Detection of Respiratory Viruses in the Clinical Outcome of Children With Fever and Neutropenia.

BACKGROUND: Several evidence-based guidelines for the management of children with febrile neutropenia (FN) have been published, with special focus in bacterial and fungal infections. However, the role of acute respiratory infections caused by respiratory viruses (RV) has not been clearly established. The aim of this study was to evaluate the epidemiology, clinical presentation and outcome of acute respiratory infections in children with FN. METHODS: Patients, <18 years of age admitted to the Pediatric Oncology-Hematology Unit after developing FN between November 2010 and December 2013, were prospectively included in the study. Children were evaluated by clinical examination and laboratory tests. Nasopharyngeal sample was obtained for detection of RV. RESULTS: There was a total of 112 episodes of FN in 73 children admitted to the hospital during a 32-month period. According to disease severity, 33% of the episodes were considered moderate or severe. Rhinovirus was the most frequently detected RV (66.6%; 24/36), followed by parainfluenza. On regard to clinical outcome, RV-infected children developed fewer episodes of moderate or severe FN compared with non-RV infected children (16.7% vs. 33.3%; P = 0.08). CONCLUSIONS: A great proportion of children with FN admitted to a tertiary hospital had a RV isolation. The rate of this RV isolation was significantly higher when a rapid molecular test was used compared with conventional microbiologic methods. Rhinovirus was the most frequently isolated, although its role as an active agent of acute infection was not clear. Children with FN and a RV isolate had a lower rate of severe disease.

Improving Time to Antibiotic Administration for Bone Marrow Transplant Patients With First Fever.

BACKGROUND AND OBJECTIVE: Timely antibiotic administration in immunocompromised patients is associated with improved outcomes. The aim of our study was to decrease the mean time to administration of antibiotics in hospitalized bone marrow transplant patients with fever from 75 to <60 minutes. METHODS: By using the Model of Improvement, we performed plan-do-study-act cycles to design, test, and implement high-reliability interventions to decrease time to antibiotics. Nursing, physician, and pharmacy interventions were successfully applied to improve timely antibiotic administration. RESULTS: The study period was from April 2014 through March of 2017. Through heightened awareness, dedicated roles and responsibilities, a standardized order set specifically used for first fever patients, notification to the pharmacy about newly febrile first fever patients through a dedicated order, the creation of a dedicated sticker ("STAT first dose antibiotic, give directly to nurse") to be printed when antibiotics were entered via the order set in the pharmacy, and prioritization of antibiotic delivery on arrival on the floor, we saw an increase in the percentage of patients receiving antibiotics within 60 minutes of documented fever from a mean of 40% to over 90%. Our mean time for antibiotic administration decreased from 75 to 45 minutes. CONCLUSIONS: Implementation of a standardized process for notifying providers of new fever in patients, prioritization of antibiotic preparation in the central pharmacy, and timely antibiotic order entry resulted in improved times to antibiotic administration in the febrile bone marrow transplant population.

MONITOR-GCSF DLBCL subanalysis: Treatment patterns/outcomes with biosimilar filgrastim for chemotherapy-induced/febrile neutropenia prophylaxis.

OBJECTIVE: Prospective data on the use of granulocyte-colony-stimulating factor (G-CSF) in non-Hodgkin's lymphoma and its aggressive subtypes, including diffuse large B-cell lymphoma (DLBCL), are limited. MONITOR-GCSF is a pan-European, multicenter, prospective, observational study aiming to describe treatment patterns and clinical outcomes in patients receiving biosimilar filgrastim in the prophylaxis of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN). METHODS: This analysis describes patient characteristics, treatment patterns, and outcomes for 245 patients with stage 3 or 4 DLBCL receiving ≤6 chemotherapy cycles as part of MONITOR-GCSF study, including patients aged ≥65 years and ≥70 years. Outcomes of interest included the incidence of CIN and FN, antibiotic prophylaxis, biosimilar filgrastim prophylaxis, and adverse events (AEs). RESULTS: MONITOR-GCSF included 245 patients with DLBCL. Of these patients, 87 (35.5%) experienced one or more CIN (any grade) episode and 24 (9.8%) experienced FN (any grade). The most frequent AE reported was bone pain (n = 7, 2.9%), followed by arthralgia (n = 2, 0.8%) and back pain (n = 2, 0.8%). CONCLUSION: In real-life practice, biosimilar filgrastim demonstrated clinical effectiveness and safety in patients with DLBCL. The large percentage of patients aged ≥65 years adds to the evidence on how to best treat older patients with DLBCL receiving myelosuppressive chemotherapy.

