RESUMEN
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 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
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
PURPOSE: Febrile neutropenia (FN) is a serious complication in hematologic malignancies, and lung infiltrates (LIs) remain a significant concern. An accurate microbiological diagnosis is crucial but difficult to establish. To address this, we analyzed the utility of a standardized method for performing bronchoalveolar lavage (BAL) along with a two-step strategy for the analysis of BAL fluid. PATIENTS AND METHODS: This prospective observational study was conducted at a tertiary cancer center from November 2018 to June 2020. Patients age 15 years and older with confirmed leukemia or lymphomas undergoing chemotherapy, with presence of FN, and LIs observed on imaging were enrolled. RESULTS: Among the 122 enrolled patients, successful BAL was performed in 83.6% of cases. The study used a two-step analysis of BAL fluid, resulting in a diagnostic yield of 74.5%. Furthermore, antimicrobial therapy was modified in 63.9% of patients on the basis of BAL reports, and this population demonstrated a higher response rate (63% v 45%; P = .063). CONCLUSION: Our study demonstrates that a two-step BAL fluid analysis is safe and clinically beneficial to establish an accurate microbiological diagnosis. Given the crucial impact of diagnostic delays on mortality in hematologic malignancy patients with FN, early BAL studies should be performed to enable prompt and specific diagnosis, allowing for appropriate treatment modifications.
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Neutropenia Febril , Neoplasias Hematológicas , Leucemia , Linfoma , Adolescente , Humanos , Líquido del Lavado Bronquioalveolar/microbiología , Neutropenia Febril/diagnóstico , Neutropenia Febril/tratamiento farmacológico , Neutropenia Febril/etiología , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/microbiología , Neoplasias Hematológicas/patología , Leucemia/complicaciones , Leucemia/patología , Pulmón/microbiología , Pulmón/patología , Linfoma/complicaciones , Linfoma/diagnóstico , Linfoma/tratamiento farmacológico , Estudios ProspectivosRESUMEN
The purpose of this study was to evaluate the association between interleukin-33 (IL-33) and its receptor Soluble Suppression of Tumorigenicity-2 (sST2) levels and bacterial infections during febrile neutropenia (FN) in pediatric patients with acute lymphoblastic leukemia (ALL). In this prospective, case-control study, participants were divided into 3 groups: ALL patients with FN (Group A), ALL patients without neutropenia and fever (Group B), and healthy children without infection and chronic disease (Group C). There were 30 cases in each group. Blood samples for IL-33 and sST2 have been drawn from patients in Group A before the initiation of treatment and on days 1 and 5 of treatment, and from patients in Groups B and C at initiation. At admission, mean IL-33 level (39.02 ± 26.40 ng/L) in Group B and mean sST2 level (185.3 ± 371.49 ng/ml) in Group A were significantly higher than the other groups (p = 0.038, p < 0.001, respectively). No difference was observed in the mean IL-33 and sST2 levels in the 5-day follow-up of patients in Group A (p = 0.82, p = 0.86, respectively). IL-33 and sST2 levels were not associated with fever duration, neutropenia duration or length of hospitalization. While C-reactive protein (CRP) was significantly higher in patients with positive blood culture (p = 0.021), IL-33 (p = 0.49) and sST2 (p = 0.21) levels were not associated with culture positivity. Conclusion: IL-33 and sST2 levels were not found valuable as diagnostic and prognostic markers to predict bacterial sepsis in patients with FN. What is Known: ⢠Neutropenic patients are at high risk of serious bacterial and viral infections, but the admission symptom is often only fever. ⢠Febrile neutropenia has a high mortality rate if not treated effectively. What is New: ⢠Febrile neutropenia is not only caused by bacterial infections. Therefore, new biomarkers should be identified to prevent overuse of antibiotics. ⢠Specific biomarkers are needed to diagnose bacterial sepsis in the early phase of febrile neutropenia.
