Renal fungus balls in neonates and very young infants treated with local amphotericin B deoxycholate: Two case reports and review of the literature / Anfotericina B desoxicolato en el neonato y en el lactante pequeño con bolas fúngicas en el riñón: presentación de 2 casos y revisión de la literatura

Introduction: Fungal urinary tract infections predominantly affect the critically ill premature infant and those with urogenital tract abnormalities. Fungal balls are an uncommon complication which require prompt detection and treatment to prevent morbidity and mortality. The evidence on the management of fungus balls in young infants with Candida urinary tract infections is very scarce. Methods: Case reports and review of the literature. Results: We report two immunocompetent young infants with urogenital abnormalities that received local amphotericin B deoxycholate, and systemic therapy, for the treatment and prevention of Candida urinary tract infection-associated fungus balls. We identified 21 similar cases in the literature, with very limited data about drug compounding, optimal dosages, dwell times and length of treatment. Different management strategies are discussed. Conclusions: Amphotericin B deoxycholate local irrigations were safe and effective for the therapeutic management and prophylaxis of Candida fungus balls in young infants, in combination with systemic antifungal therapy.(AU)

Introducción: Las infecciones urinarias fúngicas afectan preferentemente al prematuro gravemente enfermo o al afecto de malformaciones genitourinarias. Las bolas fúngicas son una complicación infrecuente que requiere un diagnóstico y tratamiento precoces para evitar morbimortalidad asociada. La evidencia científica disponible sobre el manejo de las bolas fúngicas por Candida en lactantes pequeños es muy escasa. Métodos: Casos clínicos y revisión de la literatura. Resultados: Se presentan 2 lactantes inmunocompetentes con malformaciones urogenitales que recibieron tratamiento local con anfotericina B desoxicolato junto a terapia sistémica para el tratamiento y la profilaxis del desarrollo de bolas fúngicas por Candida. Identificamos 21 casos similares en la literatura, con muy pocos datos disponibles sobre la preparación y posología, tiempos de permanencia y duración del tratamiento. Se discuten las distintas estrategias de manejo. Conclusiones: La irrigación local con anfotericina B desoxicolato resultó segura y eficaz en el tratamiento y en la profilaxis de las bolas fúngicas por Candida en el lactante pequeño, junto con el tratamiento antifúngico sistémico.(AU)

Renal fungus balls in neonates and very young infants treated with local amphotericin B deoxycholate: Two case reports and review of the literature.

INTRODUCTION: Fungal urinary tract infections predominantly affect the critically ill premature infant and those with urogenital tract abnormalities. Fungal balls are an uncommon complication which require prompt detection and treatment to prevent morbidity and mortality. The evidence on the management of fungus balls in young infants with Candida urinary tract infections is very scarce. METHODS: Case reports and review of the literature. RESULTS: We report two immunocompetent young infants with urogenital abnormalities that received local amphotericin B deoxycholate, and systemic therapy, for the treatment and prevention of Candida urinary tract infection-associated fungus balls. We identified 21 similar cases in the literature, with very limited data about drug compounding, optimal dosages, dwell times and length of treatment. Different management strategies are discussed. CONCLUSIONS: Amphotericin B deoxycholate local irrigations were safe and effective for the therapeutic management and prophylaxis of Candida fungus balls in young infants, in combination with systemic antifungal therapy.

Fusariosis in cancer patients: 13 case series report and literature review / Fusariosis en pacientes con cáncer: serie de 13 casos y revisión de la literatura

The fusariosis is an opportunistic mycosis caused by Fusarium spp. Its clinical presentation depends on the immunological status of the host, especially in patients with hematooncological diseases, whose manifestations vary from localized to invasive fungal infections. Skin or blood culture helps to guide combined antifungal treatment with amphotericin B and voriconazole. Here, we present 13 cases in a period of eleven years of patients with cancer who developed disseminated fusariosis and their outcomes, together with a review of the related literature. In this series of cases, mortality was 61.5 % (8/13), despite the use of the antifungal. Out of the 13 cases, 11 had hematological neoplasia and 2 solid neoplasia. The most determinant risk factor was profound neutropenia. Skin involvement and positive blood cultures in most cases allowed combined treatment prescription. Persistent febrile neutropenia associated with skin lesions, onychomycosis, nodules, or lung masses lead to suspicion of Fusarium spp. fungal invasive infection. The aim of this series of cases is to remind healthcare professionals that oncological patients with deep and persistent febrile neutropenia can develop fusariosis.

La fusariosis es una micosis oportunista producida por Fusarium spp. Su presentación clínica depende del estado inmunológico del huésped, especialmente, el de aquellos con enfermedades hematooncológicas, cuyas manifestaciones varían desde formas localizadas hasta infección fúngica invasora. El cultivo de piel o de sangre permite orientar el tratamiento antifúngico combinado con anfotericina B y voriconazol. Se presentan 13 casos de pacientes con cáncer en un periodo de once años que desarrollaron fusariosis diseminada; asimismo, se hizo con una revisión extensa de la literatura. En esta serie de casos, la mortalidad fue del 61,5 % (8/13), a pesar del uso del antifúngico. De los 13 pacientes, 11 tenían neoplasia hematológica y 2 neoplasia sólida. El factor de riesgo más importante fue la neutropenia profunda. El compromiso de la piel y los hemocultivos positivos facilitaron la prescripción del tratamiento combinado en la mayoría de los casos. La neutropenia febril persistente asociada a lesiones cutáneas, la onicomicosis, los nódulos o las masas pulmonares permitieron sospechar una infección fúngica invasora por Fusarium spp. El objetivo de la presentación de esta serie de casos es recordar el diagnóstico de fusariosis a la comunidad médica en contacto con pacientes oncológicos, con neutropenia febril profunda y persistentes.

