Bacteriemia asociada a neutropenia febril en pacientes hemato-oncológicos, su espectro bacteriano y patrón de susceptibilidad antibiótica / Bacteremia associated with febrile neutropenia in hematology-oncology patients, bacterial spectrum and antibiotic susceptibility pattern

La neutropenia febril es una de las complicaciones más frecuentes y de mayor morbilidad y mortalidad en los pacientes hematológicos. Su documentación microbiológica es una herramienta invaluable para el manejo; sin embargo, la cambiante tendencia en etiología de la bacteriemia y el patrón de susceptibilidad antimicrobiana comprometenla tasa de respuesta a los esquemas de tratamiento empírico. Objetivo :Determinar la etiología de bacteriemia en pacientes con neoplasias hematológicas y neutropenia febril, su patrón de susceptibilidad antimicrobiana y el grado de resistencia vigente a los medicamentos comúnmente utilizados en esquemas empíricos de manejo. Material y métodos :Se revisaron datos microbiológicos de las historias clínicas de pacientes hematológicos, hospitalizados en el HNERM entre diciembre 2010 y marzo 2012; que habían presentado neutropenia febril y bacteriemia concurrente. La información se analizó con el paquete estadístico STATA v. 10 y se empleó estadística descriptiva. Resultados : La bacteriemia fue predominantemente por bacterias gram negativas (75,9%) y post consolidación de LMA con Ara-C por gram positivas (63,6%). La mortalidad de pacientes post reinducción con bacteriemia fue 75% y se asoció a Klebsiella pneumoniae BLEE+ en 31,2%. Conclusiones: Gérmenes gram negativos fueron la etiología más frecuente de bacteriemia en la población estudiada, particularmente en pacientes que recibieron quimioterapia de reinducción, donde se vio la mayor frecuencia de bacteriemia con mayor resistencia y asociados a mayor mortalidad. Posterior a quimioterapia de consolidación con Citarabina en altas dosis para LMA, resultó más frecuente la bacteriemia a gram positivos. Carbapenems y Amoxicilina/Clavul á nico mostraron considerable menor resistencia que cefalosporinas y fluoroquinolonas.

Febrile neutropenia is one of the most common complications in hematologic patients and it is associated with increased morbidity and mortality. Microbiological documentation is an invaluable tool for treatment of these patients. However, the changing trends in the etiology of bacteremia, and the changing antimicrobial susceptibility patterns compromise the response to empiric treatment. Objective: To determine the etiology of bacteremia in patients with hematological malignancies and febrile neutropenia, their antimicrobial susceptibility pattern, and degree of resistance to existing drugs commonly used in empirical treatment regimens. Methods: We reviewed clinical records and microbiological data of hematological patients admitted in the HNERM between December 2010 and March 2012. Data were analyzed using the statistical package STATA v. 10 and descriptive statistics were used. Results: Bacteremia was mainly caused by Gram negative bacteria (75.9%), and by Gram positive (63.6%) after consolidation treatment of AML with Ara - C. The mortality of patients with bacteremia post re-induction was 75 %, and was associated with ESBL + Klebsiella pneumoniae in 31.2 %. Conclusions: Gram negative bacteria were the most common cause of bacteremia in our study, particularly in patients who received re-induction chemotherapy, where resistance and mortality rates were very high. Gram positive bacteremia follow consolidation chemotherapy with high-dose cytarabine for AML. Carbapenems and amoxicillin / clavulanate showed significantly less resistance than cephalosporins and fluoroquinolones.

Plasma levels of procalcitonin and eight additional inflammatory molecules in febrile neutropenic patients

OBJECTIVE: This study aimed to examine the association between different inflammatory markers and specific clinical endpoints in patients with febrile neutropenia. METHOD: We prospectively evaluated the expression of procalcitonin (PCT), interleukin 8 (IL-8), induced protein-10, tumor necrosis factor alpha (TNF-a), two soluble TNF-a receptors (sTNF-R I and sTNF-R II), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1 alpha, and eotaxin in 37 episodes of febrile neutropenia occurring in 31 hospitalized adult onco-hematologic patients. Peripheral blood samples were collected in the morning at inclusion (day of fever onset) and on days 1, 3, and 7 after the onset of fever. Approximately 2-3 ml of plasma was obtained from each blood sample and stored at -80°C. RESULTS: The sTNF-R II level at inclusion (day 1), the PCT level on the day of fever onset, and the change (day 3 - day 1) in the IL-8 and eotaxin levels were significantly higher in patients who died during the 28-day follow-up. A requirement for early adjustment of antimicrobial treatment was associated with higher day 3 levels of IL-8, sTNF-R II, PCT, and MCP-1. CONCLUSION: Procalcitonin, sTNF-R II, IL-8, MCP-1, and eotaxin could potentially be used to assess the risk of death and the requirement for early adjustment of antimicrobial treatment in febrile, neutropenic onco-hematologic patients. The levels of the other markers showed no association with any of the evaluated endpoints.

