Doenças fúngicas invasivas: onco-hematologia pediátrica

Esta videoaula contempla a importância de se investigar a doença fúngica invasiva no paciente onco-hematológico pediátrico

Oral moxifloxacin in the outpatient treatment of low-risk children with fever and neutropenia

Universidade Federal de São Paulo, Pediat Oncol Inst, Dept Pediat, São Paulo, BrazilUniversidade Federal de São Paulo, Pediat Oncol Inst, Dept Infect Dis, São Paulo, BrazilUniversidade Federal de São Paulo, Pediat Oncol Inst, Dept Pediat, São Paulo, BrazilUniversidade Federal de São Paulo, Pediat Oncol Inst, Dept Infect Dis, São Paulo, BrazilWeb of Scienc

Bloodstream infections in febrile neutropenic children with cancer

Universidade Federal de São Paulo, Pediat Oncol Inst, Dept Pediat, São Paulo, BrazilUniversidade Federal de São Paulo, Pediat Oncol Inst, Dept Infect Dis, São Paulo, BrazilUniversidade Federal de São Paulo, Pediat Oncol Inst, Dept Pediat, São Paulo, BrazilUniversidade Federal de São Paulo, Pediat Oncol Inst, Dept Infect Dis, São Paulo, BrazilWeb of Scienc

Diagnosis by real-time polymerase chain reaction of pathogens and antimicrobial resistance genes in bone marrow transplant patients with bloodstream infections

Background: Early identification of pathogens and antimicrobial resistance in bloodstream infections (BSIs) decreases morbidity and mortality, particularly in immunocompromised patients. the aim of the present study was to compare real-time polymerase chain reaction (PCR) with commercial kits for detection of 17 pathogens from blood culture (BC) and 10 antimicrobial resistance genes.Methods: A total of 160 BCs were taken from bone marrow transplant patients and screened with Gram-specific probes by multiplex real-time PCR and 17 genus-specific sequences using TaqMan probes and blaSHV, blaTEM, blaCTX, blaKPC, blaIMP, blaSPM, blaVIM, vanA, vanB, and mecA genes by SYBR Green.Results: Twenty-three of 33 samples identified by phenotypic testing were concordantly positive by BC and real-time PCR. Pathogen identification was discordant in 13 cases. in 12 of 15 coagulase-negative staphylococci, the mecA gene was detected and four Enterococcus spp. were positive for vanA. Two blaCTX and three blaSHV genes were found by quantitative PCR. the blaKPC and metallo-beta-lactamase genes were not detected. Five fungal species were identified only by real-time PCR.Conclusions: Real-time PCR could be a valuable complementary tool in the management of BSI in bone marrow transplants patients, allowing identification of pathogens and antimicrobial resistance genes.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Special Clin Microbiol Lab LEMC, UNIFESP, São Paulo, BrazilFed Univ São Paulo UNIFESP, Div Infect Dis, São Paulo, BrazilGRAACC Grp Apoio Adolescente & Crianca Canc Suppo, São Paulo, BrazilFed Univ São Paulo UNIFESP, Div Hematol, São Paulo, BrazilUniversidade Federal de São Paulo, Special Clin Microbiol Lab LEMC, UNIFESP, São Paulo, BrazilFed Univ São Paulo UNIFESP, Div Infect Dis, São Paulo, BrazilFed Univ São Paulo UNIFESP, Div Hematol, São Paulo, BrazilCNPq: 141636/2008-4Web of Scienc

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-1 beta, TNF-alpha, 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.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)GRAACC/Instituto de Oncologia PediatricaSao Paulo Fed Univ UNIFESP, Grp Apoio Adolescente & Crianca Canc GRAACC, IOP, Rua Pedro de Toledo 572, BR-04039001 Sao Paulo, SP, BrazilSao Paulo Fed Univ UNIFESP, Div Infect Dis, Dept Med, Escola Paulista Med, Rua Pedro de Toledo 669,10th Floor, BR-04039001 Sao Paulo, SP, BrazilSao Paulo Fed Univ UNIFESP, Grp Apoio Adolescente & Crianca Canc GRAACC, IOP, Rua Pedro de Toledo 572, BR-04039001 Sao Paulo, SP, BrazilSao Paulo Fed Univ UNIFESP, Div Infect Dis, Dept Med, Escola Paulista Med, Rua Pedro de Toledo 669,10th Floor, BR-04039001 Sao Paulo, SP, BrazilFAPESP: 2011/20401-4Web of Scienc

The water supply system as a potential source of fungal infection in paediatric haematopoietic stem cell units

