Gut microbiome in association with chemotherapy-induced toxicities among patients with breast cancer.

BACKGROUND: Little research has focused on the relationship between gut microbiome and chemotherapy-induced toxicity. METHODS: This prospective study involves 301 patients with breast cancer who had prechemotherapy stool samples collected. Gut microbiome was sequenced by shotgun metagenomics; associations with chemotherapy-induced toxicities during first-line treatment by gut microbial diversity, composition, and metabolic pathways with severe (i.e., grade ≥3) hematological and gastrointestinal toxicities were evaluated via multivariable logistic regression. RESULTS: High prechemotherapy α-diversity was associated with a significantly reduced risk of both severe hematological toxicity (odds ratio [OR] = 0.94; 95% CI, 0.89-0.99; p = .048) and neutropenia (OR = 0.94; 95% CI, 0.89-0.99; p = .016). A high abundance of phylum Synergistota, class Synergistia, and order Synergistales were significantly associated with a reduced risk of severe neutropenia; conversely, enrichment of phylum Firmicutes C, class Negativicutes, phylum Firmicutes I, and class Bacilli A, order Paenibacillales were significantly associated with an increased risk of severe neutropenia (p range: 0.012-2.32 × 10-3; false discovery rate <0.1). Significant positive associations were also observed between severe nausea/vomiting and high Chao1 indexes, ß-diversity (p < .05), 20 species belonging to the family Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae (p value range: 6.14 × 10-3 to 1.33 × 10-5; false discovery rate <0.1), and three metabolic pathways involved in reductive tricarboxylic acid cycle I and cycle II, and an incomplete reductive tricarboxylic acid cycle (p < .01). Conversely, a high abundance of species Odoribacter laneus and the pathway related to the L-proline biosynthesis II were inversely associated with severe nausea/vomiting. CONCLUSIONS: Our study suggests that gut microbiota may be a potential preventive target to reduce chemotherapy-induced toxicity.

¿Son válidos los criterios del síndrome de respuesta inflamatoria sistémica en la valoración de la neutropenia febril? / Are the systemic inflammatory response síndrome valid in the assessment of febrile neutropenia?

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Epidemiología y factores de riesgo de internación prolongada en niños con leucemia y bacteriemia: estudio de cohorte / Epidemiology and risk factors for prolonged hospital length of stay in children with leukemia and bacteremia: cohort study

Resumen Introducción: La bacteriemia constituye una complicacion frecuente en los niños con cáncer, que se asocia a mayor gravedad, internación prolongada y mortalidad. La internación prolongada condiciona mayor morbilidad y riesgo de adquisición de infecciones intranosocomiales. Objetivo: Analizar factores de riesgo de internación prolongada en niños con leucemia y bacteriemia. Pacientes y Métodos: Cohorte retrospectiva. Se incluyeron niños con leucemia internados en el Hospital Garrahan entre 1/1/2015 y 31/12/2016 con bacteriemia. Se compararon características de pacientes con internaciones menores o mayores a 14 días. Se realizó un análisis bivariado y modelo de regresión logística. Se utilizó Stata 13. Resultados: n = 121. Mediana de edad 59 meses. Tenían leucemia linfoblastica 81 pacientes (67%) y leucemia mieloblástica 40 (33%). Tenían catéter venoso central (CVC) 96 de los niños (79%), neutropenia 94 (78%), neutropenia menor a 100 neutrófilos 79 (65%). La identificación en hemocultivos fue: 55 casos (45%) enterobacterias, 28 (23%) Staphylococcus coagulasa negativa, Streptococcus spp grupo viridans 19 (16%), Pseudomonas aeruginosa 8 (7%). Huo co-infección viral en 14 pacientes (12%).Tuvieron menos de 14 días de internación 71 pacientes (59%) y mayor período 50 (41%). En el análisis multivariado la bacteriemia asociada a CVC (OR 21,73; IC95% 1,2-43,20; p 0,04), neutropenia profunda al ingreso (OR 1,75; IC95% 1,82-1,28; p 0,03) y co-infección viral (OR 27,42; IC95% 2,88-260,83; p 0,004) fueron factores de riesgo de internación > 14 días. Conclusiones: La bacteriemia asociada a CVC, la neutropenia profunda al ingreso y la co-infección se asociaron con una internación igual o mayor a 14 días.

ABSTRACT Introduction: Bacteremia is a frequent complication in children with cancer, which is associated with greater severity, prolonged hospitalization and mortality. Prolonged hospitalization conditions greater morbidity and risk of acquisition of intranosocomial infections. Aim: To describe risk factors for prolonged hospital length of stay in children with leukemia and bacteremia. Methods: Cohort study. Episodes of bacteremia in patients with leukemia at Garrahan Hospital from 1/1/2015 to 31/12/2016 were reviewed. We compared data from patients with a LOS of 14 days or more with those admitted for less than 14 days. Bivariate and logistic regression analysis was performed. We used Stata 13 statistical package. Results: n = 121. Median age 59 months.81 patients (67%) had a diagnosis of acute lymphoblastic leukemia, followed by acute myeloid leukemia in 40 (33%). 96 patients (79%) had a central venous catheter (CVC), 94 patients (78%) were neutropenic. Blood cultures were positive for Enterobacteriaceae in 55 cases (45%), coagulase-negative staphylococci in 28 cases (23%), Group viridans Streptococcus in 19 (16%), Pseudomonas aeruginosa in 8 (7%). (9%). By the multivariate analysis, three factors remained significantly associated with length of stay of more than 14 days: CVC associated bacteremia (OR 21,73; CI95% 1.2-43.2; p 0.04), severe neutropenia (OR 1.75; CI95% 1.82-1.28; p 0.03) and coinfection (OR 27.4; CI95% 2.8-260.8; p 0.004). Conclusion: CVC associated bacteremia, severe neutropenia and viral coinfection were associated with hospital LOS of more than 14 days.

Feohifomicosis nasal por Curvularia spicifera en un paciente pediátrico con neutropenia y leucemia mieloide aguda / Nasal phaeohyphomycosis by Curvularia spicifera in pediatric patient with neutropenia and acute myeloid leukemia

There are very few reports of pediatric patients with infections by dematiaceous filamentous fungi. In this publication we report a case of invasive fungal infection of the nasal septum by Curvularia spicifera in a pediatric patient with acute myeloid leukemia. The patient presented with a painful scabby wound in the nasal vestibule. Culture and universal PCR were consistent with Curvularia spicifera. Early management with surgical debridement and bi-associated antifungal therapy achieved complete resolution of the lesions, with no evidence of dissemination and relapses. Clinical management of these fungal infections represents a challenge as the antifungal selection and duration of therapy is not yet well stablished.

