Evaluation of the effect of antibiotics used during parenteral nutrition treatment on Candidemia

SUMMARY OBJECTIVE: Parenteral nutrition is an important risk factor for candidemia. In this risk analysis study, the effect of previous antibiotic administration apart from the length of hospital stay, duration of Parenteral nutrition treatment, and Candida score parameters on developing candidemia was evaluated in the non-neutropenic patients receiving Parenteral nutrition treatment. METHODS: In this double center, retrospective, and cross-sectional study, the data of patients who received Parenteral nutrition treatment were collected. Patients with or without candidemia after the initiation of Parenteral nutrition treatment were compared in terms of demographic features, Candida score, length of hospital stay, duration of Parenteral nutrition treatment, and previous use of antibiotics. Then, predictor factors affecting the probability of candidemia during Candida growth time were determined by the Cox regression analysis. RESULTS: A total of 148 patients (59.5% males) were included and 16 (10.81%) of these had candidemia after initiation of parenteral nutrition treatment. The median (min-max) duration of parenteral nutrition treatment was 11 (4-72) days and the Candida growth time was 13 (7-29) days. Statistically significant differences were found between patients with or without candidemia groups in terms of length of hospital stay (p<0.001), duration of parenteral nutrition treatment (p<0.001), and Candida score (p<0.001). To determine the effect of these variables and antibiotics on candidemia, length of hospital stay [Hazard Ratio 1.030; p=0.021] and piperacillin-tazobactam (Hazard Ratio 5.626; p=0.030) were found significant and independent risk factors on the development of candidemia. CONCLUSION: There are some well-known risk factors including length of hospital stay, duration of Parenteral nutrition treatment, and Candida score; the potential impact of piperacillin-tazobactam administration should also be considered since they may be effective on the development of candidemia.

Clinical and epidemiological aspects of Candidemia in eight medical centers in the state of Parana, Brazil: Parana Candidemia Network

ABSTRACT Objectives: Candida spp. has been reported as one of the common agents of nosocomial bloodstream infections and is associated with a high mortality. Therefore, this study evaluated the clinical findings, local epidemiology, and microbiological aspects of candidemia in eight tertiary medical centers in the state of Parana, South of Brazil. Methods: In this study, we reported 100 episodes of candidemia in patients admitted to eight different hospitals in five cities of the state of Parana, Brazil, using data collected locally (2016 and 2017) and tabulated online. Results: The incidence was found to be 2.7 / 1000 patients / day and 1.2 / 1000 admissions. C. albicans was responsible for 49% of all candidemia episodes. Cancer and surgery were the two most common underlying conditions associated with candidemia. The mortality rate within 30 days was 48%, and removal of the central venous catheter (p = 0.029) as well as empirical or prophylactic exposure to antifungals were both related to improved survival (p = 0.033). Conclusions: This study highlights the high burden and mortality rates of candidemia in hospitals from Parana as well as the need to enhance antifungal stewardship program in the enrolled medical centers.

Tratamiento satisfactorio con fluconazol de la candidemia relacionada con el catéter porCandida haemulonii: informe sobre dos pacientes neonatales / Successful fluconazole treatment of catheter-related candidemia caused by Candida haemulonii: report of 2 neonatal cases

La Candida haemulonii forma parte de la especie Candida no albicans. La candidemia por C. haemulonii es sumamente infrecuente, pero mortal, en los recién nacidos. Se informa sobre los dos primeros recién nacidos con candidemia por C. haemulonii en China tratados con fluconazol y se revisan dos artículos informados con anterioridad. Nuestro informe incrementa la sensibilización sobre la candidemia por C. haemulonii en recién nacidos críticos y resalta la importancia de un diagnóstico y un tratamiento tempranos de esta infección mortal.

Candida haemulonii forms part of the non-albicans Candida species. The candidemia caused by C. haemulonii is extremely rare but fatal in neonates. We reported the first two neonates with C. haemulonii candidemia in China which were treated with fluconazole and reviewed two papers previously reported. Our report adds further awareness on C. haemulonii candidemia in critical neonates and points out the importance of an early diagnosis and treatment of this fatal infection.