Effectiveness of biosimilar filgrastim vs. original granulocyte colony-stimulating factors in febrile neutropenia prevention in breast cancer patients.

PURPOSE: The purpose of this study is to describe the effectiveness of biosimilar filgrastim and original granulocyte colony-stimulating factors (G-CSFs), lenograstim and pegfilgrastim, in febrile neutropenia (FN) prevention in breast cancer patients receiving docetaxel/doxorubicin/cyclophosphamide (TAC) as adjuvant/neoadjuvant treatment and to analyze their treatment patterns. METHODS: A pharmacoepidemiology cohort study was developed in a university hospital (with 23 healthcare centers) with retrospective data collection (2012-2014). Effectiveness of G-CSFs was assessed by the FN incidence. Other parameters analyzed were as follows: moderate and severe neutropenia incidence, neutropenia-related hospitalizations, dosage, and duration. Data was analyzed using each cycle as a unit of analysis. RESULTS: We identified 98 patients representing 518 chemotherapy cycles, 215 with original G-CSFs (35 lenograstim and 180 pegfilgrastim) and 303 with biosimilar filgrastim. The FN incidence was similar in both groups (3.7% original vs. 3.3% biosimilar; p = 0.79). No statistically significant differences were found in moderate and severe neutropenia incidence (4.7 vs. 6.3%; p = 0.43) or neutropenia-related hospitalizations (3.3 vs. 3.6%; p = 0.19). When the three drugs were evaluated separately, a higher FN incidence was observed with lenograstim than with pegfilgratim or biosimilar (p = 0.024). The dosage and duration of biosimilar were lower than lenograstim (4.9 vs. 5.7 µg/kg/day; 5 vs. 7 days; p < 0.001). CONCLUSION: An abbreviated 5-day course of biosimilar filgrastim provided optimal primary prophylaxis against FN post-chemotherapy TAC in patients with breast cancer. The clinical relevance of the highest FN incidence in the lenograstim cohort needs further attention.

Managing febrile neutropenia in adult cancer patients: an integrative review of the literature / Manejo de la neutropenia febril en pacientes adultos oncológicos: revisión integradora de la literatura / Manejo da neutropenia febril em pacientes adultos oncológicos: revisão integrativa da literatura

ABSTRACT Objective: To analyze the interventions performed by health professionals with a view to managing chemotherapy-induced febrile neutropenia. Method: Integrative literature review, the sample of 12 primary articles was selected from the following databases: LILACS, SciELO, BVS, PubMed, CINAHL and Web of Science. Results: There was a prevalence of studies, realized by doctors, focused on pharmacological treatment and on the association of methods for greater diagnostic accuracy of febrile neutropenia. A study was found on pharmaceutical management regarding antibiotic dosing efficacy and a study indicating that nurses could contribute to the identification of elderly patients who would benefit from prophylactic use of growth factor. Conclusion: There was a shortage of studies involving the participation of other health professionals, besides the doctors, and a knowledge gap regarding interprofessional practice in the management of interventions specific to their area of specialism, joint interventions and non-pharmacological interventions.

RESUMEN Objetivo: Analizar las intervenciones realizadas por profesionales de salud visando el manejo de la neutropenia febril inducida por Quimioterapia. Método: Revisión integradora de la literatura cuya muestra de 12 artículos primarios fue seleccionada en las bases LILACS, SciELO, BVS, PubMed, CINAHL y Web of Science. Resultados: Se constató la prevalencia de estudios, desarrollados por médicos, centrados en el tratamiento farmacológico y en la asociación de métodos para mayor precisión diagnóstica de la neutropenia febril. Se encontró un estudio sobre manejo farmacéutico relativo a la eficacia del dosificación de antibióticos y un estudio indicando que los enfermeros podrían contribuir para la identificación de pacientes de edad avanzada que se beneficiarían con uso profiláctico de factor de crecimiento. Conclusión: Se evidenció la escasez de estudios con la participación de otros profesionales de salud, además de los médicos, y la laguna de conocimiento cuanto a la práctica interprofesional en la conducción de intervenciones específicas a su área de competencia, intervenciones conjuntas e intervenciones no farmacológicas.

