A Multicenter Consortium to Define the Epidemiology and Outcomes of Inpatient Respiratory Viral Infections in Pediatric Hematopoietic Stem Cell Transplant Recipients.

2018

275-282

2018 Dec 3

2048-7207

<p><strong>Background: </strong>Respiratory virus infections (RVIs) pose a threat to children undergoing hematopoietic stem cell transplantation (HSCT). In this era of sensitive molecular diagnostics, the incidence and outcome of HSCT recipients who are hospitalized with RVI (H-RVI) are not well described.</p>

<p><strong>Methods: </strong>A retrospective observational cohort of pediatric HSCT recipients (between January 2010 and June 2013) was assembled from 9 US pediatric transplant centers. Their medical charts were reviewed for H-RVI events within 1 year after their transplant. An H-RVI diagnosis required respiratory signs or symptoms plus viral detection (human rhinovirus/enterovirus, human metapneumovirus, influenza, parainfluenza, coronaviruses, and/or respiratory syncytial virus). The incidence of H-RVI was calculated, and the association of baseline HSCT factors with subsequent pulmonary complications and death was assessed.</p>

<p><strong>Results: </strong>Among 1560 HSCT recipients, 259 (16.6%) acquired at least 1 H-RVI within 1 year after their transplant. The median age of the patients with an H-RVI was lower than that of patients without an H-RVI (4.8 vs 7.1 years; P &lt; .001). Among the patients with a first H-RVI, 48% required some respiratory support, and 14% suffered significant pulmonary sequelae. The all-cause and attributable case-fatality rates within 3 months of H-RVI onset were 11% and 5.4%, respectively. Multivariate logistic regression revealed that H-RVI onset within 60 days of HSCT, steroid use in the 7 days before H-RVI onset, and the need for respiratory support at H-RVI onset were associated with subsequent morbidity or death.</p>

<p><strong>Conclusion: </strong>Results of this multicenter cohort study suggest that H-RVIs are relatively common in pediatric HSCT recipients and contribute to significant morbidity and death. These data should help inform interventional studies specific to each viral pathogen.</p>

10.1093/jpids/pix051

J Pediatric Infect Dis Soc

29106589

International Collaborative on Contemporary Epidemiology and Diagnosis of Invasive Fungal Disease in Children.

2017

S1-S2

2017 Sep 01

2048-7207

10.1093/jpids/pix039

J Pediatric Infect Dis Soc

28927199

Role of Molecular Biomarkers in the Diagnosis of Invasive Fungal Diseases in Children.

2017

S32-S44

2017 Sep 01

2048-7207

<p>Invasive fungal diseases are important clinical problems that are often complicated by severe illness and therefore the inability to use invasive measures to definitively diagnose the disease. Tests for a range of fungal biomarkers that do not require an invasive sample-collection procedure have been incorporated into adult clinical practice, but pediatric data and pediatric-specific recommendations for some of these diagnostic tools are lacking. In this review, we summarize the published literature and contemporary strategies for using the biomarkers galactomannan, (1→3)-β-d-glucan, Candida mannan antigen and anti-mannan antibody, and fungal polymerase chain reaction for diagnosing invasive fungal disease in children. Data on biomarker use in neonates and children with cancer, history of hematopoietic stem cell transplant, or primary immunodeficiency are included. Fungal biomarker tests performed on blood, other body fluids, or tissue specimens represent promising adjuncts to the diagnostic armamentarium in populations with a high prevalence of invasive fungal disease, but substantial gaps exist in the correct use and interpretation of these diagnostic tools in pediatric patients.</p>

10.1093/jpids/pix054

J Pediatric Infect Dis Soc

28927202

Risk Factors for Invasive Fungal Disease in Pediatric Cancer and Hematopoietic Stem Cell Transplantation: A Systematic Review.

