Safety and efficacy of step-down to oral outpatient treatment versus inpatient antimicrobial treatment in pediatric cancer patients with febrile neutropenia: A noninferiority multicenter randomized clinical trial.

BACKGROUND: It has been suggested that low-risk febrile neutropenia (FN) episodes can be treated in a step-down manner in the outpatient setting. This recommendation has been limited to implementation in middle-income countries due to concerns about infrastructure and lack of trained personnel. We aimed to determine whether early step-down to oral antimicrobial outpatient treatment is not inferior in safety and efficacy to inpatient intravenous treatment in children with low-risk FN. PROCEDURE: A noninferiority randomized controlled clinical trial was conducted in three hospitals in Mexico City. Low-risk FN was identified in children younger than 18 years. After 48 to 72 hours of intravenous treatment, children were randomly allocated to receive outpatient oral treatment (experimental arm, cefixime) or to continue inpatient treatment (standard of care, cefepime). Daily monitoring was performed until neutropenia resolution. The presence of any unfavorable clinical outcome was the endpoint of interest. We performed a noninferiority test for comparison of proportions. RESULTS: We identified 1237 FN episodes; 117 cases were randomized: 60 to the outpatient group and 57 for continued inpatient treatment. Of the FN episodes, 100% in the outpatient group and 93% in the inpatient group had a favorable outcome (P < 0.001). The mean duration of antibiotics was 4.1 days (SD 2.5; 95% CI, 3.4-4.8 days) in the outpatient group and 4.4 days (SD 2.5; 95% CI, 3.7-5.0 days) in the inpatient group (P = 0.70). CONCLUSIONS: In our population, step-down oral outpatient treatment of low-risk FN was as safe and effective as inpatient intravenous treatment. Clinical Trials Identifier: NCT04000711.

Performance of the clinical index of stable febrile neutropenia (CISNE) in different types of infections and tumors.

PURPOSE: The clinical index of stable febrile neutropenia (CISNE) can contribute to patient safety without increasing the complexity of decision-making. However, febrile neutropenia (FN) is a diverse syndrome. The aim of this analysis is to assess the performance of CISNE according to the type of tumor and infection and to characterize these patients. METHODS: We prospectively recruited 1383 FN episodes in situations of apparent clinical stability. Bonferroni-adjusted z tests of proportions were used to assess the association between the infections suspected at the time of onset and the type of tumor with the risk of serious complications and mortality. The performance of CISNE was appraised in each category using the Breslow-Day test for homogeneity of odds ratios and Forest Plots. RESULTS: 171 patients had a serious complication (12.3 %, 95 % confidence interval 10.7-14.2 %). The most common initial assumptive diagnoses were: fever without focus (34.5 %), upper respiratory infection (14.9 %), enteritis (12.7 %), stomatitis (11.8 %), and acute bronchitis (10.7 %). Lung and breast were the most common tumors, accounting for approximately 56 % of the series. The distribution of complications, mortality, and bacteremia varies for each of these categories. However, Breslow-Day tests indicate homogeneity of the odds ratio of the dichotomized CISNE score to predict complications in all infection and tumor subtypes. CONCLUSION: Despite FN's clinical and microbiological heterogeneity, the CISNE score was seen to be consistent and robust in spite of these variations. Hence, it appears to be a safe tool in seemingly stable FN.

Hemocultivo positivo como factor pronóstico en pacientes con patología hematooncológica y neutropenia febril / Positive blood culture as a prognostic factor in patients with hematological oncology and pathology febrile neutropenia

La neutropenia febril es considerada una emergencia en pacientes oncológicos, con una elevada tasa de mortalidad que ha disminuido a lo largo de los años. Determinar el riesgo de mortalidad en pacientes hemato-oncológicos con neutropenia febril. Estudio prospectivo, observacional, de cohorte analítico, a realizarse entre febrero y septiembre del año 2014 en el Departamento de Medicina Interna del Hospital Dr. Miguel Pérez Carreño. La muestra está conformada por pacientes con patología hemato-oncológica con neutropenia febril de alto riesgo según el índice de MASCC. Se busca relación estadísticamente significativa empleando la prueba de χ²,con un intervalo de confianza de 95% y pruebas de significancia clínica, como es el odds ratio. Existe una relación estadísticamente significativa entre hemocultivos positivos realizados durante las primeras 72 horas del inicio de la neutropenia febril y la mortalidad, con un OR>1. La duración de la neutropenia por más de 7 días se asocia fuertemente con aumento del riesgo de mortalidad. En nuestra experiencia, el hemocultivo positivo realizado en las primeras 72 horas del inicio de la neutropenia febril, se vincula con aumento del riesgo de mortalidad en pacientes con enfermedad hemato-oncológica; sin embargo, estudios con una mayor población son necesarios para establecer esta variable como factor de riesgo de mortalidad.

Febrile neutropenia is considered an emergency in oncology patients, with a high mortality rate that has been reduced in the recent years. To evaluate the mortality risk related to positive blood cultures in hematooncologic patients with febrile neutropenia. We made an analytic cohort, prospective and observational study, between February and September of 2014 at the Hospital Miguel Perez Carreño, Caracas, Venezuela. The statistical relationship between positive blood culture and mortality rate was measured with the χ²test, with a 95% of confidence interval and the clinical relationship with the Odds Ratio values. There was a statistically significative relationship between positive blood culture realized in the first 72 hours of the febrile neutropenia episode and mortality; with an OR > 1. The duration of neutropenia for more than 7 days had a strong relationship with mortality. In our experience, the positive blood culture realized in the first 72 hours of the febrile neutropenia episode has a positive relation with higher mortality rate; studies with more patients are needed to establish this variable as a negative prognosis factor.

Estratificación de riesgo de morbimortalidad en pacientes neutropénicos febriles hematooncológicos utilizando dos escalas de predicción / Risk stratification of mortality in patients febrile neutropenic hemato using two scales prediction

Determinar el pronóstico de mortalidad en los pacientes hematooncológicos con neutropenia febril a través del score de MASCC y el de PARK. Se realizó un estudio descriptivo, prospectivo constituido por 34 pacientes hematooncológicos, neutropénicos febriles hospitalizados del Hospital Universitario de Caracas, a quienes se aplicaron ambos score. No se halló correlación estadística. Sin embargo, se observó que en el grupo de bajo riesgo según el score de MASCC estuvieron todos los pacientes que fallecieron, mientras que según el score de PARK fallecieron principalmente los pacientes con valor de PCR mayor o igual a 20. El score de MASCC pareciera no ser una herramienta útil para evaluar pronóstico en estos pacientes, siendo probablemente más útil el score de PARK en especial el valor de PCR en el ingreso...

To determine the mortality prognosis in hematooncologic neutropenic febrile patients using MASCC and Park scores. Both scores were applied to 34 hospitalized patients of the Hospital Universitario de Caracas, Venezuela, in a descriptive, prospective study. No statistic correlation was found. However we found that that the patients who died were clasiffied as low risk by the Score of MASCC and had PCR values of 20 or more Parks score. MASCC ìs score seems not to be a useful tool to evaluate the prognosis of these patients versus the Park ìs, score wich was more useful especially taking in account the PCR value on the first day of admission...