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BACKGROUND: The chemotherapy regimens recommended for both rhabdomyosarcoma (RMS) and Ewing sarcoma (ES) patients are myelosuppressive and can reduce the absolute neutrophil count (ANC) and subsequently increase the risk of febrile neutropenia (FN). However, only a few studies have focused on the efficacy and safety of granulocyte-colony stimulating factor (G-CSF) drugs in pediatric and adolescent patients with RMS and ES. Our objective was to investigate the efficacy and safety of mecapegfilgrastim, a biosimilar of pegfilgrastim, in prophylaxis of FN for pediatric and adolescent patients with RMS or ES. METHODS: In this single-arm, single-center, prospective study, pediatric and adolescent patients with RMS or ES were enrolled to receive either VAC (vincristine, cyclophosphamide, dactinomycin) regimen or VDC (vincristine, cyclophosphamide, doxorubicin) regimen in a 3-week cycle, followed by treatment with mecapegfilgrastim (100 µg/kg, maximum 6 mg) given at 24 h after completing chemotherapy. The primary endpoint was the incidence rate of FN. Secondary endpoints included the incidence rate of grade 4 neutropenia, duration of ANC ≤ 0.5 × 109/L, incidence rate of chemotherapy delay or reduction, use of antibiotics, and safety profile. RESULTS: In total, 2 of the 30 (6.7%, 95% CI: 0.82-22.07) patients experienced FN after the first cycle of chemotherapy. Eight (26.7%, 95% CI: 12.28-45.89) patients experienced grade 4 neutropenia after receiving prophylactic mecapegfilgrastim. Eight patients experienced ANC ≤ 0.5 × 109/L with a median duration of 4.5 days; among them, 6 patients reached the lowest point of their ANC level on day 7, and 5 of them recovered by day 10. No dose reductions, delays, or discontinuation of chemotherapy was reported. Twenty-one (70.0%) patients received antibiotics during the treatment period. No patient experienced FN in the 0-5 years and the 13-18 years groups, and 2 patients experienced FN in the 6-12 years group. Two patients, 6 patients, and no patient experienced grade 4 neutropenia in the 0-5 years, 6-12 years, and 13-18 years groups, respectively. CONCLUSION: Mecapegfilgrastim showed acceptable efficacy and safety profile in pediatric and adolescent patients with RMS or ES. Further randomized studies with large sample size are warranted. TRIAL REGISTRATION: This clinical trial was registered at Chictr.org.cn (No.ChiCTR1900022249). Registered on March 31, 2019.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neutropenia Febril , Filgrastim , Rabdomiosarcoma , Sarcoma de Ewing , Humanos , Masculino , Femenino , Adolescente , Sarcoma de Ewing/tratamiento farmacológico , Niño , Proyectos Piloto , Estudios Prospectivos , Preescolar , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Rabdomiosarcoma/tratamiento farmacológico , Neutropenia Febril/prevención & control , Neutropenia Febril/inducido químicamente , Neutropenia Febril/etiología , Filgrastim/uso terapéutico , Filgrastim/administración & dosificación , Filgrastim/efectos adversos , Ciclofosfamida/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Dactinomicina/administración & dosificación , Dactinomicina/efectos adversos , Dactinomicina/uso terapéutico , Doxorrubicina/efectos adversos , Doxorrubicina/administración & dosificación , LactanteRESUMEN
Invasive fungal disease (IFD) presents a life-threatening condition in immunocompromised patients, thus often prompting empirical administration of antifungal treatment, without adequate mycological evidence. Over the past years, wide use of antifungal prophylaxis resulted in decreased occurrence of IFD but has contributed to changes in the spectrum of fungal pathogens, revealing the occurrence of previously rare fungal genera causing breakthrough infections. The expanding spectrum of clinically relevant fungal pathogens required the implementation of screening approaches permitting broad rather than targeted fungus detection to support timely onset of pre-emptive antifungal treatment. To address this diagnostically important aspect in a prospective setting, we analyzed 935 serial peripheral blood (PB) samples from 195 pediatric and adult patients at high risk for IFD, involving individuals displaying febrile neutropenia during treatment of hematological malignancies or following allogeneic hematopoietic stem cell transplantation. Two different panfungal-PCR-screening methods combined with ensuing fungal genus identification by Sanger sequencing were employed. In the great majority of PB-specimens displaying fungal DNAemia, the findings were transient and revealed fungi commonly regarded as non-pathogenic or rarely pathogenic even in the highly immunocompromised patient setting. Hence, to adequately exploit the diagnostic potential of panfungal-PCR approaches for detecting IFD, particularly if caused by hitherto rarely observed fungal pathogens, it is necessary to confirm the findings by repeated testing and to identify the fungal genus present by ensuing analysis. If applied appropriately, panfungal-PCR-screening can help prevent unnecessary empirical therapy, and conversely, contribute to timely employment of effective pre-emptive antifungal treatment strategies.
