Febrile Neutropenia In Children Research Articles

Safety of empirical antibiotic therapy discontinuing for fever of unknown origin during high-risk neutropenia in children

ECIL-2021 recommends discontinuing empirical antibiotic therapy (EAT) in febrile-neutropenic children after 72h of treatment and at least 24-48h of apyrexia in the case of fever of unknown origin (FUO). These guidelines are rarely applied to high-risk children's neutropenia. We retrospectively included all consecutive FUO episodes occurring during profound neutropenia ≥10 days in children in our institution. We evaluated the safety of EAT discontinuation in patients for whom the ECIL guidelines were followed compared to those for whom they didn't. We used a combined criterion of mortality and intensive care unit admission at 30 days. We identified risk factors for recurrent fever after EAT discontinuation. Fifty-one FUO episodes occurred in 37 patients. EAT discontinuation followed ECIL guidelines in 19 (37%) episodes. No deaths and-or transfers in ICU occurred in the ECIL group. The duration of EAT was shorter by nine days in the group following ECIL guidelines (p<0.001). We observed 14 (27%) episodes of recurrent fever. Mucositis was significantly associated with recurrent fever (p<0.01). EAT discontinuation seems feasible and safe in FUO during prolonged febrile neutropenia in children. However, mucosal lesions should prompt thorough surveillance due to the risk of recurrent fever.

Analysis of bacteremia at first-line antibiotic treatment for febrile neutropenia in children and adolescents: A retrospective, single-center analysis

BackgroundControl of bacterial and fungal infections is critical to improving outcomes in hematological neoplastic diseases of children and adolescents. In this study, a retrospective analysis of our previous studies on febrile neutropenia was performed to investigate bacteremia. ProcedureFrom August 2008 to December 2023, five antibiotic studies were performed for febrile and neutropenic pediatric patients who had been treated with chemotherapy, immunosuppressive therapy, or had received stem cell transplantation in the pediatric unit at Sapporo Hokuyu Hospital. The rate of positive blood culture, detected bacteria, and susceptibility of several types of antibiotics in febrile episodes were investigated. ResultsBlood culture was positive in 133 of 1604 febrile episodes of 329 patients. Detected bacteria were Gram-positive cocci (61.2 %), Gram-negative bacilli (27.6 %), Gram-negative cocci (0.7 %), and Gram-positive bacilli (10.4 %). The incidence of bacteremia over time showed a decreasing trend with each passing year. In particular, the incidence of bacteremia was around 10 % in 2008–2013, whereas it was often below 5 % after 2020; this decrease was statistically significant. Although almost all detected bacteria and their susceptibilities to antibiotics (piperacillin/tazobactam, meropenem, ceftazidime, and cefozopran) did not change over time, all Escherichia coli detected after 2014 were extended-spectrum β-lactamase-producing bacteria.

Malnutrition as a predictor of adverse outcomes of febrile neutropenia in children with acute lymphoblastic leukemia during induction phase chemotherapy

Background: Adequate nutrition is an important concern in children with leukemia. Malnutrition impairs immune function, leading to increased incidence of infection, poor quality of life, as well as death. Febrile neutropenia (FN) has a high prevalence in children with acute lymphoblastic leukemia (ALL) and a poor outcome as well. Methods: This prospective observational study was done in the department of pediatrics hematology and oncology (PHO), BSMMU, from January 2021 to October 2021. A total of 60 patients of ALL were selected purposively. Patients were evaluated by taking anthropometric parameters before getting chemotherapy and were prospectively followed up for the development and outcome of FN until recovery. Statistical analysis was performed by using SPSS (Statistical package for the social sciences) for Windows version 26.0. Result: Analysis of nutritional status as a risk factor for FN based on anthropometric indices, was found statistically significant for, weight for height (≤5 years) p=0.036, OR=0.24 (95% CI= 0.06-0.958), weight for age p=0.006, OR=0.23 (95% CI=0.07-0.67), but for BMI for age (&gt;5 years) p=0.28, OD=0.28 (95% CI=0.02-3.19), and height for age p=0.513, OD=0.66 (95% CI=0.18-2.33) no statistically significant value was found. In this study, we found mortality rate was 15%. The mortality rate was significantly worse (27.3%) for patients who were malnourished at diagnosis as compared to those who were well nourished (7.9%) at diagnosis. Conclusions: FN and its complications are more common in malnourished children with ALL. Malnutrition is associated with adverse outcomes of FN in children with ALL.