Antibioticoterapia oral versus endovenosa em crianças neutropênicas febris recebendo quimioterapia / Oral vs. intravenous empirical antimicrobial therapy in febrile neutropenic patients receiving childhood cancer chemotherapy

OBJETIVO: Comparar o uso de antibioticoterapia endovenosa versus oral. MÉTODOS: Foram selecionadas todas as crianças e adolescentes neutropênicos com idade inferior a 18 anos classificados como baixo risco para complicações e recebendo quimioterapia. O estudo ocorreu entre 2002 e 2005 na Unidade de Oncologia Pediátrica, Hospital de Clínicas de Porto Alegre, Porto Alegre (RS). Os pacientes, divididos em grupo A e grupo B, eram randomizados para receber terapia oral ou endovenosa. O tratamento utilizado para o grupo A foi ciprofloxacina e amoxicilina/clavulanato via oral e placebo endovenoso e, para o grupo B, cefepime e placebo oral. RESULTADOS: Foram selecionados 91 episódios consecutivos de neutropenia febril em 58 crianças. Para os pacientes do grupo A, a taxa de falência foi de 51,2 por cento e a média de tempo de hospitalização foi de 8 dias (variação de 2-10). Para os pacientes tratados com antibioticoterapia endovenosa, a taxa de falência foi de 45,8 por cento e a média de tempo de hospitalização foi de 7 dias (variação de 3-10). CONCLUSÃO: Neste estudo não houve diferenças entre a antibioticoterapia oral versus a terapia endovenosa. Estudos randomizados com maior número de pacientes são necessários antes de padronizar a terapêutica oral como tratamento para esta população de pacientes.

OBJECTIVE: To compare the use of intravenous vs. oral antibiotic therapy. METHODS: All febrile neutropenic patients younger than 18 years old with low risk of complications and receiving chemotherapy were selected. The study was conducted from 2002 to 2005 at the Pediatric Oncology Unit of Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. Patients were divided into group A and group B and were randomly assigned to receive oral or intravenous therapy. The empirical antimicrobial treatment used for group A consisted in oral ciprofloxacin plus amoxicillin-clavulanate and intravenous placebo, and group B received cefepime and oral placebo. RESULTS: A total of 91 consecutive episodes of febrile neutropenia in 58 children were included in the study. For patients of group A, treatment failure rate was 51.2 percent; the mean length of hospital stay was 8 days (range 2-10 days). For patients treated with intravenous antibiotic therapy, treatment failure rate was 45.8 percent; the mean length of hospital stay was 7 days (range 3-10 days). CONCLUSION: There was no difference in the outcome in oral vs. intravenous therapy. There is need of larger randomized trials before oral empirical therapy administered to this population should be considered the new standard of treatment.

Granulocyte transfusion in children.

We describe a single institution experience with the use of granulocyte transfusion in children. This is a retrospective analysis of 45 collections of granulocyte units obtained by apheresis after priming with dexamethasone, infused into 17 children with severe neutropenic infections. Ten children survived the acute infection. Granulocyte transfusion is a useful adjunct to antimicrobials and growth factors in post chemotherapy neutropenic sepsis and is highly effective in children with chronic granulomatous disease and life threatening infections.

Neutropenia febril de alto riesgo en leucemia aguda. Experiencia en un hospital público. Programa Nacional de Drogas Antineoplásicas del Adulto (PANDA), Hospital del Salvador, 1991-2001 / High risk febrile neutropenia in acute leukemia. The experience of a public hospital. National Program of Antineoplastic Drugs in Adult, Hospital del Salvador, 1991-2001