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ADN de Hongos , Neutropenia Febril , Huésped Inmunocomprometido , Humanos , Estudios Prospectivos , Adulto , Neutropenia Febril/microbiología , ADN de Hongos/análisis , Femenino , Masculino , Niño , Adolescente , Persona de Mediana Edad , Prevalencia , Adulto Joven , Anciano , Hongos/aislamiento & purificación , Hongos/genética , Neoplasias Hematológicas/complicaciones , Preescolar , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones Fúngicas Invasoras/epidemiología , Infecciones Fúngicas Invasoras/prevención & control , Infecciones Fúngicas Invasoras/etiología , Infecciones Fúngicas Invasoras/microbiología , Antifúngicos/uso terapéuticoRESUMEN
ABSTRACT: Febrile neutropenia is a common oncologic emergency that increases the risk for serious infection. This article reviews a joint American Society of Clinical Oncology and Infectious Diseases Society of America guideline for the evaluation and management of patients with cancer who present with fever and neutropenia. Knowledge and use of available risk assessment tools may reduce unnecessary hospitalizations, decrease inappropriate antibiotic use, and improve patient outcomes.
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Antibacterianos , Neutropenia Febril , Neoplasias , Humanos , Neoplasias/complicaciones , Neutropenia Febril/diagnóstico , Neutropenia Febril/etiología , Neutropenia Febril/terapia , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Guías de Práctica Clínica como Asunto , Medición de Riesgo , Fiebre/etiología , Fiebre/terapiaRESUMEN
BACKGROUND: This study aims to investigate the early kinetics of interleukin 6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) on initial antibiotic efficacy in hematological disorder patients with febrile neutropenia (FN). METHODS: A total of 40 patients with 43 episodes of FN were enrolled and divided into initial antibiotic effective group (IAE group, n = 24) and initial antibiotic ineffective group (IAI group, n = 19). The levels of IL-6, PCT, and CRP before antibacterial treatment (T0), and 12 h (T1), 24 h (T2), 48 h (T3), and 72 h (T4) post-antibacterial treatment were determined, respectively. Furthermore, the receiver operating characteristic curve (ROC) analysis was performed to evaluate the clinical value of indicators. RESULTS: In IAE group, the IL-6 levels gradually decreased from T0 to T4, and the CRP levels significantly decreased at 48 to 72 h, whereas both IL-6 and CRP remained at high levels in the IAI group. The PCT levels in both groups increased at the early stage of anti-infection (T1-T2) and reached to peak at T1-T2 in effective group. ROC curve analysis identified IL-6 as a predictive biomarker for initial antibiotic efficacy at 12, 48, and 72 h after treatment, with the AUC of 0.698, 0.744, and 0.821, respectively. In addition, CRP demonstrated predictive ability of initial antibiotics against infection at 24, 48, and 72 h after therapy, with the AUC of 0.724, 0.741, and 0.797, respectively. ROC curve analysis of percentage changes demonstrated that IL-6 percentage change showed predictive ability of antibiotic efficacy at the early stage, and both the IL-6 and CRP percentage changes showed the predictive ability of antibiotic efficacy 48 or 72 h after antibiotics therapy. CONCLUSION: This study confirmed IL-6 and CRP levels, and the percentage change in IL-6 as the biomarkers for initial antibiotic efficacy prediction in hematological disorder patients with FN.