Identifying Risk Factors and Improving Preventive Strategies for Febrile Neutropenia in Children with Leukemia Receiving Ciprofloxacin Prophylaxis.

The purpose of this study was to identify risk factors and improve preventive strategies for febrile neutropenia (FEN) in children with leukemia who were receiving ciprofloxacin prophylaxis. The study included 100 children with leukemia (n=80 with acute lymphoblastic leukemia (ALL) and n=20 with acute myeloblastic leukemia) (AML). Patients were divided into two groups based on whether they had three or fewer three FEN episodes [Group 1] or more than three FEN episodes [Group 2]. Group 1 had 63 (63%) of the 100 patients, while Group 2 had 37 (37%). Older age (≥7 years), leukemia type (AML), prolonged neutropenia (>10 days), the presence of neutropenia, and hypogammaglobulinemia at diagnosis were all risk factors for more than three FEN episodes. Our findings suggest that, in addition to ciprofloxacin prophylaxis, identifying risk factors and improving preventive strategies could help reduce FEN in children with leukemia.

Etiology and Factors Affecting Severe Complications and Mortality of Febrile Neutropenia in Children with Acute Leukemia

Febrile neutropenia (FN) is an important complication that causes high rates of morbidity and mortality in patients with malignancies. We aimed to investigate the etiology, epidemiological distribution and its change over the years, clinical courses, and outcomes of FN in children with acute leukemia. We retrospectively analyzed the demographic data, clinical characteristics, laboratory results, severe complications, and mortality rates of pediatric patients with FN between January 2010 and December 2020. In 153 patients, a total of 450 FN episodes (FNEs) occurred. Eighty-four (54.9%) of these patients were male, the median age of the patients was 6.5 (range: 3-12.2) years, and 127 patients (83%) were diagnosed with acute lymphoblastic leukemia. Fever with a focus was found in approximately half of the patients, and an etiology was identified for 38.7% of the patients. The most common fever focus was bloodstream infection (n=74, 16.5%). Etiologically, a bacterial infection was identified in 22.7% (n=102), a viral infection in 13.3% (n=60), and a fungal infection in 5.8% (n=26) of the episodes. Twenty-six (23.2%) of a total of 112 bacteria were multidrug resistant (MDR) The rate of severe complications was 7.8% (n=35) and the mortality rate was 2% (n=9). In logistic regression analysis, refractory/relapsed malignancies and high C-reactive protein (CRP) at first admission were found to be the most important independent risk factors for mortality. Prolonged neutropenia after chemotherapy, diagnosis of acute myeloid leukemia, identification of fever focus or etiological agents, invasive fungal infections, polymicrobial infections, and need for intravenous immunoglobulin treatment increased the frequency of severe complications. We found that there was no significant change in the epidemiological distribution or frequency of resistant bacteria in our center in the last 10 years compared to previous years. Prolonged duration of fever, relapsed/refractory malignancies, presence of fever focus, and high CRP level were significant risk factors for poor clinical course and outcome.

Identifying Risk Factors and Improving Preventive Strategies for Febrile Neutropenia in Children with Leukemia Receiving Ciprofloxacin Prophylaxis

The purpose of this study was to identify risk factors and improve preventive strategies for febrile neutropenia (FEN) in children with leukemia who were receiving ciprofloxacin prophylaxis. The study included 100 children with leukemia [n=80 with acute lymphoblastic leukemia and n=20 with acute myeloblastic leukemia (AML)]. Patients were divided into two groups based on whether they had three or fewer FEN episodes (Group 1) or more than three FEN episodes (Group 2). Group 1 contained 63 (63%) of the 100 patients, while Group 2 contained 37 (37%). Older age (≥7 years), leukemia type, prolonged neutropenia (>10 days), and the presence of neutropenia and hypogammaglobulinemia at diagnosis were all risk factors for having more than three FEN episodes. Our findings suggest that, in addition to ciprofloxacin prophylaxis, identifying risk factors and improving preventive strategies could help reduce FEN episodes in children with leukemia.

