Infecciones fúngicas en pacientes con COVID-19 / Fungal infections in patients with COVID-19

En diciembre de 2019 se identificó en Wuhan, China, un nuevo coronavirus denominado SARS-CoV-2, agente causal de la epidemia de neumonía atípica COVID-2019, que el 11 de marzo de 2020 fue declarada pandemia por la OMS.Hasta el 30 de septiembre de 2020, en Argentina fueron confirmados 751.001 casos y más de 16.937 muertes.La frecuencia y el impacto de las coinfecciones que afectan a los pacientes infectados por SARS-Cov-2 se ha estudiado junto con el avance de la pandemia. Entre las debidas a hongos se encuentran las fungemias por Candida sp, la aspergilosis invasora, las micosis sistémicas endémicas y la neumocistosis. Presentamos las distintas coinfecciones micosis-COVID-19 que fueron asistidas en nuestra institución entre abril y septiembre de 2020, y se realiza un análisis de las características de estas infecciones en pacientes con y sin sida. En este período se internaron 2837 pacientes, 2287 tuvieron diagnóstico confirmado de COVID-19. La coinfección de COVID-19 con micosis pulmonares o sistémicas fue menor al 1%.Dieciocho pacientes presentaron infecciones fúngicas pulmonares o sistémicas. Ocho padecieron candidemias, cinco criptococosis meningeas, dos histoplasmosis, dos aspergilosis invasoras agudas probables y una aspergilosis pulmonar crónica. La estadía prolongada en terapia intensiva facilitó las fungemias por Candida sp, los casos de histoplasmosis y criptococosis parecen relacionarse con la enfermedad avanzada por VIH y no con COVID-19. Los enfermos con un componente inflamatorio basal alto con neumonía grave por coronavirus se relacionan más con micosis invasoras que los enfermos VIH positivos con niveles bajos de LTCD4+

On December 2019 a new coronavirus (SARS-CoV2) result in atypical pneumonía epidemic, it was identified in Wuhan China and it was called COVID-19. Then on March 11 was declared pandemic by the WHO.Until September 30, 2020 in Argentina 751,001 cases and more than 16,937 deaths have been confirmed. The frequency and impact of co-infections affecting SARS-Cov2 infected patients has been studied with the advance of the pandemic. Among those due to fungi are Candida sp fungemias, invasive aspergillosis, endemic systemic mycoses, and pneumocystosis.We present the different mycosis-COVID-19 co-infections that were assisted in F. J. Muñiz Hospital between April and September of this year and review the characteristics of these infections in patients with and without AIDS is carried out.In this period, 2,837 patients were admitted in the Muñiz hospital, 2,287 had a confirmed diagnosis of COVID-19.Co-infection of COVID-19 with pulmonary or systemic mycoses was less than 1%.Eighteen patients had pulmonary or systemic fungal infections. Eight suffered from candidemia, five meningeal cryptococcosis, two histoplasmosis, two probable acute invasive aspergillosis, and one chronic pulmonary aspergillosis.Prolonged stay in intensive care facilitated fungemia due to Candida sp. Histoplasmosis and cryptococcosis cases seem to be related to advanced HIV disease and not to COVID-19.Patients with a high baseline inflammatory component with severe coronavirus pneumonia are more associated with invasive mycoses than HIV-positive patients with low levels of LTCD4 +

Risk factors associated with mortality among patients who had candidemia in a university hospital

Abstract INTRODUCTION: Bloodstream infection due to Candida spp. is a primary cause of morbidity and mortality in tertiary hospitals. METHODS: In this retrospective study, we included patients with a positive blood culture for Candida spp. after 48 h of hospitalization. RESULTS A total of 335 patients who had candidemia were included in this study. Risk factors associated with mortality were hospitalization in internal medicine units and surgical clinics, age >60 years, mechanical ventilation, orotracheal intubation, hemodialysis, corticosteroids use, and C. parapsilosis infection. CONCLUSIONS: This study highlights the importance of health care related to invasive procedures and actions to improve patient immunity.