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Antibacterianos , Biomarcadores , Proteína C-Reactiva , Neutropenia Febril , Interleucina-6 , Polipéptido alfa Relacionado con Calcitonina , Humanos , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Interleucina-6/sangre , Polipéptido alfa Relacionado con Calcitonina/sangre , Masculino , Femenino , Antibacterianos/uso terapéutico , Persona de Mediana Edad , Neutropenia Febril/tratamiento farmacológico , Neutropenia Febril/sangre , Estudios Prospectivos , Adulto , Biomarcadores/sangre , Curva ROC , Anciano , Resultado del TratamientoRESUMEN
INTRODUCTION: This study explored the efficacy of repeat blood cultures in bacteremic acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: This was a retrospective study of AML patients who experienced febrile neutropenia (FN) and bacteremia following HSCT at the Taussig Cancer Center from January 1, 2019, to December 31, 2022. The primary endpoint was the rate of positive repeat blood cultures following initial positive blood culture. RESULTS: Fifty patients were included in the study. There were 50 occurrences of FN with positive initial blood cultures that were diagnosed following HSCT. Fifty initial sets of blood cultures and 96 sets of repeat blood cultures were drawn between the 50 occurrences of FN. Twelve of 96 (12.5%) repeat blood culture sets were positive for a pathogen, which occurred over nine of 50 (18.0%) episodes of FN. Three of 96 (3.2%) repeat blood culture sets grew a pathogen that differed from the pathogen that grew in the preceding positive blood culture. CONCLUSION: Among bacteremic AML patients in the post-HSCT period, the yield of repeat blood cultures for detecting previously detected and new pathogens was low.
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Bacteriemia , Cultivo de Sangre , Neutropenia Febril , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Trasplante Homólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Bacteriemia/microbiología , Bacteriemia/diagnóstico , Bacteriemia/etiología , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/terapia , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Neutropenia Febril/microbiología , Neutropenia Febril/sangre , Adulto , Trasplante Homólogo/efectos adversos , Anciano , Adulto JovenRESUMEN
This pilot study examined differences in wait times for oncology patients who presented to the emergency department, with or without a Fast Pass, for febrile neutropenia (FN). Inadequate circulating neutrophils create a health risk for FN patients. An increased number of patients are receiving chemotherapy in an outpatient setting and may experience delays when seeking treatment in the emergency department. These delays in treatment may be due to overcrowding, patients who require life-saving medical interventions, and inconsistencies in recognizing febrile neutropenia, where fever may be the only presenting sign. The purpose of this study was to measure the impact on wait times, increasing possible risk of bacterial or viral exposure in the emergency department waiting room, for patients with a potential diagnosis of FN who presented their "Fast Pass" from the hospital cancer center's program upon arrival. Electronic medical records were reviewed over a period of 21 months, comparing wait times in the ED for oncology patients with potential FN before and after implementation of the Fast Pass program at an urban medical center in Hawai'i. Of the 1300 oncology patient chart reviews conducted, 6 patients met the study-defined inclusion criteria pre-Fast Pass and 10 met the study-defined inclusion criteria post-Fast Pass. Influence of the use of a Fast Pass on patient wait times was tested using a multivariate regression adjusted for ED patient volume. There were no differences in overall wait times pre- and post-Fast Pass.