Secular trends of candidemia at a Brazilian tertiary care teaching hospital

ABSTRACT Background Candidemia is the most frequent invasive fungal disease in hospitalized patients, and is associated with high mortality rates. The main objective of this study was to evaluate changes in the epidemiology of candidemia at a tertiary care hospital in a 21-year period. Methods We evaluated all episodes of candidemia diagnosed between 1996 and 2016 at a University-affiliated tertiary care hospital in Brazil. We arbitrarily divided the study period in 3: 1996-2002 (period 1), 2003-2009 (period 2) and 2010-2016 (period 3). Incidence rates were calculated using hospital admissions as denominator. Results We observed 331 episodes of candidemia. The incidence was 1.30 episodes per 1000 admissions, with no significant change over time. Candida albicans (37.5%), C. tropicalis (28.1%), C. parapsilosis (18.4%) and C. glabrata (6.9%) were the most frequent species. The proportion of patients receiving treatment increased (65.5%, 79.4% and 74.7% in periods 1, 2 and 3, respectively, p= 0.04), and the median time from candidemia to treatment initiation decreased from 4 days in period 1 (range 0-32 days) to 2 days in period 2 (range 0-33 days) and 2 days in period 3 (range 0-14 days, p< 0.001). We observed a significant decrease in the use of deoxycholate amphotericin B (47.4%, 14.8% and 11.9%), and an increase in the use of echinocandins (0%, 2.8% and 49.1%; p< 0.001). The APACHE II score increased over time (median 16, 17.5, and 22, p< 0.001). The overall 30-day mortality was 58.9%, and did not change significantly over the study period. Conclusions There was an improvement in patient care, with an increase in the proportion of patients receiving treatment and a decrease in the time to treatment initiation, but no improvement in the outcome, possibly because the proportion of sicker patients increased over time.

Candidemias en pediatría: distribución de especies y sensibilidad a los antifúngicos / Candidemia in Pediatrics: Species distribution and antifungal susceptibility

Las infecciones graves causadas por levaduras del género Candida son frecuentes en la población hospitalaria. Debido a las diferencias en la distribución de especies y la sensibilidad a los antifúngicos según el área geográfica y el tipo de paciente, resulta importante estudiar la epidemiología de cada institución. Con este propósito, hemos realizado un estudio retrospectivo y descriptivo sobre las candidemias ocurridas en el Hospital de Ninos «Superiora Sor María Ludovica¼ de la ciudad de La Plata. En un período de 6 años (2010-2015) se registraron 177 episodios de candidemia. Las especies predominantes fueron Candida albicans (45%) y Candida parapsilosis (28%). Las salas de internación con mayor cantidad de episodios fueron las unidades de terapia intensiva de pediatría, la neonatal y la cardiovascular (58%). En los casos donde se realizaron pruebas de sensibilidad a los antifúngicos, no se observó resistencia a la anfotericina B en todo el período y la resistencia a azoles se limitó a 4 aislamientos de especies menos frecuentes.

Serious infections caused by Candida yeasts are frequent in the hospital population. Due to differences in species distribution and antifungal susceptibility testing depending on the geographic area and the type of patient, it is important to study the epidemiology of each institution. For this purpose, we conducted a retrospective, descriptive study on the occurrence of candidemia in the Children's Hospital "Superiora Sor María Ludovica" of the city of La Plata. In a 6-year period (2010-2015), 177 candidemia episodes were recorded. The predominant species were Candida albicans (45%) and Candida parapsilosis (28%). The hospital wards with the highest number of candidemia episodes were the pediatric, neonatal and cardiovascular intensive care units (58%). No resistance to amphotericin B was observed throughout the period whereas resistance to azoles was limited to 4 strains of less frequent species.