Time of catheter removal in candidemia and mortality

ABSTRACT Background: The impact of central venous catheter (CVC) removal on the outcome of patients with candidemia is controversial, with studies reporting discrepant results depending on the time of CVC removal (early or any time during the course of candidemia). Objective: Evaluate the effect of time to CVC removal, early (within 48 h from the diagnosis of candidemia) vs. removal at any time during the course of candidemia, on the 30-day mortality. Methods: Retrospective cohort study of 285 patients with candidemia analyzing CVC removal within 48 h (first analysis) or at any time (second analysis). Results: A CVC was in place in 212 patients and was removed in 148 (69.8%), either early (88 patients, 41.5%) or late (60 patients, 28.3%). Overall, the median time to CVC removal was one day (range 1-28) but was six days (range 3-28) for those removed later. In the first analysis, APACHE II score (odds ratio [OR] 1.111, 95% confidence interval [95% CI] 1.066-1.158), removal at any time (OR 0.079, 95% CI 0.021-0.298) and Candida parapsilosis infection (OR 0.291, 95% CI 0.133-0.638) were predictors of 30-day mortality. Early removal was not significant. In the second analysis APACHE II score (OR 1.122, 95% CI 1.071-1.175) and C. parapsilosis infection (OR 0.247, 95% CI 0.103-0.590) retained significance. Conclusions: The impact of CVC removal is dependent on whether the optimal analysis strategy is deployed and should be taken into consideration in future analyses.

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.

The frequency of infective endocarditis in candida bloodstream infections: a retrospective study in a child hospital

Abstract Introduction: Fungal endocarditis is reported less frequently than bacterial endocarditis, with an incidence of 0-12% of the total pediatric infective endocarditis. Objective: In this study, the incidence of infective endocarditis in Candida bloodstream infections in a tertiary hospital during the periods of 2007 and 2016 was reviewed. Methods: Patients with positive blood or catheter cultures in terms of Candida spp. during the study period of January 2007 and January 2016 were analyzed in terms of Candida infective endocarditis. Infective endocarditis was defined according to the modified Duke criteria. The outcome, possible associated predisposing factors for Candida endocarditis were determined. Results: 221 patients and 256 attacks with positive blood or catheter cultures in terms of Candida were included in the study. The most common Candida species was Candida parapsilosis, isolated in 157 (61.3%) attacks, followed by Candida albicans in 70 (27.3%). Neurological diseases (23%), hemato-oncological diseases (12.1%), previously known heart diseases (8.2%), inborn errors of metabolism (9%) were common comorbidities. Twelve (5.4%) patients had a previous history of cardiac surgery. Among the 221 patients, Candida endocarditis was present in only two (0.9%) of them. Conclusion: Although Candida infective endocarditis is an uncommon but frequently fatal infection in pediatrics, echocardiography should be performed routinely for patients with positive blood or catheter cultures in terms of Candida. Prompt and effective antimicrobial therapy might prevent cardiac surgery in selected cases, however this could not be a general rule for all patients.

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.

Cambios clínicos y epidemiológicos de candidemias en pacientes adultos desde 2000 a 2013 / Clinical and epidemiological changes of candidemia among adult patients from 2000 to 2013

Background: Invasive Candida spp. infections have been described more frequently. Aim: To characterize the epidemiological data of candidemia in recent years. Methods: A retrospective study of adult patients in a University Hospital in Santiago, Chile, with 1 or more documented episodes of candidemia, from January 2000 to December 2013. Results: One hundred and twenty episodes of candidemia were identified in 120 patients, annual incidence of 0.4 cases per 1000 discharges, 53.3% were male patients, 58.3% > 60 years, 77,5% had at least one co-morbidity. Candida albicans was the species most frequently identified 55%, followed by C. glabrata 18.3%, C. tropicalis 11.7% and C. parapsilosis 9.2%. Comparing 2000-2006 vs 2007-2013, increased the frequency of C. parapsilosis among non-albicans and echinocandins prescription. Patients with C. albicans showed higher APACHE-II, more requirement for invasive mechanical ventilation, greater association with CVC, and shorter incubation time compared with non-albicans species. The 30-day mortality was 31.7%. Conclusions: During this 14-years period we observed that C. albicans was the predominant specie and more recently a change among C. non-albicans increasing C. parapsilosis and decreasing C. glabrata 30-days and attributable mortality decreased together with more echinocandins prescription.

