Pediatric Febrile Neutropenia Research Articles

Aminoglycoside use in paediatric febrile neutropenia - Outcomes from a nationwide prospective cohort study.

Aminoglycosides are commonly prescribed to children with febrile neutropenia (FN) but their impact on clinical outcomes is uncertain and extent of guideline compliance is unknown. We aimed to review aminoglycoside prescription and additional antibiotic prescribing, guideline compliance and outcomes for children with FN. We analysed data from the Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) prospective multicentre cohort study, in children <18 years with FN between November 2016 and January 2018. Impact of aminoglycoside use in the first 12 hours of FN on composite unfavourable outcome of death, ICU admission, relapse of infection or late-onset sepsis was assessed using multivariable Cox regression. The study was conducted in Australia where antimicrobial resistance among gram negative organisms is relatively low. Data from 858 episodes of FN in 462 children from 8 centres were assessed, median age 5.8 years (IQR 3.5–10.8 years). Early empiric aminoglycosides were prescribed in 255 episodes (29.7%). Guideline non-compliance was common: in 46% (184/400) of eligible episodes, patients did not receive aminoglycosides, while aminoglycosides were prescribed in 9% (39/458) of guideline-ineligible episodes. Adjusted hazard of the composite unfavourable outcome was 3.81 times higher among patients prescribed empiric aminoglycosides than among those who weren’t (95% confidence interval, 1.89–7.67), with no increased risk of unfavourable outcome in eligible patients who did not receive aminoglycosides. In a large paediatric FN cohort, aminoglycoside prescription was common and was often non-compliant with guidelines. There was no evidence for improved outcome with aminoglycosides, even in those who met guideline criteria, within a low-resistance setting. Empiric aminoglycoside prescription for children with FN requires urgent review in guidelines and in national practice.

Patient Outcomes With Febrile Neutropenia Based on Time to Antibiotics in the Emergency Department.

Although bacteremia in pediatric oncology patients with febrile neutropenia (FN) is not uncommon, sepsis and mortality are rare. Because of the lack of clinically meaningful decision tools to identify high-risk patients with bacteremia, time to antibiotic administration (TTA) is increasingly considered an important quality and safety measure in the emergency department. Because little evidence exists suggesting that this benchmark is beneficial, we sought to determine whether TTA of 60 minutes or less is associated with improved outcomes. We retrospectively reviewed patients presenting to a pediatric emergency department with FN from November 2013 to June 2016. Clinical outcomes including mortality, pediatric intensive care unit admission, imaging, fluid resuscitation of 40 mL/kg or greater in the first 24 hours, and length of stay were compared between TTA of 60 minutes or less and more than 60 minutes. One hundred seventy-nine episodes of FN were analyzed. The median TTA was 76 minutes (interquartile range, 58-105). The incidence of bacteremia was higher in patients with TTA of more than 60 minutes (12% vs 2%, P = 0.04), but without impact on mortality, pediatric intensive care unit admission, fluid resuscitation, or median length of stay. The median TTA was not different for those who were and were not bacteremic (91 vs 73 minutes, P = 0.11). Time to antibiotic administration of more than 60 minutes did not increase mortality in pediatric oncology patients with FN. Our study adds to the existing literature that TTA of 60 minutes or less does not seem to improve outcomes in pediatric FN. Further larger studies are required to confirm these findings and determine which features predispose pediatric FN patients to morbidity and mortality.

Re-evaluating and recalibrating predictors of bacterial infection in children with cancer and febrile neutropenia.

BackgroundNumerous paediatric febrile neutropenia (FN) clinical decision rules (CDRs) have been derived. Validation studies show reduced performance in external settings. We evaluated the association between variables common across published FN CDRs and bacterial infection and recalibrated existing CDRs using these data.MethodsProspective data from the Australian-PICNICC study which enrolled 858 FN episodes in children with cancer were used. Variables shown to be significant predictors of infection or adverse outcome in >1 CDR were analysed using multivariable logistic regression. Recalibration included re-evaluation of beta-coefficients (logistic model) or recursive-partition analysis (tree-based models).FindingsTwenty-five unique variables were identified across 17 FN CDRs. Fourteen were included in >1 CDR and 10 were analysed in our dataset. On univariate analysis, location, temperature, hypotension, rigors, severely unwell and decreasing platelets, white cell count, neutrophil count and monocyte count were significantly associated with bacterial infection. On multivariable analysis, decreasing platelets, increasing temperature and the appearance of being clinically unwell remained significantly associated. Five rules were recalibrated. Across all rules, recalibration increased the AUC-ROC and low-risk yield as compared to non-recalibrated data. For the SPOG-adverse event CDR, recalibration also increased sensitivity and specificity and external validation showed reproducibility.InterpretationDegree of marrow suppression (low platelets), features of inflammation (temperature) and clinical judgement (severely unwell) have been consistently shown to predict infection in children with FN. Recalibration of existing CDRs is a novel way to improve diagnostic performance of CDRs and maintain relevance over time.FundingNational Health and Medical Research Council Grant (APP1104527).