BACKGROUND: Febrile neutropenia is one of the most important problems to face during the treatment of acute leukemia. AIM: To assess the results of a standardized protocol for the treatment of febrile neutropenia and compare it with a period in which treatment was not standardized. PATIENTS AND METHODS: One hundred and eight episodes of febrile neutropenia in 69 patients, treated with a standardized antimicrobial protocol between 1996 and 2001, were analyzed. The protocol consisted in the use of a combination of antimicrobial whose spectrum was broadened progressively according to the isolated microorganisms and the involved foci. These were compared with 83 episodes in 54 patients, treated without standardized protocols between 1990 and 1995. RESULTS: Both groups of patients were comparable. Their ages ranged from 15 to 65 years old. The male/female ratio was 1.3 and the lymphoblastic/myeloid leukemia ratio was 1.4. Sixty one percent of episodes occurred during induction chemotherapy and mean duration of neutropenia was 17 days. A clinically significant focus was identified in 72 per cent of episodes and a microorganism was isolated blood culture in 35 per cent of them. There was a predominance of gram negative organisms. The mortality decreased from 18 to 9 per cent in the period 1996-2000 (p = 0.094). CONCLUSIONS: The use of a standardized antimicrobial protocol reduced the mortality in febrile neutropenia, even when colony stimulating factors and filtered air rooms are unavailable.

Criterios de bajo riesgo de mortalidad en niños con neutropenia y fiebre durante la quimioterapia por cancer / Criteria of low risk of mortality in children with neutropenia and fever during cancer chemotherapy

Con el objetivo de validar el uso de un perfil de bajo riesgo de mortalidad, y evaluar la eficacia de un esquema de tratamiento secuencial parenteral-oral en niños con neutropenia y fiebre durante la terapia de enfermedades malignas, se llevó a cabo un estudio prospectivo entre mayo de 1997 y diciembre de 1999. En el período de estudio fueron incluídos 247 episodios de neutropenia y fiebre en 215 pacientes. Los niños en tratamiento por enfermedades malignas que presentaban: neutropia (recuento absoluta de neutrófilos<500/mm3), fiebre (> 38§C) buen estado general, que no presentaban un foco clínico de riesgo, que no tenían factores comorbilidad severos asociados, sin bacteriemia y familias continente, fueron elegidos para recibir un tratamiento inicial con ceftrixona y amikacina en el hospital seguido de cefixima o ciprofloxacina por vía oral en forma ambulatoria hasta completar 7 días. La edad media de los niños fue de 64 meses (r: 8-200). El 48 porciento (118) tuvo leucemia y el 57 porciento (141) catéteres endovasculares. El 47 porciento (122) tuvo foco clínico de infección, donde predominó la infección respiratoria alta (81 porciento). El tiempo medio de fiebre fue de 1.1 días (r: 1-8) y de neutropenia 3.9 días (r: 1-9). El 61 porciento (150) de los niños fue dado de alta con neutropenia. La media de internación fue de 1.5 días. Se registraron 4 fallos (1.6 porciento), los cuáles fueron tratados satisfactoriamente y ninguno presentó complicaciones mayores, falleció o abandonó el tratamiento. El perfil de riesgo utilizado fue seguro, y el tratamiento secuencial fue eficaz en el manejo de los niños con neutropenia y fiebre de origen hemato-oncológico y bajo riesgo de mortalida.

Causas de mortalidad en el sector protegido de inmunoneutropénicos (SEPIN). I.N.E.N. (1989-1991) / Causes of death in the isolation unit

Entre enero 1989 y diciembre 1991, 243 pacientes fueron hospitalizados en el Instituto Nacional de Enfermedades Neoplásicas en la Unidad de Aislamiento Invertido (SEPIN), de ellos 171 (70.3 por ciento) eran portadores de leucemia aguda (LA) que ingresaron para tratamiento de inducción y/o consolidación. Tres pacientes ingresaron con hemorragia generalizada antes de iniciar tratamiento. La mortalidad general fue de 15.4 por ciento (26/168) y las causas fueron: sepsis en 15/26 (57.6 por ciento), sepsis + hemorragia en 5/26 (19.2 por ciento), hemorragia sola en 3/26 (11.5 por ciento) y hemorragia asociada a otras complicaciones en 3/26 (11.5 por ciento). En el caso de fallecidos por sepsis los focos infecciosos fueron: piel (5), pulmón (4), orofaringe (4), abdominal (4), otros (3). los gérmenes aislados fueron: Pseudomona (3), Enterobacter (3), Klebsiella (3), Estafilococo aureus (2), Acinetobacter (1) y Candida (1). Bacteremia estuvo presente en 4/20 (20 por ciento) y todos fueron Gram negativos. Hemorragia ocurrió por plaquetopenia severa (<20.000/mm3) o por coagulación intravascular diseminada, con compromiso multisistémico y principalmente del sistema nervioso central. Las causas más frecuentes de muerte en pacientes con leucenmia aguda en tratamiento con quimioterapia continúan siendo sepsis y hemorragia, y ambas requieren una estrategia permanente de manejo de las complicaciones infecciosas y un soporte hematológico oportuno, que les permita a estos pacientes superar el período de mielosupresión