Lenfoma ve Solid Tümörlü Çocuklarda Febril Nötropenide Sefaperazon-Sulbaktam Monoterapisinin Etkinliği

Objective: Monotherapy with a beta lactam or a cephalosporin has become the standard of care for the treatment of febrile neutropenia (FEN). We aimed to evaluate the efficacy of cefoperazone/sulbactam (CS) as empirical monotherapy for febrile neutropenia in children with solid tumors and lymphomas. Material and Methods: Children with FEN received cefaperazone-sulbactam (80 mg/kg/day, every 8 hours). Treatment responses (a) successful, complete resolution of all signs and symptoms of infection at 72 hours and after 7 days of CS treatment; (b) success with modification, change of therapy for viral, parasitic or fungal infection or addition of glycopeptides; (c) failure was defined as the emergence of a new or resistant infection, treatment-resistant bacteremia, the need to switch to carbapenems. Results: Our study included 157 patients and 350 febrile neutropenia episodes. The most common diagnoses were osteosarcoma (35%), Ewing sarcoma (30%), non-hodgkin lymphoma (13%) and rhabdomyosarcoma (9%), respectively. The origin of fever could not be determined in 223 (64%) of FEN episodes, 79 (22%) had microbiologically documented infection (MDI), and 48 (14%) had clinically documented infection (CDI). The success rate was 65% (229), the success rate with modification was 9% (31) and the failure rate was 26% (90). SC monotherapy was successful in 33% of attacks with MDI and in 60% of attacks with CDI. However, SC monotherapy was successful in 82% of febrile episodes of unknown origin. Conclusion: Cefoperazone/sulbactam is effective and safe in febrile neutropenic children with solid tumors and lymphomas for monotherapy.

Pegfilgrastim on febrile neutropenia in pediatric and adolescent cancer patients: a systematic review and meta-analysis

ABSTRACTObjectivesThere is no meta-analysis about the effects of pegfilgrastim on the occurrence of febrile neutropenia (FN) in pediatric/adolescent cancer patients. The study explored the efficacy of prophylactic pegfilgrastim in preventing FN in children/adolescents with cancer.MethodsPubMed, Embase, and the Cochrane Library were searched for studies published before April 7, 2020. The primary outcome was the rate of FN. Effect size (ES) and odds ratio (OR) with 95% confidence intervals (CIs) were used to evaluate the outcome. The ES represented the rate of FN, and the STATA ‘metaprop’ command was used to synthesize the rate.ResultsEight studies were included, comprising 167 patients and 550 courses of treatment. There was no difference between pegfilgrastim and filgrastim for the rate of FN in children receiving chemotherapy (OR = 0.68, 95% CI: 0.20–2.23, P = 0.520). In patients receiving pegfilgrastim, the rate of FN was 25.6% (95% CI: 14.9%−36.3%), the rate of grade 4 FN was 38.3% (95% CI: 19.2%−59.5%), the rate of severe neutropenia (SN) was 40.5% (95% CI: 35.1%−46.1%), and the rate of treatment delays due to FN was 4.8% (95% CI: 0.8%−11.3%).DiscussionThe number of studies that could be included was small; therefore, a specific type of cancer or a specific treatment could be studied. Heterogeneity was high.ConclusionThere was no difference between pegfilgrastim and filgrastim for the rate of FN. The use of pegfilgrastim was still associated with rates of FN, grade 4 FN, severe neutropenia, and treatment delays due to FN in pediatric cancer patients.