Pediatric Febrile Neutropenia: Change in Etiology of Bacteremia, Empiric Choice of Therapy and Clinical Outcomes.

The optimal choice of initial antibiotic therapy for patients with high-risk febrile neutropenia (FN) in children is unclear and varies by the institution on the basis of local antibiograms and epidemiology of specific pathogens. The authors evaluated the appropriateness of antibiotics for the empiric treatment of FN in pediatric patients with cancer in our institution on the basis of changes in the epidemiology of organisms isolated from blood cultures (BCx). The authors conducted a retrospective medical record review of pediatric patients who received any oncology care (including patients with cancer and patients who had stem cell transplant) at University of Chicago Medicine Comer Children's Hospitals (March 2009 to December 2016) with a diagnosis of FN who had at least 1 BCx obtained. They reviewed pathogens isolated from BCx and determined whether they were pathogens or contaminants using the Infectious Diseases Society of America (IDSA) guidelines and the team's decision to treat. They investigated the microbiologic spectrum and susceptibility patterns of pathogens causing bacteremia in pediatric FN and whether the empiric therapy chosen may have affected clinical outcomes. A total of 667 FN episodes were identified in 268 patients. BCx were negative in 497 (74.5%) and were determined to be contaminants in 27 (4%). In 143 episodes (21.5%), the BCx were positive for a pathogenic species. Polymicrobial bacteremia was identified in 25 episodes; a total of 176 pathogens were isolated. The majority of pathogens (95/176, 54%) were Gram-positive (GP), whereas 64 of 162 (36%) were Gram-negative (GN), 5 were fungal, and 4 were mycobacterial. The most common GP pathogens were viridans group streptococci (VGS) (n=34, 19.3%), coagulase-negative staphylococci (n=25, 14%), and methicillin-susceptible Staphylococcus aureus (n=12, 6.8%). Of aerobic GN bacilli, 15 (8.5%) were AmpC producers and 3 (1.7%) carried extended-spectrum beta-lactamases. There was no increase in the prevalence of multidrug-resistant GN isolates during the study period. Patients with VGS and multidrug-resistant GN bacteremia were more likely to be admitted to the pediatric intensive care unit [odds ratio (OR), 3.24; P=0.017; and OR, 2.8; P=0.07, respectively]. There were trends toward a higher prevalence of GP pathogens causing bacteremia and the emergence of VGS with decreased penicillin sensitivity. The prevalence of bacteremia with VGS was higher in acute myelogenous leukemia and neuroblastoma (OR, 2.3; P<0.01) than in patients with other solid tumors. Empiric antibiotic treatment should be tailored to patients' risk for VGS and multidrug-resistant organisms. Individual hospitals should monitor the pathogens causing FN among patients with cancer to guide choice of empiric therapy.

Updated systematic review and meta-analysis of the predictive value of serum biomarkers in the assessment and management of fever during neutropenia in children with cancer.

Routinely measurable biomarkers as predictors for adverse outcomes in febrile neutropenia could improve management through risk stratification. This systematic review assesses the predictive role of biomarkers in identifying events such as bacteraemia, clinically documented infections, microbiologically documented infection, severe sepsis requiring intensive care or high dependency care and death. This review collates 8319 episodes from 4843 patients. C-reactive protein (CRP), interleukin (IL)-6, IL-8 and procalcitonin (PCT) consistently predict bacteraemia and severe sepsis; other outcomes have highly heterogeneous results. Performance of the biomarkers at admission using different thresholds demonstrates that PCT>0.5ng/mL offers the best compromise between sensitivity and specificity: sensitivity 0.67 (confidence interval [CI] 0.53-0.79) specificity 0.73 (CI 0.66-0.77). Seventeen studies describe the use of serial biomarkers, with PCT having the greatest discriminatory role. Biomarkers, potentially with serial measurements, may predict adverse outcomes in paediatric febrile neutropenia and their role in risk stratification is promising.

