate use has increased during the past years in parallel with the increase in the number of immunosuppressed patients suffering invasive fungal infections. This drug is associated with a high rate of side effects, especially renal toxicity. Lipid formulations (liposomal, lipid complex, colloidal suspension and the Indian liposomal formulation) have been developed, which share the same antifungal spectrum but differ in efficacy and toxicity. A review of amphotericin lipid formulations is presented, focusing on differences in efficacy and, especially renal toxicity. The main problem for use of these formulations in Latin America is their highcost.

Dado el aumento en el número de pacientes inmunosuprimidos en los últimos años, el uso de anfotericina B desoxicolato también se incrementó debido a una mayor incidencia de las infecciones fúngicas invasoras en esta población. Este medicamento tiene una alta frecuencia de efectos adversos, especialmente nefrotoxicidad. Se han desarrollado modificaciones de la presentación de anfotericina B con el desarrollo de formas lipídicas (liposomal, complejo lipídico, suspensión coloidal y fórmula liposomal procedente de la India) que tienen el mismo espectro y con variaciones en su efectividad y toxicidad. Se presenta una revisión de las formas lipídicas de anfotericina, sus diferencias en efectividad y, especialmente, nefrotoxicidad. El principal problema para su implementación en América Latina es el alto costo de estas presentaciones.

Evaluation of Efficacy, Safety and Tolerability of a Combination of Clobetasol, Neomycin and Miconazole Versus Betamethasone, Clotrimazole and Neomycin Versus Betamethasone, Gentamycin and Miconazole in Subjects with Eczematous Disorders Associated with underlying Tinea or Yeast Infections.

Lobate GM Neo, 15 mg is a triple drug combination of a steroid clobetasol with anti-fungal miconazole and antibacterial neomycin in treatment of Eczematous disorders associated with underlying Tinea or Yeast Infections. Aims and Objectives: The study was designed to evaluate the efficacy, safety and tolerability of a combinations of clobetasol, neomycin and miconazole (Group A) versus betamethasone, clotrimazole, neomycin (Group B) versus betamethasone, gentamicin, miconazole (Group C) in subjects with any type of eczematous disorder associated with underlying tinea or yeast infection. Materials and Methods: This was an open label, parallel group, randomized comparative study. The primary endpoint analyzed was improvement in clinical score from baseline at the end of day 7 and other primary endpoint like hyperpigmentation were analyzed by the visual analogue scale of 1 to 10 at the end of day 7. Results: Thirty-six subjects were randomized to three groups. The clinical score showed a significant reduction from baseline at the end of day 7 in all the groups, i.e. 82.9%, 81.3% and 85.6% in Group A, B and C respectively. However, the difference between the groups were not statistically significant. Mean hyper pigmentation score showed significant decrease of 82.9% in Group A, 81.6% in Group B and 92.2% in Group C from baseline at the end of day 7. Conclusion: The triple combination of antifungal, antibacterial and potent steroid was found to be efficacious, safe and tolerable in reducing signs and symptoms (scaling, inflammation, burning and itching) of eczematous disorder associated with underlying tinea/yeast infection.

Febrile neutropenia in the tropics: A description of clinical and microbiological findings and their impact on inappropriate therapy currently used at an oncological reference center in Colombia / Neutropenia febril en el trópico: una descripción de los hallazgos clínicos y microbiológicos y el impacto de la terapia inapropiada que utilizan en un centro de referencia oncológica en Colombia

Introduction. Febrile neutropenia is a common complication of chemotherapy treatment of malignant hematological diseases. However, there is insufficient information regarding the infectious complications of febrile neutropenia in our country. Objective. We will evaluate the microbial characteristics of bacterial and fungal isolates and the clinical outcome of patients with febrile neutropenia who received medical attention at an oncological reference center in Colombia. Materials and methods. A prospective case series included patients with histologically confirmed oncological disease, who were admitted because of febrile neutropenia or presented with febrile neutropenia during hospitalization. Patients with benign hematological diseases were excluded. Demographic, microbiological, and clinical features as well as treatment and outcome information from patients with febrile neutropenia were obtained. We performed univariate and multivariate analyses, with mortality defined as the outcome. Results. One hundred and thirty episodes of febrile neutropenia were identified in 104 patients. The mean patient age was 19, and 53% of the patients were male. Approximately 86% of the episodes occurred in patients with hematological disorders. An infectious site was identified in 65% of patients; 41% and 24% of the febrile neutropenia pateints´ episodes exhibited a localized infectious focus and developed bloodstream infections, respectively. The majority of infections were found in blood, urine, gastrointestinal tract, and soft tissue. Distribution analysis of microbiological isolates revealed 46.4% Gram-negative bacilli, 38.4% Gram-positive cocci, 8% fungi, and 7.1% parasites; there was a 7.7% mortality rate. Appropriate empirical antimicrobial therapy was a protection-related factor in multivariate analyses (OR= 0.17; 0.034 - 0.9 95% CI; p= 0.037). Conclusions. The mortality rate was relatively low and comparable to the rate reported by developed countries. Inappropriate empirical antimicrobial therapy was the main factor associated with mortality.