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Biomarcadores , Neutropenia Febril , Proteína 1 Similar al Receptor de Interleucina-1 , Interleucina-33 , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Interleucina-33/sangre , Femenino , Masculino , Proteína 1 Similar al Receptor de Interleucina-1/sangre , Niño , Estudios Prospectivos , Estudios de Casos y Controles , Preescolar , Neutropenia Febril/sangre , Neutropenia Febril/etiología , Neutropenia Febril/diagnóstico , Biomarcadores/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Adolescente , Lactante , Infecciones Bacterianas/sangre , Infecciones Bacterianas/diagnósticoRESUMEN
OBJECTIVES: To evaluate the diagnostic performance and clinical impact of metagenomic next-generation sequencing (mNGS) of plasma microbial cell-free DNA (mcfDNA) in febrile neutropenia (FN). METHODS: In a 1-year, multicentre, prospective study, we enrolled 442 adult patients with acute leukaemia with FN and investigated the usefulness of mNGS of plasma mcfDNA for identification of infectious pathogens. The results of mNGS were available to clinicians in real time. The performance of mNGS testing was evaluated in comparison with blood culture (BC) and a composite standard that incorporated standard microbiological testing and clinical adjudication. RESULTS: In comparison with BC, the positive and negative agreements of mNGS were 81.91% (77 of 94) and 60.92% (212 of 348), respectively. By clinical adjudication, mNGS results were categorized by infectious diseases specialists as definite (n = 76), probable (n = 116), possible (n = 26), unlikely (n = 7), and false negative (n = 5). In 225 mNGS-positive cases, 81 patients (36%) underwent antimicrobials adjustment, resulting in positive impact on 79 patients and negative impact on two patients (antibiotics overuse). Further analysis indicated that mNGS was less affected by prior antibiotics exposure than BC. DISCUSSION: Our results indicate that mNGS of plasma mcfDNA increased the detection of clinically significant pathogens and enabled early optimization of antimicrobial therapy in patients with acute leukaemia with FN.
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Ácidos Nucleicos Libres de Células , Neutropenia Febril , Leucemia Mieloide Aguda , Adulto , Humanos , Estudios Prospectivos , Leucemia Mieloide Aguda/complicaciones , Secuenciación de Nucleótidos de Alto Rendimiento , Antibacterianos , Metagenómica , Neutropenia Febril/diagnóstico , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Pediatric oncology patients with prolonged (≥96 hours) febrile neutropenia (absolute neutrophil count < 500/µL) often undergo an evaluation for invasive fungal disease (IFD) and other infections. Current literature suggests that beta-D-glucan (BDG), galactomannan, bronchoalveolar lavage (BAL), and computed tomography (CT) scans (sinus, chest, and abdomen/pelvis) may help determine a diagnosis in this population. METHODS: In a retrospective cohort study of all cancer/stem cell transplant patients (diagnosed 2005-2019) from one pediatric hospital, all episodes with prolonged febrile neutropenia or IFD evaluations (defined as sending a fungal biomarker or performing a CT scan to assess for infection) were identified. RESULTS: In total, 503 episodes met inclusion criteria and 64% underwent IFD evaluations. In total, 36.4% of episodes documented an infection after initiation of prolonged febrile evaluation, most commonly Clostridioides difficile colitis (6.4%) followed by a true bacterial bloodstream infection (BSI) (5.2%), proven/probable IFD (4.8%), and positive respiratory pathogen panel (3.6%). There was no difference in sinus CTs showing sinusitis (74% vs 63%, p = 0.46), whereas 32% of abdomen/pelvis CTs led to a non-IFD diagnosis, and 25% of chest CTs showed possible pneumonia. On chest CT, the positive predictive value (PPV) for IFD was 19% for nodules and 14% for tree and bud lesions. BDG had a PPV of 25% for IFD and GM 50%. BAL diagnosed IFD once and pneumocystis jirovecii pneumonia twice. CONCLUSIONS: Chest CTs and abdomen/pelvis CTs provide clinically relevant information during the prolonged febrile neutropenia evaluation, whereas BDG, galactomannan, BAL, and sinus CTs have less certain utility.