Efficacy of Levofloxacin Versus Amoxicillin/Clavulanate and Ciprofloxacin in the Outpatient Management of Low-Risk Febrile Neutropenia in Children with Cancer; A Randomised Control Study

Background and Aims Outpatient management of low-risk fever and neutropenia should be implemented if close monitoring is accessible and patient compliance is feasible. the use of Amoxicillin/ Clavulanate plus ciprofloxacin, Levofloxacin, and Moxifloxacin for the treatment of low-risk febrile neutropenia. There are not enough studies assessing the tolerance, safety, and efficacy of these agents in children. In this study, we aimed to assess the efficacy and safety of single-agent Levofloxacin versus the Augmentin /ciprofloxacin regimen used in our institute. Methods This is a randomized prospective interventional 2 arm study of low-risk febrile neutropenia patients presenting to the emergency department at the National Cancer Institute, Cairo University starting from December 2021 to July 2022.Eligible patients were children<18 years with haematological malignancies or haemopoietic and Low-risk febrile neutropenia without aetiological diagnosis. Lottery method was used to randomly enrol patients (1:1) to both arms. Patients were randomized to double agent ciprofloxacin and amoxicillin-clavulanic acid in comparison to single-agent levofloxacin. Follow up of the outpatient cases at; Day 1: Start oral antibiotics, obtain guardians contacts, and assure compliance, Day 3: Follow up the patient clinically and follow up count, and Day 7: Resolution of infection and stopping of antibiotics regardless of neutropenia. Primary outcomes included Safe marrow recovery and improvement of fever in all eligible patients. Drug-related side effects encountered in both arms of the study were reported. Results A preliminary analysis of the first 120 patients (60 in each group) was done. 100% of patients achieved marrow recovery in both arms by D7. Fever subsided in 100% on the Levofloxacin arm compared to 60% in the group receiving Augmentin/Ciprofloxacin. only one patient on the double agent arm was upgraded to HR and admitted to the inpatient. Levofloxacin was tolerable in all patients with no significant side effects apart from insomnia reported by the parents in 1 patient, while patients in the double agent arm; 4 had diarrhoea, 2 nausea and 2 complained of bad drug taste. Conclusions Levofloxacin has better efficacy and can be administered safely in children with low-risk FN, however close follow-up for long-term side effects and monitoring of possible emerging bacterial resistance is warranted.

Once-a-Day Ceftriaxone-Amikacin Combination as Empiric Antibiotic Therapy to Enable Outpatient Management of Febrile Neutropenia in Children-16-Year Experience from a Single Institute.

Shailesh KanvindeBackground To enable outpatient department (OPD) management of febrile neutropenia (FN), we used once-a-day (OD) ceftriaxone-amikacin (CFT-AMK) as empiric antibiotic therapy. Our experience over 16-year period is presented. Methods This was a retrospective study conducted from January2002 to December2017. Inclusion criteria were <18 years of age, undergoing cancer chemotherapy, and having FN. Exclusion criteria were FN after palliative chemotherapy, bone marrow transplantation, or at diagnosis of malignancy. Empiric CFT-AMK was used in all, except those having respiratory distress, hypotension, altered sensorium, paralytic ileus, or clinical evidence of peritonitis. Admission criteria were age <1 year, acute myeloid leukemia (AML) chemotherapy, poor performance status, need for blood transfusions, convenience, insurance, or persistent fever >48 to 72 hours after CFT-AMK. Outcomes analyzed were response (defervescence within 48-72 hours), OPD management, antibiotic upgrade, and mortality. AML diagnosis, >7 days to absolute neutrophil count >0.5 × 10 9 /L, poor performance status, and malignancy not in remission were considered high-risk FN criteria. Results CFT-AMK was given in 877/952 (92.2%) FN episodes. Seventy-six percent had hematolymphoid malignancies. Response, antibiotic upgrade, and mortality were seen in 85.7 and 65.5% ( p < 0.0001), 15 and 45.5% ( p < 0.0001), and 0 and 2% ( p = 0.003) of low- and high-risk patients, respectively. Treatment was started in OPD in 52%, of which 21.6% required subsequent admission. Of those initially admitted, early discharge (hospital stay < 5 days) was possible in 24.6%. Forty-one percent episodes were managed entirely on OPD. Overall, 80% of low-risk and 42% of high-risk episodes received treatment wholly or partially on OPD. Conclusion Our results show empiric OD CFT-AMK allows OPD management for most of the low-risk and a proportion of high-risk FN following chemotherapy in children, without compromising clinical outcomes.

