Neutropenia In Pediatric Patients Research Articles

Antibiotic-associated neutropenia is marked by the depletion of intestinal Lachnospiraceae and associated metabolites in pediatric patients.

Prolonged antibiotic exposure causes dangerous hematologic side effects, including neutropenia, in up to 34% of patients. Murine studies established a link between the intestinal microbiota and hematopoiesis. To identify factors that predispose to neutropenia in pediatric patients, we evaluated changes in microbiota-derived metabolites and intestinal microbiota composition after prolonged courses of antibiotics. In this multi-center study, patients with infections requiring anticipated antibiotic treatment of two or more weeks were enrolled. Stool samples were obtained at the start and completion of antibiotics or at neutropenia onset (prospective arm). Some patients were enrolled in a retrospective arm in which a stool sample was collected at the time of neutropenia during antibiotic therapy and 2-4 weeks after completion of antibiotics with recovery of blood counts. We identified 10 patients who developed neutropenia on antibiotics and 29 controls matched for age, sex, race, and ethnicity. Clinical data demonstrated no association between neutropenia and the type of infection or antibiotic used; however, patients with neutropenia were admitted to the intensive care unit more often and received longer courses of antibiotics. Reduced intestinal microbiome richness and, specifically, decreased abundance of Lachnospiraceae family members correlated with neutropenia. Untargeted stool metabolomic profiling revealed several metabolites that were depleted exclusively in patients with neutropenia, including members of the urea cycle pathway, pyrimidine metabolism, and fatty acid metabolism that are known to be produced by Lachnospiraceae. Our study shows a relationship between intestinal microbiota disruption and abnormal hematopoiesis and identifies taxa and metabolites likely to contribute to microbiota-sustained hematopoiesis.

Application of the Weighted-Incidence Syndromic Combination Antibiogram (WISCA) to guide the empiric antibiotic treatment of febrile neutropenia in oncological paediatric patients: experience from two paediatric hospitals in Northern Italy

BackgroundGuidelines about febrile neutropenia in paediatric patients are not homogeneous; the best empiric treatment of this condition should be driven by local epidemiology. The Weighted-Incidence Syndromic Combination Antibiogram (WISCA) addresses the need for disease-specific local susceptibility evidence that could guide empiric antibiotic prescriptions based on outcome estimates of treatment regimens obtained as a weighted average of pathogen susceptibilities. This study developed a WISCA model to inform empirical antibiotic regimen selection for febrile neutropenia (FN) episodes in onco-haematological paediatric patients treated at two Italian paediatric tertiary centres.MethodsWe included blood cultures from patients with a bloodstream infection and neutropenia admitted to the Paediatric Haematology-Oncology wards in Padua and Genoa Hospitals from 2016 to 2021. WISCAs were developed by estimating the coverage of 20 antibiotics as monotherapy and of 21 combined regimens with a Bayesian probability distribution.ResultsWe collected 350 blood cultures, including 196 g-negative and 154 g-positive bacteria. Considering the most used antibiotic combinations, such as piperacillin–tazobactam plus amikacin, the median coverage for the pool of bacteria collected in the study was 78%. When adding a glycopeptide, the median coverage increased to 89%, while the replacement of piperacillin–tazobactam with meropenem did not provide benefits. The developed WISCAs showed that no monotherapy offered an adequate coverage rate for the identified pathogens.ConclusionsThe application of WISCA offers the possibility of maximizing the clinical utility of microbiological surveillance data derived from large hospitals to inform the choice of the best empiric treatment while contributing to spare broad-spectrum antibiotics.