Existen pocos reportes de infecciones por hongos dematiáceos en pediatría. Comunicamos el caso de una infección fúngica invasora del tabique nasal en un niño con una leucemia mieloide aguda, que se presentó como una lesión costrosa dolorosa en el vestíbulo nasal. Se realizó desbridamiento quirúrgico precoz y recibió tratamiento antifúngico biasociado, lográndose resolución completa de las lesiones, sin diseminación ni recaídas. El cultivo y la RPC universal fueron compatibles con Curvularia spicifera. El manejo de estas infecciones fúngicas representa un desafío, considerando que la elección del agente antifúngico y la duración de la terapia no están completamente establecidas.

Diagnostic-driven antifungal therapy in neutropenic patients using the D-index and serial serum galactomannan testing

Abstract Introduction Invasive mold disease is an important complication of patients with hematologic malignancies, and is associated with high mortality. A diagnostic-driven approach has been an alternative to the classical empiric antifungal therapy. In the present study we tested an algorithm that incorporated risk stratification using the D-index, serial serum galactomannan and computed tomographic-scan to guide the decision to start antifungal therapy in neutropenic patients. Patients and methods Between May 2010 and August 2012, patients with acute leukemia in induction remission were prospectively monitored from day 1 of chemotherapy until discharge or death with the D-index and galactomannan. Patients were stratified in low, intermediate and high risk according to the D-index and an extensive workup for invasive mold disease was performed in case of positive galactomannan (≥0.5), persistent fever, or the appearance of clinical manifestations suggestive of invasive mold disease. Results Among 29 patients, 6 (21%), 11 (38%), and 12 (41%) were classified as high, intermediate, and low risk, respectively. Workup for invasive mold disease was undertaken in 67%, 73% and 58% (p = 0.77) of patients in each risk category, respectively, and antifungal therapy was given to 67%, 54.5%, and 17% (p = 0.07). Proven or probable invasive mold disease was diagnosed in 67%, 45.5%, and in none (p = 0.007) of high, intermediate, and low risk patients, respectively. All patients survived. Conclusion A risk stratification using D-index was a useful instrument to be incorporated in invasive mold disease diagnostic approach, resulting in a more comprehensive antifungal treatment strategy, and to guide an earlier start of treatment in afebrile patients under very high risk.

Factores de riesgo de colonización por Enterococcus spp resistente a vancomicina en pacientes pediátricos hospitalizados con patología oncológica / Risk factor of intestinal colonization with vancomycin resistant Enterococcus spp in hospitalized pediatric patients with oncological disease

Background: The isolation of vancomycin-resistant Enterococcus spp (ERV) has increased significantly within the last few years, along with the risk of infection and dissemination of these bacteria. Our aim was to determine risk factors (RF) for intestinal colonization in hospitalized pediatric patients with oncological disease at Hospital de Niños Roberto del Río. Methods: Between January 2012 and December 2013 a transversal study was performed with 107 rectal swabs and processed with a PCR for ERV. The patients were classified as "colonized with ERV" and "not colonized with ERV" and we evaluated possible RF for intestinal colonization in both groups. Results: VRE colonization was found in 51 patients (52%). The median of time elapsed between oncological diagnosis and VRE colonization was 35 days. The significant RF associated with VRE colonization were days of hospitalization prior to study, neutropenia and treatment with antibiotics within 30 days prior to study and mucositis. Conclusions: According to the RF revealed in this study we may suggest prevention standards to avoid ERV colonization. This is the first investigation in our country in hospitalized pediatric patients with oncological disease and processed with a multiplex PCR for ERV, therefore it is a great contribution about this subject in Chile.

Introducción: El aislamiento de Enterococcus spp resistentes a vancomicina (ERV) ha presentado un incremento significativo en los últimos años, aumentando el riesgo de infección por esta bacteria y favoreciendo su diseminación. Nuestro objetivo es determinar los factores de riesgo (FR) de colonización intestinal de ERV en pacientes oncológicos internados en el Hospital de Niños Roberto del Río. Método: Entre enero de 2012 y diciembre de 2013 se realizó un estudio transversal de colonización rectal por ERV mediante muestras de hisopado rectal obtenidas en 107 pacientes efectuando RPC múltiple para ERV. Se dividió en grupo "portador" y "no portador" y se evaluó los posibles FR para colonización por ERV. Resultados: Se encontró colonización por ERV en 51 pacientes (52%). El tiempo transcurrido desde el diagnóstico oncológico y la colonización presentó una mediana de 35 días. Los FR encontrados con asociación significativa fueron el número de días de hospitalización previa, neutropenia, uso de antimicrobianos 30 días previos y mucositis. Conclusión: De acuerdo a los FR encontrados podemos sugerir medidas de prevención para colonización por ERV. Esta es la primera investigación realizada en nuestro país en pacientes oncológicos pediátricos y que utiliza la técnica de RPC múltiple para ERV, lo que permite un aporte significativo sobre este tema en Chile.

Agentes causantes de bacteriemia en niños con cáncer y neutropenia febril de alto riesgo en seis hospitales de Santiago, Chile, período 2004-2009 / Bloodstream infections in children with cancer and high risk fever and neutropenia episodes in six hospitals of Santiago, Chile between 2004 and 2009

Introduction: To determine the etiology of invasive bacterial infection in high risk febrile neutropenia (HRFN) episodes in children with cancer is essential because of the favorable impact on mortality of the early empiric antibiotic treatment. Objective: To determine the etiology of bacteremia in pediatric patients with cancer and HRFN in the National Child Program of Antineoplastic Drugs during the 2004-2009 period, and compare these agents and their antimicrobial susceptibility with the period 1994-1998 described in a previous study. Methods: The causative agents of bacteremia were prospectively recorded in patients less than 18 years of age receiving chemotherapy for cancer with HRFN and positive blood cultures admitted to one of the six hospitals from the Child Program of Antineoplastic Drugs network during the period 2004-2009. Results: 839 episodes of HRFN were identified; 181 blood cultures were positive in the following proportion: gram positive cocci (56%), gram negative bacilli (42%) and yeast (2%).The most common etiologic agents were Staphylococcus coagulase negative (25%), Escherichia. coli (20%), group viridans Streptococcus (14%), Staphylococcus aureus (13%) and Pseudomonas aeruginosa (9%). Comparing the two periods, the relative frequency of Streptococcus spp increased from 4 to 17%, coagulase negative Staphylococcus decreased from 44 to 25%, showing an increase in their resistance to oxacillin from 55% to 77%. Conclusions: We describe the main etiological agents from HRFN episodes in children with cancer in a 5 years period. This information could help for a better approach in the empirical antimicrobial therapy in this population.