Near-universal hospitalization of US emergency department patients with cancer and febrile neutropenia.

ImportanceFebrile neutropenia (FN) is the most common oncologic emergency and is among the most deadly. Guidelines recommend risk stratification and outpatient management of both pediatric and adult FN patients deemed to be at low risk of complications or mortality, but our prior single-center research demonstrated that the vast majority (95%) are hospitalized.ObjectiveFrom a nationwide perspective, to determine the proportion of cancer patients of all ages hospitalized after an emergency department (ED) visit for FN, and to analyze variability in hospitalization rates. Our a priori hypothesis was that >90% of US cancer-associated ED FN visits would end in hospitalization.DesignAnalysis of data from the Nationwide Emergency Department Sample, 2006–2014.SettingStratified probability sample of all US ED visits.ParticipantsInclusion criteria were: (1) Clinical Classification Software code indicating cancer, (2) diagnostic code indicating fever, and (3) diagnostic code indicating neutropenia. We excluded visits ending in transfer.ExposureThe hospital at which the visit took place.Main outcomes and measuresOur main outcome is the proportion of ED FN visits ending in hospitalization, with an a priori hypothesis of >90%. Our secondary outcomes are: (a) hospitalization rates among subsets, and (b) proportion of variability in the hospitalization rate attributable to which hospital the patient visited, as measured by the intra-class correlation coefficient (ICC).ResultsOf 348,868 visits selected to be representative of all US ED visits, 94% ended in hospitalization (95% Confidence Interval [CI] 93–94%). Each additional decade of age conferred 1.23x increased odds of hospitalization. Those with private (92%), self-pay (92%), and other (93%) insurance were less likely to be hospitalized than those with public insurance (95%, odds ratios [OR] 0.74–0.76). Hospitalization was least likely at non-metropolitan hospitals (84%, OR 0.15 relative to metropolitan teaching hospitals), and was also less likely at metropolitan non-teaching hospitals (94%, OR 0.64 relative to metropolitan teaching hospitals). The ICC adjusted for hospital random effects and patient and hospital characteristics was 26% (95%CI 23–29%), indicating that 26% of the variability in hospitalization rate was attributable to which hospital the patient visited.Conclusions and relevanceNearly all cancer-associated ED FN visits in the US end in hospitalization. Inter-hospital variation in hospitalization practices explains 26% of the limited variability in hospitalization decisions. Simple, objective tools are needed to improve risk stratification for ED FN patients.

1550. Pediatric Febrile Neutropenia: Does Depth and Duration of Neutropenia at Presentation Predict Outcomes?

BackgroundThe 2010 Infectious Diseases Society of America (IDSA) guidelines define febrile neutropenia (FN) patients as high risk if they have profound neutropenia [ANC (absolute neutrophil count) ≤100 cells/μL] anticipated to last >7 days. Formal studies to clearly evaluate the significance of the depth of neutropenia are lacking.MethodsA retrospective cohort study of all pediatric oncology patients presenting with FN between July 2009–December 2016 was performed to evaluate if the depth and duration of neutropenia prior to presentation was correlated with blood stream infection (BSI), invasive fungal disease (IFD), pediatric intensive care unit (PICU) admission or length of stay (LOS). Patients were categorized into three groups based on ANC at time of presentation: <100, 100–500, and >500 cells/mL with decreasing ANC over the subsequent 48 hours. Durations of neutropenia prior to presentation were also assessed.ResultsA total of 585 FN episodes (FNEs) were identified in 265 patients presenting with 411(70%) ANC <100, 119(20%) ANC 100–500 and 55 (10%) ANC >500 with subsequent decline over 48 hours. Underlying diagnoses included ALL (32%), AML (29%), lymphoma (16%), neuroblastoma (16%) and other solid tumors (9%). In group ANC >500; 70% (39/55) of received chemotherapy within 2 weeks of presentation and 35% were s/p SCT. Rates of IFD and BSI were higher in the group with ANC > 500 with decline in 48 hours compared with ANC < 100 (OR = 5.9, P = 0.03) and ANC 100–500 (OR = 5.6, P = 0.034). Patients with ANC>500 cells/mL were significantly more likely to be admitted to the PICU (OR = 5.00, P = 0.017) and had an increased LOS (hazard ratio = 0.55, P = 0.002) when compared with the other two groups. No difference in PICU admission or mortality was found when patients presenting with fevers and ANC < 100 were compared with ANC 100–500. Neutropenia ≥7 days prior to FN was an independent risk factor for BSI (OR = 2.8, P = 0.001).ConclusionPediatric patients presenting with febrile neutropenia and initial ANC >500 cells/mL with decine over 48 hours had a higher incidence of BSI, IFD, PICU admissions Clinicians should not be reassured when patients present with fever and initial ANC >500 cells/mL after undergoing recent chemotherapy if continued decline is expected. More work needs to be done to evaluate for risk factors at the time of presentation with FN to guide clinical care.Disclosures All authors: No reported disclosures.