Introducción: Las infecciones invasoras por Candida spp. se describen cada vez con mayor frecuencia. Objetivo: Precisar datos epidemiológicos de candidemia en nuestro hospital en los últimos años. Metodología: Estudio retrospectivo de pacientes adultos de un hospital universitario en Santiago, Chile, con un o más episodios de candidemia, acaecidas desde enero de 2000 a diciembre de 2013. Resultados: Se identificaron 120 episodios de candidemia, incidencia anual 0,4 casos x 1.000 egresos, 53,3% pacientes masculinos, 58,3% > 60 años y 77,5% presentaban al menos una co-morbilidad. Candida albicans fue la especie más frecuente (55%), seguida por C. glabrata (18,3%), C. tropicalis (11,7%) y C. parapsilosis (9,2%). Los tiempos de incubación e identificación fueron más prolongados para C. glabrata. Al comparar el período 2000-2006 vs 2007-2013, aumentó la frecuencia de C. parapsilosis entre las C. no-albicans y el uso de equinocandinas. Los pacientes con C. albicans presentaban puntaje APACHE-II más elevado, mayor requerimiento de ventilación mecánica invasora, mayor asociación a CVC y menor tiempo de incubación respecto C. no-albicans. La mortalidad a 30 días fue de 31,7%. Conclusiones: Durante este período de 14 años observamos predominio de C. albicans y en el período reciente incremento de C. parapsilosis con disminución de C. glabrata, una disminución de mortalidad global y atribuible junto a mayor uso de equinocandinas.

Thyroid abnormalities in term infants with fungal sepsis / Alterações tireoidianas no recém-nascido de termo com sepse fúngica

Summary Objective: To describe thyroid alterations in term newborns (TNB) with fungal sepsis during NICU hospitalization. Method: The study included six TNB that during the clinical and laboratory manifestations of sepsis with positive cultures for fungus showed changes in thyroid hormones, called low T3 syndrome and low T3-T4 syndrome. TNB that could present hormonal changes caused by disease as those born to mothers with thyroid disease, or who had perinatal asphyxia and major surgeries were excluded. Results: Of six TNB with fungal sepsis, five had positive culture for Candida albicans and one had positive culture for Candida tropicalis. Low T3 syndrome was observed in two TNB (50%), while T3-T4 syndrome was observed in other two (100%). The four children progressed to septic shock. Conclusion: Fungal sepsis is becoming more common among newborns admitted to NICU. Thyroid insufficiency could be a marker of disease severity with possible need for hormone supplementation.

Resumo Objetivo: descrever as alterações tireoidianas em recém-nascidos de termo (RNT) que apresentaram sepse fúngica durante internação na UTI neonatal. Método: foram incluídos seis RNT que, durante as manifestações clínicas e laboratoriais de sepse, com culturas positivas para fungo, apresentaram alterações dos hormônios tireoidianos, denominadas síndrome do T3 baixo e síndrome do T3 e T4 baixo. Foram excluídos RNT que apresentaram alteração hormonal por doença, como RNT filhos de mães com doença tireoidiana, asfixia perinatal e cirurgias de grande porte. Resultados: dos seis RNT com sepse fúngica, cinco apresentavam cultura positiva para Candida albicans e um para C. tropicalis. A síndrome do T3 baixo foi observada em duas crianças (50%) e a do T3 e T4 baixo em dois RN (100%). As quatro crianças evoluíram com choque séptico. Conclusão: a sepse fúngica é cada vez mais frequente nos recém-nascidos internados em UTI neonatal. A insuficiência tireoidiana pode vir a ser marcadora de gravidade da doença, e a suplementação hormonal pode ser necessária.

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.