Epidemiología, especies, resistencia antifúngica y evolución de las candidemias en un hospital universitario de Buenos Aires, Argentina, durante 16 años / Epidemiology, species, antifungal resistance and outcome of candidemia in a university hospital in Buenos Aires, Argentina for 16 years

Resumen Introducción: La epidemiologia de las candidemias varía en cada región. Objetivos: Conocer la epidemiología de las candidemias en un hospital durante 16 años. Material y Métodos: Se revisaron los episodios de candidemia ocurridos en el Hospital de Clínicas de Buenos Aires desde 01/01/98 al 31/12/13. Resultados: Se identificaron 374 episodios de candidemia. La incidencia fue de 2,21/1.000 egresos y aumentó de 1,96 (1998-2005) a 2,25 (2006-2013) (p = 0,023). Se diagnosticaron: 5,4% en neonatos, 1,7% en lactantes, 6,5% en niños mayores, 31,8% en adultos y 52,7% en adultos mayores de 64 años. Los episodios fueron causados por C. albicans (40,9%), C. parapsilosis (21,7%), C. tropicalis (15,5%), C. glabrata (13,9%), otras especies de Candida (5,1%) y candidemias multiespecies (2,9%). El 5,3% de los aislados fue resistente a fluconazol. Setenta y cuatro por ciento de los pacientes recibió tratamiento; 70,3% lo inició con fluconazol, 25% con anfotericina B desoxicolato y 4,7% con equinocandinas o anfotericinas lipídicas. Se retiró 81% de los catéteres venosos centrales. La mortalidad fue de 47,9%, pero fue de 60,8% para los adultos mayores. Conclusión: La incidencia de candidemias se incrementó a través de los años, fue mayor en los adultos mayores y esta población tuvo peor evolución.

Background: The epidemiology of candidemia vary by region. Aim: To determine the epidemiology of candidemia in a hospital for 16 years. Material and Methods: Episodes of candidemia occurred in the Hospital de Clinicas of Buenos Aires were reviewed, from 01/01/98 to 31/12/13. Results: 374 episodes of candidemia were identified. The incidence was 2.21/1,000 discharges and increased from 1.96 (1998-2005) to 2.25 (2006-2013) (p = 0.023). Candidemia was diagnosed: 5.4% in neonates, 1.7% in infants, 6.5% in children, 31.8% in adults and 52.7% in elderly adults over 64 years old. The episodes were caused by C. albicans (40.9%), C. parapsilosis (21.7%), C. tropicalis (15.5%), C. glabrata (13.9%), other species of Candida (5.1%) and more than one species of Candida (2.9%). The 5.3% of the isolates were resistant to fluconazole. 74% of patients were treated. Initial treatments were with fluconazole (70.3%), amphotericin B deoxycholate (25%), echinocandins or lipidic amphotericin (4,7%). The 81% of central venous catheters were taken off. Mortality rate was of 47.9%, but in the elderly adults was of 60.8%. Conclusion: The incidence of candidemia showed an increase over the years. It was higher in the elderly adults, being the group with worse outcomes.

Epidemiología y susceptibilidad antifúngica de especies causantes de candidemia en la ciudad de Valdivia, Chile / Epidemiology and antifungal susceptibility of species producing candidemia in Valdivia, Chile

Resumen Introducción: La epidemiología de la candidemia en Chile es poco conocida, a pesar de ser una enfermedad frecuente y grave. Objetivos: Analizar la incidencia y perfil de susceptibilidad in vitro de especies del género Candida causantes de candidemia en el Hospital Base Valdivia. Material y Métodos: Se identificó todos los casos de candidemia ocurridos en la institución entre marzo de 2009 y agosto de 2011. Se estudió la distribución de especies y susceptibilidad in vitro por el método de disco difusión. Resultados: Se estudiaron 27 episodios de candidemia. La incidencia varió de 0,3 a 0,7 por 1.000 egresos (según servicio clínico). Fueron factores de riesgo: la hospitalización, uso previo de antimicrobianos, edad avanzada y enfermedad de base (insuficiencia renal, enfermedad cardiaca y pulmonar). La especie más frecuente fue C. albicans seguida de C. tropicalis, C. glabrata y C. krusei. Voriconazol fue el antifúngico con mejor actividad in vitro y hubo resultados variables para anfotericina B, fluconazol e itraconazol. Discusión: La incidencia encontrada fue superior a la de países desarrollados. Candida albicans, constituye la especie más frecuente, con alta sensibilidad in vitro a fluconazol, debiendo ser vigiladas las especies de Candida no albicans. Es fundamental desarrollar nuevas investigaciones para detectar potenciales variaciones epidemiológicas.