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Neutropenia Febril , Infecciones Fúngicas Invasoras , Neoplasias , Neumonía por Pneumocystis , beta-Glucanos , Niño , Humanos , Estudios Retrospectivos , Infecciones Fúngicas Invasoras/diagnóstico , Neoplasias/complicaciones , Neutropenia Febril/diagnósticoRESUMEN
To investigate the value of metagenomic next-generation sequencing (mNGS) in acute leukemia (AL) patients with febrile neutropenia (FN). We retrospectively reviewed 37 AL patients with FN and compared the results of mNGS with blood culture (BC) and the clinical features of the mNGS-positive group and the mNGS-negative group. A total of 14 detected pathogens were the final clinical diagnosis, of which 9 strains were detected only by mNGS and 5 strains were detected by both mNGS and BC. The top pathogens were Klebsiella pneumoniae, Pseudomonas aeruginosa and Stenotrophomonas maltophilia. A total of 67.57% (25/37) were bacterial infections, and 2.7% (1/37) were fungal or viral infections. The diagnostic positivity rate of mNGS (25/37, 67.6%) was significantly higher than that of BC (7/37, 18.9%), and the difference was statistically significant (p < 0.05). Then, we explored the clinical distinction between the mNGS-positive group and the mNGS-negative group, and 3 features were filtered, including lymphocyte count (LY), creatinine levels (Cr), and white blood cell count (WBC). Our study demonstrated that early implementation of mNGS can effectively improve the efficacy of pathogen detection in AL patients with FN. The higher diagnostic positivity rate and the ability to detect additional pathogens compared to BC made mNGS a valuable tool in the management of infectious complications in this patient population. Furthermore, the identified clinical features associated with mNGS results provided additional insights for the clinical indication of infection in AL patients with FN.
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Neutropenia Febril , Leucemia Mieloide Aguda , Humanos , Estudios Retrospectivos , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Plasma , Neutropenia Febril/diagnóstico , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Multidrug-resistant Gram-negative bacterial (MRGNB) infections represent a major public health threat. Cancer patients and, among them, hematological patients are most vulnerable to these infections. Gut colonization by MRGNB is a common phenomenon occurring during hospitalization and chemotherapy exposure. In the neutropenic phase that occurs after chemotherapy, MRGNB translocation occurs increasing patient's mortality. Fluoroquinolone prophylaxis with ciprofloxacin or levofloxacin efficacy is now being questioned due to the increase of incidence in MRGNB. METHODS: A phase III randomized, controlled, clinical trial, open-label parallel-group with a 1:1 ratio, aimed to demonstrate the non-inferiority of oral fosfomycin versus oral ciprofloxacin for febrile neutropenia prevention in patients with acute leukemia (AL) or hematopoietic cell transplant (HSC) receptors. Weekly surveillance cultures are planned to detect gut colonization. Changes in fecal microbiome at the beginning and end of prophylaxis will also be analyzed. DISCUSSION: This trial will provide evidence of the efficacy of an alternative drug to ciprofloxacin for febrile neutropenia prevention in high-risk hematological patients. The battery of planned microbiological studies will allow us to evaluate prospectively the microbiological safety of both pharmacological strategies in terms of the selection of MRGNB occurring in each arm. In addition, valuable information on the way in which each drug changes the fecal microbiome of the patients throughout the treatment will be generated. TRIAL REGISTRATION: Clinical trials NCT05311254, Registered on 5 April 2022, https://clinicaltrials.gov/ct2/show/NCT05311254?term=FOVOCIP&cntry=ES&draw=2&rank=1 . PROTOCOL VERSION: 3.0, dated 20 May 2022.