Geotricosis: fungemia en paciente con leucemia linfoblástica aguda / Geotrichosis: fungemia in a patient with acute lymphoblastic leukemia

La fungemia por Geotrichum spp. es poco frecuente y altamente letal. En el Instituto Nacional de Cancerología de Bogotá solo se han reportado dos casos: uno entre el 2001 y el 2007, y el otro entre el 2012 y el 2018. Este tipo de infección es más común en pacientes con algún grado de compromiso del sistema inmunitario, por lo que puede presentarse en pacientes con neoplasias hematológicas malignas. Se presenta el caso de un hombre de 27 años con recaída de leucemia linfoblástica aguda, que ingresó con poliartralgias de cinco días de duración. También cursaba con neutropenia febril, celulitis sin abscesos y bacteriemia por Staphylococcus aureus resistente a la meticilina para lo cual recibió terapia con oxacilina y cefepime. Sin embargo, persistía la neutropenia febril por lo que se sospechó una infección fúngica invasora. Se tomó un nuevo set de hemocultivos y se inició tratamiento antifúngico. En los hemocultivos se identificaron artroconidias y mediante espectrometría de masas por láser de matriz asistida de ionización-desorción se confirmó la presencia de Geotrichum spp. Se ajustó el tratamiento antifúngico con deoxicolato de anfotericina B por 14 días y voriconazol por cuatro semanas. Luego de una estancia prolongada se le dio de alta. Aunque la incidencia de la fungemia por Geotrichum spp. es baja, en pacientes con neoplasias hematológicas malignas debe considerarse en el contexto de una neutropenia febril que es persistente a pesar del tratamiento antimicrobiano de amplio espectro. La identificación de los agentes causantes de fungemias con herramientas de proteómica, como la espectrometría de masas mencionada, permite ajustar el tratamiento dirigido y reducir las complicaciones, la estancia hospitalaria y la mortalidad.

Fungemia caused by Geotrichum spp. is rare and highly lethal. The Instituto Nacional de Cancerología in Bogotá reported just two cases: one in the period 2001-2007 and the other in 2012-2018. This type of infection is more common in any kind of immunocompromised patients, so it can occur in those with hematological malignancies. Here we present the case of a 27-year-old man, diagnosed with acute lymphoblastic leukemia in relapse and admitted with polyarthralgia for five days, febrile neutropenia, non- abscessed cellulitis, and bacteremia due to methicillin-sensitive Staphylococcus aureus. The patient received therapy with oxacillin and cefepime, but the febrile neutropenia persisted. A new set of blood cultures was taken, and antifungal treatment was started because of the suspicion of invasive fungal infection. Arthroconidia were identified in blood cultures and Geotrichum spp. was confirmed using matrix-assisted laser desorption-ionization mass spectrometry. The antifungal treatment was adjusted with amphotericin B deoxycholate for 14 days and voriconazole for four weeks, and after a prolonged stay, the patient was discharged. Although the incidence of fungemia caused by Geotrichum spp. is low, it must be considered in patients with hematological malignancies and persistent febrile neutropenia despite the broadspectrum antimicrobial treatment. The confirmation of fungemia causing agents, with proteomic tools such as the mentioned mass spectrometry, allows treatment adjustment and decreases complications, hospital stay, and mortality.

Fusariosis en pacientes con cáncer: serie de 13 casos y revisión de la literatura / Fusariosis in cancer patients: 13 case series report and literature review

La fusariosis es una micosis oportunista producida por Fusarium spp. Su presentación clínica depende del estado inmunológico del huésped, especialmente, el de aquellos con enfermedades hematooncológicas, cuyas manifestaciones varían desde formas localizadas hasta infección fúngica invasora. El cultivo de piel o de sangre permite orientar el tratamiento antifúngico combinado con anfotericina B y voriconazol. Se presentan 13 casos de pacientes con cáncer en un periodo de once años que desarrollaron fusariosis diseminada; asimismo, se hizo con una revisión extensa de la literatura. En esta serie de casos, la mortalidad fue del 61,5 % (8/13), a pesar del uso del antifúngico. De los 13 pacientes, 11 tenían neoplasia hematológica y 2 neoplasia sólida. El factor de riesgo más importante fue la neutropenia profunda. El compromiso de la piel y los hemocultivos positivos facilitaron la prescripción del tratamiento combinado en la mayoría de los casos. La neutropenia febril persistente asociada a lesiones cutáneas, la onicomicosis, los nódulos o las masas pulmonares permitieron sospechar una infección fúngica invasora por Fusarium spp. El objetivo de la presentación de esta serie de casos es recordar el diagnóstico de fusariosis a la comunidad médica en contacto con pacientes oncológicos, con neutropenia febril profunda y persistentes.

The fusariosis is an opportunistic mycosis caused by Fusarium spp. Its clinical presentation depends on the immunological status of the host, especially in patients with hemato-oncological diseases, whose manifestations vary from localized to invasive fungal infections. Skin or blood culture helps to guide combined antifungal treatment with amphotericin B and voriconazole. Here, we present 13 cases in a period of eleven years of patients with cancer who developed disseminated fusariosis and their outcomes, together with a review of the related literature. In this series of cases, mortality was 61.5 % (8/13), despite the use of the antifungal. Out of the 13 cases, 11 had hematological neoplasia and 2 solid neoplasia. The most determinant risk factor was profound neutropenia. Skin involvement and positive blood cultures in most cases allowed combined treatment prescription. Persistent febrile neutropenia associated with skin lesions, onychomycosis, nodules, or lung masses lead to suspicion of Fusarium spp. fungal invasive infection. The aim of this series of cases is to remind healthcare professionals that oncological patients with deep and persistent febrile neutropenia can develop fusariosis.

Oxigenoterapia hiperbárica como tratamiento complementario en mucormicosis asociada a COVID-19: a propósito de dos casos / Hyperbaric oxygen therapy as an adjunctive treatment for COVID-19-associated mucormycosis: a report of two cases

Reportamos los dos primeros casos, en Perú, sobre el uso del tratamiento con oxigeno hiperbárico coadyuvante (TOHC) en pacientes con mucormicosis asociado a COVID-19 (MAC). El primer caso es una mujer de 41 años, con dolor en hemicara y región palatina izquierdas con rinorrea purulenta de un mes de evolución. Al examen físico, solo evidencia fístula oroantral. El segundo caso se trata de un varón de 35 años, con disminución de agudeza visual izquierda y dolor palatino con fístula que drena secreción purulenta de cuatro meses de evolución. Ambos pacientes tienen el antecedente de diabetes, tuvieron COVID-19 moderado cuatro meses antes del ingreso, y recibieron corticoterapia por este diagnóstico. Ambos pacientes tuvieron una evaluación tomográfica que mostró compromiso del seno maxilar y tejido óseo circundante, con endoscopia nasal diagnóstica y terapéutica para desbridamiento. Se obtuvieron muestras compatibles con mucormicosis en estudio histológico. Los pacientes fueron tratados con limpieza quirúrgica y anfotericina B desoxicolato, sin embargo, presentaron evoluciones tórpidas. Por lo tanto, se adicionó la TOHC y mostraron una mejoría evidente tras cuatro semanas de tratamiento con controles subsiguientes sin presencia de mucormicosis. Resaltamos la evolución de estos pacientes con TOHC, en una enfermedad con importante morbimortalidad, que ha sido emergente durante la pandemia.