Background: Candidemia disease in Chile is not very known, despite being a very common and serious disease. Aim: To analyze incidence and susceptibility profile of species from the genus Candida in Hospital Base Valdivia. Material and Methods: All candidemia cases presented between March 2009 and August 2011 in our institution were identified. Species distribution and susceptibility were studied through the disk diffusion method. Results: Twenty-seven candidemia episodes were studied. Incidence varied from 0.3 to 0.7 by a thousand discharges (according to clinical service). Risk factors were hospitalization, preliminary use of antibiotics, aged people and underlying disease (renal failure, heart and lung disease). The most frequent species was C. albicans, followed by C. tropicalis, C. glabrata and C. krusei. Voriconazole was the antifungal showing the best in vitro performance. Amphotericin B, fluconazole and itraconazole presented variable results. Discussion: Incidence found was superior to that described in developed countries. Candida albicans constitute the most frequent species, with high sensitivity levels to fluconazole; Candida no albicans species must be monitored. Developing new research on the topic appears as fundamental to detect potential epidemiological variations.

Risk factors for candidemia mortality in hospitalized children / Fatores de risco de mortalidade por candidemia em crianças internadas

Abstract Objective: To evaluate risk factors associated with death due to bloodstream infection caused by Candida spp. in pediatric patients and evaluate the resistance to the main anti-fungal used in clinical practice. Methods: This is a cross-sectional, observational, analytical study with retrospective collection that included 65 hospitalized pediatric patients with bloodstream infection by Candida spp. A univariate analysis was performed to estimate the association between the characteristics of the candidemia patients and death. Results: The incidence of candidemia was 0.23 cases per 1000 patients/day, with a mortality rate of 32% (n = 21). Clinical outcomes such as sepsis and septic shock (p = 0.001), comorbidities such as acute renal insufficiency (p = 0.01), and risks such as mechanical ventilation (p = 0.02) and dialysis (p = 0.03) are associated with increased mortality in pediatric patients. The resistance and dose-dependent susceptibility rates against fluconazole were 4.2% and 2.1%, respectively. No resistance to amphotericin B and echinocandin was identified. Conclusion: Data from this study suggest that sepsis and septic shock, acute renal insufficiency, and risks like mechanical ventilation and dialysis are associated with increased mortality in pediatric patients. The mortality among patients with candidemia is high, and there is no species difference in mortality rates. Regarding the resistance rates, it is important to emphasize the presence of low resistance in this series.

Resumo Objetivo: Avaliar os fatores de risco associados ao óbito por infecção da corrente sanguínea causada pela Candida spp em pacientes pediátricos e avaliar a resistência ao principal antifúngico usado na prática clínica. Métodos: Este é um estudo transversal, observacional e analítico com coleta retrospectiva que incluiu 65 pacientes pediátricos internados com infecção da corrente sanguínea por Candida spp. Foi feita uma análise univariada para estimar a associação entre as características dos pacientes com candidemia e o óbito. Resultados: A incidência de candidemia foi de 0,23 casos em cada 1.000 pacientes/dia, com taxa de mortalidade de 32% (n = 21). O resultado clínico como sepse e choque séptico (p = 0,001), comorbidades como insuficiência renal aguda (p = 0,01) e riscos como ventilação mecânica (p = 0,02) e diálise (p = 0,03) estão associados ao aumento da mortalidade em pacientes pediátricos. As taxas de resistência e susceptibilidade dose-dependente contra o fluconazol foram de 4,2% e 2,1%, respectivamente. Não foi identificada resistência à anfotericina B e equinocandina. Conclusão: Os dados de nosso estudo sugerem que a sepse e o choque séptico, a insuficiência renal aguda e riscos como ventilação mecânica e diálise estão associados ao aumento da mortalidade em pacientes pediátricos. A mortalidade entre pacientes com candidemia é alta e não há diferença nas taxas de mortalidade entre as espécies. Sobre a resistência, é importante enfatizar a presença de baixa resistência nesta série.