Introducción: Conocer la etiología de los episodios de neutropenia febril de alto riesgo (NFAR) en pacientes con cáncer tiene importancia para implementar tratamientos antimicrobianos ajustados a la epidemiología local, lo que tiene impacto en la morbilidad y mortalidad. Objetivo: Describir la etiología de las bacteriemias en niños con cáncer y NFAR en el período 2004-2009, en la red PINDA de Santiago (Región Metropolitana), Chile, y comparar estos agentes y su susceptibilidad antimicrobiana con un estudio previo realizado en el período 1994-1998. Material y Métodos: Se registraron prospectivamente los agentes causantes de bacteriemia y su susceptibilidad a antimicrobianos de los pacientes bajo 18 años de edad en tratamiento quimioterápico por cáncer, ingresados con diagnóstico de NFAR a los seis hospitales de la red, durante el período 2004-2009. Resultados: De 839 episodios de NFAR, 181 tuvieron hemocultivos positivos, correspondientes a cocáceas grampositivas (56%), bacilos gramnegativos (42%) y levaduras (2%). Los agentes más frecuentemente aislados fueron: Staphylococcus coagula-sa negativa (25%), Escherichia coli (20%), Streptococcus grupo viridans (14%), Staphylococcus aureus (13%) y Pseudomonas spp (9%). Al comparar los dos períodos de tiempo, destacan los siguientes cambios significativos: disminución en frecuencia relativa de Staphylococcus coagulasa negativa (desde 44 a 25%), aumento de Streptococcus spp (desde 4 a 17%), y aumento de la resistencia de Staphylococcus coagulasa negativa a oxacilina (desde 55 a 77%). Conclusiones: Se dan a conocer los principales agentes etiológicos de los episodios de NFAR y la susceptibilidad a antimicrobianos en un período de cinco años. Esto permite racionalizar el manejo antimicrobiano empírico de los episodios de NFAR en esta población.

Bacteriemia en pacientes oncológicos: Experiencia en un hospital pediátrico / Bacteremia in cancer patients: Experience in a pediatric hospital

The use of intensive chemotherapy has improved survival of children with cancer. However, this is associated to severe and maintained neutropenia, increasing risks of severe infections like bacteremia. Aim: To update information on microorganisms involved in bloodstream infections in cancer patients and their antimicrobial resistance patterns during the last 3 years in our hospital, comparing it with our previous experience and with other Chilean centres. Material and Methods: Analysis of positive blood cultures belonging to cancer patients during 2006-2008 registered in the Microbiology Lab at the Roberto Del Rio Children's Hospital. Results: In 52 patients, 96 blood cultures yielded bacteria: 59.4% gram positive cocci and 34.4%, gram negative rods. Coagulase negative Staphylococci (CNS) were the most frequent bacteria isolated and enterobacteria were in the second place. Susceptibility to cloxacillin was 11% in CNS and 70 % in Staphylococcus aureus isolates. Enterobacteria maintained susceptibility to third generation cephalosporins and aminoglycosides. Conclusion: Despite the low sensitivity of CNS to cloxacillin, the empirical antibiotic treatment in our unit must include cloxacillin because of the high susceptibility of S. aureus. Switching to vancomycin should be considered only if SCN is isolated or there is an unfavorable evolution.

El uso de quimioterapia más intensiva ha mejorado la sobrevida de los niños con cáncer. Sin embargo, esto se asocia a neutropenia intensa y mantenida, aumentando el riesgo de infecciones graves como bacteriemias. Objetivo: Actualizar la información sobre los microorganismos implicados en las infecciones del torrente circulatorio en pacientes oncológicos atendidos en nuestro hospital, comparar con la literatura médica y describir el patrón de resistencia antimicrobiana. Material y Métodos: Se revisaron los registros de hemocultivos del Laboratorio de Microbiología del Hospital de Niños Roberto Del Río entre los años 2006 y 2008, seleccionando aquellos con resultado positivo y que pertenecieran a pacientes con cáncer. Resultados: En 52 pacientes, 96 hemocultivos resultaron positivos: cocáceas grampositivas 59,4% (Staphylococcus coagulasa negativa-SCN fue el más frecuente); bacilos gramnegativos 34,4%, predominando las enterobacterias, en segundo lugar. Se observó en SCN una susceptibilidad a cloxacilina de 11% y en Staphylo-coccus aureus de 70%. Las enterobacterias mantuvieron una susceptibilidad estable para cefalosporinas de tercera generación y aminoglucósidos. Conclusión: A pesar de la baja susceptibilidad de SCN a cloxacilina, el tratamiento antimicrobiano empírico de primera línea en nuestra unidad debe incluir cloxacilina dada la alta susceptibilidad de S. aureus, y el cambio a vancomicina debería plantearse frente al aislamiento de SCN o evolución desfavorable.

Infection profile of patients undergoing autologous bone marrow transplantation in a Brazilian institution / Perfil de infecção em pacientes submetidos a transplante autólogo de medula óssea em uma instituição brasileira

CONTEXT AND OBJECTIVE: Hematopoietic stem cell transplantation (HSCT) has been widely used for treating oncological and hematological diseases. Although HSCT has helped to improve patient survival, the risk of developing infection during hospitalization is an important cause of morbidity and mortality. This study aimed to analyze the infection profile during hospitalization and the associated risk factors among patients undergoing autologous HSCT at the University Hospital, Universidade Federal de Juiz de Fora. DESIGN AND SETTING: This was a cross-sectional study on patients undergoing autologous HSCT at a public university hospital. METHODS: Patients with febrile neutropenia between 2004 and 2009 were retrospectively evaluated regarding their infection profile and associated risk factors. RESULTS: Infection occurred in 57.2 percent of 112 patients with febrile neutropenia. The main source of infection was the central venous catheter (25.9 percent). Infection was chiefly due to Gram-positive bacteria, although Gram-negative-related infections were more severe and caused a higher death rate. Sex, age, skin color, nutritional status and underlying disease were not associated with the development of infection. Patients with severe mucositis (Grades III and IV) had a higher infection rate (P < 0.001). Patients who developed pulmonary complications during hospitalization had higher infection rates (P = 0.002). Infection was the main cause of death (57.1 percent) in the study sample. CONCLUSION: Strategies aimed at reducing infection-related mortality rates among patients undergoing autologous HSCT are necessary.