We present the first two cases reported in Peru of the use of adjuvant hyperbaric oxygen therapy (HBOT) in patients with COVID-19-associated mucormycosis (CAM). The first case is a 41-year-old woman, with pain in the left side of the face and palatine region with purulent rhinorrhea for a month. Only an oroantral fistula was found during physical examination. The second case is a 35-year-old male, with decreased left visual acuity and palatal pain with a fistula, draining purulent secretion for four months. Both patients have history of diabetes, had moderate COVID-19 four months prior to admission, and received corticosteroid therapy for this diagnosis. Tomographic evaluation of both patients showed involvement of the maxillary sinus and surrounding bone tissue; both received diagnostic and therapeutic nasal endoscopy for debridement. Histological analysis showed that the samples were compatible with mucormycosis. The patients underwent debridement and were treated with amphotericin B deoxycholate; however, they presented torpid evolution. Then, HBOT was added and the patients showed an evident improvement after four weeks of treatment with subsequent controls without the presence of mucormycosis. We highlight the favorable evolution of these patients while receiving HBOT as treatment for a disease with high morbimortality, which emerged during the pandemic.

Uso de anfotericina B liposomal en leishmaniasis cutánea diseminada causada por Leishmania braziliensis en un paciente pediátrico con síndrome de Down / Use of liposomal anfotericin B in diseminated cutaneous leishmaniasis caused by Leishmania braziliensis in a pediatric patient with Down syndrome

Se presenta un caso de leishmaniasis selvática cutánea diseminada con manifestación extensa en una paciente pediátrica con síndrome de Down. El caso se confirmó a través de estudios parasitológicos e inmunológicos, mientras que la identificación se realizó mediante la técnica de reacción en cadena de la polimerasa-polimorfismos de longitud de fragmentos de restricción (PCR-RFLP, por sus siglas en inglés), determinándose la especie como Leishmania (Viannia) braziliensis. La manifestación clínica agresiva y prolongada con poca respuesta a estibogluconato y anfotericina desoxicolato pueden deberse al déficit inmunológico que se presenta como parte del síndrome de Down. La paciente eventualmente recibió tratamiento con anfotericina B liposomal y al término de la terapia, mostró mejoría clínica de las lesiones. El presente reporte ilustra los desafíos tanto de diagnóstico como tratamiento de leishmaniasis cutánea en pacientes pediátricos inmunosuprimidos, especialmente en un entorno de difícil acceso social, económico y geográfico, a los servicios de salud. Se recomienda considerar a la leishmaniasis en el diagnóstico diferencial cuando se atienda ulceras crónicas dermatológicas atípicas; así como tener en cuenta el uso de anfotericina liposomal en pacientes inmunocomprometidos.

We present a case of disseminated cutaneous leishmaniasis with extensive manifestation in a pediatric patient with Down syndrome. The case was confirmed by parasitological and immunological tests. The species was identified as Leishmania (Viannia) braziliensis by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP). The immune deficit that occurs as part of Down syndrome may have been the reason for the aggressive and prolonged clinical manifestations as well as the poor response to stibogluconate and deoxycholate amphotericin. The patient was treated with liposomal amphotericin B and at the end of therapy, showed clinical improvement of the lesions. This report highlights the challenges of the diagnosis and treatment of cutaneous leishmaniasis in immunosuppressed pediatric patients, especially under difficult social, economic and geographic conditions. Leishmaniasis should be considered as a differential diagnosis when treating atypical chronic dermatologic ulcers; the use of liposomal amphotericin in immunocompromised patients should also be considered in these cases.

Disseminated mucormycosis in a child with acute lymphoblastic leukemia: autopsy findings / Mucormicosis diseminada en un paciente pediátrico con leucemia linfoblástica aguda: hallazgos de la autopsia

Abstract Background: Mucormycosis is a rare infection caused by ubiquitous fungi of the Mucorales order that mainly affects immunocompromised patients. These fungi have an important tropism for blood vessels that allows them to spread rapidly and cause thromboembolic events. Case report: We present a case of an 8-year-old male patient diagnosed with acute lymphoblastic leukemia treated with chemotherapy. He presented icteric syndrome, hepato-splenomegaly, and data of intestinal obstruction. Although he underwent intestinal resection, he did not improve and died. The autopsy identified disseminated mucormycosis involving the brain, lungs, esophagus, small intestine, colon, and pancreas. Conclusions: Hematological neoplastic diseases and their treatment are important risk factors for developing infections by opportunistic microorganisms such as mucormycosis. Early diagnosis and adequate treatment are essential due to their intrinsic difficulty and the high mortality rate of these cases.

Resumen Introducción: La mucormicosis es una infección poco frecuente causada por hongos ubicuos del orden de los Mucorales que afecta principalmente a pacientes inmunocomprometidos. Estos hongos poseen un importante tropismo por vasos sanguíneos que les permite diseminarse rápidamente y provocar lesiones trombo-embólicas. Caso clínico: Se presenta el caso de un paciente de sexo masculino de 8 años con diagnóstico de leucemia linfoblástica aguda tratada con quimioterapia. Presentó síndrome ictérico, hepato-esplenomegalia y datos de obstrucción intestinal. A pesar de que fue sometido a resección intestinal, no presentó mejoría y falleció. En la autopsia se identificó mucormicosis diseminada con afección de cerebro, pulmones, esófago, intestino delgado, colon y páncreas. Conclusiones: Las enfermedades neoplásicas hematológicas y su tratamiento son importantes factores de riesgo para el desarrollo de infecciones por microorganismos oportunistas como la mucormicosis. El diagnóstico temprano y adecuado tratamiento son importantes debido a la dificultad intrínseca de los mismos y la alta tasa de mortalidad de estos casos.