1598. Oral Step Down Therapy With Levofloxacin for Low-Risk Febrile Neutropenia in Children

BackgroundIntravenous antibiotic therapy is used for most children with febrile neutropenia (FN). For some children, therapy is completed with outpatient parenteral antibiotic therapy (OPAT). Adult data support step-down therapy to a quinolone-based oral antibiotic regimen for selected patients and recent pediatric FN guidelines recommend consideration of this strategy, but pediatric data are sparse. Because oral therapy is associated with lower costs and fewer adverse events compared with OPAT, we sought to evaluate the safety and feasibility of an oral step-down program for selected pediatric FN.MethodsThis was a retrospective pre–post study evaluating oral-step down therapy at discharge with levofloxacin for low-risk FN children. Eligibility criteria for oral therapy were: age >1 year, no documented bacteremia, anticipated neutropenia <7 days at discharge, afebrile >24 hours, and were tolerating an enteral diet. Informal discussion began in 2015; the formal practice change was implemented in September 2017. Intervention periods were defined as: pre-intervention (January 2014–March 2015), peri-implementation (March 2015–September 2017); post-intervention (October 2017–March 2018).The primary outcomes were was the percentage of FN patients who were discharged on oral levofloxacin and OPAT during each period. A secondary outcome was the percentage of patients readmitted within 7 days requiring receipt of IV antibiotics. Chi-square tests were used to compare outcomes between periods and statistical process control charts to monitor the changes during the intervention.ResultsDuring the pre-intervention period, 4/107 (3.7%) nonbacteremic FN were discharged on oral levofloxacin. This increased to 62/239 (26%) during the peri-implementation period and 37/68 (54%) during the post-implementation period (P < 0.001) (Figure 1).The percentage of patients discharged on OPAT decreased from 74% in the pre-intervention to 9% in the post-intervention period (P < 0.001). Readmission rates within 7 days of discharge receiving IV antibiotics in the first 24 hours were similar across the study periods (11%, 16%, and 9%, respectively; P = 0.19) (Figure 2).ConclusionAn oral step-down program reduced OPAT use for low-risk pediatric FN with no change in readmissions Disclosures All authors: No reported disclosures.

Quest for certainty regarding early discharge in paediatric low-risk febrile neutropenia: a multicentre qualitative focus group discussion study involving patients, parents and healthcare professionals in the UK

ObjectivesA systematic review of paediatric low-risk febrile neutropenia found that outpatient care is safe, with low rates of treatment failure. However, this review, and a subsequent meta-ethnography, suggested that early...

Factors Associated with Adverse Outcome in Pediatric Febrile Neutropenia: Results from a Tertiary Care Hospital