CONTEXTO E OBJETIVO: O transplante de células-tronco hematopoiéticas (TCTH) vem sendo amplamente utilizado no tratamento das doenças onco-hematológicas. Embora o TCTH tenha colaborado para a melhora na sobrevida dos pacientes, o risco de desenvolver infecção no período de internação é uma importante causa de morbi-mortalidade. O presente estudo teve como objetivo analisar o perfil das infecções no período de internação e os fatores de risco associados entre os pacientes submetidos ao TCTH autólogo, no Hospital Universitário da Universidade Federal de Juiz de Fora. TIPO DE ESTUDO E LOCAL: Trata-se de um estudo transversal sobre pacientes submetidos a transplante autólogo, em um hospital público universitário. MÉTODOS: Foram analisados retrospectivamente os pacientes que apresentaram neutropenia febril no período de 2004 a 2009, com relação ao perfil infeccioso e os fatores de risco associados. RESULTADOS: A infecção foi determinada em 57,2 por cento dos 112 pacientes com neutropenia febril. A principal fonte de infecção foi o cateter venoso central (25,9 por cento). A infecção ocorreu principalmente devido a bactérias Gram-positivas, apesar de as infecções causadas por bactérias Gram-negativas terem sido mais graves e causado maior taxa de morte. Sexo, idade, cor da pele, estado nutricional e doença de base não estiveram associados com o desenvolvimento da infecção. Pacientes com mucosite grave (graus III e IV) apresentaram maior taxa de infecção (P < 0.001). Os pacientes que desenvolveram complicações pulmonares durante a internação apresentaram maiores taxas de infecção (P = 0,002). A infecção foi a principal causa do óbito (57,1 por cento) na amostra estudada. CONCLUSÃO: São necessárias estratégias voltadas para a redução da taxa de mortalidade relacionada com infecção entre pacientes submetidos ao TCTH autólogo.

Fatal neutropenic enterocolitis due to Clostridium septicum / Enterocolitis neutropénica fatal a causa de Clostridium septicum

We describe a case of Clostridium septicum enterocolitis in a patient with pre-B acute lymphoblastic leukaemia undergoing autologous stem cell transplant. In the setting of neutropenia, Clostridium septicum should be suspected in patients who develop signs and symptoms of acute abdomen.

Se describe el caso de una enterocolitis por Clostridium septicum en un paciente con leucemia linfoblástica aguda (LLA) pre-B sometido a trasplante de células madre autológico. En el marco de una neutropenia, debe sospecharse la presencia de Clostridium septicum en pacientes que desarrollan signos y síntomas de abdomen agudo.

Febrile neutropaenia in cancer patients / Neutropenia febril en pacientes con cáncer

BACKGROUNDS: Febrile neutropaenia is a common complication of chemotherapy in cancer patients. Empirical antibiotic regimes are based on the epidemiological characteristics of bacterial isolates globally and locally. METHOD: This study retrospectively reviewed all cases of febrile neutropaenia in patients with confirmed cancer admitted at the University Hospital of the West Indies in the four-year period between, January 1, 2003 and December 31, 2006 and who received chemotherapy. Cases were identified from blood culture records and hospital charts which were reviewed to determine the aetiological agents causing bacteraemia, their antimicrobial susceptibilities and clinical features. These cases were compared with non-neutropaenic cancer patients admitted with fever. RESULTS: A total of 197 febrile episodes in cancer patients were reviewed. Thirty-seven per cent had febrile neutropaenia while 62% were non-neutropaenic. Acute myeloid leukaemia was the most common haematological malignancy and the most common solid tumour was breast cancer. Twenty-six per cent of patients had a positive blood culture. In febrile neutropaenic patients, Escherichia coli was the most common organism isolated followed by coagulase-negative staphylococci while in non-neutropaenic patients, coagulase-negative staphylococci was most common. Acinetobacter infections was prominent in non-neutropaenic patients but absent in neutropaenic patients. More than one organism was cultured in 9 neutropaenic and 18 non-neutropaenic patients. Mortality was 10.8% in neutropaenic and 24.4% in non-neutropaenic patients. CONCLUSION: Gram-negative organisms are the predominant isolates in febrile neutropaenic episodes in this cohort of patients. Non-neutropaenic patients had an increased mortality with an increase in Acinetobacter infections and multiple isolates.

ANTECEDENTES: La neutropenia febril es una complicación común de la quimioterapia en pacientes con cáncer. Los regimenes de antibióticos empíricos se basan en las características epidemiológicas de aislados bacterianos, tanto global como localmente. MÉTODO: Este estudio examinó retrospectivamente todos los casos de neutropenia febril con confirmación de cáncer, ingresados y tratados con quimioterapia en el Hospital Universitario de West Indies, Jamaica, en el período de cuatro años entre el 1ero, de enero de 2003 y el 31 de diciembre de 2006. Se identificaron casos con historias de cultivos de sangre e historias clínicas que fueron examinadas para determinar los agentes etiológicos causantes de la bacteriemia, sus susceptibilidades antimicrobianas y características clínicas. Estos casos fueron comparados con pacientes de cáncer no neutropénicos ingresados con fiebre. RESULTADOS: Se examinaron un total de 197 episodios febriles en pacientes de cáncer. El treinta y siete por ciento tuvo neutropenia febril, mientras que el 62% eran no neutropénicos. La leucemia mieloide aguda fue la malignidad hematológica más común, y el tumor sólido más común fue el cáncer de mamas. Veintiséis por ciento de .los pacientes tuvieron cultivos de sangre positivos. En los pacientes neutropénicos febriles, Escherichia coli fue el organismo aislado más común, seguido de los estafilococos coagulasa-negativos, mientras que en los pacientes no neutropénicos, los estafilococos coagulasa-negativos fueron los más comúnes. Las infecciones por Acinetobacter fueron prominentes en pacientes no neutropénicos pero ausentes en los pacientes neutropénicos. Más de un organismo fue cultivado en 9 pacientes neutropénicos y 18 en no neutropénicos. La mortalidad fue de 10.8% en los pacientes neutropénicos y 24.4% en los no neutropénicos. CONCLUSIÓN: Los organismos gram-negativos son los aislados que predominan en los episodios neutropénicos febriles en Jamaica. Los pacientes no neutropénicos vieron su mortalidad aumentada con el incremento en infecciones Acinetobacter y aislados múltiples.