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Neutropenia Febril , Fosfomicina , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Ciprofloxacina/efectos adversos , Fosfomicina/uso terapéutico , Neutropenia Febril/diagnóstico , Neutropenia Febril/tratamiento farmacológico , Antibacterianos/efectos adversosRESUMEN
BACKGROUND: Point-of-care decision support, embedded into electronic medical record (EMR) workflows, has the potential to improve efficiency, reduce unwarranted variation and improve patient outcomes. A clinical-facing best practice advisory (BPA) in the Epic EMR system was developed to identify children admitted with low-risk febrile neutropenia (FN) who should be considered for treatment at home after a brief inpatient stay. We evaluated the accuracy and impact of this BPA and identify areas for improvement. METHODS: The low-risk FN BPA was co-designed with key-stakeholders and implemented after a one-month testing phase. Mixed methodology was used to collect and analyse data. The sensitivity and positive predictive value of the BPA was calculated using FN episodes captured in a prospectively collected database. Overall effectiveness was defined as the proportion of alerts resulting in completion of a FN risk assessment flowsheet. RESULTS: Over the 12-month period 176 FN episodes were admitted. Overall, the alert had poor sensitivity (58%) and positive predictive value (75%), failing to trigger in 62 (35%) episodes. In the episodes where the alert did trigger, the alert was frequently dismissed by clinicians (76%) and the overall effectiveness was extremely low (3%). Manual review of each FN episode without a BPA identified important design limitations and incorrect workflow assumptions. DISCUSSION: Given the poor sensitivity and limited impact on clinician behaviour the low-risk BPA, in its current form, has not been an effective intervention at this site. While work is ongoing to enhance the accuracy of the BPA, alternative EMR workflows are likely required to improve the clinical impact.
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Registros Electrónicos de Salud , Neutropenia Febril , Humanos , Niño , Hospitalización , Medición de Riesgo , Neutropenia Febril/diagnósticoRESUMEN
OBJECTIVE: To evaluate the need for routine urine studies in children with febrile neutropenia with cancer. DESIGN: A prospective, observational study was conducted in two hospitals between November 2019 and October 2021. PATIENTS: We recruited 205 patients in total. MAIN OUTCOME MEASURES: The primary outcome was presence of positive urine culture (UC). Urinary tract infection (UTI) was defined as urinary signs/symptoms and positive UC with or without pyuria. A descriptive analysis of data is provided.We conducted a prospective study of paediatric patients with cancer with urinary continence. Data were analysed using descriptive statistics. The diagnostic performance of urinalysis was calculated using positive UC as the gold standard. RESULTS: Positive UC was found in 7 of the 205 patients (3.4%; 95% CI 1.4% to 6.9%), 2 presenting urinary symptoms. UTI prevalence was 1.0% (95% CI 0.1% to 3.5%). A 23.8% prevalence of positive UC was found in patients with urinary symptoms and/or history of urinary tract disease (95% CI 8.2% to 47.2%) as compared with 1.1% of those without symptoms or history (95% CI 0.1% to 3.9%) (p<0.001). The sensitivity, specificity, negative predictive value, and area under the curve for urinalysis were 16.7% (95% CI 3.0% to 56.4%), 98.4% (95% CI 95.3% to 99.4%), 97.3% (95% CI 93.9% to 98.9%), and 0.65 (95% CI 0.51 to 0.79), respectively. CONCLUSIONS: UTI is an infrequent cause of infection in these patients. Urinalysis is indicated only in children with febrile neutropenia with urinary signs/symptoms and in asymptomatic patients with a history of urinary tract disease or unknown history. When urine is collected, UC should be requested regardless of the result of the urinalysis.