Eficacia y seguridad del uso de anidulafungina en pacientes no neutropénicos con candidemia y respuesta inadecuada o reaccion adversa a fluconazol / Efficacy and safety of the use of anidulafungin in non-neutropenic patients with candidemia and inadequate response or adverse reaction to fluconazole

INTRODUCCIÓN: Antecedentes: El presente dictamen expone la evaluación de tecnología de la eficacia y seguridad del uso Anidulafungina en pacientes no neutropénicos con candidemia y respuesta inadecuada o reacción adversa a fluconazol. Aspectos Generales: La candidiasis sistémica es una patología con alta morbilidad y mortalidad (1). La colonización por candida spp. se desarrolla en hasta el 80 % de los pacientes críticos que permanecen más de una semana en cuidados intensivos, mientras que la candidiasis invasiva se documenta en sólo un 5 a un 10% de ellos. El tiempo de diagnóstico puede ser afectado por la complejidad que representa en sus criterios, causando retrasos en el inicio del tratamiento adecuado, haciendo que las candidemia y las candidiasis invasivas tengan peores pronósticos que otras infecciones de reconocimiento más sencillo. Tecnologia Sanitaria de Interés: La anidulafungina es una equinocandina semisintética, un lipopéptido obtenido a partir de un producto de fermentación de Aspergillus nidulans. Este producto farmacéutico actúa inhibiendo selectivamente la 1,3-3-D glucanosintetasa, enzima presente en las células fúngicas, pero no en las células de mamíferos. Como resultado no se forma 1,3-13- D glucano, el cual es esencial en la pared celular fúngica. La anidulafungina ha demostrado actividad fungicida frente a candida spp. y actividad frente a Aspergillus fumigatus; la actividad in vitro de anidulafungina frente a las especies de candida spp. no es homogénea. En concreto, la concentración mínima inhibitoria de la anidulafungina en el caso de la C. parapsilosis es superior a la observadas en otras especies de candida spp. METODOLOGIA: Estrategia de Búsqueda: Se realizó una estrategia de búsqueda sistemática de la evidencia científica con respecto a la eficacia y seguridad de Anidulafungina en pacientes adultos no neutropénicos con candidemia que son intolerantes o resistentes a fluconazol. Para la búsqueda primaria se revisó la información disponible por entes reguladoras y normativas como la Food and Drug Administration (FDA), la Agencia Europea de Medicamentos (EMA), y la Dirección General de Medicamentos y Drogas (DIGEMID). Posteriormente se buscaron Guías de Práctica Clínica a través de los metabuscadores: Translating Research into Practice (TRIPDATABASE), National Library of Medicine (Pubmed-Medline), The National Guideline Clearinghouse (NGC), UpToDate y Health Systems Evidence (HSE). Finalmente, se realizó una búsqueda dentro de la información generada por grupos internacionales que realizan revisiones sistemáticas, evaluación de tecnologías sanitarias y guías de práctica clínica, tales como The Cochrane Library, The National Institute for Health and Care Excellence (NICE), The Canadian Agency for Drugs and Technologies in Health (CADTH), The Scottish Medicines Consortium (SMC), que a su vez fue complementada con una búsqueda en ww.clinicaltrials.gov , para identificar estudios primarios en elaboración o que no hayan sido publicados aún. RESULTADOS: Sinopsis de la Evidencia: Se realizó búsqueda bibliográfica y de evidencia científica que sustente el uso de Anidulafungina en pacientes adultos no neutropénicos con candidemia que son intolerantes o resistentes a fluconazol según la pregunta PICO establecida. En relación a los estudios encontrados para la población de interés descrita en la pregunta PICO no se encontraron estudios que comparen directamente mediante un ensayo clínico las equinocandinas (anidulafungina, caspofungina y micafungina) en pacientes con candidemia o infecciones sistémicas por candida spp. Se encontraron 2 revisiones sistemáticas con evidencia indirecta. Además, se encontró un ensayo clínico de evidencia indirecta que puede ser usada para responder la pregunta PICO, que compara Anidulafungina con Fluconazol en pacientes con candidiasis invasiva. CONCLUSIONES: El Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) aprueba el uso de anidulafungina según el esquema planteado en la pregunta PICO para pacientes no neutropénicos con candidemia y respuesta inadecuada o reacción adversa a fluconazol.