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Servicio de Urgencia en Hospital , Neutropenia Febril , Neoplasias , Humanos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Servicio de Urgencia en Hospital/organización & administración , Femenino , Masculino , Hawaii/epidemiología , Persona de Mediana Edad , Neutropenia Febril/tratamiento farmacológico , Neutropenia Febril/complicaciones , Proyectos Piloto , Neoplasias/complicaciones , Anciano , Listas de Espera , Adulto , Factores de Tiempo , Tiempo de Tratamiento/estadística & datos numéricosRESUMEN
BACKGROUND: This study was conducted to compare the accuracy of two noninvasive thermometers (axillary and infrared non-contact forehead thermometer) in measuring core temperature compared to the gold standard oral thermometer in the detection of fever in pediatric cancer patients with febrile neutropenia. METHODS: The study was conducted with a single group of 42 children with febrile neutropenia between 23 December 2020 and 25 January 2023 in the pediatric hematology and oncology clinic of a training and research hospital, which provides a specialized environment for both medical education and advanced scientific research in the field of pediatric hematology and oncology. The participants' body temperature was measured with an oral, axillary, and non-contact infrared forehead thermometer immediately after admission to the clinic and at 5 and 10 min after admission. The inter-rater agreement for each method and inter-method agreement between axillary and non-contact infrared temperature readings and oral readings were analyzed for each time point using intraclass correlation coefficients (ICC). RESULTS: The children in the study had a mean age of 11.62 ± 3.00 years and 28 (66.7%) were boys, 19 (45.2%) were younger children (5-10 years of age), and 23 (54.8%) were adolescents (11-16 years of age). In the analysis of agreement between the thermometers at admission and at 5 and 10 min after admission in children with febrile neutropenia, the highest agreement was between the oral and axillary thermometers (ICC: 0.584, 0.835, 0.536, respectively) and the lowest agreement was between the oral and non-contact infrared thermometers (ICC: 0.219, 0.022, 0.473, respectively). CONCLUSION: Compared to orally measured body temperature, axillary temperature readings showed better agreement than non-contact infrared temperature readings from the forehead in pediatric patients with febrile neutropenia. PRACTICE IMPLICATIONS: The research findings may guide nurses and families caring for pediatric patients with febrile neutropenia and should contribute to the prevention of false findings of fever and the reduction of its adverse consequences.
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Temperatura Corporal , Neutropenia Febril , Neoplasias , Termómetros , Humanos , Niño , Masculino , Femenino , Adolescente , Neutropenia Febril/diagnóstico , Neoplasias/complicaciones , Temperatura Corporal/fisiología , Preescolar , Axila , Fiebre/diagnósticoRESUMEN
INTRODUCTION: Chemotherapy for breast cancer can cause neutropenia, increasing the risk of febrile neutropenia (FN) and serious infections. The use of granulocyte colony-stimulating factors (G-CSF) as primary prophylaxis has been explored to mitigate these risks. To evaluate the efficacy and safety of primary G-CSF prophylaxis in patients with invasive breast cancer undergoing chemotherapy. METHODS: A systematic literature review was conducted according to the "Minds Handbook for Clinical Practice Guideline Development" using PubMed, Ichushi-Web, and the Cochrane Library databases. Randomized controlled trials (RCTs) and cohort studies assessing using G-CSF as primary prophylaxis in invasive breast cancer were included. The primary outcomes were overall survival (OS) and FN incidence. Meta-analyses were performed for outcomes with sufficient data. RESULTS: Eight RCTs were included in the qualitative analysis, and five RCTs were meta-analyzed for FN incidence. The meta-analysis showed a significant reduction in FN incidence with primary G-CSF prophylaxis (risk difference [RD] = 0.22, 95% CI: 0.01-0.43, p = 0.04). Evidence for improvement in OS with G-CSF was inconclusive. Four RCTs suggested a tendency for increased pain with G-CSF, but statistical significance was not reported. CONCLUSIONS: Primary prophylactic use of G-CSF is strongly recommended for breast cancer patients undergoing chemotherapy, as it has been shown to reduce the incidence of FN. While the impact on OS is unclear, the benefits of reducing FN are considered to outweigh the potential harm of increased pain.