Depletion of Lachnospiraceae Marks the Development of Antibiotic-Associated Neutropenia in Pediatric Patients

Prolonged antibiotic administration has been associated with peripheral cytopenias in up to 10-15% of patients. Of these, neutropenia is particularly notable because of the associated risk of severe bacterial infections. Yet, the mechanisms underlying antibiotic-associated neutropenia remain poorly understood. Recent studies in murine models demonstrate that antibiotics suppress hematopoiesis by depletion of the intestinal microbiota, with concomitant suppression of basal Type I interferon (IFN) and STAT1 signaling. Oral administration of the microbial metabolites that induce Type I IFN restores normal hematopoiesis in antibiotic-treated mice. These findings support a paradigm in which products of the intestinal microbiota enter the bloodstream and travel to the bone marrow where they promote production of growth cytokines that support normal hematopoiesis. To identify microbiota and microbiota-derived metabolites altered in patients with antibiotic-associated neutropenia, we enrolled pediatric patients receiving antibiotic therapy for a planned duration of fourteen days or more in a multicenter-IRB approved study. We analyzed pre- and post-treatment stool samples from 51 subjects by 16S rRNA sequencing and untargeted metabolomics profiling. Neutropenia occurred in 13% of prospectively enrolled subjects. In total, 10 neutropenic patients were included in the study, with 29 control patients selected by frequency matching for age, race, and ethnicity. Length of intravenous antibiotic treatment, total length of antibiotic treatment, length of stay and admission to the intensive care unit were correlated with the development of neutropenia, whereas type of antibiotic or type of infection were not. Based on 16S rRNA sequencing, alpha diversity was significantly decreased in the stool of patients with neutropenia but not in controls (p= 0.027 vs p= 0.059). Analysis of taxa abundance showed significant depletion of Lachnospiraceae in patients with neutropenia (p=0.043), while no significant difference was identified in controls. Lachnospiraceae are a main producer of short chain fatty acids and have been linked to hematopoietic stem cell transplant outcomes. Partial least square-discriminant analysis (sPLS-DA) showed that the metabolomes of neutropenic and control stools were similar at baseline. However, 17 metabolites were differentially abundant after antibiotic treatment in the neutropenic group but not in the control group including citrulline, tyrosine, and N-acetylglucosamine/N-acetylgalactosamine. Future work will assess whether these compounds can rescue antibiotic-associated neutropenia in the animal model. This is the first clinical study linking changes in the intestinal microbiota with antibiotic associated neutropenia. An improved understanding of the molecular mechanisms by which the microbiome sustains normal hematopoiesis will lead to ways to prevent and treat antibiotic-associated bone marrow suppression.

Guideline for the Management of Fever and Neutropenia in Pediatric Patients With Cancer and Hematopoietic Cell Transplantation Recipients: 2023 Update.

To update a clinical practice guideline (CPG) for the empiric management of fever and neutropenia (FN) in pediatric patients with cancer and hematopoietic cell transplantation recipients. The International Pediatric Fever and Neutropenia Guideline Panel reconvened to conduct the second update of this CPG. We updated the previous systematic review to identify new randomized controlled trials (RCTs) evaluating any strategy for the management of FN in pediatric patients. Using the Grading of Recommendations Assessment, Development and Evaluation framework, evidence quality was classified as high, moderate, low, or very low. The panel updated recommendations related to initial management, ongoing management, and empiric antifungal therapy. Changes from the 2017 CPG were articulated, and good practice statements were considered. We identified 10 new RCTs in addition to the 69 RCTs identified in previous FN CPGs to inform the 2023 FN CPG. Changes from the 2017 CPG included two conditional recommendations regarding (1) discontinuation of empiric antibacterial therapy in clinically well and afebrile patients with low-risk FN if blood cultures remain negative at 48 hours despite no evidence of marrow recovery and (2) pre-emptive antifungal therapy for invasive fungal disease in high-risk patients not receiving antimold prophylaxis. The panel created a good practice statement to initiate FN CPG-consistent empiric antibacterial therapy as soon as possible in clinically unstable febrile patients. The updated FN CPG incorporates important modifications on the basis of recently published trials. Future work should focus on addressing knowledge gaps, improving CPG implementation, and measuring the impact of CPG-consistent care.

Characterization of Febrile Neutropenia in Pediatric Patients With Cancer Before and After Implementation of Coronavirus Disease 2019 Precautions.