Clinical and epidemiological characteristics and risk factors for mortality in patients with candidemia in hospitals from Bogotá, Colombia

Background: Bloodstream infection by Candida species has a high mortality in Latin American countries. The aim of this study was to describe the characteristics of patients with documented bloodstream infections caused by Candida species in third level hospitals and determine the risk factors for in-hospital-mortality. Methods: Patients from seven tertiary-care hospitals in Bogotá, Colombia, with isolation of a Candida species from a blood culture were followed prospectively from March 2008 to March 2009. Epidemiologic information, risk factors, and mortality were prospectively collected. Isolates were sent to a reference center, and fluconazole susceptibility was tested by agar-based E-test. The results of susceptibility were compared by using 2008 and 2012 breakpoints. A multivariate analysis was used to determinate risk factors for mortality. Results: We identified 131 patients, with a median age of 41.2 years. Isolates were most frequently found in the intensive care unit (ICU). Candida albicans was the most prevalent species (66.4% of the isolates), followed by C. parapsilosis (14%). Fluconazole resistance was found in 3.2% and 17.6% of the isolates according to the 2008 and 2012 breakpoints, respectively. Fluconazole was used as empirical antifungal therapy in 68.8% of the cases, and amphotericin B in 22%. Hospital crude mortality rate was 35.9%. Mortality was associated with age and the presence of shock at the time of Candida detection. Fluconazole therapy was a protective factor for mortality. Conclusions: Candidemia is associated with a high mortality rate. Age and shock increase mortality, while the use of fluconazole was shown to be a protective factor. A higher resistance rate with new breakpoints was noted. .

SUSCEPTIBILITY OF Candida spp. ISOLATED FROM BLOOD CULTURES AS EVALUATED USING THE M27-A3 AND NEW M27-S4 APPROVED BREAKPOINTS / Suscetibilidade de Candida spp. isoladas de hemocultivos, avaliadas pelos breakpoints dos documentos M27-A3 e M27-S4 do CLSI

The high mortality rates associated with candidemia episodes and the emergence of resistance to antifungal agents necessitate the monitoring of the susceptibility of fungal isolates to antifungal treatments. The new, recently approved, species-specific clinical breakpoints (SS-CBPs)(M27-S4) for evaluating susceptibility require careful interpretation and comparison with the former proposals made using the M27-A3 breakpoints, both from CLSI. This study evaluated the susceptibility of the different species of Candida that were isolated from candidemias based on these two clinical breakpoints. Four hundred and twenty-two isolates were identified and, among them, C. parapsilosis comprised 46.68%, followed by C. albicans (35.78%), C. tropicalis (9.71%), C. glabrata (3.55%), C. lusitaniae (1.65%), C. guilliermondii (1.65%) and C. krusei (0.94%). In accordance with the M27-A3 criteria, 33 (7.81%) non-susceptible isolates were identified, of which 16 (3.79%) were resistant to antifungal agents. According to SS-CBPs, 80 (18.95%) isolates were non-susceptible, and 10 (2.36%) of these were drug resistant. When the total number of non-susceptible isolates was considered, the new SS-CBPs detected 2.4 times the number of isolates that were detected using the M27-A3 interpretative criteria. In conclusion, the detection of an elevated number of non-susceptible species has highlighted the relevance of evaluating susceptibility tests using new, species-specific clinical breakpoints (SS-CBPs), which could impact the profile of non-susceptible Candida spp. to antifungal agents that require continuous susceptibility monitoring.