Leishmaniasis visceral con hemorragia masiva

RESUMEN Las complicaciones potencialmente mortales por el uso de la anfotericina B desoxicolato se presentan en menos del 1% de los casos. Entre ellas se describe el sangrado masivo principalmente por trombocitopenia. Se presenta caso de un paciente de sexo masculino de 38 años de edad, oriundo de una zona endémica, portador de leishmaniasis visceral grave que posterior al inicio de tratamiento con anfotericina B desoxicolato presenta hemorragia alveolar masiva por trombocitopenia.

ABSTRACT Life-threatening complications from the use of amphotericin B deoxycholate occur in less than 1% of cases. Among them, massive bleeding is described mainly due to thrombocytopenia. We present the case of a 38-year-old male patient, from an endemic area, with severe visceral leishmaniasis who, after starting treatment with amphotericin B deoxycholate, presented massive alveolar hemorrhage due to thrombocytopenia.

Amphotericin B is usually underdosed in the treatment of experimental cutaneous leishmaniasis / La anfotericina B normalmente es subdosificada en el tratamiento de la leishmaniasis cutánea experimental

Introduction: Amphotericin B is an effective drug for the treatment of the different clinical forms of leishmaniasis. However, there are reports of its ineffectiveness in animals experimentally infected withLeishmaniaspp. That is why, the objective of the present work was to evaluate the balance of activity-toxicity at amphotericin B doses over 1 mg/kg, so that its use as a positive control antileishmanial drug were adequate. Method: BALB/c mice were experimentally infected withL. amazonensisand treated with amphotericin B by intraperitoneal route at doses from 5 mg/kg to 12.5 mg/kg, beginning 21 days after infection. The size of the lesions and the body weight of the mice were measured for eleven weeks after the commencement of treatment. The number of parasites was also determined three days after the end of treatment. Results: Amphotericin B at 5 mg/kg retarded lesions growth but neither reduced lesion size nor the parasite load at lesion site. Doses of 7.5 mg/kg to 10 mg/kg, every 48 h for 14 days (7 doses) caused a significant reduction of lesion size and parasite load without evident loss of body weight and without signs of toxicity. Amphotericin B at 12.5 mg/kg was more effective but produced unacceptable toxicity. Conclusions: The results support the use of amphotericin B as a positive control drug in BALB/c mice experimentally infected withL. amazonensisat doses of 7.5 mg/kg to 10 mg/kg to achieve an effect comparable to that observed in clinical practice. (AU)

Introducción: La anfotericina B es un fármaco eficaz para el tratamiento de las distintas formas de leishmaniosis. Sin embargo, existen informes sobre su ineficacia en animales de laboratorio infectados experimentalmente conLeishmaniaspp.Es por ello que el objetivo del presente trabajo fue evaluar el balance de actividad-toxicidad a dosis de Anfotericina B superiores a 1 mg/kg, de modo que su uso como fármaco leishmanicida control positivo sea adecuado. Método: Se infectaron experimentalmente ratones BALB/c conL. amazonensisy se trataron con anfotericina B por vía intraperitoneal a dosis desde 5 mg/kg hasta 12,5 mg/kg, comenzando 21 días después de la infección. Durante once semanas a partir del comienzo del tratamiento se evaluó el tamaño de las lesiones y el peso corporal de los ratones. Tres días después de concluido el tratamiento se determinó el número de parásitos en las lesiones. Resultados: La anfotericina B a 5 mg/kg retrasó el crecimiento de las lesiones, pero no redujo su tamaño ni disminuyó significativamente el número de parásitos en la lesión. Dosis de 7,5 mg/kg a 10 mg/kg, cada 48 h durante 14 días (7 dosis) causaron una reducción significativa del tamaño de la lesión y de la carga parasitaria sin pérdida manifiesta de peso corporal y sin signos de toxicidad. La anfotericina B a 12,5 mg/kg fue más eficaz, pero produjo una toxicidad inaceptable. Conclusiones: Los resultados avalan el uso de la anfotericina B como control positivo en ratones BALB/c infectados experimentalmente conL. amazonensisen dosis de 7,5 mg/kg a 10 mg/kg para lograr un efecto comparable al observado en la práctica clínica. (AU)

Incidencia de hipopotasemia en pacientes con neutropenia febril que reciben tratamiento con anfotericina B liposomal / Incidence of hypokalemia in patients with febrile neutropenia receiving treatment with liposomal amphotericin B

Objetivos: Describir la incidencia, la gravedad y los factores asociados a la aparición de hipopotasemia en pacientes con neutropenia febril en tratamiento con anfotericina B liposomal.Métodos: Estudio unicéntrico retrospectivo (enero 2010- mayo 2020), que incluyó a aquellos pacientes hematológicos con neutropenia febril que recibieron tratamiento con anfotericina B liposomal durante al menos 72 h. Se evaluó la incidencia de aparición de hipokalemia asociada al empleo del fármaco, la gravedad de la misma, así como el impacto del empleo de una suplementación de potasio sobre la aparición de hipokalemia en este grupo de pacientes.Resultados: Se incluyeron 89 pacientes (50,6% mujeres [n=45]; edad media 63,5 años [20-90]). El 59,6% (n=53) de los pacientes desarrolló hipopotasemia durante el tratamiento con anfotericina B liposomal: leve (52,8%, n=28), moderada (35,8%, n=19) y grave (11,3%, n=6). El empleo de una suplementación de inicio precoz a base de potasio disminuyó la tasa de aparición de hipokalemia en estos pacientes (p=0,001). El periodo entre el inicio del fármaco y el aporte de potasio fue menor en pacientes que no desarrollaron hipokalemia (p<0,001). Asimismo, este grupo de pacientes se benefició de periodos más prolongados de suplementación (p=0,002) y terapia antifúngica (p=0,039).Conclusiones: La hipopotasemia es un efecto adverso muy frecuente en pacientes con neutropenia febril que reciben tratamiento con anfotericina B liposomal, siendo necesario el establecimiento de protocolos de suplementación de potasio que disminuyan el riesgo de aparición de esta reacción adversa. (AU)