Historically, febrile neutropenia (FN) has constituted a common but life-threatening emergency in pediatric oncology patients. As such, hygiene precautions have consistently been recommended for immunosuppressed patients. These precautions, however, were more strictly and widely adopted during the coronavirus disease 2019 pandemic. Universal mask mandates, emphasis on hand hygiene, and encouragement of social distancing were some of the many initiatives introduced in an effort to reduce transmission of the virus. There is little data available regarding whether the universal adoption of these precautions was associated with any changes in the incidence of hospitalizations for FN in pediatric oncology patients. A retrospective chart review was utilized to evaluate newly diagnosed patients admitted for FN in the first 14 months of the pandemic compared with the same time period during the previous year. During the pandemic, the admission rate for FN was 28.9%, compared with 29.1% prepandemic ( P = 0.97). There was no significant difference in causative organisms when comparing time periods. In addition, the presence of a state government-enforced mask mandate was associated with an increased admission rate for FN during the pandemic period.

Association of Vancomycin Trough Concentration and Clearance With Febrile Neutropenia in Pediatric Patients.

Febrile neutropenia promotes renal drug excretion. Adult and pediatric patients with febrile neutropenia exhibit a lower vancomycin concentration/dose (relative to bodyweight) ratio than those with other infections. In pediatric patients, renal function relative to bodyweight varies depending on age, and vancomycin clearance is age dependent. This study aimed to analyze the effects of febrile neutropenia on the pharmacokinetics of vancomycin in age-stratified pediatric patients. This retrospective, single-center, observational cohort study analyzed 112 hospitalized pediatric patients who met the selection criteria and intravenously received vancomycin at the Department of Pediatrics of the Oita University Hospital between April 2011 and October 2019. The febrile neutropenia (n = 46) cohort exhibited a significantly higher estimated glomerular filtration rate than the nonfebrile neutropenia (n = 66) cohort. Compared with those in the nonfebrile neutropenia cohort, the daily vancomycin dose relative to bodyweight and vancomycin clearance were significantly higher, and the vancomycin trough concentration and vancomycin concentration/dose ratio were significantly lower in the febrile neutropenia cohort. In the age groups of 1-6 and 7-12 years, compared with those in the nonfebrile neutropenia cohort, the vancomycin concentration/dose ratio was significantly lower, and vancomycin clearance was significantly higher in the febrile neutropenia cohort. Univariate and multivariate analyses identified febrile neutropenia as the independent factor influencing vancomycin concentration/dose ratio and clearance only in pediatric patients aged 1-6 years. Increased initial dosage and therapeutic drug monitoring-guided dose optimization are critical for the therapeutic efficacy of vancomycin in pediatric patients with febrile neutropenia, especially in those aged 1-6 years.

Antibiotic-Induced Neutropenia in Pediatric Patients: New Insights From Pharmacoepidemiological Analyses and a Systematic Review

Aim: to characterize pediatric cases of antibiotic-associated neutropenia through a multidisciplinary approach, focusing on the temporal association between the wide spectrum of treatment options and the occurrence of this relatively uncommon but potentially clinically relevant adverse event. Methods: we carried out a pharmacoepidemiological analysis based on the FDA Adverse Event Reporting System (FAERS) database, a retrospective chart review and a systematic review of the literature, focusing on the time to onset (TTO) of this side effect, in the pediatric clinical setting. Results: A total of 281 antibiotic-related neutropenia events, involving 11 categories of antibiotics, were included in the time to onset analysis. The median TTO ranged from 4 to 60 days after the start of the therapy. A shorter median TTO was found from the retrospective chart review [16 patients: median days (25th-75th percentiles) = 4 (3–5)], compared to 15 (9–18) vs. 10 (6–18) for literature (224 patients) and FAERS (41 cases), respectively. The Anatomical Therapeutic Chemical classes, J01X, J01F, J01E and J04A, and the median TTOs retrieved from more than one source revealed high accordance (p > 0.05), with J01X causing neutropenia in less than a week and J01F/J01E/J04A in more than 10 days. Antibiotics were discontinued in nearly 34% of cases. In FDA Adverse Event Reporting System reports, half of the patients experiencing neutropenia were hospitalized. Conclusion: Whereas antibiotic associated neutropenia is benign in the majority of cases, yet it should not be neglected as, even if rarely, it may put children at higher risk of clinical consequences. Clinicians’ awareness of antibiotic-associated neutropenia and its mode of presentation contributes to the continuous process of monitoring safety of antibiotics.