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Neoplasias de la Mama , Factor Estimulante de Colonias de Granulocitos , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Guías de Práctica Clínica como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Neutropenia Febril/prevención & control , Neutropenia Febril/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
In contrast to transplant recipients, there is a paucity of data regarding frequency and clinical significance of viraemia in children receiving conventional chemotherapy. In a prospective observational study, we assessed the frequency of and clinical impact of viraemia with cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus, human herpesvirus-6 (HHV6) and herpes-simplex virus 1/2 (HSV1/2) in paediatric cancer patients at diagnosis, at a routine examination during intensive chemotherapy, and during febrile neutropenia (FN). Seventy-nine patients (median age 6 years; 66 children with haematological malignancies) were included in the study. Overall, 362 blood samples were analysed, 72 from the time at diagnosis (11.1% with positive PCR result), 118 during a regular control after chemotherapy (11.0% positive), and 159 during FN (8.8% positive). The overall positivity rate was 9.6% (CMV 3.3%, HHV6 2.7%, HSV 2.2%, EBV 0.8% and adenovirus 0.3%). There were no significant differences between FN episodes with and without viraemia in terms of duration of fever or neutropenia/lymphopenia, severity of mucositis (> II0), incidence of diarrhea and ICU admission. Our results indicate that viraemia in paediatric cancer patients generally does not have a major clinical impact, and may help in the decision regarding the indication of routine evaluation for viraemia in febrile neutropenic, but otherwise asymptomatic children.
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Neoplasias , Viremia , Humanos , Niño , Femenino , Masculino , Preescolar , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Adolescente , Estudios Prospectivos , Lactante , Neutropenia Febril/epidemiología , Neoplasias Hematológicas/terapiaRESUMEN
Background: Metagenomic next-generation sequencing (mNGS) is a novel non-invasive and comprehensive technique for etiological diagnosis of infectious diseases. However, its practical significance has been seldom reported in the context of hematological patients with high-risk febrile neutropenia, a unique patient group characterized by neutropenia and compromised immune responses. Methods: This retrospective study evaluated the results of plasma cfDNA sequencing in 164 hematological patients with high-risk febrile neutropenia. We assessed the diagnostic efficacy and clinical impact of mNGS, comparing it with conventional microbiological tests. Results: mNGS identified 68 different pathogens in 111 patients, whereas conventional methods detected only 17 pathogen types in 36 patients. mNGS exhibited a significantly higher positive detection rate than conventional methods (67.7% vs. 22.0%, P < 0.001). This improvement was consistent across bacterial (30.5% vs. 9.1%), fungal (19.5% vs. 4.3%), and viral (37.2% vs. 9.1%) infections (P < 0.001 for all comparisons). The anti-infective treatment strategies were adjusted for 51.2% (84/164) of the patients based on the mNGS results. Conclusions: mNGS of plasma cfDNA offers substantial promise for the early detection of pathogens and the timely optimization of anti-infective therapies in hematological patients with high-risk febrile neutropenia.
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Neutropenia Febril , Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Humanos , Metagenómica/métodos , Masculino , Estudios Retrospectivos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Femenino , Persona de Mediana Edad , Neutropenia Febril/microbiología , Neutropenia Febril/sangre , Neutropenia Febril/diagnóstico , Adulto , Anciano , Adulto Joven , Adolescente , Anciano de 80 o más Años , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/microbiología , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/clasificación , Micosis/diagnóstico , Micosis/microbiología , Virosis/diagnóstico , Virosis/virologíaRESUMEN
BACKGROUND: ECIL-2021 recommends discontinuing empirical antibiotic therapy (EAT) in febrile-neutropenic children after 72 h of treatment and at least 24-48 h of apyrexia in the case of fever of unknown origin (FUO). These guidelines are rarely applied to high-risk children's neutropenia. MATERIAL AND METHODS: We retrospectively included all consecutive FUO episodes occurring during profound neutropenia ≥ 10 days in children in our institution. We evaluated the safety of EAT discontinuation in patients for whom the ECIL guidelines were followed compared to those for whom they didn't. We used a combined criterion of mortality and intensive care unit admission at 30 days. We identified risk factors for recurrent fever after EAT discontinuation. RESULTS: Fifty-one FUO episodes occurred in 37 patients. EAT discontinuation followed ECIL guidelines in 19 (37 %) episodes. No deaths and-or transfers in ICU occurred in the ECIL group. The duration of EAT was shorter by nine days in the group following ECIL guidelines (p < 0.001). We observed 14 (27 %) episodes of recurrent fever. Mucositis was significantly associated with recurrent fever (p < 0.01). CONCLUSION: EAT discontinuation seems feasible and safe in FUO during prolonged febrile neutropenia in children. However, mucosal lesions should prompt thorough surveillance due to the risk of recurrent fever.