Background Febrile neutropenia with childhood cancer alters the outcome significantly. To study the clinical and laboratory parameters, which predict the outcome among cancer patients with febrile neutropenia this study was undertaken. Materials and Methods The study included children less than 18 years with febrile neutropenia episodes. Clinical and hematological / laboratory parameters were recorded during each episode. Hemoglobin, total leucocyte count, platelet count, absolute neutrophil count, absolute monocyte count and serum C- reactive protein (CRP) levels at the onset of febrile neutropenia episode were analyzed as predictors of outcome of febrile neutropenia. The outcome was measured in terms of mortality, duration of fever and need for Intensive care unit (ICU) stay. Results The study consisted of 88 episodes in 40 children with a median (IQR) age of 5.9 (3.79, 10) years. In 67.5% of Children's Leukaemiawas the underlying disease. Mean (±SD) hemoglobin concentration was 8.8 ± 1.71 g/dl. Profound neutropenia was seen in 32(36.5%) episodes. Most common infection was lower respiratory infection (30.7%). Absolute monocyte count 7 days (p=0.030).Thrombocytopenia ( 90 mg/L) were found to be significant predictors of mortality (p Conclusion Thrombocytopenia and elevated CRP are significant predictors of mortality and the need for prolonged ICU stay, whereas low hemoglobin level, leukopenia and low absolute neutrophil count (ANC) were not associated with of adverse outcome in febrile neutropenia episodes.

Predictive Indicators to Identify High-Risk Paediatric Febrile Neutropenia in Paediatric Oncology Patients in a Middle-Income Country.

To validate a clinical risk prediction score (Ammann score) to predict adverse events (AEs) in paediatric febrile neutropenia (FN). Patients <16 years of age were enrolled. A risk prediction score (based on haemoglobin ≥ 9g/dl, white cell count (WCC) < 0.3G/l, platelet count <50G/l and chemotherapy more intensive than acute lymphoblastic leukaemia maintenance therapy) was calculated and AEs were documented. In total, 100 FN episodes occurred in 52 patients, male:female ratio was 1.8:1 and median age was 56 months. At reassessment, AEs occurred in 18 of 55 (45%) low-risk FN episodes (score < 9) and 21 of 42 (55%) high-risk episodes (score ≥9) (sensitivity 60%, specificity 65%, positive predictive value 53%, negative predictive value 71%). Total WCC and absolute monocyte count (AMC) were significantly associated with AEs. This study identified total WCC and AMC as significantly associated with AEs but failed to validate the risk prediction score.

Management of chemotherapy-induced febrile neutropenia in pediatric oncology patients: A North American survey of pediatric hematology/oncology and pediatric infectious disease physicians.

Chemotherapy-induced febrile neutropenia (FN) is traditionally managed with hospital admission for parenteral antibiotics until neutropenia resolves. Recent studies have explored risk stratification and the safety of managing "low-risk" patients as outpatients. Few studies have directly assessed pediatric provider preferences for managing FN. We conducted a survey of practicing US and Canadian pediatric hematology/oncology (PHO) and pediatric infectious disease (PID) physicians to assess their FN management preferences using case scenarios with varying risk profiles. Twenty-one percent (n = 186) of PHO and 32% (n = 123) of PID physicians completed the survey. Overall, both groups of providers agreed regarding which patients with FN could be managed outpatient. For a child with acute lymphoblastic leukemia receiving maintenance chemotherapy with an absolute neutrophil count (ANC) of 400 cells/μl, 35% (n = 66) of PHO and 49% (n = 60) of PID physicians would consider outpatient management (P = 0.02). Of those physicians selecting inpatient management, 41% (n = 49) of PHO and 52% (n = 33) of PID physicians would be willing to discharge the patient without an increase in ANC, if afebrile with a negative blood culture (P = 0.16). For a similar patient with an ANC of 100 cells/μl, only 23% (n = 35) of PHO and 42% (n = 39) of PID physicians would consider discharge without an increase in ANC (P = 0.002). Despite the lack of established guidelines for low-risk pediatric FN, a significant proportion of North American physicians report willingness to modify traditional management. This reinforces the need for evidence-based low-risk criteria and outpatient management guidelines to optimize consistency of care for these patients.

Pediatric Oncology Discharges With Febrile Neutropenia: Variation in Location of Care.