Objectives: To describe the incidence, severity and factors associated with the appearance of hypokalemia in patients with febrile neutropenia in treatment with liposomal amphotericin B. Methods: Retrospective unicenter study (January 2010-May 2020), which included those hematological patients with febrile neutropenia who were treated with liposomal amphotericin B for at least 72 h. The incidence of hypokalemia associated with the use of the drug, its severity, and the influence of potassium supplementation on the occurrence of hypokalemia in this group of patients were evaluated. Results: 89 patients were included (50.6% women [n=45]; mean age 63.5 years [20-90]). 59.6% (n=53) of patients developed hypokalemia during treatment with liposomal amphotericin B: mild (52.8%, n=28), moderate (35.8%, n=19) and severe (11.3%, n=6). The use of early-onset potassium-based supplementation decreased the rate of occurrence of hypokalemia in these patients (p=0.001). The period between drug initiation and potassium intake was lower in patients who did not develop hypokalemia (p<0.001). Likewise, this group of patients benefited from longer periods of supplementation (p=0.002) and antifungal therapy (p=0.039).Conclusions: Hypokalemia is a very frequent adverse effect in patients with febrile neutropenia who are treated with liposomal amphotericin B. It is necessary to establish protocols for potassium supplementation to reduce the risk of this adverse reaction. (AU)

An epidemiologic analysis of Candida spp. urinary infections in intensive care unit / Uma análise epidemiológica das infecções urinárias por Candida spp. em unidade de terapia intensiva / Un análisis epidemiológico de las infecciones urinarias por Candida spp. en la unidad de cuidados intensivos

Background and objectives: The finding of Candida species in urine is an usual finding and is called candiduria. There is an increase in the frequency of urinary tract infections (UTI) caused by Candida especially in critically ill patients. This study aimed to determine the epidemiological, clinical, and mycological characteristics of Candida urinary infections in intensive care unit (ICU) and antifungal susceptibilities. Methods: Urine cultures of 394 ICU patients with clinical suspicion of UTI were evaluated. After 24-48 hours of incubation, colonies appeared to grow as yeast, were morphologically examined by Gram staining. Candida strains that grew 104 ≥ CFU/mL in urine cultures were accepted as candiduria. The susceptibilities of the Candida strains to amphotericin B, itraconazole, fluconazole, voriconazole, flucytosine, and caspofungin were investigated with broth microdilution method. Results: The distribution of the isolated 100 urinary Candida strains were as, 54 Candida albicans, 34 C. glabrata, 7 C. tropicalis, 2 C. kefyr, 2 C. lusitaniae, and 1 as C. parapsilosis. Among 100 Candida species isolated in our study susceptibility rates of amphotericin B, flucytosine, caspofungin, fluconazole, itraconazole, and voriconazole were 100%, 100%, 91%, 23%, 13%, 25.8%, respectively. Conclusion: Accurate identification of Candida spp., as well as the investigating the antifungal susceptibility, will be beneficial in terms of the effectiveness of the treatment and the prevention of resistance development.(AU)

Justificativa e objetivos: O achado de espécies de Candida na urina é um achado comum e é chamado de candidúria. Há um aumento na frequência de infecções do trato urinário (ITU) causadas por Candida, principalmente em pacientes críticos. Este estudo teve como objetivo determinar as características epidemiológicas, clínicas e micológicas das infecções urinárias por Candida em unidade de terapia intensiva (UTI) e a susceptibilidade aos antifúngicos. Métodos: Foram avaliadas culturas de urina de 394 pacientes de UTI com suspeita clínica de ITU. Após 24-48 horas de incubação, as colônias pareceram crescer como leveduras, foram morfologicamente examinadas por coloração de Gram. As cepas de Candida que cresceram ≥104 UFC/mL em culturas de urina foram aceitas como candidúria. As suscetibilidades das cepas de Candida à anfotericina B, itraconazol, fluconazol, voriconazol, flucitosina e caspofungina foram investigadas com o método de microdiluição em caldo. Resultados: A distribuição das cepas 100 isoladas de Candida urinária foi de 54 Candida albicans, 34 C. glabrata, 7 C. tropicalis, 2 C. kefyr, 2 C. lusitaniae e 1 como C. parapsilosis. Entre 100 espécies de Candida isoladas em nosso estudo, as taxas de susceptibilidade de anfotericina B, flucitosina, caspofungina, fluconazol, itraconazol e voriconazol foram de 100%, 100%, 91%, 23%, 13%, 25,8%, respectivamente. Conclusão: A identificação precisa de Candida spp., bem como a investigação da susceptibilidade aos antifúngicos, será benéfica em termos de eficácia do tratamento e prevenção do desenvolvimento de resistência.(AU)

Justificación y objetivos: El hallazgo de especies de Candida en la orina es un hallazgo habitual y se denomina candiduria. Hay un aumento en la frecuencia de infecciones del tracto urinario (ITU) causadas por Candida, especialmente en pacientes críticamente enfermos. Este estudio tuvo como objetivo determinar las características epidemiológicas, clínicas y micológicas de las infecciones urinarias por Candida en la unidad de cuidados intensivos (UCI) y la susceptibilidad antifúngica. Métodos: Se evaluaron urocultivos de 394 pacientes de UCI con sospecha clínica de ITU. Después de 24-48 horas de incubación, las colonias parecían crecer como levadura, se examinaron morfológicamente mediante tinción de Gram. Las cepas de Candida que crecieron 104 ≥ UFC / ml en urocultivos se aceptaron como candiduria. Las susceptibilidades de las cepas de Candida a la anfotericina B, itraconazol, fluconazol, voriconazol, flucitosina y caspofungina se investigaron con el método de microdilución en caldo. Resultados: La distribución de las cepas 100 urinarias aisladas de Candida fue de, 54 C. albicans, 34 C. glabrata, 7 C. tropicalis, 2 C. kefyr, 2 C. lusitaniae y 1 como C. parapsilosis. Entre las 100 especies de Candida aisladas en nuestro estudio, las tasas de susceptibilidad de anfotericina B, flucitosina, caspofungina, fluconazol, itraconazol y voriconazol fueron 100%, 100%, 91%, 23%, 13%, 25,8%, respectivamente. Conclusión: La identificación precisa de Candida spp., así como la investigación de la susceptibilidad antifúngica, será beneficiosa en términos de la eficacia del tratamiento y la prevención del desarrollo de resistencias.(AU)