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Antibacterianos , Fiebre de Origen Desconocido , Neutropenia , Humanos , Fiebre de Origen Desconocido/tratamiento farmacológico , Fiebre de Origen Desconocido/etiología , Estudios Retrospectivos , Masculino , Femenino , Niño , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Preescolar , Neutropenia/inducido químicamente , Adolescente , Factores de Riesgo , Lactante , Neutropenia FebrilRESUMEN
INTRODUCTION: A target trough concentration (Cmin) of teicoplanin ≥ 15-20 mg/L between the fourth and sixth day has been suggested for severe infections or management of febrile neutropenia (FN). Owing to no reports discussing the impact of early target attainment on treatment outcomes, this study aimed to evaluate the dose-Cmin relationship and clinical outcome and estimate the optimal early target Cmin for FN in patients with hematological malignancies. METHODS: This single-center, prospective study enrolled patients with hematological malignancies who were treated with teicoplanin either as an empirical antibiotic for FN or as targeted treatment for Gram-positive bacteria. Blood samples were collected on day three (48 h) post-loading doses, day 5 (96 h), and day 8 (when applicable) and determined by ultrahigh-pressure liquid chromatography-triple quadruple mass spectrometry. A total of 117 samples from 47 patients with FN (27 men, 20 women) were consecutively analyzed. A two-tailed α value of 0.05 was considered statistically significant. RESULTS: The mean Cmin values at 48 h, 96 h, and on day 8 were 23.4, 21.4, and 27.8 mg/L, respectively. The patients achieving Cmin ≥ 20 mg/L at 48 h had a higher likelihood of treatment success. The areas under the receiver operating characteristic curves were 0.71 for clinical efficacy and the cutoff value of Cmin at 48 h was 18.85 mg/L (95% confidence interval 0.55-0.87; P = 0.018). CONCLUSIONS: The Cmin of teicoplanin after completion of loading doses could predict the treatment response, with a target concentration ≥ 18.85 mg/L.
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Antibacterianos , Monitoreo de Drogas , Neutropenia Febril , Neoplasias Hematológicas , Teicoplanina , Humanos , Teicoplanina/administración & dosificación , Teicoplanina/uso terapéutico , Teicoplanina/farmacocinética , Masculino , Femenino , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/tratamiento farmacológico , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/farmacocinética , Monitoreo de Drogas/métodos , Estudios Prospectivos , Anciano , Adulto , Neutropenia Febril/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Febrile neutropenia represents a critical oncologic emergency, and its management is pivotal in cancer therapy. In several guidelines, the use of granulocyte colony-stimulating factor (G-CSF) in patients with chemotherapy-induced febrile neutropenia is not routinely recommended except in high-risk cases. The Japan Society of Clinical Oncology has updated its clinical practice guidelines for the use of G-CSF, incorporating a systematic review to address this clinical question. METHODS: The systematic review was conducted by performing a comprehensive literature search across PubMed, the Cochrane Library, and Ichushi-Web, focusing on publications from January 1990 to December 2019. Selected studies included randomized controlled trials (RCTs), non-RCTs, and cohort and case-control studies. Evaluated outcomes included overall survival, infection-related mortality, hospitalization duration, quality of life, and pain. RESULTS: The initial search yielded 332 records. Following two rounds of screening, two records were selected for both qualitative and quantitative synthesis including meta-analysis. Regarding infection-related mortality, the event to case ratio was 5:134 (3.73%) in the G-CSF group versus 6:129 (4.65%) in the non-G-CSF group, resulting in a relative risk of 0.83 (95% confidence interval, 0.27-2.58; p = 0.54), which was not statistically significant. Only median values for hospitalization duration were available from the two RCTs, precluding a meta-analysis. For overall survival, quality of life, and pain, no suitable studies were found for analysis, rendering their assessment unfeasible. CONCLUSION: A weak recommendation is made that G-CSF treatment not be administered to patients with febrile neutropenia during cancer chemotherapy. G-CSF treatment can be considered for patients at high risk.