Factors associated with bacteremia due to multidrug-resistant Gram-negative bacilli in hematopoietic stem cell transplant recipients

The epidemiology of bacteremia developing during neutropenia has changed in the past decade, with the re-emergence of Gram-negative (GN) bacteria and the development of multidrug resistance (MDR) among GN bacteria. We conducted a case-control study in order to identify factors associated with bacteremia due to multidrug-resistant Gram-negative (MDRGN) isolates in hematopoietic stem cell transplant recipients. Ten patients with MDRGN bacteremia were compared with 44 patients with GN bacteremia without MDR. Bacteremia due to Burkholderia or Stenotrophomonas sp was excluded from analysis (3 cases), because the possibility of intrinsical resistance. Infection due to MDRGN bacteria occurred in 2.9 percent of 342 hematopoietic stem cell transplant recipients. Klebsiella pneumoniae was the most frequent MDRGN (4 isolates), followed by Pseudomonas aeruginosa (3 isolates). Among non-MDRGN, P. aeruginosa was the most frequent agent (34 percent), followed by Escherichia coli (30 percent). The development of GN bacteremia during the empirical treatment of febrile neutropenia (breakthrough bacteremia) was associated with MDR (P < 0.001, odds ratio = 32, 95 percent confidence interval = 5_190) by multivariate analysis. Bacteremia due to MDRGN bacteria was associated with a higher death rate by univariate analysis (40 vs 9 percent; P = 0.03). We were unable to identify risk factors on admission or at the time of the first fever, but the occurrence of breakthrough bacteremia was strongly associated with MDRGN bacteria. An immediate change in the antibiotic regimen in such circumstances may improve the prognosis of these patients.

Etiología de episodios de neutropenia febril en pacientes adultos con cáncer hematológico y de órganos sólidos en el Hospital Clínico Universidad Católica, Santiago-Chile / Etiology of febrile neutropenia episodes among cancer patients from Hospital Clinico Universidad Catolica, Santiago-Chile

Introduction: The surveillance of febrile neutropenia (FN) episodes in every center allows adapt the antibiotic therapy guidelines to local epidemiology. Aim: To characterize clinical features and compare the FN etiology between hematological cáncer (HC) and solid organ cancer (SOC) in our center. Patients and Methods: Surveillance study in adult patients with FN admitted to Hospital Clinico Universidad Católica, in Santiago, Chile, from January 2004 to August 2007. Results: 154 FN episodes corresponding to 87 patients were included. Mean age: 47 ± 6 years-old; 71 percent had HC and 29 percent SOC. A clinical and/or microbiologically documented infection was recognized in 76 percent. Gastrointestinal 31.5 percent, upper respiratory 30.3 percent and lower respiratory 16.9 percent were the more frequent clinical focus. In 30.5 percent blood culture resulted positive: gram negative rods 51 percent, gram positive cocci 41 percent and yeasts 8 percent; being Escherichia coli 22 percent, S. coagulase negative (SCoN) 20 percent and Klebsiella pneumoniae 12 percent most frequent bacteria; 22.2 percent Enterobacteriaceae were ESBL producers and 55.6 percent 5CoN were methicillin resistant. In 18.3 percent of FN episodes the etiology was not established. Highest mortality was observed in episodes with microbiologically documented infection (14.5 percent vs 1.3 percent, p < 0.005). A clinical observed focus and positive blood cultures were more frequently obtamed among HC than SOC associated episodes: 37.3 percent vs 13.6 percent; (p < 0.01) and 67.2 percent vs 50 percent; (p = 0.045), respectively. Conclusions: The etiological profile of FN in our center and the necessity to continue the surveillance was described. Future studies are needed regarding risk factors of invasive infection that have worst prognosis.

Introducción: La vigilancia de la etiología de los episodios de neutropenia febril (NF) en cada centro permite adaptar guías de antibioterapia a la epidemiología local. Objetivo: Caracterizar y comparar la etiología de la NF en pacientes con cáncer hematológico (CH) y de órganos sólidos (COS). Pacientes y Métodos: Estudio de vigilancia de NF de pacientes adultos en el Hospital Clínico Universidad Católica, en Santiago, Chile, entre enero 2004 y agosto 2007. Resultados: 154 episodios de NF correspondientes a 87 pacientes: 47 ± 6 años; 71 por ciento CH y 29 por ciento COS. Se documentó infección clínica y/o microbiológicamente en 76 por cientoo. Más frecuente fueron: foco gastrointestinal 31,5 por ciento, respiratorio alto 30,3 por cientoo y respiratorio bajo 16,9 por cientoo. En 30,5 por cientoo hubo hemocultivos positivos: bacilos gramne-gativos en 51 por ciento, cocáceas grampositivas en 41 por ciento, levaduras en 8 por cientoo; predominando: Escherichia coli 22 por cientoo, Staphylococcus coagulasa negativa (SCoN) 20 por cientoo y Klebsiella pneumoniae 12 por ciento; 22,2 por cientoo de las entero-bacterias eran productoras de (3-lactamasa de espectro expandido y 55,6 por cientoo >SCoN meticilina resistentes. En 18,3 por cientoo de los episodios no se identificó causa de fiebre. Hubo mayor mortalidad en episodios con documentación microbiológica (14,5 por ciento vs 1,3 por ciento, p < 0,005). En los pacientes con CH fue más frecuente obtener hemocultivos positivos (37,3 por cientoo vs 13,6 por ciento; p < 0,01) e identificar foco clínico (67,2 por ciento vs 50 por ciento; p = 0,045). Conclusiones: Se establece el perfil etiológico de las NF en nuestro centro y la necesidad de mantener vigilancia. En futuros estudios será necesario evaluar factores de riesgo de pacientes con infecciones invasores que tendrían peor pronóstico.