As elevadas taxas de mortalidade associadas com episódios de candidemia e a emergência da resistência aos antifúngicos, requerem o monitoramento da suscetibilidade de Candida spp., isoladas das candidemias, frente aos agentes antifúngicos. Os novos breakpoints, chamados “espécie-específicos,” foram recentemente aprovados (M27-S4) requerendo, pois, cuidadosa interpretação e comparações com aqueles até agora utilizados (M27-A3); ambos são propostos pelo Clinical Laboratory Standard Institute (CLSI). O presente estudo avaliou a suscetibilidade de espécies de Candida isoladas de candidemias baseando-se nestes dois breakpoints. Quatrocentos e vinte e dois isolados de Candida foram identificados e assim distribuídos: C. parapsilosis (48,68%), C. albicans (35,78%), C. tropicalis (9,71%), C. glabrata (3,55%), C. lusitaniae (1,65%), C. guilliermondii (1,65%), C. krusei (0,94%). Com base nos critérios do M27-A3, um total de 33 (7,81%) isolados foram julgados não-sensíveis, dos quais 16 (3,79%) como resistentes aos antifúngicos. De acordo com os breakpoints espécie-específicos (M27-S4) um total de 80 (18,95%) isolados foram considerados não-sensíveis, dos quais 10 (2,36%) resistentes a algum dos antifúngicos testados. Com base nos novos breakpoints espécie-específicos, o número de isolados não-sensíveis foi 2,4 vezes maior do que o número de não-sensíveis detectado pelos breakpoints do documento M27-A3. A detecção de um elevado número de isolados não-sensíveis através dos breakpoints propostos pelo M27-S4 destaca a importância dos testes de suscetibilidade, os quais trarão impactos no reconhecimento de isolados de Candida spp. não-sensíveis em episódios de candidemias, requerendo, portanto, continua avaliação.

FUNGEMIA CAUSED BY Candida SPECIES IN A CHILDREN'S PUBLIC HOSPITAL IN THE CITY OF SÃO PAULO, BRAZIL: STUDY IN THE PERIOD 2007-2010 / Fungemia por espécies de Candida em Hospital Pediátrico da cidade de São Paulo, Brasil: estudo no período de 2007 a 2010

Candidemia remains a major cause of morbidity and mortality in the health care environment. The epidemiology of Candida infection is changing, mainly in relation to the number of episodes caused by species C. non-albicans. The overall objective of this study was to evaluate the frequency of yeasts of the genus Candida, in a four-year period, isolated from blood of pediatric patients hospitalized in a public hospital of the city of São Paulo, Brazil. In this period, yeasts from blood of 104 patients were isolated and, the identified species of Candida by phenotypic and genotypic methods were: C. albicans (39/104), C. tropicalis (25/104), C. parapsilosis (23/104), Pichia anomala (6/104), C. guilliermondii (5/104), C. krusei (3/104), C. glabrata (2/104) and C. pararugosa (1/104). During the period of the study, a higher frequency of isolates of C. non-albicans (63.55%) (p = 0.0286) was verified. In this study we verified the increase of the non-albicans species throughout the years (mainly in 2009 and 2010). Thus, considering the peculiarities presented by Candida species, a correct identification of species is recommended to lead to a faster diagnosis and an efficient treatment.

Candidemia permance como a maior causa de morbidade e mortalidade em ambiente hospitalar. A epidemiologia de infecções por Candida vem se alterando, principalmente em relação ao número de episódios causados por espécies não-albicans. Este estudo teve como objetivo avaliar a frequência, em um período de quatro anos, de leveduras do gênero Candida isoladas de sangue de pacientes pediátricos internados em hospital público da cidade de São Paulo, Brasil. Neste período foram isoladas leveduras de sangue de 104 pacientes, e as espécies de Candida identificadas, por métodos fenotípicos e genotípicos, foram: C. albicans (39/104), C. tropicalis (25/104), C. parapsilosis (23/104), Pichia anomala (6/104), C. guilliermondii (5/104), C. krusei (3/104), C. glabrata (2/104) e C. pararugosa (1/104). Em todo período do estudo foi observada maior frequência de isolamento de C. não-albicans (63,55%) (p = 0,0286). Neste estudo verificou-se aumento das espécies não-albicans ao longo dos anos (principalmente em 2009 e 2010), assim, ressalta-se que correta identificação em nível de espécie é recomendável, para que isso acarrete diagnóstico rápido e tratamento eficaz.

Epidemiologia de candidemia en Córdoba Republica Argentina. Estudio de vigilancia de cinco instituciones / [Candidemia epidemiology in Córdoba Argentina. Surveillance study of five institutions].