RESUMO Objetivo: Analisar as intervenções realizadas por profissionais de saúde visando ao manejo da neutropenia febril induzida por Quimioterapia. Método: Revisão integrativa da literatura cuja amostra de 12 artigos primários foi selecionada nas bases LILACS, SciELO, BVS, PubMed, CINAHL e Web of Science. Resultados: Constatou-se a prevalência de estudos, desenvolvidos por médicos, centrados no tratamento farmacológico e na associação de métodos para maior precisão diagnóstica da neutropenia febril. Encontrou-se um estudo sobre manejo farmacêutico relativo à eficácia de dosagem de antibióticos e um estudo indicando que os enfermeiros poderiam contribuir para a identificação de pacientes idosos que se beneficiariam com uso profilático de fator de crescimento. Conclusão: Evidenciou-se a escassez de estudos com a participação de outros profissionais de saúde, além dos médicos, e a lacuna de conhecimento quanto à prática interprofissional na condução de intervenções específicas a sua área de competência, intervenções conjuntas e intervenções não farmacológicas.

Managing febrile neutropenia in adult cancer patients: an integrative review of the literature.

OBJECTIVE: To analyze the interventions performed by health professionals with a view to managing chemotherapy-induced febrile neutropenia. METHOD: Integrative literature review, the sample of 12 primary articles was selected from the following databases: LILACS, SciELO, BVS, PubMed, CINAHL and Web of Science. RESULTS: There was a prevalence of studies, realized by doctors, focused on pharmacological treatment and on the association of methods for greater diagnostic accuracy of febrile neutropenia. A study was found on pharmaceutical management regarding antibiotic dosing efficacy and a study indicating that nurses could contribute to the identification of elderly patients who would benefit from prophylactic use of growth factor. CONCLUSION: There was a shortage of studies involving the participation of other health professionals, besides the doctors, and a knowledge gap regarding interprofessional practice in the management of interventions specific to their area of specialism, joint interventions and non-pharmacological interventions.

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 (AU)

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Relationship between PK/PD of Cefepime and Clinical Outcome in Febrile Neutropenic Patients with Normal Renal Function.

The efficacy of cefepime (CFPM) is known to depend on the ratio of the time that the serum levels exceed the minimum inhibitory concentration (MIC) to the dosing interval (%T>MIC). The objective of this study was to clarify the relation between %T>MIC and clinical outcome of CFPM, and to identify the optimal dosage regimen. We investigated the outcome of CFPM treatment for febrile neutropenia (FN) patients with normal renal function. Treatment success was defined as the completion of FN therapy with CFPM only. And we calculated %T>MIC for each case based on population pharmacokinetic parameters. The MIC value for simulation was set as 8 µg/mL. In logistic regression analysis, treatment success was significantly associated with the elevation of %T>MIC in the group with persistent neutropenia, yielding a receiver operating characteristic curve with an optimal cutoff value of 73.1%. Next, we simulated %T>MIC for each case under various dosing regimens. For patients whose creatinine clearance (CLcr) exceeded 100 mL/min, it was found to be difficult to attain the objective under the current regimen. In contrast, it was calculated that treatment with 2 g three times a day (t.i.d.) could attain the objective for most of the patients with 3 h of infusion. These results suggest that CFPM treatment under the current regimen is ineffective for FN patients with normal or augmented renal function, and that 2 g t.i.d. is necessary in quite a lot cases, although such use is off-label.

Capillary refill time in febrile neutropenia.

INTRODUCTION: Febrile neutropenia is a major cause of morbidity and mortality in patients presenting this condition following chemotherapy against several malignancies. OBJECTIVE: To evaluate if capillary refill time (CRT) allows the prediction of poor clinical outcome with or without antibiotic dose escalation. METHOD: Capillary refill time was assessed in 50 patients with febrile neutropenia at its nadir after chemotherapy admitted to the emergency department at Hospital Universitário de Brasília. All patients included had a minimum average arterial blood pressure of 75 mmHg, O2/FiO2 saturation rate > 300, and 15 points in the Glasgow coma scale. Inclusion depended on at least three of the systemic inflammatory response syndrome (SIRS) criteria, suspected infection, and neutropenia after chemotherapy. Capillary refill time was calculated by pressing the index finger for 15 seconds, and then timing the return to the initial color. We studied whether there is a relationship between CRT and antibiotic escalation. The gold standard used to gravity was the level of lactate. RESULTS: 31 patients had CRT ≥ 3 seconds, which it is associated with increased serum concentration of lactate (> 2 mmol/L; p<0.05). 32 patients underwent antibiotic escalation, which it is associated with CRT ≥ 3 seconds (p<0.01). CONCLUSION: CRT higher than three seconds was effective to predict antibiotic escalation.