We examined the use of Pediatric Cancer Specialty Centers (PCSCs) over time and the length of stay (LOS) in pediatric oncology patients with a diagnosis of febrile neutropenia. PCSCs were defined as Children's Oncology Group and California Children's Services designated centers. We performed a retrospective analysis on all discharges of pediatric (0 to 18) oncology patients with febrile neutropenia in California (1983 to 2011) using the private Office of Statewide Health Planning and Development database. We examined influence of age, sex, race/ethnicity, payer, income, distance, tumor type, and complications on utilization of PCSCs and LOS (SAS 9.2). Analysis of 24,559 pediatric oncology febrile neutropenia discharges showed hospitalizations in PCSCs increasing from 48% in 1983 to 94% in 2011. The adjusted regression analysis showed decreased PCSC utilization for ages 15 to 18, Hispanic patients, and those living >40 miles away. The median PCSC LOS was 9 days compared with 7 days at a non-PCSC (P<0.0001). Discharge from a PCSC was associated with a LOS >8 days after controlling for complications. Inpatient PCSC care for febrile neutropenia in California has increased since 1983. Receiving care at a PCSC is influenced by age, tumor type, ethnicity, geography, and complications.

Risk stratification in febrile neutropenic episodes in adolescent/young adult patients with cancer

BackgroundRisk-stratified management of febrile neutropenia (FN) allows intensive management of high-risk cases and early discharge of low-risk cases. Most risk stratification systems predicting severe infection from admission variables have been derived from childhood or adult populations and consequently their value in adolescents/young adults (AYA) may vary. Our objective was to determine their value in this population. MethodsData from the ‘predicting infectious complications in children with cancer’ (PICNICC) individual participant data collaboration were used to evaluate six previously described risk stratification schema in the AYA population. Complete case analyses were undertaken for five ‘paediatric’ rules, with imputation for specific missing variables of the ‘adult’ rule. The predictive performance of the rules or the outcome microbiologically defined infection (sensitivity, specificity and predictive values) were compared. ResultsAmong the 5,127 episodes of FN in 3,504 patients in the PICNICC collaboration data set, 603 episodes of FN from 478 patients in 20 studies were of patients 16–25 years old. The six rules demonstrated variable sensitivity (33–96%) and specificity (13–83%). Their overall discriminatory ability was poor (area under the receiver operator curve estimates 0.514–0.593). ConclusionsBoth paediatric and adult FN risk stratification schema perform poorly in AYA with cancer. An alternative rule or clinical recognition of their limitations is required.

Indication-Based Antimicrobial Derestriction: Ceftazidime Derestriction for Febrile Neutropenia

Sta2s2cal Analysis Febrile neutropenia (FN) is a common condi2on in children receiving chemotherapy and can be life-­‐threatening. The University of Chicago Comer Children’s Hospital has a rigorous an2microbial restric2on and prior authoriza2on policy overseen by the An2microbial Stewardship Program (ASP). • CeIazidime (CTZ), our agent of choice for FN, is restricted. • Use requires calling Infec2ous Diseases (ID) on call for approval, followed by ID calling pharmacy with authoriza2on, leading to a poten2al delay in order processing. • FN is recognized as a 2me-­‐sensi2ve disease state with a clear indica2on for empiric an2bio2c (i.e. CTZ) use. • FN clinical pathway was revised, removing the need for prior approval, or “derestric2on”. • Goal of the revised clinical pathway and derestric2on is to promote the most appropriate, targeted and 2mely care to those high-­‐risk pediatric FN pa2ents. • Derestric2on serves to minimize the 2me between ini2al pa2ent presenta2on and 2me to an2bio2c administra2on. • New clinical pathway provides guidance for the ini2al workup and an2microbial management. • Indica2on-­‐based an2bio2c ordering and derestric2on can be successfully implemented in an ASP with a historically restric2on-­‐based system, without significant change in the appropriate use of the derestricted agent, change in the rate of bloodstream infec2ons or pa2ent outcomes. • The ED serves as the most efficient administrator of CTZ within the goal of less than 60 minutes. • Other units (i.e. clinic and inpa2ent unit) do not meet the desired less than 60 minute standard. Future efforts will be directed towards evalua2ng addi2onal factors affec2ng 2me to CTZ administa2on administra2on, specifically within the clinic and inpa2ent seYngs.

1586 Oral vs intravenous antibiotics in low risk paediatric febrile neutropenia: A meta-analysis of randomised controlled trials

1586 Oral vs intravenous antibiotics in low risk paediatric febrile neutropenia: A meta-analysis of randomised controlled trials

Blood Cultures for Persistent Fever in Neutropenic Pediatric Patients Are of Low Diagnostic Yield.

The incidence of bacteremia at the onset of pediatric febrile neutropenia (FN) at 2 academically linked institutions was 9.84%, and subsequent blood cultures performed for children with persistent FN yielded an incidence of 4.21%. Until the risk factors for new-onset bacteremia in patients being treated for FN can be identified and diagnostic methods can be improved, compliance with national guidelines is recommended.