2017

2017 May 26

2048-7207

<p><strong>Background.: </strong>Although a number of risk factors have been associated with invasive fungal disease (IFD), a systematic review of the literature to document pediatric-specific factors has not been performed.</p>

<p><strong>Methods.: </strong>We used the Ovid SP platform to search Medline, Medline In-Process, and Embase for studies that identified risk factors for IFD in children with cancer or those who undergo hematopoietic stem cell transplantation (HSCT). We included studies if they consisted of children or adolescents (&lt;25 years) who were receiving treatment for cancer or undergoing HSCT and if the study evaluated risk factors among patients with and those without IFD.</p>

<p><strong>Results.: </strong>Among the 3566 studies screened, 22 studies were included. A number of pediatric factors commonly associated with an increased risk for IFD were confirmed, including prolonged neutropenia, high-dose steroid exposure, intensive-timing chemotherapy for acute myeloid leukemia, and acute and chronic graft-versus-host disease. Increasing age, a factor not commonly associated with IFD risk, was identified as a risk factor in multiple published cohorts.</p>

<p><strong>Conclusions.: </strong>With this systematic review, we have confirmed IFD risk factors that are considered routinely in daily clinical practice. Increasing age should also be considered when assessing patient risk for IFD. Future efforts should focus on defining more precise thresholds for a particular risk factor (ie, age, neutropenia duration) and on development of prediction rules inclusive of individual factors to further refine the risk prediction.</p>

10.1093/jpids/pix030

J Pediatric Infect Dis Soc

28549148

Guideline for the Management of Fever and Neutropenia in Children With Cancer and Hematopoietic Stem-Cell Transplantation Recipients: 2017 Update.

2017

JCO2016717017

2017 May 01

1527-7755

<p>Purpose To update a clinical practice guideline (CPG) for the empirical management of fever and neutropenia (FN) in children with cancer and hematopoietic stem-cell transplantation recipients. Methods The International Pediatric Fever and Neutropenia Guideline Panel is a multidisciplinary and multinational group of experts in pediatric oncology and infectious diseases that includes a patient advocate. For questions of risk stratification and evaluation, we updated systematic reviews of observational studies. For questions of therapy, we conducted a systematic review of randomized trials of any intervention applied for the empirical management of pediatric FN. The Grading of Recommendation Assessment, Development and Evaluation approach was used to make strong or weak recommendations and to classify levels of evidence as high, moderate, low, or very low. Results Recommendations related to initial presentation, ongoing management, and empirical antifungal therapy of pediatric FN were reviewed; the most substantial changes were related to empirical antifungal therapy. Key differences from our 2012 FN CPG included the listing of a fourth-generation cephalosporin for empirical therapy in high-risk FN, refinement of risk stratification to define patients with high-risk invasive fungal disease (IFD), changes in recommended biomarkers and radiologic investigations for the evaluation of IFD in prolonged FN, and a weak recommendation to withhold empirical antifungal therapy in IFD low-risk patients with prolonged FN. Conclusion Changes to the updated FN CPG recommendations will likely influence the care of pediatric patients with cancer and those undergoing hematopoietic stem-cell transplantation. Future work should focus on closing research gaps and on identifying ways to facilitate implementation and adaptation.</p>

10.1200/JCO.2016.71.7017

J. Clin. Oncol.

28459614

Galactomannan, Beta-D-Glucan and PCR-Based Assays for the Diagnosis of Invasive Fungal Disease in Pediatric Cancer and Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.

2016

2016 Nov

1537-6591

<p>We systematically reviewed and analyzed the available data for galactomannan (GM), beta-D-glucan (BG), and polymerase-chain reaction (PCR)-based assays to detect invasive fungal disease (IFD) in pediatric cancer or hematopoietic stem cell transplantation (HSCT) patients when used as screening tools during immunosuppression or as diagnostic tests in patients presenting with symptoms such as fever during neutropenia (FN). Out of 1,532 studies screened, 25 studies reported on GM (n=19), BG (n=3) and PCR (n=11). All fungal biomarkers demonstrated highly variable sensitivity, specificity and positive predictive values, and these were generally poor in both clinical settings. GM negative predictive values were high, ranging from 85-100% for screening and 70-100% in the diagnostic setting, but failure to identify non-Aspergillus molds limits its usefulness. Future work could focus on the usefulness of combinations of fungal biomarkers in pediatric cancer and HSCT.</p>

10.1093/cid/ciw592

Clin. Infect. Dis.

27567122

Failure to Validate a Multivariable Clinical Prediction Model to Identify Pediatric Intensive Care Unit Patients at High Risk for Candidemia.

2015

2015 Apr 29

2048-7207

<p>We attempted to validate a previously derived clinical prediction rule for candidemia in the pediatric intensive care unit. This multicenter case control study did not identify significant association of candidemia with most of the previously identified predictors. Additional study in larger cohorts with other predictor variables is needed.</p>

10.1093/jpids/piv024

J Pediatric Infect Dis Soc

26407259

Results from a prospective, international, epidemiologic study of invasive candidiasis in children and neonates.