Capillary refill time in febrile neutropenia / Tempo de enchimento capilar e neutropenia febril

Summary Introduction: Febrile neutropenia is a major cause of morbidity and mortality in patients presenting this condition following chemotherapy against several malignancies. Objective: To evaluate if capillary refill time (CRT) allows the prediction of poor clinical outcome with or without antibiotic dose escalation. Method: Capillary refill time was assessed in 50 patients with febrile neutropenia at its nadir after chemotherapy admitted to the emergency department at Hospital Universitário de Brasília. All patients included had a minimum average arterial blood pressure of 75 mmHg, O2/FiO2 saturation rate > 300, and 15 points in the Glasgow coma scale. Inclusion depended on at least three of the systemic inflammatory response syndrome (SIRS) criteria, suspected infection, and neutropenia after chemotherapy. Capillary refill time was calculated by pressing the index finger for 15 seconds, and then timing the return to the initial color. We studied whether there is a relationship between CRT and antibiotic escalation. The gold standard used to gravity was the level of lactate. Results: 31 patients had CRT ≥ 3 seconds, which it is associated with increased serum concentration of lactate (> 2 mmol/L; p<0.05). 32 patients underwent antibiotic escalation, which it is associated with CRT ≥ 3 seconds (p<0.01). Conclusion: CRT higher than three seconds was effective to predict antibiotic escalation.

Resumo Introdução: a neutropenia febril é uma das principais causas de morbimortalidade nos pacientes neutropênicos febris pós-quimioterapia para neoplasias diversas. Objetivo: avaliar se o tempo de enchimento capilar (TEC) é capaz de predizer pior desfecho clínico, pelo escalonamento ou não da antibioticoterapia. Método: foi pesquisado o TEC em 50 pacientes neutropênicos febris no nadir de pós-quimioterapia, que deram entrada no departamento de emergência do Hospital Universitário de Brasília. Todos os incluídos estavam com uma pressão arterial média mínima de 75 mmHg, relação saturação de O2/FiO2 > 300 e escala de coma de Glasgow de 15. Os critérios de inclusão foram pelo menos três da síndrome da resposta inflamatória sistêmica (SRIS), suspeita de infecção e neutropenia pós-quimioterapia. O TEC foi calculado através da pressão sobre o indicador por 15 segundos e cronometrado o tempo de retorno à cor inicial. Foi estudado se há relação entre valor encontrado no TEC e escalonamento de antibiótico. O padrão-ouro utilizado para gravidade foi o nível de lactato. Resultados: trinta e um pacientes tiveram o TEC ≥ 3 segundos, que se associou com o aumento da concentração de lactato (> 2 mmol/L; p<0,05). Trinta e dois pacientes tiveram escalonados seus antibióticos, que se associou com o TEC ≥ 3 segundos (p<0,01). Conclusão: o TEC maior que três segundos mostrou-se eficaz para predizer escalonamento de antibiótico.

Augmented Renal Clearance in Pediatric Patients With Febrile Neutropenia Associated With Vancomycin Clearance.

