Fabianne Carlesse

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

Background: Fever during neutropenia (FN) is a frequent and potentially life-threatening complication of the treatment of childhood cancer. The role of biomarkers in predicting morbidity and mortality associated with FN in children has been explored with varying results. This systematic review identified, critically appraised and synthesized information on the use of biomarkers for the prediction of outcome of FN in children/young adults, updating a review of initial assessment and adding further analysis of their value at reassessment. Methods: This review was conducted in accordance with the Centre for Reviews and Dissemination Methods, using 3 different random effects meta-analysis models. Results: Thirty-seven studies involving over 4689 episodes of FN in children were assessed, including an additional 13 studies investigating 18 biomarkers in 1670 FN episodes since the original review. Meta-analysis was possible for admission C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 and interleukin-8 in their ability to detect significant infection. Marked heterogeneity exists, precluding clear clinical interpretation of the results. Qualitative synthesis of the role of serial biomarkers suggests their predictive ability may be more pronounced at 24 to 48 hours compared with admission. Direct comparisons of the discriminatory power of admission values of PCT and CRP showed PCT generally had a better discriminatory estimate of serious infection than CRP. Conclusions: There remains a paucity of robust and reproducible data on the use of biomarkers in prediction of serious infection in children with FN. Available evidence suggests PCT has better discriminatory ability than CRP and that the role of serial biomarkers warrants further study.

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

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.

Vancomycin serum concentrations in pediatric oncologic/hematologic intensive care patients

BACKGROUND Usual treatment regimens with vancomycin often fail to provide adequate serum levels in patients with severe infections. METHODS Retrospective analysis of vancomycin trough serum measurements. The following parameters were calculated by Bayesian analysis: vancomycin clearance, distribution volume, and peak estimated concentrations. The area under the concentration curve (AUC) (total daily dose/24 h clearance of vancomycin) was used to determine the effectiveness of treatment through the ratio of AUC/minimum inhibitory concentration (MIC) above 400, using MIC=1 μg/mL, based on isolates of Staphylococci in cultures. RESULTS Sixty-one vancomycin trough measurements were analyzed in 31 patients. AUC/MIC>400 was obtained in 34 out of 61 dosages (55.7%), but the mean vancomycin dose required to achieve these levels was 81 mg/kg/day. In cases where the usual doses were administered (40-60 mg/kg/day), AUC/MIC>400 was obtained in nine out of 18 dosages (50%), in 13 patients. Trough serum concentrations above 15 mg/L presented a positive predictive value of 100% and a negative predictive value of 71% for AUC/MIC>400. CONCLUSION Higher than usual vancomycin doses may be required to treat staphylococcal infections in children with oncologic/hematologic diseases. Since the best known predictor of efficacy is the AUC/MIC ratio, serum trough concentrations must be analyzed in conjunction with MICs of prevalent Staphylococci and pharmacokinetic tools such as Bayesian analysis.

Oral gatifloxacin in the outpatient treatment of children with cancer fever and neutropenia

Fever in neutropenic (FN) patients requires immediate broad‐spectrum antibiotics, however, such patients do not represent a homogeneous population and the majority of them are at low risk of developing complication. Gatifloxacin (GA) is an alternative, though it has not been thoroughly studied in Pediatrics yet. The aim of this study was to evaluate oral GA in oncology pediatric patients with FN and low risk of infectious complications.

High mortality outbreak of carbapenem-resistant Pseudomonas aeruginosa infection in a Brazilian pediatric oncology hospital

Carbapenem-resistant Pseudomonas aeruginosa is an important nosocomial pathogen associated with high mortality rates and can persist in moist environments in hospitals. Several outbreaks have been associated with environmental contamination, contaminated medical equipment, and healthcare cross-transmission. The production of acquired metallolactamase SPM-1 has been frequently associated to these infections. Here, we report an outbreak of carbapenem-resistant P. aeruginosa encoding the blaSPM-1 M L gene affecting nine

Adherence and immune response to revaccination following hematopoietic stem cell transplantation at a pediatric onco-hematology reference center

Revaccination after hematopoietic stem cell transplantation (HSCT) is necessary to compensate for the loss of immunological memory. The aims of this study were to evaluate the adherence to revaccination schedule and the humoral immune response to different vaccine antigens in HSCT pediatric and young adult patients.