Clinical And Hematological Profile Of Febrile Neutropenia In Pediatric Patients Who Suffered From Malignancy At Dr. Soetomo General Academic Hospital Surabaya

Background: Febrile neutropenia is a common complication found in the practice of hematology-oncology caused by malignancy and immune-stimulating cytotoxic therapy. The appearance of febrile neutropenia in patients with malignancy often has a negative impact on the patient's prognosis. There has been no research on febrile neutropenia, especially those using data from Dr. Soetomo General Academic Hospital Surabaya until now. This study aims to determine febrile neutropenia's clinical and hematological profile in pediatric patients who suffered from malignancy at Dr. Soetomo General Academic Hospital Surabaya. Methods: A retrospective study using the medical records of febrile neutropenia patients with malignancy at the Division of Hematology-Oncology, Department of Pediatrics, Dr. Soetomo General Academic Hospital Surabaya from January 2018 to December 2019. The descriptive analysis in this study describes the clinical and hematological profile of febrile neutropenia in pediatric patients who suffered from malignancy, including underlying clinical diagnosis, clinical symptoms, clinical signs, and hematological examination results. Results: Thirty febrile neutropenia patients suffered from malignancy. From the data obtained, the most common clinical diagnosis underlying the incidence of febrile neutropenia was acute lymphoblastic leukemia (73%). The most common clinical symptom experienced by patients was fever (100%). The most common clinical sign experienced by patients was anemia (67%). The most common hematological examination results were neutropenia (100%) with absolute neutrophil count <500 cells/?L. Conclusion: Acute lymphoblastic leukemia dominates the clinical diagnosis underlying the development of febrile neutropenia in pediatric patients with malignancy. The most common clinical and hematological profiles were fever, anemia, and neutropenia.

Use of Pegfilgrastim in Japanese Pediatric Patients With Solid Tumors: A Retrospective Analysis.

There are no detailed analyses of regarding pegfilgrastim usage in Japanese pediatric solid tumor patients. The approved dose of pegfilgrastim in Japan is 3.6 mg. We retrospectively evaluated the incidence of dose delays and dose reductions due to neutropenia in pediatric patients with solid tumors receiving chemotherapy with pegfilgrastim between 2015 and 2018. The effects of the timing of pegfilgrastim administration were evaluated. In chemotherapies administered every 2 and 3 weeks, prolongation of chemotherapy cycles was analyzed. Fifty-nine patients received chemotherapy with prophylactic pegfilgrastim for a total 247 cycles. No significant incidence of dose delays was observed with pegfilgrastim administration during the first 1 to 3 days after chemotherapy. When 77 cycles in 2-week regimens were compared with 166 cycles in 3-week regimens, mean cycle durations were 15.19±2.06 and 21.97±2.88 days, respectively (P<0.001). A total of 77 chemotherapy cycles administered every 14 days were subdivided. The incidence of dose delays in pediatric patients receiving chemotherapy for 5 consecutive days was similar to that for 1 day and 2 consecutive days. Pegfilgrastim prophylaxis could be of use for Japanese pediatric patients with solid tumors receiving chemotherapy, including administration every 2 weeks. Its use aids in maintaining the chemotherapy schedule.

Interleukin-6 versus C-reactive protein as markers for early detection of bacteremia in febrile neutropenia in pediatric population