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Neutropenia Febril , Factor Estimulante de Colonias de Granulocitos , Humanos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Neutropenia Febril/tratamiento farmacológico , Neutropenia Febril/inducido químicamente , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Japón , Neutropenia Febril Inducida por Quimioterapia/tratamiento farmacológico , Oncología Médica , Guías de Práctica Clínica como AsuntoRESUMEN
Bacteremia is a major cause of morbidity and mortality in patients with cancer and episodes of high-risk febrile neutropenia (HRFN). OBJECTIVE: To identify the frequency of microorganisms isolated from blood cultures (BC) and their antimicrobial resistance (R) profile in children with HRFN, compared with the same data from previous studies of the same group. METHOD: Prospective, multicenter, epidemiological surveillance study of microorganisms isolated from BC in patients under 18 years of age, from 7 PINDA network hospitals, between 2016 and 2021. RESULTS: 284 episodes of HRFN with positive BC were analyzed out of 1091 enrolled episodes (26%). Median age 7.2 years [3.0-12.3]. The main isolates were gram-negative bacilli (GNB) 49.2%, gram-positive cocci (GPC) 43.8%, and fungi 3.6%. The most frequently isolated microorganisms were viridans group Streptococci (VGS) (25.8%), Escherichia coli (19.8%), Pseudomonas spp. (11.2%), Klebsiella spp. (10.9%), and coagulase negative Staphylococci (CoNS) (10.9%). There was an increase in R to third-generation cephalosporins (p = 0.011) in GNB and to oxacillin in CoNS (p = 0.00), as well as a decrease in R to amikacin in non-fermenting GNB (p = 0.02) and to penicillin in VGS (p = 0.04). CONCLUSION: VGS is the main agent isolated in BC from pediatric patients with cancer and episodes of HRFN, followed by E. coli, Pseudomonas spp., and Klebsiella spp. Having epidemiological surveillance of microorganisms isolated from BC and their antimicrobial R profile is essential to favor the rational use of antimicrobials.
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Antibacterianos , Bacteriemia , Cultivo de Sangre , Neutropenia Febril , Neoplasias , Humanos , Niño , Neoplasias/microbiología , Estudios Prospectivos , Preescolar , Neutropenia Febril/microbiología , Neutropenia Febril/tratamiento farmacológico , Chile/epidemiología , Bacteriemia/microbiología , Bacteriemia/epidemiología , Bacteriemia/diagnóstico , Femenino , Masculino , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Pruebas de Sensibilidad Microbiana , Adolescente , Bacterias Gramnegativas/aislamiento & purificación , Bacterias Gramnegativas/efectos de los fármacosRESUMEN
BACKGROUND: Two approaches are used to manage invasive fungal disease (IFD) in febrile neutropenic patients viz. empirical therapy (without attempting to confirm the diagnosis), or pre-emptive therapy (after screening tests for IFD). OBJECTIVE: This systematic review was undertaken to compare these approaches in children. METHODS: We searched PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, CINAHL, Clinical Trial Registries and grey literature, for randomized controlled trials (RCT) comparing empirical versus pre-emptive antifungal therapy in children with FN suspected to have IFD. We used the Cochrane Risk of bias 2 tool for quality assessment, and evaluated the certainty of evidence using the GRADE approach. RESULTS: We identified 7989 citations. Stepwise screening identified only one relevant RCT that administered empirical (n = 73) or pre-emptive (n = 76) antifungal therapy. There were no significant differences in all-cause mortality (RR 1.56, 95% CI: 0.46, 5.31), IFD mortality (RR 1.04, 95% CI:0.15, 7.20) and other clinically important outcomes such as duration of fever, duration of hospitalization and proportion requiring ICU admission. There were no safety data reported. The number of days of antifungal therapy was significantly lower in the pre-emptive therapy arm. The certainty of evidence for all outcomes was 'moderate'. CONCLUSIONS: This systematic review highlighted the paucity of data, comparing empirical versus pre-emptive antifungal therapy in children with febrile neutropenia having suspected invasive fungal disease. Data from a single included trial suggests that both approaches may be comparable in research settings. Robust trials are warranted to address the gap in existing knowledge about the optimal approach in clinical practice.