Neutropenia febril de bajo riesgo en pacientes oncológicos / Low risk febrile neutropenia in oncological pediatric patients: clinical experience

Background: Infections constitute the major cause of morbimortality in pediatric patients treated with chemotherapy. The PINDA Infectology Committee (National Program of Antineoplasic Drugs) validated a model to predict the risk of invasive bacterial infection (IBI) in oncological patients with febrile neutropenia (FN), in order to differentiate episodes of low risk (LRFN) versus high risk (HRFN) of IBI. Objective: Characterize LRFN episodes in patients treated at the Oncology Unit of Hospital Roberto del Rio, between 2003-2006. Method: Retrospective study of clinical charts of patients with cancer and LRFN in the period of time selected. Results: 185 patients with 202 FN episodes registered, where 47 correspond to LRFN (23 percent). 8.5 percent of LRFN episodes had an unfavourable outcome (not statistically significant). In these patients, cultures were negative and required more days of hospitalization. No patients were readmitted and had no infection associated mortality. Conclusion: The selective management of patients with LRFN following the current criteria is safe and effective.

Las infecciones son la principal causa de morbimortalidad en pacientes oncológicos en quimioterapia. El Comité de Infectología del PINDA (Programa Infantil Nacional de Drogas Antineoplásicas) validó un modelo de predicción de riesgo de infección bacteriana invasora (IBI) en niños oncológicos con neutropenia febril (NF), que discrimina episodios de bajo (NFBR) y alto riesgo (NFAR) de IBI. Objetivo: Caracterizar los episodios de NFBR de pacientes atendidos en la Unidad de Oncología del Hospital de Niños Roberto del Río (2003-2006). Pacientes y Métodos: Revisión retrospectiva de fichas clínicas de pacientes que debutaron con patología oncológica en ese período que presentaron episodios de NFBR consignando edad, sexo, diagnóstico oncológico de base, catéter venoso central, foco infeccioso, quimioterapia y cultivos. Se evaluó la evolución clínica por parámetros clínicos y de laboratorio, y se analizaron las variables mediante prueba de X cuadrado, con un p < 0,05. Resultados: En 185 pacientes, se registraron 202 episodios de NF, 47 fueron NFBR (23 por ciento). Presentaron evolución desfavorable un 8,5 por ciento de NFBR (p > 0,05). En ellos no se logró aislamiento microbiológico y tuvieron mayor número de días de hospitalización. No hubo en este grupo reingresos ni mortalidad asociada. Conclusión: El manejo selectivo de los pacientes con NFBR, según criterios actuales, es seguro y efectivo.

Recommendations for the management of candidemia in adults in Latin America

La candidemia es una de las micosis oportunistas más frecuentes en todo el mundo. El escaso número de estudios epidemiológicos llevados a cabo en América Latina indica que las tasas de incidencia en esta región son mayores que las descritas en el hemisferio norte. A menudo el diagnóstico de la infección se establece tardíamente, lo que afecta al inicio del tratamiento antimicótico. Por esta razón, para el diagnóstico y el manejo de la candidemia está justificada una estrategia más científica, basada en parámetros específicos. Recomendaciones para el diagnóstico y manejo de la candidemia constituye una serie de artículos preparados por miembros del grupo Latin America Invasive Mycosis Network. Su objetivo es proporcionar las mejores evidencias disponibles para el diagnóstico y el manejo de la candidemia. El presente artículo, Recomendaciones para el manejo de la candidemia en adultos en América Latina, ha sido redactado con el objetivo de orientar a los profesionales de la salud en el manejo de los pacientes adultos que padecen, o pueden padecer, candidemia. Mediante la base de datos PubMed se emprendió una búsqueda informatizada de los estudios publicados. Los miembros del grupo revisaron y analizaron exhaustivamente los datos. El grupo también se reunió en dos ocasiones para proponer preguntas, abordar los puntos de vista conflictivos y deliberar sobre las recomendaciones terapéuticas. Recomendaciones para el manejo de la candidemia en adultos en América Latina está orientado al tratamiento de pacientes neutropénicos y no neutropénicos, e incluye aspectos sobre la profilaxis, el tratamiento empírico, el tratamiento de la candidemia confirmada, el seguimiento del paciente después del diagnóstico de la candidemia, la duración del tratamiento y el manejo del catéter venoso central. Esta publicación es la segunda de los artículos de esta serie dedicada al diagnóstico y tratamiento de las candidiasis invasoras. Otras publicaciones de esta serie son Recomendaciones para el diagnóstico de la candidemia en América Latina, Recomendaciones para el manejo de la candidemia en ni˜nos en América Latina, y Recomendaciones para el manejo de la candidemia en neonatos en América Latina (AU)

Candidemia is one of the most frequent opportunistic mycoses worldwide. Limited epidemiological studies in Latin America indicate that incidence rates are higher in this region than in the Northern Hemisphere. Diagnosis is often made late in the infection, affecting the initiation of antifungal therapy. A more scientific approach, based on specific parameters, for diagnosis and management of candidemia in Latin America is warranted. ‘Recommendations for the diagnosis and management of candidemia’ are a series of manuscripts that have been developed by members of the Latin America Invasive Mycosis Network. They aim to provide a set of best-evidence recommendations for the diagnosis and management of candidemia. This publication, ‘Recommendations for the management of candidemia in adults in Latin America’, was written to provide guidance to healthcare professionals on the management of adults who have, or who are at risk of, candidemia. Computerized searches of existing literature were performed by PubMed. The data were extensively reviewed and analyzed by members of the group. The group also met on two occasions to pose questions, discuss conflicting views, and deliberate on a series of management recommendations. ‘Recommendations for the management of candidemia in adults in Latin America’ includes prophylaxis, empirical therapy, therapy for proven candidemia, patient work-up following diagnosis of candidemia, duration of candidemia treatment, and central venous catheter management in patients with candidemia. This manuscript is the second of this series that deals with diagnosis and treatment of invasive candidiasis. Other publications in this series include: ‘Recommendations for the diagnosis of candidemia in Latin America’, ‘Recommendations for the management of candidemia in children in Latin America’, and ‘Recommendations for the management of candidemia in neonates in Latin America’ (AU)

Tratamiento antimicrobiano en niños con neutropenia febril de alto riesgo / Antibiotic treatment in children with high risk febrile neutropenia