Abstract Introduction: Systemic infection leading to multiorgan failure during neutropenia is one of the leading causes of treatment-related mortality among children receiving chemotherapy. Reliable markers are needed to diagnose or rule out infection, to reduce the empirical use of broad-spectrum antibiotic therapy. Aims and Objectives: The aim is to compare the role of interleukin-6 versus C-reactive protein (CRP) as markers of sepsis in febrile neutropenia in pediatric patients while on chemotherapy for malignancy. Materials and Methods: This was a prospective observational study carried out in the Department of Paediatrics of a tertiary care Hospital in South India. All children with malignancy in the age group from 1 month to 18 years diagnosed to have febrile neutropenia during any phase of chemotherapy were included in the study. Multiple episodes of febrile neutropenia in the same child were analyzed as separate episodes. Results: Thirty-two episodes of febrile neutropenia were analyzed. There were 7 microbiologically documented infections (MDI), 19 clinically documented infections and 6 episodes of fever of unknown origin. Out of the 7 MDI, 5 were Gram-negative sepsis and 2 were Gram-positive sepsis. Gram-negative sepsis had a much higher median IL-6 value (169) than Gram-positive sepsis (17.5) and sterile blood cultures (52). However, median value of CRP was only slightly higher in Gram-positive sepsis (85.5) than in Gram-negative sepsis (60.7) and sterile blood cultures (44.2). Conclusion: In this study, higher IL-6 values predicted Gram-negative sepsis better than CRP.

Analysis of antibiotics discontinuation during bone marrow suppression in childhood, adolescent and young adult patients with febrile neutropenia.

Antibiotics have been widely and efficaciously used for febrile neutropenia in pediatric patients. However, reports are scant regarding the risk factors for recurrent fever after discontinuation of antibiotics in a neutropenic state. Here, we investigated these factors using data from our previously reported randomized study regarding meropenem and piperacillin/tazobactam for pediatric patients with febrile neutropenia. We analyzed a total of 170 febrile episodes where first line antibiotic treatment was effective and discontinued before neutrophil recovery. Recurrent fever was observed in 31 episodes (18%). The median interval from antibiotics discontinuation to recurrent fever was 5 days (0-27 days). Risk factors for recurrent fever were: incomplete remission of original disease; and high white blood cell count, neutrophil count, and C reactive protein levels at start of antibiotics. Moreover, lower neutrophil count at discontinuation of antibiotics, duration of neutropenia, and onset day of febrile neutropenia from start of neutropenia were also risk factors of recurrent fever. In multivariate analysis, neutrophil count at discontinuation of antibiotics <0.011×109/L, neutrophil count at start of antibiotics ≥0.061×109/L, febrile onset following <1 day after onset of neutropenia, and incomplete remission of original disease were independent risk factors for recurrent fever. Discontinuation of antibiotics while pediatric patients were still neutropenic was almost safe. However, physicians should note the risk factors of recurrent fever.

Guidance Statement for the Management of Febrile Neutropenia in Pediatric Patients Receiving Cancer-Directed Therapy in Central America and the Caribbean.

PURPOSEOur objective was to provide regionally appropriate, resource-conscious recommendations for the diagnosis and treatment of pediatric patients with febrile neutropenia.METHODSA multinational panel of Central American and Caribbean clinicians who deliver pediatric oncology care prioritized clinically important questions and then used the Grading of Recommendations Assessment, Development and Evaluation methodology to provide recommendations on the selected topics.RESULTSTwenty-two questions and 2 definitions were included in the guideline, which was intended to establish minimum care standards for pediatric patients treated in regional centers. Of all the included studies, 6.9% were conducted in low- and middle-income countries, and no studies were performed in countries represented on the panel.CONCLUSIONThe panel made recommendations on the basis of existing evidence but identified important gaps in knowledge from the region and from resource-limited settings that may affect the clinical applicability of these recommendations. These deficiencies suggest a research agenda that will enable future guidelines to be more responsive to the local context.

Prophylactic piperacillin administration in pediatric patients with solid tumors following different intensities of chemotherapy.