Asunto(s)
Antifúngicos , Neutropenia Febril , Infecciones Fúngicas Invasoras , Niño , Humanos , Antifúngicos/uso terapéutico , Neutropenia Febril/tratamiento farmacológico , Hospitalización , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/prevención & controlRESUMEN
BACKGROUD: Granulocyte colony-stimulating factor (G-CSF) is widely used for the primary prophylaxis of febrile neutropenia (FN). Two types of G-CSF are available in Japan, namely G-CSF chemically bound to polyethylene glycol (PEG G-CSF), which provides long-lasting effects with a single dose, and non-polyethylene glycol-bound G-CSF (non-PEG G-CSF), which must be sequentially administrated for several days. METHODS: This current study investigated the utility of these treatments for the primary prophylaxis of FN through a systematic review of the literature. A detailed literature search for related studies was performed using PubMed, Ichushi-Web, and the Cochrane Library. Data were independently extracted and assessed by two reviewers. A qualitative analysis or meta-analysis was conducted to evaluate six outcomes. RESULTS: Through the first and second screenings, 23 and 18 articles were extracted for qualitative synthesis and meta-analysis, respectively. The incidence of FN was significantly lower in the PEG G-CSF group than in the non-PEG G-CSF group with a strong quality/certainty of evidence. The differences in other outcomes, such as overall survival, infection-related mortality, the duration of neutropenia (less than 500/µL), quality of life, and pain, were not apparent. CONCLUSIONS: A single dose of PEG G-CSF is strongly recommended over multiple-dose non-PEG G-CSF therapy for the primary prophylaxis of FN.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos , Polietilenglicoles , Humanos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Polietilenglicoles/administración & dosificación , Guías de Práctica Clínica como Asunto , Neutropenia Febril/prevención & control , Neutropenia Febril/inducido químicamente , Proteínas RecombinantesRESUMEN
OBJECTIVES: To validate the efficacy and safety of withholding antimicrobial therapy in a new cohort of children with cancer and febrile neutropenia (FN) having a demonstrated viral respiratory tract infection. METHODS: Prospective, multicenter, noninferiority, randomized study, approved by the ethical committee, in children presenting with FN at seven hospitals in Chile, evaluated at admission for diagnosis of bacterial and viral pathogens. Children who were positive for a respiratory virus, negative for a bacterial pathogen, and had a favourable evolution after 48-72 hours of antimicrobial therapy were randomized to either maintain or withhold antimicrobial therapy. The primary endpoint was the percentage of episodes with an uneventful resolution, whereas the secondary endpoints were days of fever, days of hospitalization, requirement of antimicrobial treatment readministration, sepsis, paediatric intensive care unit admission, and death. RESULTS: A total of 301 of 939 children with FN episodes recruited between March 2021 and December 2023 had a respiratory virus as a unique identified microorganism, of which 139 had a favourable evolution at 48-72 hours and were randomized, 70 to maintain and 69 to withdraw antimicrobial therapy. The median days of antimicrobial therapy was 5 (IQR 3-6) versus 3 (IQR 3-6) days (p < 0.001), with similar frequency of uneventful resolution 66/70 (94%) and 66/69 (96%); relative risk, 1.01; (95% CI, 0.93 to 1.09), absolute risk difference 0.01; (95% CI, -0.05 to 0.08) and similar number of days of fever and days of hospitalization. No cases of sepsis, paediatric intensive care unit admission, or death were reported. DISCUSSION: We validated the strategy of withdrawal antimicrobial therapy in children with FN and viral respiratory tract infection based on clinical and microbiological/molecular diagnostic criteria. This will enable advances in antimicrobial stewardship strategies with a possible future impact on antimicrobial resistance.