Background: We conducted a prospective study to investigate the presence of microfungal contamination in the water supply system of the Oncology Paediatric Institute, São Paulo - Brazil after the occurrence of one invasive Fusarium solani infection in a patient after Haematopoietic Stem Cell Transplantation (HSCT). During a twelve-month period, we investigated the water supply system of the HSCT unit by monitoring a total of fourteen different collection sites.Methods: One litre of water was collected in each location, filtered through a 0.45 mu m membrane and cultured on SDA to detect the presence of filamentous fungi. Physicochemical analyses of samples were performed to evaluate the temperature, turbidity, pH, and the concentration of free residual chlorine.Results: Over the 12 months of the study, 164 samples were collected from the water supply system of the HSCT unit, and 139 of the samples tested positive for filamentous fungi (84.8%), generating a total of 2,362 colonies. Cladosporium spp., Penicillium spp., Purpureocillium spp. and Aspergillus spp. were ranked as the most commonly found genera of mould in the collected samples. of note, Fusarium solani complex isolates were obtained from 14 out of the 106 samples that were collected from tap water (mean of 20 CFU/L). There was a positive correlation between the total number of fungal CFU obtained in all cultures and both water turbidity and temperature parameters. Our findings emphasise the need for the establishment of strict measures to limit the exposure of high-risk patients to waterborne fungal propagules.Conclusions: We were able to isolate a wide variety of filamentous fungi from the water of the HSCT unit where several immunocompromised patients are assisted.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Med, Disciplina Infectol, BR-04024002 São Paulo, BrazilUniv Austral Chile, Inst Clin Microbiol, Valdivia, ChileUniv Antofagasta, Antofagasta, ChileUniversidade Federal de São Paulo, Inst Oncol Pediat, GRAACC, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Disciplina Infectol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Inst Oncol Pediat, GRAACC, BR-04023062 São Paulo, BrazilFAPESP: 2005/02138-3CNPq: 133621/2007-3CAPES: PNPD 2312/2011CNPq: 150368/2005-4Web of Scienc

Clinical Practice Guideline for Systemic Antifungal Prophylaxis in Pediatric Patients With Cancer and Hematopoietic Stem-Cell Transplantation Recipients

PURPOSE: To develop a clinical practice guideline for systemic antifungal prophylaxis in pediatric patients with cancer and hematopoietic stem-cell transplantation (HSCT) recipients. METHODS: Recommendations were developed by an international multidisciplinary panel that included a patient advocate. We conducted a systematic review of systemic antifungal prophylaxis in children and adults with cancer and HSCT recipients. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to make strong or weak recommendations and to classify level of evidence as high, moderate, low, or very low. The panel considered directness of the data to pediatric patients. RESULTS: There were 68 randomized trials included in the systematic review, of which 6 (9%) were conducted in a solely pediatric population. Strong recommendations were made to administer systemic antifungal prophylaxis to children and adolescents receiving treatment of acute myeloid leukemia, to those undergoing allogeneic HSCT pre-engraftment, and to those receiving systemic immunosuppression for graft-versus-host disease treatment. A strong recommendation was made to administer a mold-active agent with an echinocandin or a mold-active azole when systemic antifungal prophylaxis is warranted. For children younger than 13 years of age, an echinocandin, voriconazole, or itraconazole is suggested. Posaconazole may also be used in those age 13 years or older. A strong recommendation against routine administration of amphotericin as systemic antifungal prophylaxis was made. CONCLUSION: We developed a clinical practice guideline for systemic antifungal prophylaxis administration in pediatric patients with cancer and HSCT recipients. Implementation and assessment of guideline-concordant rates and impacts are important future steps

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

PURPOSE 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. METHODS 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. RESULTS 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. CONCLUSION 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

Antibiotic Resistant Bloodstream Infections in Pediatric Patients Receiving Chemotherapy or Hematopoietic Stem Cell Transplant: Factors Associated with Development of Resistance, Intensive Care Admission and Mortality

Bloodstream infections (BSI) are a severe complication of antineoplastic chemotherapy or hematopoietic stem cell transplantation (HSCT), especially in the presence of antibiotic resistance (AR). A multinational, multicenter retrospective study in patients aged ≤ 18 years, treated with chemotherapy or HSCT from 2015 to 2017 was implemented to analyze AR among non-common skin commensals BSI. Risk factors associated with AR, intensive care unit (ICU) admission and mortality were analyzed by multilevel mixed effects or standard logistic regressions. A total of 1291 BSIs with 1379 strains were reported in 1031 patients. Among Gram-negatives more than 20% were resistant to ceftazidime, cefepime, piperacillin-tazobactam and ciprofloxacin while 9% was resistant to meropenem. Methicillin-resistance was observed in 17% of S. aureus and vancomycin resistance in 40% of E. faecium. Previous exposure to antibiotics, especially to carbapenems, was significantly associated with resistant Gram-negative BSI while previous colonization with methicillin-resistant S. aureus was associated with BSI due to this pathogen. Hematological malignancies, neutropenia and Gram-negatives resistant to >3 antibiotics were significantly associated with higher risk of ICU admission. Underlying disease in relapse/progression, previous exposure to antibiotics, and need of ICU admission were significantly associated with mortality. Center-level variation showed a greater impact on AR, while patient-level variation had more effect on ICU admission and mortality. Previous exposure to antibiotics or colonization by resistant pathogens can be the cause of AR BSI. Resistant Gram-negatives are significantly associated with ICU admission and mortality, with a significant role for the treating center too. The significant evidence of center-level variations on AR, ICU admission and mortality, stress the need for careful local antibiotic stewardship and infection control programs