Introducción. La neutropenia febril es una complicación frecuente de la quimioterapia para las neoplasias hematológicas. Se dispone de escasa información de sus complicaciones infecciosas en nuestro medio. Objetivo. Evaluar las características clínicas y microbiológicas de pacientes con neutropenia febril, así como su resultado clínico en una institución de referencia oncológica en Colombia. Materiales y métodos. Se conformó prospectivamente una serie de casos con pacientes con enfermedad oncológica confirmada, que consultaron o presentaron neutropenia febril durante la hospitalización. Se excluyeron aquellos con enfermedad hematológica benigna. Se recolectaron datos sobre variables demográficas, microbiológicas, clínicas, de tratamiento y de resultado de los pacientes. Se llevaron a cabo un análisis univariado y uno multivariado, con la mortalidad como resultado. Resultados. Se identificaron 130 episodios de neutropenia febril en 104 pacientes, con una edad media de 19 años y 53 % masculinos. El 86 % de los episodios ocurrieron en pacientes con alteraciones hematológicas. Se demostró infección en 65 % de los casos: 41 % con un foco infeccioso localizado y 27,7 % con bacteriemia. Los principales focos infecciosos se localizaron en el torrente sanguíneo, el aparato urinario, el sistema gastrointestinal, la piel y los tejidos blandos. De los aislamientos microbiológicos, 46,4 % fueron bacilos Gram negativos, 38,4 %, cocos Gram positivos, 9 %, hongos y, 7,1%, parásitos. La mortalidad global fue de 7,7 %. En el análisis multivariado la utilización de un tratamiento empírico apropiado se correlacionó con una menor mortalidad, de forma independiente (OR=0,17; IC 95% 0,034-0,9; p=0,037). Conclusiones. La tasa de mortalidad fue relativamente baja y fue comparable con lo reportado en países desarrollados. El tratamiento antimicrobiano inapropiado fue el principal factor asociado con mortalidad.

Posaconazole Treatment in Korea: Single-Center Experience Over 5 Years

PURPOSE: Posaconazole is a second-generation triazole with a broad spectrum. However, there is a lack of data to support a significant role for posaconazole in the treatment of invasive fungal infection (IFI), especially in Korea. Until recently, posaconazole was available only through the Korean Orphan Drug Center. This study was designed to review the use of posaconazole at a single-center in Korea. MATERIALS AND METHODS: Data from patients who received posaconazole treatment at Catholic Blood and Marrow Transplantation Center were retrospectively reviewed between January 2007 and September 2012. RESULTS: A total of 11 cases (3 males and 8 females, median age 52 years) received posaconazole. Five patients were given the drug for mucormycosis, two for invasive aspergillosis, and four for unspecified IFI for which galactomannan (GM) assays were negative. The treatment duration ranged from 4-250 days. Three patients received posaconazole for management refractory IFI, two for intolerance of previous antifungal therapy, and six for long-term maintenance treatment. The overall successful response rate to posaconazole was 55% (six of eleven patients). Five of eleven patients died during the study period. However, only one death was attributed to the progression of IFI. None of the patients discontinued posaconazole therapy due to adverse events. CONCLUSION: Posaconazole is an attractive oral antifungal agent for salvage treatment of IFI, particularly upon diagnosis of mucormycosis or in cases in which mucormycosis cannot be ruled out due to a negative GM.

Fungal infections of the oral mucosa.

Fungal infections in humans occur as a result of defects in the immune system. An increasing emergence in oral Candidal and non-Candidal fungal infections is evident in the past decade owing to the rise in the immunodeficient and immunocompromised population globally. Oral Candidal infection usually involves a compromised host and the compromise may be local or systemic. Local compromising factors include decreased salivation, poor oral hygiene, wearing dentures among others while systemic factors include diabetes mellitus, nutritional deficiency, HIV infection/AIDS and others. Oral candidiasis is generally a localized infection and rarely appears as a systemic fungal disease whereas oral non-Candidal fungal infections are usually signs of disseminated disease. Some of the non-Candidal fungi that were once considered exotic and geographically restricted are now seen worldwide, beyond their natural habitat, probably attributed to globalization and travels. Currently infections from these fungi are more prevalent than before and they may present either as primary oral lesions or as oral manifestations of systemic mycoses. This review discusses the various predisposing factors, clinical presentations, clinical differential diagnosis, diagnosis and management of oral candidiasis, as well as briefly highlights upon a few of the more exotic non-Candidal fungi that infect the oral mucosa.