Background: In children with cancer and high risk febrile neutropenia (HRFN), the initial empirical treatment used in our hospital for 5 years includes the association of Cloxacillin + Ceftazidime + Amikacin. There is no chilean literature that reviews the effectiveness of this therapy. Objective: Evalúate the clinical and microbiological effectiveness of this associated therapy in children with HRFN. Method: A prospective-descriptive study evaluating children with HRFN admitted at Hospital Luis Calvo Mackenna between January 2005-August 2006. Results: 100 HRFN episodes were evaluated. In 48 percent of cases, the antimicrobial treatment was considered effective, whereas in 52 percent of episodes the therapy required modifications (15 percent cases within the first 72 hours). The most frequent diagnoses were fever without clinical focus (51 percent) and sepsis (13 percent). 36 percent had microbiological identification and the most frequently isolated bacteria were Escherichia coli (9 percent) and Staphylococcus aureus (9 percent). Conclusions: A favorable answer with the initial empirical therapy was obtained for 48 percent of cases; meanwhile in the remaining episodes, 28 percent required antibiotics modifications without justification. This fact remarks the importance of following the established guidelines for antimicrobial treatment modification in these patients.

Introducción: En los niños con cáncer y netropenia febril (NF) de alto riesgo, se utiliza en nuestro centro hace 5 años, como esquema empírico inicial, la asociación de ceftazidima-amikacina-cloxacilina. No hay literatura nacional que analice la eficacia de este esquema. Objetivo: Evaluar la eficacia clínica y microbiológica de la asociación de ceftazidima, amikacina y cloxacilina en niños con NF de alto riesgo. Método: Protocolo descriptivo, prospectivo. Evaluar niños con NF de alto riesgo hospitalizados en el HLCM entre enero 2005 y agosto 2006. Resultados: 100 episodios de NF de alto riesgo. El tratamiento antimicrobiano fue considerado eficaz en 48 por ciento de los casos, y requirió ajustes en 52 por ciento de los casos. En 13 por ciento se cambia tratamiento sin justificación y en 15 por ciento se realiza antes de 72 horas de iniciado el tratamiento antimicrobiano. Foco mßs frecuente fue: ausencia de foco clínico 51 por ciento, presentando sepsis 13 por ciento de los niños. Hubo identificación microbiológica en 36 por ciento, microorganismos mßs frecuentemente aislados Echerichia coli (9 por ciento) y Staphylococcus aureus (9 por ciento). Conclusiones: Se obtuvo una respuesta favorable de 48 por ciento con el esquema antimicrobiano empírico inicial, de el 52 por ciento restante, en un 28 por ciento se efectúan cambios de antibióticos no justificados, esto recalca la importancia de seguir las pautas ya establecidas para cambio de esquema antimicrobiano en estos pacientes.

Neutropenia febril en niños con cáncer en un centro asistencial en Santiago, Chile / Febrile neutropenia in children with cancer in a medical center of Santiago, Chile

La neutropenia febril (NF) en pacientes oncológicos es una complicación frecuente de la quimioterapia y primera manifestación de una infección potencialmente letal. Con el propósito de adecuar nuestra práctica médica a las guías clínicas vigentes en Chile, revisamos la experiencia de la Unidad de Pediatría, Clínica Dávila, entre mayo 1°, de 2003 y diciembre 31, de 2004. Se analizaron 57 episodios (25 pacientes); se encontró foco infeccioso en 44 por ciento (25/57) siendo respiratorio en 11/25. Se identificó el agente infeccioso en 28 por ciento (16/57): 12 cepas desde sangre (42 por ciento Staphylococcus coagulasa negativa, 17 por ciento Streptococcus grupo viridans, 17 por ciento Escherichia coli y Enterococcus sp, Candida albicans y Pseudomonas aeruginosa en 8 por ciento cada uno), 3 de cultivos de catéter (S. coagulasa negativa) y 1 en lavado bronquioalveolar (Pneumocystis jiroveci). Al ingreso, 63 por ciento recibió tratamiento con 2 antibacterianos, de preferencia ceftazidima y amikacina (39 por ciento), en 21 por ciento se utilizó vancomicina. Por falta de respuesta, en 37 por ciento de los pacientes se cambió la terapia. Cincuenta y seis episodios tuvieron una evolución favorable y un paciente falleció por shock séptico. La proporción de episodios con causa infecciosa documentada, los microorganismos aislados y la resolución favorable de esta grave complicación en pacientes oncológicos demuestran un nivel de diagnóstico y manejo comparable con países industrializados.

Febrile neutropenia in cancer patients is a common complication associated to chemotherapy and can be the first manifestation of a potentially lethal infection. In order to adapt our clinical practice to national clinical guidelines, we performed a retrospective review of clinical charts of all children admitted to the Pediatric Unit of Clinica Davila, from May 1, 2003 to December 31, 2004, with cancer, fever and neutropenia. A total of 57 febrile neutropenic episodes occurred in 25 children and in 44 percent (25/57) of them an infectious focus could be identified; respiratory infections were the most common (11/25). A microorganism could be identified in 16/57 (x percent) of episodes, e.g. 12 recovered from blood cultures (42 percent coagulase negative Staphylococcus, 17 percent group viridans Streptococci, 17 percent Escherichia coli and Enterococcus sp, Candida albicans y Pseudomonas aeruginosa in 8 percent each one), 3 from a catheter (coagulase negative Staphylococci) and 1 from a bronchoalveolar lavage (Pneumocystis jiroveci). At admission, 63 percent of children received treatment with 2 antibiotics, mostly ceftazidime and amikacin (39 percent) and 21 percent received vancomycin. In 37 percent of patients therapy required adjustment due to a poor response. Fifty six episodes had a favorable resolution with one patient diying of septic shock. Frequency of microorganism detection, the distribution of species recovered and the favorable resolution are comparable to that reported from industrialized countries.