Prophylactic antibiotics decrease mortality and morbidity in patients with hematological malignancies following intensive chemotherapy. However, the efficacy of prophylactic antibiotics for pediatric patients with solid tumors remains unclear. We retrospectively assessed 103 neutropenic periods from 26 patients with neuroblastoma or brain tumors following three different intensity chemotherapy regimens (05A3, A, and B). While piperacillin was intravenously administered as prophylaxis (PIPC prophylaxis group), the historical control group received no prophylaxis. As patients exhibited a variable degree of myelosuppression based on the intensity of the chemotherapy regimen, we separately evaluated the frequency and severity of febrile neutropenia (FN) in each regimen. Following intensive chemotherapy, we observed a significantly lower frequency of FN in the PIPC prophylaxis group compared with the historical control group in both regimen 05A3 (20% vs 65%; P = 0.01) and regimen A (56% vs 93%; P = 0.02). We also observed a shorter duration of fever, lower maximum fever, and lower C-reactive protein levels in the PIPC prophylaxis group compared with the historical control group after regimens 05A3 and A. Conversely, the frequency and severity of FN were not different between the two groups after moderate-intensity chemotherapy (regimen B). However, a longitudinal routine surveillance study of Pseudomonas aeruginosa also indicated a reduction in the susceptibility to PIPC throughout the study period. Although PIPC prophylaxis might provide an advantage for severe neutropenia in pediatric patients with solid tumors, there is concern regarding bacterial resistance to antibiotics. Therefore, further careful examination is necessary for adaptation.

Posaconazole in prophylaxis and salvage treatment of invasive fungal infections during neutropenia in pediatric patients with leukemia: a retrospective analysis

Objective To investigate the efficacy and safety of Posaconazole (Posa) in prophylaxis and salvage treatment of invasive fungal infections (IFI) during neutropenia in pediatric patients with leukemia. Methods A total of 18 pediatric patients (55 case-time) with leukemia in neutropenia stage receiving Posa treatment from December 2015 to August 2017 in Zhujiang Hospital of Southern Medical University, were analyzed retrospectively.Taking one induction chematherapy or one consolidation chemotherapy stage receiving Posa treatment was defined as 1 case-time. Results Out of 18 participants, 13 cases were patients with acute myeloid leukemia (AML) and 5 cases were patients with acute lymphocytic leukemia (ALL), including 36 males and 19 females.Median age of the participants was 7 years, ranged from 10 months to 14 years.Out of 55 case times, 45 of them were of primary prevention and the neutropenia periods ranged from 4 to 46 days, with the median of 15 days, and 93.33% of them were prevented from fungal infection.However, 3 of the 45 cases had sudden fungal infections and the Voriconazole was an effective treatment, and no one died.Six cases in this study experienced secondary prevention, and no patient experienced reinfection.The neutropenia terms of the 6 cases ranged from 10 to 17 days, with the median of 14 days.Four patients who suffered from Voriconazole and/or Carbophenol therapy failure received Posa as a rescue therapy and the response rate was 100%.None of patients had Posa intolerance due to severe adverse reaction and no Posa treatment-related grade Ⅱ toxic effects occurred. Conclusions Posa is an effective and safe therapy for pediatric patients with leukemia and IFI, and available for long-time usage.Serious adverse reaction is rare. Key words: Posaconazole; Leukemia; Invasive fungal infection; Neutropenia; Child

Oral Magnesium for Reduce Febrile Neutropenia in Children with Solid Tumors Treated with Cisplatin-Based Chemotherapy: Randomized Clinical Trial

Background: Hypomagnesemia has been associated with febrile neutropenia (FN) in pediatric patients receiving cisplatin-based chemotherapy (CDDPBC). The primary aim was to determine whether oral magnesium supplementation reduces FN episodes in pediatric patients with solid tumors treated with CDDPBC. Methods: This randomized clinical trial, open label, single center, parallel groups and superiority design was conducted in Hospital Infantil de Mexico Federico Gomez at Mexico City. Children ≥ 9 years with solid tumors that were to receive a CDDPBC cycle were invited to participate. Each cycle of chemotherapy with CDDPBC were randomly assigned to receive oral magnesium supplementation (250 mg per day) or not receive magnesium supplementation (control group). Efficacy was determined by relative risks (RR) with 95% confidence intervals (95%CI) as well as with numbers needed to treat (NNT). Active surveillance was conducted to assess safety in both groups. Analyzes were made by intention to treat. This study is registered with ClinicalTrials.gov, number NCT03449693. Findings: between October 2017 and February 2019, eighty-two cycles of chemotherapy with CDDP were analyzed (42 in the magnesium supplement arm and 40 in control group). Baseline clinical characteristics were similar comparing both groups. Oral magnesium supplementation reduces FN episodes compared to control group (RR= 0.48, [95%CI, 0.26 to 0.89], NNT= 4). In the group supplemented with magnesium presented lower risk of septic shock secondary to FN (RR= 0.29, [95%CI, 0.09 to 0.96], NNT= 6). Adverse evets were similar across both groups. Interpretation: Oral supplementation with magnesium reduces episodes of febrile neutropenia in pediatric patients with solid tumors treated with CDDPBC. Trial Registration Number: This study is registered with ClinicalTrials.gov, number NCT03449693. Funding: This work was supported by Direccion General de Asuntos del Personal Academico, Universidad Nacional Autonoma de Mexico (DGAPA, UNAM), PAPIIT Grant IA207417. Declaration of Interest: Nothing to declare. Ethical Approval: The study was approved by HIMFG Institutional Review Board (HIM 2017-85) and registered prospectively in Clinical Trial Registry (NCT03449693).