Rhodotorula fungemia in a patient with acute lymphoblastic leukemia / Fungemia de Rhodotorula em paciente com leucemia linfoblástica aguda / Fungemia por Rhodotorula en un paciente con leucemia linfoblástica aguda

Objectives: Rhodotorula is an environmental yeast that belongs to Basidiomycota Phylum. Rhodotorula species are ubiquitous in nature, can be found in soil and freshwater. Immunocompromised patients can develop Rhodotorulosis due to wide-ranging exposure to Rhodotorula in the hospital environment. Case Discussion: The patient was a 3-year-old male with a diagnosis of Pro B-Acute Lymphoblastic Leukemia (ALL). He was admitted to the hospital with complaints of malaise, fatigue, weight loss, and diarrhea between courses of chemotherapy. Rhodotorula was isolated from the patient's blood culture obtained during the elevation of temperature. After 14 days of amphotericin B treatment, clinical situation of the patient was improved and he was discharged. Conclusion: Rhodotorula spp. as a rare yet emerging pathogen, often presents as fever of unknown etiology resistant to antibacterial treatment and can be associated with fungemia and other severe complications.(AU)

Objetivos: Rhodotorula é uma levedura ambiental que pertence ao filo Basidiomycota. As espécies de Rhodotorula são onipresentes na natureza, podem ser encontradas no solo e na água doce. Pacientes imunocomprometidos podem desenvolver rodotorulose devido à ampla exposição a Rhodotorula no ambiente hospitalar. Descrição do caso: O paciente era uma criança de 3 anos de idade com diagnóstico de Leucemia Linfoblástica Aguda Pro B (LLA). O paciente deu entrada no hospital com queixas de mal-estar, cansaço, perda de peso e diarreia entre os ciclos de quimioterapia. A Rhodotorula foi isolada da hemocultura do paciente obtida durante a elevação da temperatura. Após 14 dias de tratamento com anfotericina B, a situação clínica do paciente melhorou e o paciente recebeu alta. Conclusão: Rhodotorula spp. como um patógeno raro, porém emergente, frequentemente se apresenta como febre de etiologia desconhecida resistente ao tratamento antibacteriano e pode estar associada a fungemia e outras complicações graves.(AU)

Objetivos: Rhodotorula es una levadura ambiental que pertenece al filo Basidiomycota. Las especies de Rhodotorula son ubicuas en la naturaleza, se pueden encontrar en el suelo y en agua dulce. Los pacientes inmunodeprimidos pueden desarrollar Rhodotorulosis debido a una amplia exposición a Rhodotorula en el entorno hospitalario. Descripción del caso: El paciente era un niño de 3 años con diagnóstico de leucemia linfoblástica aguda Pro B (LLA). El paciente ingresó en el hospital con quejas de malestar, fatiga, pérdida de peso y diarrea entre ciclos de quimioterapia. Se aisló Rhodotorula del hemocultivo del paciente que se obtuvo durante la elevación de la temperatura. Después de 14 días de tratamiento con anfotericina B, la situación clínica del paciente mejoró y fue dado de alta. Conclusión: Rhodotorula spp. como patógeno poco común pero emergente, a menudo se presenta como fiebre de etiología desconocida resistente al tratamiento antibacteriano y puede asociarse con fungemia y otras complicaciones graves.(AU)

In vitro activity of immunosuppressive agents against Cryptococcus neoformans.

INTRODUCTION: Infections caused by Cryptococcus neoformans are a major cause of fungal mortality in HIV-infected/AIDS patients and in those receiving organ transplants. We evaluated the in vitro activity of tacrolimus and cyclosporine in combination with amphotericin B and fluconazole against C. neoformans. METHODS: MICs were determined against a total of 30 clinical isolates of C. neoformans by the microdilution method following the CLSI M27-A3 guidelines and by the checkerboard method. RESULTS: Tacrolimus and cyclosporine A showed in vitro activity against cryptococcal isolates. The combination of amphotericin B with cyclosporine A or tacrolimus was synergistic against 90% and 30% of isolates, respectively. Synergism was also observed with the combination of fluconazole with cyclosporine A or tacrolimus, against 70% and 20% of isolates, respectively. CONCLUSIONS: The synergistic interactions between the calcineurin inhibitors and antifungal drugs against C. neoformans isolates, could potentially have a role in devising novel therapeutic strategies for this opportunistic mycosis.

In vitro activity of immunosuppressive agents against Cryptococcus neoformans / Actividad in vitro de agentes inmunosupresores frente a Cryptococcus neoformans

IntroductionInfections caused by Cryptococcus neoformans are a major cause of fungal mortality in HIV-infected/AIDS patients and in those receiving organ transplants. We evaluated the in vitro activity of tacrolimus and cyclosporine in combination with amphotericin B and fluconazole against C. neoformans.MethodsMICs were determined against a total of 30 clinical isolates of C. neoformans by the microdilution method following the CLSI M27-A3 guidelines and by the checkerboard method.ResultsIntroductionInfections caused by Cryptococcus neoformans are a major cause of fungal mortality in HIV-infected/AIDS patients and in those receiving organ transplants. We evaluated the in vitro activity of tacrolimus and cyclosporine in combination with amphotericin B and fluconazole against C. neoformans.MethodsMICs were determined against a total of 30 clinical isolates of C. neoformans by the microdilution method following the CLSI M27-A3 guidelines and by the checkerboard method.ResultsTacrolimus and cyclosporine A showed in vitro activity against cryptococcal isolates. The combination of amphotericin B with cyclosporine A or tacrolimus was synergistic against 90% and 30% of isolates, respectively. Synergism was also observed with the combination of fluconazole with cyclosporine A or tacrolimus, against 70% and 20% of isolates, respectively.ConclusionsThe synergistic interactions between the calcineurin inhibitors and antifungal drugs against C. neoformans isolates, could potentially have a role in devising novel therapeutic strategies for this opportunistic mycosis.