UNLABELLED: The incidence rate of invasive infections due to Candida species has increased drastically in the last 20 years, causing a 40

mortality rate in hospitalized patients. In order to comprehend the epidemiology of Candida bloodstream infection, the study was carried out. MATERIALS AND METHODS: A retrospective study was done based on microbiology laboratory reports from five terciary care hospitals from the city of Cordoba between January 2010 and August 2012. RESULTS: 158 patients had candidemia, the average age was 55,8 years, and 54

of patients were in the intensive care unit. Candida albicans (44

) and Candida tropicalis (12

) were the main fungi isolated. Candida parapsilosis was commonly associated with catether infections. CONCLUSIONS: The data from the city of Cordoba showed that C. albicans, C. parapsilosis y C. tropicalis were the more frequent species isolated from blood cultures. This is similar to what is seen in other series published from Argentina and Latinamerica. This study may have implications when it comes to deciding which empiric antifugal agent is best for the treatment of candidemia.

Incidencia y prevalencia de candidemia en pacientes críticamente enfermos en Colombia / Incidence and prevalence of candidemia in critically ill patients in Colombia

Introduction: Candidemia is an infectious complication with high morbidity and mortality in intensive care patients. Objective: The aim of this study was to determine the incidence and prevalence of candidemia in critically ill patients in Colombian hospitals between 2004 and 2008. Materials and Methods: Data from microbiologically confirmed candidemia cases, ICU stay and admissions were retrospectively recorded in 7 Colombian hospitals between 2004 and 2008. Time series analysis was performed with monthly incidence (number of cases of candidemia in relation to the number of patient-days) and prevalence (number of cases of candidemia in relation to the number of admissions) for each institution and the whole group. Results: 382 cases of candidemia were identified, with an incidence of 2,3 cases per 1.000 patient-days in ICU, and a prevalence of 1,4%. There was a trend to increased incidence (0,0066 additional cases per 1.000 ICU-days per month) and prevalence (0,0016 additional cases por 100 patients per month) of candidemia. This increase of candidemia cases was due to a rise of non- albicans Candida species, which corresponded to 44% of total isolates. Discusion and Conclusions: Candidemia cases in colombian ICUs are increasing, especially those caused by non albicans Candida species.

Introducción: La candidemia es una complicación con alta morbilidad y mortalidad en pacientes en cuidado intensivo. Objetivo: Determinar la incidencia y prevalencia de candidemia en hospitales colombianos entre 2004 y 2008. Materiales y Métodos: En siete hospitales colombianos se obtuvieron retrospectivamente los datos de candidemia confirmada por el laboratorio y de estancia y egreso en unidades de cuidado intensivo. Se construyeron series de tiempo de densidad de incidencia (definida como el número de casos de candidemias en el mes en relación al número de días-pacientes hospitalizados) y de densidad de prevalencia mensuales (número de casos de candidemias en el mes en relación al número de egresos) para cada institución y para el conjunto de hospitales. Resultados: Se identificaron 3 82 casos, con una incidencia de 2,3 casos por 1.000 días de estancia en UCI, y una prevalencia fue de 1,4%. Se observó una tendencia al aumento en la incidencia (0,0066 casos adicionales por cada 1.000 días de estancia por mes) y en la prevalencia de candidemia (0,0016 casos adicionales por 100 pacientes por mes). El aumento en la prevalencia y en la incidencia se observó a partir de un incremento en las especies de Candida no albicans, la cual correspondió a 44% de los aislados totales. Discusión y conclusiones: La incidencia y la prevalencia de candidemia en Colombia son elevadas y van en aumento, especialmente a expensas de casos de Candida no albicans.