Microbial blood culture patterns and antibiotic susceptibility in pediatric febrile neutropenia at Sanglah General Hospital Bali

Background: Febrile neutropenia is defined as a fever with a temperature more than or equal to 38.3°C in two measurements within 24 hours and accompanied by severe neutropenia (≤500/μL). Gram-positive bacteria have been the most common cause of febrile neutropenia in children for the previous two decades. However, the contradiction in some studies reported that gram-negative bacteria were the main pathogens causing infection. Because there are differences and shifts in the bacterial spectrum, information on the bacterial pattern and antibiotic susceptibility is critical to reaching the optimal management of febrile neutropenia patients. Methods: This observational, descriptive study was conducted in Sanglah Hospital, Bali, Indonesia, involving pediatric patients (&lt;18 years old) with febrile neutropenia. Data on antibiotic susceptibility and microbial patterns were collected retrospectively from the blood culture registry taken from febrile neutropenia patients from October 2017 to August 2020. Collected data were analyzed using the SPSS program for Windows, version 21.0. Univariate analysis was conducted, and data with a categorical scale were reported in frequency distribution and percentage, then displayed in a table and graph. Result: A total of 180 episodes of febrile neutropenia were collected from 89 patients. Among 180 blood cultures, there were found 44 (24.44%) blood cultures with positive results. A higher proportion of gram-negative organisms (33; 75%) is found compared to gram-positive organisms (11; 25%). The susceptibility rates were 100% for Azithromycin, Amoxicillin Clavulanate, Cefoperazone Sulbactam, Meropenem, Linezolid, and Doxycycline, while Cefepime, the previous empirical antibiotic, was susceptible at 79.31% isolates. Conclusion: Gram-negative bacteria were the most frequent cause of infection among febrile neutropenic patients. Although the research evidence is still weak due to the small sample size, Cefoperazone Sulbactam could be a better option to replace Cefepime as an empirical antibiotic due to its significantly higher susceptibility.

Clinical Epidemiology Characteristics and Etiology of Febrile Neutropenia in Children: Analysis of 421 Cases.

: IntroductionThe congenital immune system includes neutrophils, which perform a variety of functions. Congenital and acquired neutropenia are rare illnesses with an underestimated prevalence in children. The aim of this study is to examine the epidemiology and etiology of febrile neutropenia in children at Haiphong Children’s Hospital, Haiphong, Vietnam. Methods: A cross-sectional study was carried out on 421 febrile neutropenia children. Clinical and laboratory characteristics were examined. Results: The median age (IQR) was 25.0 (12.5–59.5) months. The male-to-female ratio was 1.35/1. There were twice as many children living in the suburbs (66.98%) as in urban areas (33.02%). The mean (SD) temperature at admission was 38.50 ± 0.59 °C. Diagnosed causes associated with neutropenia included acute respiratory infections 250 (59.45%), gastrointestinal infections 68 (16.1%), erythema 37 (8.79%), acute leukemia 15 (3.56%), urinary tract infection 5 (1.19%), and encephalitis/meningitis 4 (0.95%). Viral etiology accounted for 61.52% (259): influenza type A—50.19% (130), influenza type B—31.27% (81), dengue virus—14.67% (38), measles virus 1—93% (5), rotavirus—1.54% (4), and EBV—0.4% (1). Twenty-five patients (5.94%) were found to have bacteria in their cultures, with Streptococcus pneumonia being the most common (eight patients; 32%). Conclusions: Febrile neutropenia was common in children under 2 years old. Primary clinical manifestations were acute upper respiratory tract infections, and viruses most commonly caused febrile neutropenia. Further studies with larger sample sizes are needed to determine the cause of febrile neutropenia.