Proteína C reactiva y procalcitonina como marcadores de infección bacteriana en niños con neutropenia febril posterior a trasplante alogénico de progenitores hematopoyéticos / C reactive protein and procalcitonin levels for the diagnosis of invasive bacterial infections in allogenic hematopoietic stem cell transplantation recipients

Background: The main causes of complications of allogenic hematopoietic stem cell transplantation are infections and graft versus host disease. Aim: To assess the predictive value of C reactive protein (CRP) and procalcitonin (PCT) in the diagnosis of invasive bacterial infections in children with febrüe neutropenia after an allogenic hematopoietic stem cell transplantation. Material and methods: Prospective follow up of patients aged 18 years or íess, with febrile neutropenia after an allogenic hematopoietic stem cell transplantation. In all patients, cultures from sterile sites, CRP and PCT determinations were done. CRP levels were also measured prior to transplantation and three times per week for 30 days after the procedure. An independent evaluator, blinded to the results of CRP and PCT, classified children as with or without invasive bacterial infection. Results: Thirty three patients aged 9±5 years (21 males) were studied. Eight had an invasive bacterial infection. Sensitivity, specificity, positive and negative predictive values of a CRP ³90 mg/L for the diagnosis of invasive bacterial infection were 25, 80, 29 and 77 percent, respectively. The figures for a PCT ³0.7 ng/ml were 43, 78, 38 and 82 percent, respectively. No differences in repeated CRP values measured during evolution, were observed. Conclusions: A CRP ³90 mg/L or a PCT ³0.7 ng/ml had a high specificity and negative predictive value but low sensitivity for the diagnosis of invasive bacterial infections in recipients of allogenic hematopoietic stem cell transplantation.

Profilaxis y tratamiento de la infección fúngica invasora en el paciente neutropénico / Prophylaxis and treatment of invasive fungal infection in neutropenic patients

La profilaxis y el tratamiento son las dos herramientas para reducir la mortalidad de la infección fúngica invasora (IFI). La profilaxis es, en la actualidad, una práctica estándar en la mayoría de los hospitales y la recomendación de las principales guías terapéuticas. Su principal limitación es la ausencia de actividad sobre los hongos filamentosos, por lo que, en los pacientes de alto riesgo para la IFI por este tipo de hongos, es necesario el empleo de antifúngicos de espectro extendido. Además de la profilaxis, la estrategia frente a la IFI debe incluir el tratamiento empírico, el anticipado y el dirigido (en monoterapia o combinado). En el empírico y anticipado es necesario tener en cuenta que hongos hay que cubrir y cuál es el espectro de los antifúngicos disponibles. En el dirigido de las infecciones por Candida spp, antes de la identificación de especie, hay que valorar una serie de factores dependientes del huésped (como la toma o no de fluconazol profiláctico) y de su clínica (como la evidencia o no de infección diseminada o criterios de sepsis grave) infección local o ha recibido previamente fluconazol. En cuanto a la aspergilosis invasora, el empleo de tratamiento combinado en primera línea debe valorarse en caso de afección del sistema nervioso central, fracaso respiratorio, criterios de sepsis grave y si hay lesión pulmonar extensa o cavitada(AU)

Prophylaxis and treatment constitute the basis for reducing the mortality due to IFI. Prophylaxis is currently the standard practice in most hospitals and is recommended by the principal guidelines. Fluconazole has proved to be useful to prevent and reduce the mortality due to yeast IFI in several contexts. Although its use has led to the emergence of some resistant strains of Candida, it has not been a generalized problem and the number of lives saved has been worth it. But its major disadvantage is the lack of impact on IFI by molds. So, in patients at high risk for IFI due to filamentous fungi, it is necessary the employ of extended spectrum drugs. Besides the prophylaxis, the strategy against the IFI must include the empirical, pre-emptive and directed (monotherapy or combination) treatment. For the empirical and preemptive approach, it is necessary to have in mind which fungi has to be covered and what is the spectrum of the available antifungal agents. For the treatment of established infection by Candida spp., before the identification of species, we must consider different host (like the use or not of prophylactic fluconazole) and clinical factors (like the evidence or not of diseminated infection or severe sepsis). Primary combination of antifungal agents for the treatment of invasive aspergillosis has to be considered in cases of central nervous system disease, respiratory failure, serious sepsis and extensive or cavitated pulmonary lesions(AU)

Infecciones en pacientes oncohematológicos no trasplantados / Infections in non-transplanted oncohaematological patients

Los pacientes oncohematológicos presentan elevadaincidencia de infecciones siendo éstas una de lasprincipales causas de morbimortalidad. Existen distintostipos de inmunodepresión relacionados con laenfermedad, el momento evolutivo y el tratamientorecibido. A efectos prácticos vamos a distinguir lospacientes con neutropenia severa, los que tienen algunaalteración de la inmunidad humoral y por último lasinmunodeficiencias celulares. No existen inmunodeficienciasasociadas a cada enfermedad, sino que en unamisma entidad clínica se pueden asociar varias deficienciasinmunitarias. Los pacientes neutropénicos,generalmente con leucemias agudas y tras quimioterapiaintensiva, tienen infecciones bacterianas y fúngicascondicionadas por la intensidad y la duración de laneutropenia. En el caso de los pacientes con inmunodeficienciahumoral (mieloma múltiple, leucemia linfáticacrónica, esplenectomizados) son frecuentes lasinfecciones por gérmenes encapsulados. Cuando hayinmunodepresión celular (enfermedad de Hodgkin, síndromeslinfoproliferativos crónicos avanzados, tratamientocon glucocorticoides, análogos de las purinas ytratamientos con anticuerpos monoclonales) el riesgode infecciones por gérmenes oportunistas viene condicionadopor la reducción de la cifra de linfocitos CD4.Revisaremos las distintas estrategias de profilaxis ytratamiento en cada una de las situaciones

Oncohaematological patients present a highincidence of infections, which are one of the principlecauses of morbility and mortality. There are differenttypes of immunodepression related to the disease, themoment of its evolution and the treatment received.For practical purposes we will distinguish betweenpatients with severe neutropenia, those with somealteration to humoral immunity and, finally, cellularimmunodeficiencies. There are no immunodeficienciesassociated to each disease, instead severalimmunitarian deficiencies can be associated in a singleclinical entity. Neutropenic patients, generally withacute leukaemias and following intensivechemotherapy, have bacterial and fungal infectionsconditioned by the intensity and duration of theneutropenia. In the case of patients with humouralimmunodeficiency (multiple mieloma, chroniclymphatic leukaemia, splenectomised) there arefrequent infections by encapsulated germs. Whenthere is cellular immunodepression (Hodgkin’sdisease, advanced chronic lymphoproliferativesymdromes, treatment with glucocorticoids, analoguesof the purines and treatment with monoclonalantibodies) the risk of infection by opportunist germsis conditioned by the reduction of the figure of CD4lymphocytes. We review the different strategies ofprophylaxis and treatment in each of the situations