Is timely and appropriate antifungal drug enough for survival of adult cases with candidaemia? Five-year experience / ¿Es el uso oportuno y adecuado de antimicóticos suficiente para la supervivencia de casos de adultos con candidemia? Cinco años de experiencia

OBJECTIVE: Candidaemia is the fourth most common cause of nosocomial bloodstream infections. The objective of this paper was to evaluate the risk factors associated with mortality in patients with candidaemia with respect to Candida species and their susceptibilities, retrospectively. METHODS: All consecutive patients who developed candidaemia at an 800-bed training and research hospital were enrolled in this retrospective, observational, single centre study during the period June 2006 to December 2011. RESULTS: A total of 97 candidaemia episodes were identified in 97 patients during the study period with an overall incidence of four episodes/10 000 admissions in adults. Crude 30-day mortality rates among patients with candidaemia were 56% (55 of 97 cases). Urinary catheterization, immunosuppressive therapy, acute physiology and chronic health evaluation (APACHE) II score (>16) and hypoal-buminaemia were found to be independent risk factors for fatal candidaemia. CONCLUSIONS: Adult cases with candidaemia who have risk factors associated with mortality are more likely to have poor prognosis despite appropriate and timely initiated antifungal drug treatment. Empiric antifungal drug should be tailored according to the severity of the patients ' conditions and local antifungal susceptibility.

OBJETIVO: La candidemia es la cuarta causa más común de infecciones nosocomiales del flujo sanguíneo. El objetivo del presente trabajo fue evaluar los factores de riesgo asociados con la mortalidad en pacientes con candidemia con respecto a las especies de Candida y sus susceptibilidades, de manera retrospectiva. MÉTODOS: Todos los pacientes consecutivos que desarrollaron candidemia en un hospital de capacitación e investigación de 800 camas, fueron inscritos en este estudio retrospectivo, observacional, monocéntrico, durante el período de junio de 2006 a diciembre de 2011. RESULTADOS: Se identificaron un total de 97 episodios de candidemia en 97 pacientes durante el período de estudio con una incidencia general de cuatro episodios/10 000 ingresos en adultos. Las tasas brutas de mortalidad de 30 días entre los pacientes con candidemia fueron 56% (55 de 97 casos). Se halló que la cateterización urinaria, la terapia inmunosupresiva, y la puntuación (> 16) de la escala de Evaluación de la fisiología aguda y salud crónica (APACHE II) así como la hipoalbuminemia, constituyen factores de riesgo para una candidemia fatal. CONCLUSIONES: Los casos adultos con candidemia que tienen factores de riesgo asociados con mortalidad son más propensos a tener un pronóstico pobre a pesar del tratamiento apropiado y oportuno con medicamentos antimicóticos. Los antimicóticos empírico se deben adaptar según la severidad de las condiciones de los pacientes y la susceptibilidad antifúngica local.

Historical trends in the epidemiology of candidaemia: analysis of an 11-year period in a tertiary care hospital in Brazil

Candida species are an important cause of bloodstream infections (BSI). To evaluate the epidemiological, clinical and microbiological aspects of two cohorts {1994-1999 [period 1 (P1) ]; 2000-2004 [period 2 (P2) ]} of candidaemic patients, we performed a retrospective analysis from a laboratory-based survey. A total of 388 candidaemias were identified, with an incidence of 0.20/1,000 patient-days and a significant increase in P2 vs. P1 (0.25 vs. 0.15, p = 0.04). Cancer and prior antibiotic use were frequent and Candida albicans was the most prevalent species found (42.4%). Resistance to fluconazole was found in 2.47% of the strains. No differences were observed in the species distribution of Candida during the study periods. In the P2 cohort, there were higher prevalence of elderly individuals, cardiac, pulmonary and liver diseases, renal failure, central venous catheters and antibiotic therapy. In P1, there were higher prevalence of neurological diseases and chemotherapy. The crude mortality was 55.4%. In conclusion, our incidence rates remained high. Furthermore, the distribution pattern of Candida species and the fluconazole resistance profile remained unchanged. Moreover, we found a clear trend of higher prevalence of candidaemia among the elderly and among patients with comorbidities. Finally, it is necessary to discuss strategies for the prevention and control of Candida BSI in Brazil.

A review of Candida species causing blood stream infection.