Contribution of the interferon-gamma release assay to tuberculosis diagnosis in children and adolescents

SETTING As conclusive data on the performance of interferon-gamma release assays (IGRAs) in paediatric TB are lacking, many guidelines do not recommend their use for TB diagnosis in this population in Brazil. OBJECTIVE To evaluate the performance of an IGRA by investigating its concordance with the tuberculin skin test (TST) and the role of IGRAs in clinical management and treatment outcomes in children with TB. DESIGN A historic cohort study was used to evaluate the performance of T-SPOT®.TB (ELISpot) and other tests, such as the TST, in paediatric patients with or without immunodeficiency who were under investigation for latent tuberculous infection (LTBI) or active tuberculosis (TB). RESULTS Of 86 paediatric patients evaluated, 41 (48%) were immunocompetent and 45 (52%) immunocompromised. All patients underwent T-SPOT.TB, while 63 underwent both ELISpot and TST; test results were concordant in 50 patients (79.4%): 22/31 (71%) in immunocompetent (κ = 0.418, P = 0.02) and 28/32 (87.5%) in immunocompromised patients (κ = 0.526, P = 0.003). TB was diagnosed on the basis of the ELISpot result in 21% (18/86) cases; the contribution of the ELISpot assay was greater in immunocompetent patients than in those who were immunocompromised (13/41, 31.7% vs. 5/45, 11.1%, χ2 P = 0.038). CONCLUSION ELISpot and TST results were moderately concordant in both groups of patients. ELISpot contribution was higher among immunocompetent patients than among immunocompromised patients.

Cytokine Kinetics in Febrile Neutropenic Children: Insights on the Usefulness as Sepsis Biomarkers, Influence of Filgrastim, and Behavior of the IL-23/IL-17 Pathway

Background The study aimed to describe the kinetics of various cytokines from day 1 to day 14 of the onset of fever in neutropenic children and to evaluate their performances as discriminators of sepsis in the first 24 hours of fever, the possible influence of filgrastim, and the functioning of the IL-23/IL-17 axis. Methods IL-1β, TNF-α, IL-10, IL-12/23p40, IL-21, IL-6, IL-8, IL-17, G-CSF, and GM-CSF were measured in plasma on days 1, 2, 3, 5, and 14 from the onset of fever in 35 patients. Results Thirteen patients (37.1%) developed sepsis. In mixed models, IL-6, IL-8, IL-10, and G-CSF showed higher estimated means in septic patients (P < 0.005), and IL-12/23p40 and IL-17 in nonseptic patients (P < 0.05). On day 1, IL-6, IL-8, and IL-10 appeared upregulated in patients who received filgrastim. Only IL-6, IL-8, IL-10, and procalcitonin were useful as discriminators of sepsis. Associating the markers with each other or to a risk assessment model improved performance. Conclusions Cytokines kinetics showed proinflammatory and anti-inflammatory responses similar to what is described in nonneutropenic patients. IL-8, IL-6, IL-10, and procalcitonin are useful as early biomarkers of sepsis. Filgrastim upregulates expression of these markers, and we observed deficiency in the IL-23-IL-17 axis accompanying sepsis.

Renal aspergillosis in a 6-year-old male with Burkitt's lymphoma.

© 2015 Wolters Kluwer Health, Inc. All rights reserved. www.pidj.com | 679 specificity in neutropenic patients with pulmonary aspergillosis, but the sensitivity of this test is not well defined in extra pulmonary lesions, such as renal aspergilloma. Encapsulated and localized aspergillosis, as in our case with renal aspergilloma, might hamper the release of the galactomannan to the blood stream and have a negative serum assay result. IA restricted to the urinary tract is rare and has been described in immunocompromised patients with AIDS or in transplant recipients. Galactomannan assay was not performed in a urinary sample, and blood and urinary cultures never grew any organism. Renal aspergillosis can be secondary to hematogenous infection, bezoar formation in renal pelvis and ascending panurothelial aspergillosis. Ascending panurothelial fungal infection is a clinical presentation of primary urinary aspergillosis that has been described in kidney transplant recipients but not after hematopoietic stem cell transplantation. Voriconazole is the best drug to treat IA, but it reaches limited urinary tract tissue concentrations. Most patients with renal aspergillosis reported in the literature were treated with combination antifungal therapy (voriconazole and liposomal amphotericin B or amphotericin B deoxycholate) and surgery. Our patient did not respond to amphotericin B followed by voriconazole probably because of the intense immunosuppression and the low tissue penetration of the drugs in the encapsulated renal lesion. From a surgical standpoint, resection of the entire kidney or spleen and lobectomies is usually recommended over nodulectomy in immunosuppressed patients.