Efficacy and Safety of Piperacillin-Tazobactam and Cefepime as Empirical Therapy for Febrile Neutropenic Children with Acute Lymphoblastic Leukaemia (ALL)

Background: Infection is a major clinical challenge in ALL treatment. Prompt administration of empirical antibiotic in febrile neutropenic patients has reduced the mortality. Both Cefepime or Piperacillin-Tazobactam has been used as empirical treatment.&#x0D; Objective: To compare the efficacy and safety between Piperacillin-Tazobactam with Cefepime in febrile neutropenic children with ALL.&#x0D; Materials and methods: This randomized study was conducted from August 2015 to August 2016 in BSMMU. Sixty one episodes of febrile neutropenia in children with ALL, aged 0 to18 years were included in this study. Patients were randomized into two groups. One group received Piperacilln/Tazobactam and another group received Cefepime and data of 60 febrile neutropenic episodes were analyzed.&#x0D; Results: Febrile neutropenic episodes in the Piperacillin/Tazobactam group were 28 and in Cefepime group was 32 episodes and 34(57.63%) were male and 25 (42.37%) female. Median age was 5 years and 38(62.3%) neutropenic episodes were in induction phase. Majority had fever without focus 21(35%). Microorganisms isolated in 13 (21.66%) patients and majority 6 (46.15%) had blood infection. Most of the isolated organisms were Gram negative 11(84.61%). Overall treatment success without modification in the Piperacillin/Tazobactam group was 17(60.7%) and in Cefepime group 18 (56.3%) and that comparison was not statistically significant (p= 0.732). Significant difference was also not found comparing the mean duration of fever, neutropenia and hospital stay.&#x0D; Conclusion: Both Piperacillin/Tazobactam and Cefepime were found effective and safe as an empirical therapy for febrile neutropenic children with ALL.&#x0D; BANGLADESH J CHILD HEALTH 2021; VOL 45 (2) : 83-88

Frequency and Culture Sensitivity for Bacteremia During Febrile Neutropenia in Children with Acute Lymphoblastic Leukemia. Do Age and Gender Matter?

Objectives: To determine the frequency of bacteremia and its association with age and gender in febrile neutropenic children suffering from acute lymphoblastic leukemia and identify the commonest pathogens and their antibiotic susceptibility identified on blood cultures.&#x0D; Study Design: Cross-sectional analytical study&#x0D; Place and Duration of Study: Pediatrics Inpatient Department, Shifa International Hospital, Islamabad Pakistan, from Sep 2018 to Mar 2019.&#x0D; Methodology: Children with acute lymphoblastic leukemia aged 1-12 years, presenting with temperature &gt;100ºF and absolute neutrophil count of &lt;500 cells/µL were enrolled. An automated blood culture system was used and Clinical and Laboratory Standards Institute Guidelines 2017 were used for susceptibility testing. Antibiotics were started empirically in all cases and changed after susceptibility testing.&#x0D; Results: A total of 62 children were enrolled. The mean age was 8.6 ± 2.4 years. Majority of the children i.e., 32 (51.6%) were females. The frequency of bacteremia was 16 (25.8%) and there was no significant association with age or gender (p=0.475 and p=0.881 respectively). Majority of the isolates were gram-positive. The organism isolated in the highest frequency was Methicillin-Resistant Staphylococcus Epidermidis (MRSE) 5 (31.25%). Susceptibility to Vancomycin was present in 10 isolates while seven isolates were sensitive to penicillins/cephalosporins.&#x0D; Conclusion: Bacteremia, primarily caused by gram-positive bacteria was found in 25.8% of our sample and was uninfluenced by age or gender. MRSE was the most frequent isolate. The bacterial isolates were susceptible primarily to vancomycin and penicillins/cephalosporins.

PAnTher Cub: procalcitonin-guided antibiotic therapy for febrile neutropenia in children and young people with cancer - a single-arm pilot study

BackgroundFebrile neutropenia (FN) is a common complication of cancer treatment in children and young people, and many episodes are over-treated. Procalcitonin, may be an appropriate tool to guide the stopping...