2012

1252-7

2012 Dec

1532-0987

<p><strong>BACKGROUND: </strong>Candida species are the third most common cause of pediatric health care-associated bloodstream infection in the United States and Europe. To our knowledge, this report from the International Pediatric Fungal Network is the largest prospective, multicenter observational study dedicated to pediatric and neonatal invasive candidiasis.</p>

<p><strong>METHODS: </strong>From 2007 to 2011, we enrolled 196 pediatric and 25 neonatal patients with invasive candidiasis.</p>

<p><strong>RESULTS: </strong>Non-albicans Candida species predominated in pediatric (56%) and neonatal (52%) age groups, yet Candida albicans was the most common species in both groups. Successful treatment responses were observed in pediatric (76%) and neonatal patients (92%). Infection with Candida parapsilosis led to successful responses in pediatric (92%) and neonatal (100%) patients, whereas infection with Candida glabrata was associated with a lower successful outcome in pediatric patients (55%). The most commonly used primary antifungal therapies for pediatric invasive candidiasis were fluconazole (21%), liposomal amphotericin B (20%) and micafungin (18%). Outcome of pediatric invasive candidiasis was similar in response to polyenes (73%), triazoles (67%) and echinocandins (73%). The most commonly used primary antifungal therapies for neonatal invasive candidiasis were fluconazole (32%), caspofungin (24%) and liposomal amphotericin B (16%) and micafungin (8%). Outcomes of neonatal candidiasis by antifungal class again revealed similar response rates among the classes.</p>

<p><strong>CONCLUSIONS: </strong>We found a predominance of non-albicans Candida infection in children and similar outcomes based on antifungal class used. This international collaborative study sets the foundation for large epidemiologic studies focusing on the unique features of neonatal and pediatric candidiasis and comparative studies of therapeutic interventions in these populations.</p>

10.1097/INF.0b013e3182737427

Pediatr. Infect. Dis. J.

22982980

Guideline for the management of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation.

2012

4427-38

2012 Dec 10

1527-7755

<p><strong>PURPOSE: </strong>To develop an evidence-based guideline for the empiric management of pediatric fever and neutropenia (FN).</p>

<p><strong>METHODS: </strong>The International Pediatric Fever and Neutropenia Guideline Panel is a multidisciplinary and multinational group composed of experts in pediatric oncology and infectious disease as well as a patient advocate. The Panel was convened for the purpose of creating this guideline. We followed previously validated procedures for creating evidence-based guidelines. Working groups focused on initial presentation, ongoing management, and empiric antifungal therapy. Each working group developed key clinical questions, conducted systematic reviews of the published literature, and compiled evidence summaries. The Grades of Recommendation Assessment, Development, and Evaluation approach was used to generate summaries, and evidence was classified as high, moderate, low, or very low based on methodologic considerations.</p>

<p><strong>RESULTS: </strong>Recommendations were made related to initial presentation (risk stratification, initial evaluation, and treatment), ongoing management (modification and cessation of empiric antibiotics), and empiric antifungal treatment (risk stratification, evaluation, and treatment) of pediatric FN. For each recommendation, the strength of the recommendation and level of evidence are presented.</p>

<p><strong>CONCLUSION: </strong>This guideline represents an evidence-based approach to FN specific to children with cancer. Although some recommendations are similar to adult-based guidelines, there are key distinctions in multiple areas. Implementation will require adaptation to the local context.</p>

10.1200/JCO.2012.42.7161

J. Clin. Oncol.

22987086

Antifungal prophylaxis in pediatric hematology/oncology: new choices & new data.

2012

21-6

2012 Jul 15

1545-5017

<p>A severe complication of the treatment of pediatric cancers is the development of an invasive fungal infection (IFI). The data to support antifungal prophylaxis in pediatric oncology patients derive primarily from adult patients, and thus the optimal agent to utilize is not clear. Fluconazole has been a standard option, but agents with antimold activity are now available, each with limitations. Pediatric dosing for voriconazole and posaconazole is uncertain and multiple drug interactions exist. The echinocandins are well-tolerated, but only available in intravenous form. Ultimately, studies demonstrating biologic risk factors for the development of IFI may lead to personalized prophylactic strategies.</p>

10.1002/pbc.23415

Pediatr Blood Cancer

22102607