BACKGROUND: Vancomycin (VCM) dosage optimization in the early stages of therapy is required to achieve target trough serum concentrations, particularly in critically ill patients. Augmented renal clearance (ARC), commonly characterized by an enhanced renal clearance, has been associated with subtherapeutic concentrations of antibiotics. The aim of this study was to investigate the risk factors including febrile neutropenia for both ARC and VCM clearance in Japanese pediatric patients. METHODS: A total of 109 pediatric patients with normal renal function were included in this observational study. From VCM serum concentrations, individual VCM clearance was estimated by the Bayesian method using a 1-compartment model. Patients were classified on the basis of the presence of febrile neutropenia, cancer, trauma, systemic inflammatory response syndrome, and surgical operation. Risk factors for ARC, as defined by estimated glomerular filtration rate (eGFR) above median value (≥160 mL·min·1.73 m), were evaluated. RESULTS: Febrile neutropenia was only an independent risk factor for ARC (odds ratio, 5.86; 95% confidence interval, 1.98-21.66, P = 0.0030), which was the result of a stepwise multivariate logistic regression analysis. Although univariate analysis demonstrated a significant association of febrile neutropenia with VCM clearance, the significant independent factors of VCM clearance were age and eGFR but not febrile neutropenia, as estimated by the stepwise multivariate linear regression analysis. CONCLUSIONS: This observational study concluded that febrile neutropenia, a significant risk factor for ARC, indirectly influenced VCM clearance towing to an elevated eGFR. Cancer, trauma, systemic inflammatory response syndrome, and surgical operation were not significantly associated with ARC; however, more studies are needed to validate this observation. Adjustment of the initial dosage of VCM is required for achieving optimal therapeutic concentrations in pediatric patients with febrile neutropenia.

[Initial management of febrile neutropenia]. / Prise en chargede la neutropénie fébrile.

Despite major advances in prevention and treatment, febrile neutropenia remains one of the most concerning complications of cancer chemotherapy. Its prognosis depends directly on the quality of the initial management in the emergency department (ED). An initial assessment of circulatory and respiratory function, with vigorous resuscitation where necessary, should be followed by careful examination for potential source of infection. A broad-spectrum empirical antibacterial therapy should be given in a timespan < 1 hour. Multinational Association for Supportive Care in Cancer (MASCC) criteria were developed to help physicians make decisions about the site of care and overall management of these patients.

Malgré les progrès réalisés dans sa prévention et son traitement, la neutropénie fébrile reste une complication sérieuse et fréquente de la chimiothérapie anticancéreuse. Son pronostic dépend directement de la qualité de la prise en charge initiale. Les priorités pour l'urgentiste sont l'évaluation et le soutien des fonctions vitales, la recherche méticuleuse du foyer infectieux et une antibiothérapie empirique à large spectre administrée impérativement dans la première heure. Le choix de l'antibiotique et la décision d'hospitalisation sont guidés par les critères (MASCC) de la « Multinational association for supportive care in cancer ¼.

¹8F-FDG-PET/CT Imaging in Patients with Febrile Neutropenia and Haematological Malignancies.

The aim of the present study was to assess the prevalence of hyper-metabolic infection sites revealed by fluorine-18 ((18)F) fluorodeoxyglucose (FDG) positron-emission tomography (PET) combined with computed tomography (CT) in patients with febrile neutropenia (FN). Forty-eight consecutive patients with haematological malignancies and persistent FN (temperature ≥ 38°C and neutrophil count <500 cells/µl for more than two days) as a consequence of intensive chemotherapy were prospectively included. Pathological FDG uptakes identified 31 foci of infections located in the lungs (n=15, 48.4 %), colon (n=4, 12.9%), pancreas (n=2, 6.5%), skin (n=3, 9.7%), ear-nose-throat area (n=5, 16.1%), central venous catheter tract (n=1, 3.2%) and gallbladder (n=1, 3.2%). These pathological FDG uptakes were observed in half of the 48 patients (n=24). Among the 38 patients with a clinical diagnosis of infection, 23 showed a pathological FDG uptake, resulting in a FDG-PET/CT sensitivity of 61% (95% CI, 43-76%). Our study confirmed the ability of FDG-PET/CT to diagnose infections in patients with persistent FN.

Independent factors for prediction of poor outcomes in patients with febrile neutropenia.