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Neutropenia Febril , Neoplasias , Infecciones Urinarias , Humanos , Niño , Estudios Prospectivos , Sensibilidad y Especificidad , Urinálisis , Infecciones Urinarias/complicaciones , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/epidemiología , Fiebre/etiología , Neoplasias/complicaciones , Neutropenia Febril/complicaciones , Neutropenia Febril/diagnósticoRESUMEN
Improved methods are needed for diagnosing infectious diseases in children with cancer. Most children have fever for other reasons than bacterial infection and are exposed to unnecessary antibiotics and hospital admission. Recent research has shown that host whole blood RNA transcriptomic signatures can distinguish bacterial infection from other causes of fever. Implementation of this method in clinics could change the diagnostic approach for children with cancer and suspected infection. However, extracting sufficient mRNA to perform transcriptome profiling by standard methods is challenging due to the patient's low white blood cell (WBC) counts. In this prospective cohort study, we succeeded in sequencing 95% of samples from children with leukaemia and suspected infection by using a low-input protocol. This could be a solution to the issue of obtaining sufficient RNA for sequencing from patients with low white blood cell counts. Further studies are required to determine whether the captured immune gene signatures are clinically valid and thus useful to clinicians as a diagnostic tool for patients with cancer and suspected infection.
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Infecciones Bacterianas , Neutropenia Febril , Leucopenia , Neoplasias , Niño , Humanos , Estudios Prospectivos , Fiebre/tratamiento farmacológico , Infecciones Bacterianas/tratamiento farmacológico , Neoplasias/genética , Neoplasias/tratamiento farmacológico , Antibacterianos/uso terapéutico , ARN , Neutropenia Febril/diagnóstico , Neutropenia Febril/genéticaRESUMEN
Febrile neutropenia is one of the main infectious complications experienced by paediatric patients with blood or solid tumours, which, despite the advances in diagnosis and treatment, are still associated with a significant morbidity and mortality. These patients have several risk factors for infection, chief of which are chemotherapy-induced neutropenia, the disruption of cutaneous and mucosal barriers and the use of intravascular devices. Early diagnosis and treatment of febrile neutropenia episodes based on the patient's characteristics is essential in patients with blood and solid tumours to improve their outcomes. Therefore, it is important to develop protocols in order to optimise and standardise its management. In addition, the rational use of antibiotics, with careful adjustment of the duration of treatment and antimicrobial spectrum, is crucial to address the increase in antimicrobial drug resistance. The aim of this document, developed jointly by the Spanish Society of Pediatric Infectious Diseases and the Spanish Society of Pediatric Hematology and Oncology, is to provide consensus recommendations for the management of febrile neutropenia in paediatric oncology and haematology patients, including the initial evaluation, the stepwise approach to its treatment, supportive care and invasive fungal infection, which each facility then needs to adapt to the characteristics of its patients and local epidemiological trends.
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Enfermedades Transmisibles , Neutropenia Febril , Hematología , Neoplasias , Humanos , Niño , Consenso , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Neutropenia Febril/diagnóstico , Neutropenia Febril/tratamiento farmacológicoRESUMEN
El Comité de Infecciones en Inmunocomprometidos de la Sociedad Chilena de Infectología presenta aquí una actualización en el Manejo de episodios de neutropenia febril en adultos y niños con cáncer, derivado de los grandes cambios ocurridos en los últimos años en el enfrentamiento de estos pacientes. Para estos efectos, un grupo multidisciplinario desarrolló recomendaciones en relación a: su enfrentamiento inicial, exámenes de laboratorio requeridos, el tratamiento antimicrobiano inicial empírico y frente a focos infecciosos conocidos, las infecciones fúngicas invasoras y profilaxis antimicrobiana.
The Committee of Infections in Immunocompromised Patients of the Chilean Society of Infectious Diseases presents an update in the Management of febrile neutropenia in adults and children with cancer. It comes from the significant changes that occurred in recent years in the confrontation of these patients. For which a multidisciplinary task force group developed recommendations in relation to their initial handling, laboratory exams required, the initial empirical antimicrobial treatment and in front of known infectious focus, invasive fungal infections and antimicrobial prophylaxis.