Malnutrition as Risk Factor for Febrile Neutropenia in Children with Acute Lymphoblastic Leukemia

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Febrile neutropenia is one of medical emergencies in ALL patients. One of the risk factors that associate with febrile neutropenia is malnutrition. Malnutrition reduce the body’s immunity that increase incidence of infection.&#x0D; AIM: aimed to prove malnutrition as risk factor in children with ALL who had febrile neutropenia&#x0D; METHOD: This is case-control study with samples a hundred children aged 1 month to 18 years old with ALL at Sanglah Hospital Denpasar between 2015 - 2021. Subjects were grouped into two, those with febrile neutropenia and without febrile neutropenia. The relationship between malnutrition and febrile neutropenia was analyzed by using chi-square bivariate analysis test.&#x0D; &#x0D; RESULTS: A hundred subjects were devided into two groups with 50 subjects each group. Bivariate analysis showed significant association between malnutrition and febrile neutropenia (OR 4.53; 95%CI 1.95 - 10.51; p-value &lt;0.001).&#x0D; CONCLUSION: Malnutrition as risk factor for febrile neutropenia in children with ALL.&#x0D;

A national study of antibiotic use in Greek pediatric hematology oncology and bone marrow transplant units.

We surveyed antimicrobials used in Greek pediatric hematology-oncology (PHO) and bone marrow transplant (BMT) units before and after an intervention involving education regarding the 2017 clinical practice guidelines (CPG) for the management of febrile neutropenia in children with cancer and hematopoietic stem-cell transplant recipients. Antibiotic prescribing practices were prospectively recorded between June 2016 and November 2017. In December 2017, baseline data feedback was provided, and CPG education was provided. Prescribing practices were followed for one more year. For antibiotic stewardship, days of therapy, and length of therapy were calculated. Five of the 6 PHO units in Greece and the single pediatric BMT unit participated. Admitted children in each unit who received the first 15 new antibiotic courses each month. Administration of ≥4 antibiotics simultaneously and administration of antibiotics with overlapping activity for ≥2 days were significantly more common in PHO units in general hospitals compared to children's hospitals. Use of at least 1 antifungal was recorded in ∼47% of the patients before and after the intervention. De-escalation and/or discontinuation of antibiotics on day 6 of initial treatment increased significantly from 43% to 53.5% (P = .032). Although the number of patients requiring intensive care support for sepsis did not change, a significant drop was noted in all-cause mortality (P = .008). We recorded the antibiotic prescribing practices in Greek PHO and BMT units, we achieved improved prescribing with a simple intervention, and we identified areas in need of improvement.

Blood transcriptomics identifies immune signatures indicative of infectious complications in childhood cancer patients with febrile neutropenia.

ObjectivesFebrile neutropenia (FN) is a major cause of treatment disruption and unplanned hospitalization in childhood cancer patients. This study investigated the transcriptome of peripheral blood mononuclear cells (PBMCs) in children with cancer and FN to identify potential predictors of serious infection.MethodsWhole‐genome transcriptional profiling was conducted on PBMCs collected during episodes of FN in children with cancer at presentation to the hospital (Day 1; n = 73) and within 8–24 h (Day 2; n = 28) after admission. Differentially expressed genes as well as gene pathways that correlated with clinical outcomes were defined for different infectious outcomes.ResultsGlobal differences in gene expression associated with specific immune responses in children with FN and documented infection, compared to episodes without documented infection, were identified at admission. These differences resolved over the subsequent 8–24 h. Distinct gene signatures specific for bacteraemia were identified both at admission and on Day 2. Differences in gene signatures between episodes with bacteraemia and episodes with bacterial infection, viral infection and clinically defined infection were also observed. Only subtle differences in gene expression profiles between non‐bloodstream bacterial and viral infections were identified.ConclusionBlood transcriptome immune profiling analysis during FN episodes may inform monitoring and aid in defining adequate treatment for different infectious aetiologies in children with cancer.