IntroducciónLas infecciones causadas por Cryptococcus neoformans son la principal causa de mortalidad por hongos en pacientes con infección por el VIH/SIDA o en pacientes trasplantados. Evaluamos la actividad in vitro de tacrolimus y ciclosporina A en combinación con anfotericina B y fluconazol frente a C. neoformans.MétodosSe determinaron las CMI de ciclosporina A y tacrolimus frente a 30 aislados clínicos de C. neoformans mediante microdilución, según el documento CLSI M27-A3 y por el método del tablero de ajedrez.ResultadosTacrolimus y ciclosporina A mostraron actividad in vitro frente a C. neoformans. La combinación de anfotericina B con ciclosporina A o tacrolimus fue sinérgica frente al 90 y 30% de aislados, respectivamente. Se observó sinergismo con fluconazol y ciclosporina A o tacrolimus, frente al 70 y 20% de aislados, respectivamente.ConclusionesLa actividad sinérgica entre inhibidores de la calcineurina y antimicóticos frente a C. neoformans podría ser una nueva estrategia terapéutica para esta micosis.

Refractory rhino-orbito-cerebral mucormycosis treated with intraconal amphotericin B / Mucormicose rino-orbito-cerebral refratária tratada com anfotericina B intraconal

ABSTRACT We report the case of a 46-year-old diabetic man receiving treatment for rhino-orbital-cerebral mucormycosis with liposomal amphotericin B and surgical debridement. The patient's condition worsened clinically, accompanied by the loss of ocular motility and a visual acuity of absence of light perception. Radiological extension of the infection was evidenced, with invasion of the cavernous sinus. Based on ophthalmological findings, exenteration (a potentially disfiguring procedure) was indicated, but we opted for wide surgical debridement and administration of amphotericin B via intraconal catheter. Clinical improvement and resolution of inflammation occurred after 2 weeks of treatment. Thus, rhino-orbital-cerebral mucormycosis was effectively controlled through intraconal administration of amphotericin B, while avoiding exenteration. The intervention should be considered as an adjuvant treatment in selected rhino-orbital-cerebral mucormycosis cases before attempting exenteration.

RESUMO Os autores relatam o caso de um homem diabético de 46 anos de idade em tratamento para mucormicose rino-orbital-cerebral com anfotericina B lipossomal e desbridamento cirúrgico. Piora clínica foi observada, com acometimento de motilidade ocular e acuidade visual de ausência de percepção luminosa, sendo evidenciada extensão radiológica da infecção, com invasão do seio cavernoso. Com base nos achados oftalmológicos, uma exenteração, procedimento potencialmente desfigurante, foi indicada, mas optamos por realizar amplo desbridamento cirúrgico e administração intraconal de anfotericina B por cateter. Melhora clínica e resolução da inflamação ocorreram após duas semanas de tratamento. Dessa forma, a mucormicose rino-orbital-cerebral foi efetivamente controlada com a administração intraconal de anfotericina B, evitando a exenteração. A intervenção deve ser considerada como um tratamento adjuvante em casos selecionados de mucormicose rino-orbital-cerebral antes que a exenteração seja realizada.

Avaliação da eficácia das formulações lipossomal e desoxicolato de anfotericina B sobre espécies de Candida: estudo in vitro e in vivo em Galleria mellonella / Evaluation of the efficacy of liposomal and deoxycholate amphotericin B formulations on Candida species: in vitro and in vivo study in Galleria mellonella

Anfotericina B pertence a primeira classe (polienos) de medicamentos antifúngicos introduzidos no mercado. O amplo espectro de ação e a baixa taxa de resistência microbiana, definiram a anfotericina B como tratamento de escolha para as infecções graves por Candida spp. Porém, os efeitos colaterais causados pela sua toxicidade impulsionaram o desenvolvimento de novas formulações a base de lipídios. Assim, o objetivo desse estudo foi comparar os efeitos antifúngicos da formulação lipossomal da anfotericina B (AmB-L) com a formulação convencional de anfotericina B desoxicolato (AmB-D). Para isso a atividade antifúngica foi testada sobre diferentes espécies de Candida, incluindo Candida albicans (cepa clínica 70), Candida glabrata (cepa clínica 64), Candida tropicalis (cepa clínica 11) e Candida parapsilosis (cepa ATCC 90018), utilizando-se métodos de estudo in vitro e in vivo. Em estudo in vitro, foi determinada a concentração inibitória mínima (CIM) em células planctônicas por meio do método de microdiluição em caldo. A seguir, concentrações de 10x, 20x e 50x a CIM foram testadas sobre os biofilmes de Candida, verificando-se seus efeitos pela contagem de unidades formadoras de colônias (UFC). Para o estudo in vivo, foi utilizado o modelo invertebrado Galleria mellonella. Os animais foram infectados por Candida e tratados com as formulações de anfotericina B, então foram monitorados diariamente para determinação da curva de sobrevivência e índice de saúde. Os resultados dos testes in vitro demonstraram atividade antifúngica semelhante entre AmB-L e AmB-D em crescimento planctônico. Ambas as formulações apresentaram valores de CIM de 0,5 µg/mL para C. albicans e C. parapsilosis, e de 1 µg/mL para C. glabrata e C. tropicalis. Nos biofilmes, AmB-D apresentou maior atividade inibitória em relação à AmB-L, para todas as cepas de Candida estudadas. Nos testes in vivo, o tratamento com AmB-L ou AmB-D aumentou a sobrevida e índice de saúde das larvas infectadas por Candida, sendo observada maior eficácia da formulação AmB-D em relação à AmB-L. Portanto, concluiu-se que AmB-L e AmB-D apresentam a mesma efetividade sobre células planctônicas, mas AmB-D mostrou maior ação antifúngica sobre biofilmes e infecção experimental no modelo G. mellonella (AU)