Episodes of fever in neutropenia in pediatric patients with cancer in Bern, Switzerland, 1993\u20132012

Fever in neutropenia (FN) is the most frequent potentially life threatening complication of chemotherapy for cancer. Prediction of the risk to develop complications, integrated into clinical decision rules, would allow for risk-stratified treatment of FN. This retrospective, single center cohort study in pediatric patients diagnosed with cancer before 17 years, covered two decades, 1993 to 2012. In total, 703 FN episodes in 291 patients with chemotherapy (maximum per patient, 9) were reported here. Twenty-nine characteristics of FN were collected: 6 were patient- and cancer-related, 8 were characteristics of history, 8 of clinical examination, and 7 laboratory results in peripheral blood, all known at FN diagnosis. In total 28 FN outcomes were assessed: 8 described treatment of FN, 6 described microbiologically defined infections (MDI), 4 clinically defined infections, 4 were additional clinical composite outcomes, and 6 outcomes were related to discharge. These data can mainly be used to study FN characteristics and their association with outcomes over time and between centers, and for derivation and external validation of clinical decision rules.

Low-dose computed tomography in assessment of pulmonary abnormalities in children with febrile neutropenia suffering from malignant diseases.

Management of febrile neutropenia in pediatric patients is challenging. Chest X-ray and CT scan help to identify infective foci; however, exposure to radiation is a risk factor for development of secondary cancer. For this reason, attention is paid to reducing radiation exposure. The aim of the study was to define the role of LDCT examination in the early detection of pulmonary lesions in children during oncology or autoimmune treatment complicated by neutropenia-related fever. Additionally, we focused on the possibility to optimize image quality in low-dose protocols. The study included 138 pediatric patients (mean age 8.08 years) with fever of 38.2°C or higher with an absolute neutrophil count of 10 mm with or without surrounding GGO or cavitations was sensitive at 77% and specific at 65% for fungal infection insert after neutrophil count: < 500/pL who underwent chest X-ray and LDCT in the maximal interval of 24 h. CT findings were compared with initial and final diagnosis as well as with clinical information. LDCT detected pulmonary abnormalities in 116 patients (84.06%) showing ground-glass opacities (GGO) (n = 79), nodules (n = 60) and air-space consolidations (n = 58). Radiologists correctly diagnosed infective lesions in 94 out of 116 patients (81.03%). The presence of random or pleural-based nodules. Diagnosis of pyogenic infection based on the presence of air-space consolidation, pleural effusion, GGO or centrilobular nodules showed a sensitivity of 78% and specificity of 67%, whereas patchy or diffuse GGO, interstitial thickening and/or air-space consolidation showed a high sensitivity of 81% and specificity of 68% for Pneumocystis jirovecii pneumonia. LDCT is an excellent modality in the diagnostic algorithm in patients with febrile neutropenia. It allows early detection and detailed characterization of pulmonary abnormalities. Using contrast, unenhanced CT examinations can further reduce radiation dose and diminish the number of complications without a negative influence on the diagnostic process.

Implementation of a Pathway for the Treatment of Fever and Neutropenia in Pediatric Patients With Cancer.