The incidence of candidemia has been on a rise worldwide. The epidemiology of invasive fungal infections in general and of candidemia in particular has changed in the past three decades because of a variety of factors like the AIDS epidemic, increased number of patients receiving immunosuppressive therapy for transplantation and the increasing use of antimicrobials in the hospital setups and even in the community. The important risk factors for candidemia include use of broad-spectrum antimicrobials, cancer chemotherapy, mucosal colonization by Candida species, indwelling vascular catheters like central venous catheters, etc. More than 90% of the invasive infections due to Candida species are attributed to five species-Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis and Candida krusei. However, the list of new species of Candida isolated from clinical specimens continues to grow every year. Early diagnosis and proper treatment is the key for management of candidemia cases.

Colonização fúngica em recém-natos de muito baixo peso: um estudo de coorte / Fungal colonization in newborn babies of very low birth weight: a cohort study

OBJETIVOS: Conhecer o perfil de colonização fúngica e os fatores de risco associados em recém-nascidos prematuros. MÉTODOS: Coorte prospectiva, de 01/04/10 a 31/04/11, com 44 pacientes admitidos na unidade de terapia intensiva neonatal, nascidos na maternidade do hospital, com peso menor que 1.500 g. Na admissão, coletaram-se dados sobre pré-natal e parto. Informações clínico-laboratoriais, swabs nasal, retal e hemocultura periférica foram coletados nos dias 1, 7, 10 e 14 de permanência na unidade de terapia intensiva neonatal e, então, a cada 7 dias até alta ou óbito. Para análise estatística, utilizou-se teste qui-quadrado, exato de Fisher, curva de Kaplan-Meier e modelo de regressão logística. RESULTADOS: A incidência de colonização foi de 13,5/1.000 pacientes/dia. A de candidemia foi de 0,9/1.000 paciente/dia. A média de internamento foi de 30,5 dias (±20,27), sendo o início da colonização, em média, aos 11,13 dias (±8,82). O parto vaginal foi um fator de risco independente para desenvolvimento de colonização fúngica ao longo da internação [p = 0,042; odds ratio = 4,38; intervalo de confiança de 95% (IC95%) = 1,13-16,99]. Da mesma forma, a leucocitose (> 30.000/mm3) na admissão foi um sinalizador para a presença concomitante de colonização (p = 0,048). A presença de displasia broncopulmonar tende a ser um fator de maior chance para desenvolvimento de colonização (p = 0,067). O sítio de colonização mais acometido foi a mucosa retal: 89,09 versus 10,9% da nasal. CONCLUSÃO: Parto vaginal e leucocitose acima de 30.000/mm3 na admissão foram fatores de risco para colonização fúngica no decorrer da hospitalização.

OBJECTIVES: To learn about the profile of fungal colonization and related risk factors in premature newborns. METHODS: Prospective cohort, from 04/01/2010 to 04/31/2011, with 44 patients admitted to the neonatal intensive care unit, born at the hospital maternity, weighing less than 1,500 g. On admission, data were collected on pre-natal care and childbirth. Clinical and laboratory information, nasal and rectal swabs, and peripheral blood cultures were collected on days 1,7,10 and 14 of stay in neonatal intensive care unit and then, every 7 days until discharge or death. For statistical analysis, we used chi-square test, Fisher exact test, Kaplan-Meier and logistic regression model. RESULTS: The incidence of colonization was 13.5/1,000 patients/day. The incidence of candidemia was 0.9/1,000 patients/day. The average hospitalization time was 30.5 days (± 20.27), and the onset of colonization occurred, in average, at 11.13 days (±8.82). Vaginal delivery was found to be an independent risk factor for the development of fungal colonization during hospitalization (p = 0.042, odds ratio = 4.38, 95% confidence interval [95%CI] = 1,13-16,99). Likewise, leukocytosis (> 30,000/mm3) on admission was an indicator for the simultaneous presence of fungal colonization (p = 0.048). The presence of bronchopulmonary dysplasia tends to be a factor of higher probability for the development of colonization (p = 0.067). The most affected colonization site was the rectal mucosa: 89.09 versus 10.9% of the nasal mucosa. CONCLUSION: Vaginal delivery and leukocytosis over 30,000/mm3 on admission were found to be risk factors for fungal colonization during hospitalization.