Amphotericin B belongs to the first class (polyenes) of antifungal drugs introduced commercially. The broad spectrum of action and the low rate of microbial resistance have defined amphotericin B as the treatment of choice for serious infections by Candida spp. However, the side effects caused by toxicity stimulated the development of new formulations based on lipids. Thus, the aim of this study was to compare the antifungal effects of the liposomal amphotericin B formulation (AmB-L) with the conventional formulation deoxycholate amphotericin B (AmB-D). For this, the antifungal activity was tested on different Candida species, including Candida albicans (clinical strain 70), Candida glabrata (clinical strain 64), Candida tropicalis (clinical strain 11) and Candida parapsilosis (ATCC strain 90018), using in vitro and in vivo study methods. In in vitro tests, the minimum inhibitory concentration (MIC) was determined using the broth microdilution method. Next, concentrations of 10x, 20x and 50x the MIC were tested on Candida biofilms, verifying their effects by counting colonyforming units (CFU). For the in vivo study, the Galleria mellonella invertebrate model was used. The animals were infected with Candida and treated with amphotericin B formulations, then monitored daily to determine the survival curves and health index score. The results of in vitro tests demonstrated similar antifungal activity between AmB-L and AmB-D in planktonic cells. Both formulations showed MIC values of 0.5 µg/mL for C. albicans and C. parapsilosis, and 1 µg/mL for C. glabrata and C. tropicalis. In biofilms, AmB-D showed greater inhibitory activity in relation to AmB-L for all Candida strains studied. In in vivo tests, the treatment with AmB-L or AmB-D increased the survival and health index of larvae infected by Candida, with greater efficacy for the AmB-D formulation in relation to AmB-L. Therefore, it was concluded that AmB-L and AmB-D have the same effectiveness on planktonic cells, but AmB-D showed greater antifungal action on biofilms and experimental infection in the G. mellonella model (AU)

Factores de Riesgo de Mortalidad en Pacientes Hematológicos con Aspergilosis Pulmonar en Clínica Médica Instituto de Previsión Social - Hospital Central. Año 2016 A 2018

ResumenIntroducción: Es una de las infecciones oportunistas de mayor impacto en el paciente con patologías hematooncológicas, su detección precoz y tratamiento oportuno impide su diseminación. Objetivo: Determinar factores de riesgo de mortalidad en pacientes hematológicos con aspergilosis pulmonar de pacientes internados en clínica médica en el Instituto de Previsión Social del Hospital Central durante 2016 a 2018. Metodología: Estudio observacional, descriptivo, transversal, se incluyó a pacientes con patologías hematooncológicas e infección por aspergillus internados por un periodo de tres años. Resultados: Se incluyó a 55 pacientes, con edad promedio de 57,2±19,5 años. El 36,3% con edades comprendidas entre 40 a 59 años. 52,8% fue sexo femenino. 56,3% presentó hipertensión arterial. 27,2% linfoma no Hodking. 34,5% se encontraba en fase de mantenimiento al momento del diagnóstico de aspergilosis pulmonar. Respecto al grado de neutropenia el 34,7% presentó neutropenia severa. El 83,6% fue diagnosticado a traves de TACAR y galactomanano. El tiempo de inicio de síntomas hasta el momento del diagnóstico en promedio de días fue de 12,4±4,7 días. 38,1% presentó esputo con aislamiento positivo. Del tratamiento antifúngicos el 78,2% recibió anfotericina B y 21,8% Voriconazol. En relación a la evolución clínica 50,9% fueron alta, el 25,45% requirieron de Unidad de cuidados intensivos, 23,6%obitaron. Conclusión: Las aspergilosis pulmonar se presentó con predominio femenino, la mayoría se encontraba con neutropenia severa en fase de mantenimiento quimioterápico, dos tercios fue tratado con anfotericina B y la mitad fue dado de alta médica.

AbstractIntroduction: It is one of the opportunistic infections with the greatest impact on the patient with hemato-oncological pathologies, its early detection and timely treatment prevents its spread. Objective: To determine risk factors for mortality in hematological patients with pulmonary aspergillosis of patients hospitalized in a medical clinic at the Social Security Institute of the Central Hospital during 2016 to 2018. Methodology: Observational, descriptive, cross-sectional study included patients with hemato-oncological pathologies and infection by aspergillus hospitalized for a period of three years. Results: 55 patients were included, with an average age of 57.2 ± 19.5 years. 36.3% with ages between 40 to 59 years. 52.8% were female. 56.3% presented hypertension. 27.2% non-Hodking lymphoma. 34.5% were in the maintenance phase at the time of pulmonary aspergillosis diagnosis. Regarding the degree of neutropenia, 34.7% presented severe neutropenia. 83.6% were diagnosed through TACAR and galactomannan. Symptom onset time until diagnosis on average days was 12.4 ± 4.7 days. 38.1% presented sputum with positive isolation. Of the antifungal treatment, 78.2% received amphotericin B and 21.8% Voriconazole. In relation to the clinical evolution, 50.9% were high, 25.45% required an intensive care unit, 23.6% obliged. Conclusion: Pulmonary aspergillosis presented with a female predominance, the majority were with severe neutropenia in the phase of chemotherapy maintenance, two thirds were treated with amphotericin B and half were discharged medically.

[Systemic antifungal drugs]. / Antifúngicos de uso sistémico.

Invasive fungal infections have increased over the last decades and the therapeutic choices to treat them are limited. The antifungal agents currently available are useful and have optimal in vitro activity; however, their activity can be lowered due to the development of fungal resistance. The increase in primary or secondary resistance to some antifungal drugs has led to the search of alternatives such as the combination of drugs or the development of new antifungals. In this paper, the activity of the main families of antifungal drugs, polyenes, azoles, echinocandins, 5-fluorocytosine and other new antifungal drugs, are reviewed. The main resistance mechanisms developed by fungi are also described.

[Individualized antifungal therapy in critically ill patients with invasive fungal infection]. / Tratamiento antifúngico individualizado en el paciente crítico con infección fúngica invasora.

Invasive candidiasis (IC) is the most common invasive fungal infection (IFI) affecting critically ill patients, followed by invasive pulmonary aspergillosis (IPA). International guidelines provide different recommendations for a first-line antifungal therapy and, in most of them, echinocandins are considered the first-line treatment for IC, and triazoles are so for the treatment of IPA. However, liposomal amphotericinB (L-AmB) is still considered a second-line therapy for both clinical entities. Although in the last decade the management of IFI has improved, several controversies persist. The antifungal drugs currently available may have a suboptimal activity, or be wrongly used in certain IFI involving critically ill patients. The aim of this review is to analyze when to provide individualized antifungal therapy to critically ill patients suffering from IFI, emphasizing the role of L-AmB. Drug-drug interactions, the clinical status, infectious foci (peritoneal candidiasis is discussed), the fungal species involved, and the need of monitoring the concentration of the antifungal drug in the patient are considered.