Candida parapsilosis: principal causa de candidemia en un hospital de referencia para adultos de Costa Rica / Candida parapsilosis: a major cause of bloodstream infection in a tertiary care hospital in Costa Rica

Background: Invasive Candida bloodstream infections are frequent and display high mortality in clinical practice. There is scarce published on this topic in Central America. Objective: To characterize the epidemiology of candidemia in a hospital setting in Costa Rica. Methods: 210 cases of nosocomial candidemia were analyzed in patients over 17 years of age, admitted to Hospital Mexico, between 2007 and 2011. Descriptive and temporary analyses were performed and the risk factors associated with C. parapsilosis and survival were evaluated. Results: The incidence rate of candidemia was 1.47 cases per 1,000 admissions. The non-albicans Candida represented 62% of the isolated yeasts. Except for 2009, C. parapsilosis was the most commonly isolated species in four out of the five years reviewed, followed by C. albicans. There was a strong association between C. parapsilosis, the presence of a central venous catheter (OR: 4.8, CI 95%: 1.8-14.6, p < 0.001) and the use of parenteral nutrition (p: 0.008). The 30-day mortality was 50%. Candida albicans displayed the highest mortality and C. parapsilosis the lowest. Patients who did not receive anti-fungal treatment showed a significantly higher probability of death. Conclusions: The high incidence of candidemia from C. parapsilosis is directly related to the use of central venous catheters and parenteral nutrition. There is a need for creating local guidelines addressing the use of central venous catheters and parenteral nutrition, as well as implementing hand hygiene protocols.

Introducción: Las infecciones invasoras por Candida son frecuentes y de alta mortalidad. Existe poca información publicada de la región centroamericana. Objetivo: Caracterizar la epidemiología de la candidemia en un hospital de Costa Rica. Métodos: Se analizaron 210 episodios de candidemia nosocomial en pacientes sobre 17 años de edad, entre los años 2007 y 2011. Se realizó un análisis descriptivo y temporal de la serie y evaluación de las características clínicas asociadas haciendo énfasis en C. parapsilosis. Resultados: La incidencia acumulada de candidemia fue 1,47 casos/1.000 admisiones. Las especies de Candida no albicans constituyeron 62% de las levaduras aisladas. Exceptuando el año 2009, C. parapsilosis fue la especie predominante en cuatro de los cinco años estudiados, seguida por C. albicans. Se demostró una fuerte asociación entre C. parapsilosis, la presencia de catéter venoso central (OR: 4,8, IC 95%: 1,8-14,6, p < 0,001) y el uso de nutrición parenteral (p: 0,008). La mortalidad a 30 días fue de 50%. Candida albicans mostró la mortalidad más alta y C. parapsilosis la más baja. Los pacientes que no recibieron tratamiento antifúngico presentaron un aumento significativo en la mortalidad. Conclusiones: La incidencia elevada de candidemia por C. parapsilosis está relacionada con los catéteres venosos centrales y la administración de nutrición parenteral. Para su control es necesario establecer guías locales para uso de los catéteres venosos centrales y la nutrición parenteral, así como implementar estrategias para promocionar la higiene de las manos.