小児の発熱性好中球減少症におけるLinezolidの有効性と安全性に関する検討

In this study, we investigated the efficacy and safety of administration of Linezolid (LZD) to pediatric febrile neutropenia (FN) patients after cancer chemotherapy. The study period was from January 2008 to June 2014, and the subjects were patients under the age of 16 receiving LZD administration (9 subjects, 16 cases, average age 9.2 ± 4.4 years). The dose of LZD was 30.7 ± 3.1 mg/kg/day, and the administration period was 12.1 ± 6.3 days. The test values were as follows: the CRP decreased from 3.9 ± 4.5 mg/dL to 0.4 ± 0.7 mg/dL (P < 0.01), the PLT increased from 7.1 ± 4.69 × 104 /μL to 14.5 ± 9.1 × 104 /μL (P < 0.01) and the WBC increased from 9.4 ± 21.6 × 102 /μL to 42.2 ± 38.5 × 102 /μL (P < 0.01); thus, statistically significant differences were obtained. The reason for the termination of LZD administration was due to the alleviation of the symptoms, which was observed in 14 cases (14/16 87.5%). Survival after 30 days was confirmed in all of the cases. The results suggest that LZD administration to FN pediatric patients is effective and safe.

Effect of meropenem with or without immunoglobulin as second‐line therapy for pediatric febrile neutropenia

Meropenem (MEPM) is widely used for treatment of febrile neutropenia. There have been many reports on MEPM for pediatric febrile neutropenia showing success rates of approximately 50-75%. Although i.v. immunoglobulin (IVIG) is widely used for treatment of infection with antibiotics, there has been no report on the efficacy of IVIG for pediatric febrile neutropenia. This prospective randomized study was therefore carried out to clarify the usefulness of MEPM with or without IVIG as second line-therapy for pediatric febrile neutropenia. A total of 61 pediatric patients with 146 episodes were judged to have failure of first-line therapy (August 2008-April 2010: cefozopran vs cefepime; April 2010-April 2012: cefepime vs piperacillin/tazobactam) for febrile neutropenia, and were randomized to MEPM and MEPM + IVIG groups. MEPM with or without IVIG as second-line therapy was effective in 68.1% of a total of 144 episodes. Success rates in the MEPM and MEPM + IVIG groups were 66.3% and 70.5%, respectively. Furthermore, success rates for patients with IgG <500 mg/dL were 62.5% in the MEPM group and 81.3% in the MEPM + IVIG group. This result, however, was not statistically significant, possibly because of the small sample size. MEPM is effective and safe for second-line treatment of febrile episodes in neutropenic pediatric patients. Moreover, IVIG is effective for patients with low serum IgG.

Risk predictors for adverse outcome in pediatric febrile neutropenia: Single center experience from a low and middle-income country.

Risk stratification of patients with febrile neutropenia (FN) into those at "High Risk" and "Low Risk" of developing complications helps in making decisions regarding optimal treatment, such as whether to treat with oral or intravenous antibiotics, whether to treat as inpatient or outpatient and how long to treat. Risk predictors obtained from Western studies on pediatric FN are unlikely to be relevant to low middle-income country (LMICs). Our study aimed to identify clinical and laboratory parameters predictive of poor outcomes in children with chemotherapy-induced FN in a LMIC. Two hundred and fifty consecutive episodes of chemotherapy-induced FN in pediatric (<15 years) patients were analyzed prospectively. Adverse outcomes were defined as per SPOG 2003 FN study as serious medical complications (SMC) due to infection, microbiologically defined infection, and radiologically defined pneumonia (RDP). Variables found to be significant for adverse outcome (P < 0.05) on univariate analysis were selected for multivariate analysis. Five factors that were found to independently predict adverse outcome were (a) previously documented infection in the past 6 months, (b) presence of significant focus of infection, (c) absolute phagocyte count <100/mm3, (d) peak temperature more than 39°C in this episode of FN, and (e) fever lasting more than 5 days during this episode of FN. Identifying the risk factors for adverse outcome in pediatric FN, which are objective and applicable across LMICs would contribute in developing guidelines for the management of FN in a resource-limited setting.