Fever and neutropenia is an oncologic emergency. Time-to-antibiotics (TTA) refers to the amount of time from initial provider evaluation for fever and neutropenia to intravenous antibiotic administration. Research supports that rapid time-to-antibiotics (RTTA) is associated with improved patient outcomes. This quality improvement project evaluated the success of implementing an RTTA pathway in pediatric oncology patients with fever and neutropenia. The setting was an advanced practice nurse-managed pediatric ambulatory infusion center where patients with fever and neutropenia were often evaluated and treated. In order to improve TTA, a multidisciplinary pathway was implemented with a goal of TTA that was less than 60 minutes from initial provider evaluation. Implementation of the RTTA pathway included discussion of shared expectations with the pharmacy and education departments and discussion of shared expectations with the bedside nurses and advanced practice nurses staffing the unit. Additionally, a preliminary lab test was utilized. Success of the implementation was evaluated through 2 measures: TTA and nurses' knowledge of fever and neutropenia and the importance of RTTA. The aims of this project were to improve TTA as well as nurses' knowledge of fever and neutropenia and the importance of RTTA, and both these aims were successfully attained.

Antibiotic prophylaxis with teicoplanin on alternate days reduces rate of viridans sepsis and febrile neutropenia in pediatric patients with acute myeloid leukemia

Intensive chemotherapy directed against acute myeloid leukemia of childhood is followed by profound neutropenia and high risk for bacterial and fungal infections, including viridans group streptococci as a common cause for gram-positive septicemia. Few retrospective studies have shown the efficacy of various antibiotic prophylactic regimens in children. We retrospectively studied 50 pediatric patients treated on the AML-BFM 2004 protocol between 2005 and 2015 at St. Anna Children’s Hospital and assessed the effect of antibiotic prophylaxis on the frequency of febrile neutropenia and bacterial sepsis. Fifty pediatric patients underwent 199 evaluable chemotherapy cycles. Viridans sepsis occurred after none of 98 cycles with prophylactic administration of teicoplanin/vancomycin in comparison to 12 cases of viridans sepsis among 79 cycles without systemic antibacterial prophylaxis (0 vs. 15 %, p < 0.0001). In addition, there were significantly fewer episodes of febrile neutropenia in the teicoplanin/vancomycin group (44 % vs. no prophylaxis 82 %, p < 0.0001). Severity of infection seemed to be worse when no antibiotic prophylaxis had been administered with a higher rate of intensive care unit treatment (0/98, 0 %, vs. 4/79, 5 %, p = 0.038). So far, no increase of vancomycin-resistant enterococcus isolates in surveillance cultures was noticed. Antibiotic prophylaxis with teicoplanin (or vancomycin) appears safe and feasible and resulted in eradication of viridans sepsis and decreased incidence of febrile neutropenia in pediatric AML patients. The possibility to administer teicoplanin on alternate days on an outpatient basis or at home could contribute to patient’s quality of life and decrease health care costs.

The role of mannose binding lectin on fever episodes in pediatric oncology patients.

Despite significant changes in pediatric oncological therapy, mortality is still high, mainly due to infections. Complement system as an ancient immune defense against microorganisms plays a significant role in surmounting infections, therefore, deficiency of its components may have particular importance in malignancies. The present paper assesses the effect of promoter (X/Y) and exon 1 (A/0) polymorphisms of the MBL2 gene altering mannose binding lectin (MBL) serum level in pediatric oncological patients with febrile neutropenia. Furthermore, frequency distribution of MBL2 alleles in children with malignancies and age-matched controls was analysed. Fifty-four oncohematological patients and 53 children who had undergone pediatric surgery were enrolled into this retrospective study. No significant differences were found in the frequency of MBL2 alleles between the hemato-oncologic and control group. The average duration of fever episodes was significantly shorter (p=0.035) in patients carrying genotypes (AY/AY and AY/AX) that encode normal MBL level, compared to individuals with genotypes associated with lower functional MBL level (AX/AX, AY/0, AX/0, or 0/0) (days, median(IQ range) 3.7(0-5.4) vs. 5.0(3.8-6.6), respectively). In conclusion, our data suggest that MBL2 genotypes may influence the course of febrile neutropenia in pediatric patients with malignancies, and may contribute to clarification of the importance of MBL in infections.