BACKGROUND: Febrile neutropenia (FN) is a life-threatening condition that requires urgent management in the emergency department (ED). Recent progress in the treatment of neutropenic fever has underscored the importance of risk stratification. In this study, we aimed to determine independent factors for prediction of poor outcomes in patients with FN. MATERIAL AND METHODS: We retrospectively evaluated 200 chemotherapy-induced febrile neutropenic patients who visited the ED. Upon arrival at the ED, clinical data, including sex, age, vital signs, underlying systemic diseases, laboratory test results, estimated GFR, blood cultures, CRP, radiologic examinations, and Multinational Association of Supportive Care in Cancer (MASCC) score of all febrile neutropenic patients were obtained. Outcomes were categorized as "poor" if serious complications during hospitalization, including death, occurred. RESULTS: The platelet count <50 000 cells/mm3 (OR 3.90, 95% CI 1.62-9.43), pulmonary infiltration (OR 3.45, 95% CI 1.48-8.07), hypoproteinemia <6 g/dl (OR 3.30, 95% CI 1.27-8.56), respiratory rate >24/min (OR 8.75, 95% CI 2.18-35.13), and MASCC score <21 (OR 9.20, 95% CI 3.98-21.26) were determined as independent risk factors for the prediction of death. The platelet count <50 000 cells/mm3 (OR 3.93, 95% CI 1.42-10.92), serum CRP >50 mg/dl (OR 3.80, 95% CI 1.68-8.61), hypoproteinemia (OR 7.81, 95% CI 3.43-17.78), eGFR ≤90 ML/min/1.73 m2 (OR 3.06, 95% CI 1.13-8.26), and MASCC score <21 (OR 3.45, 95% CI 1.53-7.79) were determined as independent risk factors for the prediction of poor clinical outcomes of FN patients. Platelet count, protein level, respiratory rate, pulmonary infiltration, CRP, MASCC score, and eGFR were shown to have a significant association with outcome. CONCLUSIONS: The results of our study may help emergency medicine physicians to prevent serious complications with proper use of simple independent risk factors besides MASCC score.

Evaluation of febrile neutropenia in patients undergoing hematopoietic stem cell transplantation.

The aim of this study was to determine the incidence and causes of fever as a major problem contributing to transplantation related mortality among patients undergoing hematopoietic stem cell transplantation (HSCT) and evaluation of antibiotic use, according to reliable guidelines.We retrospectively reviewed hospital records of 195 adult patients who underwent HSCT between 2009-2011 at hematology-oncology and bone marrow transplantation research center. Baseline information and also data related to fever and neutropenia, patient's outcomes, duration of hospitalization and antibiotic use pattern were documented.A total of 195 patients were analyzed and a total of 268 febrile episodes in 180 patients were recorded (mean 1.5 episodes per patient). About 222 episodes (82%) were associated with neutropenia which one-fourth of them were without any documented infection sources. Microbiologic documents showed that the relative frequencies of gram positive and gram negative bacteria were 62.5% and 37.5%, respectively. The hospital stay duration was directly related to the numbers of fever episodes (P<0.0001).The rate of febrile episodes in autologous stem cell transplantation was significantly higher compared to allogeneic type (P<0.05).It is necessary to determine not only the local profile of microbiologic pattern, but also antibiotic sensitivities in febrile neutropenic patients following hematopoietic stem cell transplantation, and reassess response to antibiotic treatment to establish any necessity for modifications to treatment guidelines in order to prevent any fatal complications from infection.

Transient neutropenia in children with febrile illness and associated infectious agents: 2 years' follow-up.

The aim of the study was to identify the relationship of acquired neutropenia with childhood infections and to assess its clinical course, complications, and outcome. Children admitted to two pediatric wards over a 4-year period with febrile neutropenia were prospectively investigated for underlying infections with inflammatory markers, cultures of body fluids, and serological tests. The study included 161 previously healthy children with febrile neutropenia/leukopenia aged (mean ± SD) 3.02 ± 3.86 years (range, 0.1-14). One hundred and thirty-six out of 161 patients (84.5 %) had transient neutropenia (TN), while in 25 patients, neutropenia was chronic (CN) and persisted for ≥180 days. An infectious agent was isolated in 98/161 (60.9 %) cases, in 68.4 % patients with TN, and in 20 % of those with CN (p = 0.001). Among the patients with CN, seven had positive antineutrophil antibodies (autoimmune neutropenia) and four were eventually diagnosed with hematological malignancy. In all age groups, TN was of short duration (<1 month), of mild to moderate severity, and was predominantly associated with viral infections. Two years after diagnosis, 143/161 children (88.8 %) were available for follow-up. One hundred and thirty-seven of 143 (95.8 %) had recovered completely, while the rest remained neutropenic. The latter patients had a benign course despite severe neutropenia. In conclusion, febrile neutropenia during childhood is usually transient, often following viral and common bacterial infections, without serious complications and in the majority of cases it resolves spontaneously. However, in a considerable percentage of patients, neutropenia is discovered incidentally during the course of an infection on the ground of an underlying hematological disease.