Decision-tree derivation and external validation of a new clinical decision rule (DISCERN-FN) to predict the risk of severe infection during febrile neutropenia in children treated for cancer

In 2017, international guidelines proposed new management of febrile neutropenia in children with cancer, adapted to the risk of severe infection by clinical decision rules (CDRs). Until now, none of the proposed CDRs has performed well enough in high-income countries for use in clinical practice. Our study aimed to build and validate a new CDR (DISCERN-FN) to predict the risk of severe infection in children with febrile neutropenia. We did two prospective studies. First, a prospective derivation study included all episodes of febrile neutropenia in children (aged <18 years) with a cancer diagnosis and receiving treatment for it who were admitted for an episode of febrile neutropenia, excluding patients already treated with antibiotics for this episode, febrile neutropenia not induced by chemotherapy, those receiving palliative care, and those with a stem cell allograft for less than 1 year, from April 1, 2007, to Dec 31, 2011 from two paediatric cancer centres in France. We collected the children's medical history, and clinical and laboratory data, and analysed their associations with severe infection. Sipina software was used to derive the CDR as a decision tree. Second, a prospective, national, external validation study was done in 23 centres from Jan 1, 2012, to May 31, 2016. The primary outcome was severe infection, defined by bacteraemia, a positive bacterial culture from a usually sterile site, a local infection with a high potential for extension, or an invasive fungal infection. The CDR was applied a posteriori to all episodes to evaluate its sensitivity, specificity, and negative likelihood ratio. The derivation set included 539 febrile neutropenia episodes (270 episodes in patients with blood cancer [median age 7·5 years, IQR 3·7-11·2; 158 (59 %) boys and 112 (41%) girls] and 269 in patients with solid tumours [median age 6·6 years, IQR 2·9-14·2; 140 (52 %) boys and 129 (48%) girls]). Significant variables introduced into the decision tree were cancer type (solid tumour vs blood cancer), age, high-risk chemotherapy, level of fever, C-reactive protein concentration (at 24-48 h after admission), and leucocyte and platelet counts and procalcitonin (at admission and at 24-48 h after admission). For the derivation set, the CDR sensitivity was 98% (95% CI 93-100), its specificity 56% (51-61), and the negative likelihood ratio 0·04 (0·01-0·15). 1806 febrile neutropenia episodes were analysed in the validation set (mean age 8·1 years [SD 4·8], 1014 (56%) boys and 792 (44%) girls), of which 332 (18%, 95% CI 17-20) were linked with severe infection. For the validation set, the CDR had a sensitivity of 95% (95% CI 91-97), a specificity of 38% (36-41), and a negative likelihood ratio of 0·13 (0·08-0·21). Our CDR reduced the risk of severe infection to a post-test probability of 0·8% (95% CI 0·2-2·9) in the derivation set and 2·4% (1·5-3·9) in the validation set. The validation study is registered at ClinicalTrials.gov, NCT03434795. The use of our CDR substantially reduced the risk of severe infection after testing in both the derivation and validation groups, which suggests that this CDR would improve clinical practice enough to be introduced in appropriate settings. Ligue Nationale Contre le Cancer.

Cost-effectiveness of home-based care of febrile neutropenia in children with cancer.

Home-based treatment of febrile neutropenia (FN) in children with cancer with oral or intravenous antibiotics is safe and effective. There are limited data on the economic impact of this model of care. We evaluated the cost-effectiveness of implementing an FN programme, incorporating home-based intravenous antibiotics for carefully selected patients, in a tertiary paediatric hospital. A decision analytic model was constructed to compare costs and outcomes of the home-based FN programme, with usual in-hospital treatment with intravenous antibiotics. The programme included a clinical decision rule to stratify patients by risk for severe infection and home-based eligibility criteria using disease, chemotherapy and patient-level factors. Health outcomes (quality of life) and probabilities of FN risk classification and home-based eligibility were based on prospectively collected data between 2017 and 2019. Patient-level costs were extracted from hospital administrative records. Cost-effectiveness was expressed as the incremental cost per quality-adjusted life year (QALY). The mean health care cost of home-based FN treatment in low-risk patients was Australian dollars (A$) 7765 per patient compared to A$20,396 for in-hospital treatment (mean difference A$12,632 [95% CI: 12,496-12,767]). Overall, the home-based FN programme was the dominant strategy, being more effective (0.0011 QALY [95% CI: 0.0011-0.0012]) and less costly. Results of the model were most sensitive to proportion of children eligible for home-based care programme. Compared to in-hospital FN care, the home-based FN programme is cost-effective, with savings arising from cheaper cost of caring for children at home. These savings could increase as more patients eligible for home-based care are included in the programme.