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Humanos , Niño , Adulto , Consenso , Neutropenia Febril/diagnóstico , Neutropenia Febril/tratamiento farmacológico , Neoplasias/complicaciones , Neutropenia Febril/etiología , Antiinfecciosos/uso terapéuticoRESUMEN
Traditional microbiological methodology has limited sensitivity, detection range, and turnaround times in diagnosis of bloodstream infection in Febrile Neutropenia (FN) patients. A more rapid and sensitive detection technology is urgently needed. Here we used the newly developed Nanapore targeted sequencing (NTS) to diagnose the pathogens in blood samples. The diagnostic performance (sensitivity, specificity and turnaround time) of NTS detection of 202 blood samples from FN patients with hematologic disease was evaluated in comparison to blood culture and nested Polymerase Chain Reaction (PCR) followed by sanger sequence. The impact of NTS results on antibiotic treatment modification, the effectivity and mortality of the patients under the guidance of NTS results were assessed. The data showed that NTS had clinical sensitivity of 92.11%, clinical specificity of 78.41% compared with the blood culture and PCR combination. Importantly, the turnaround time for NTS was <24 h for all specimens, and the pre-report time within 6 h in emergency cases was possible in clinical practice. Among 118 NTS positive patients, 98.3% patients' antibiotic regimens were guided according to NTS results. There was no significant difference in effectivity and mortality rate between Antibiotic regimen switched according to NTS group and Antibiotic regimen covering pathogens detected by NTS group. Therefore, NTS could yield a higher sensitivity, specificity and shorter turnaround time for broad-spectrum pathogens identification in blood samples detection compared with traditional tests. It's also a good guidance in clinical targeted antibiotic treatment for FN patients with hematologic disease, thereby emerging as a promising technology for detecting infectious disease.
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Antiinfecciosos , Enfermedades Transmisibles , Neutropenia Febril , Enfermedades Hematológicas , Nanoporos , Sepsis , Humanos , Neutropenia Febril/diagnóstico , Neutropenia Febril/tratamiento farmacológico , Antibacterianos/uso terapéuticoRESUMEN
Febrile neutropenia (FN) is a frequently occurring treatment-related complication with significant morbidity and mortality for childhood acute leukemia. Early diagnosis and assessment of severity are essential steps for early comprehensive treatment to reduce FN-related morbidity and mortality. Biomarkers like C-reactive protein (CRP) and procalcitonin (PCT) can be used to assess and predict the bacterial infection in children with febrile neutropenia. The objective of the study was to determine the role of procalcitonin and CRP as a biomarker for prediction of bacterial infection in children with FN in acute leukemia. This prospective observational study was conducted in the Department of Pediatric Hematology and Oncology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh from August 2020 to July 2021. Total 58 Children with acute leukemia aged 1 to <18 years with FN were analyzed in this study. A proper history and thorough physical examination were carried out. The blood sample was sent for biomarkers (Procalcitonin and CRP) within 24 hours of the onset of FN and other investigations, such as Complete blood count, Blood C/S, Urine R/E and C/S. Metabolic workup (SGPT, Serum Creatinine, Serum Electrolytes, Serum Ca+) was also done in every patient. Stool R/E & C/S, Chest X-ray, Wound swab for C/S were done when the patient presented with diarrhoea, cough, respiratory distress and focal sepsis respectively. In this study, the mean age of the patients was 6.62±4.07 years (1.10-16.0 years) and 34 patients (58.6%) were male. In 65.5% of patients, localizing signs of infection were not identified. Of the 58 patients, 12 patients (20.7%) showed positive blood culture and 2 patients (3.4%) showed positive urine culture. Klebsiella spp (41.0%) was the most frequent organism isolated followed by Acinetobacter (17.0%), Pseudomonas (17.0%) and E. coli (17.0%). The median PCT levels were significantly higher in patients with bacterial infection than patients without bacteremia (26.10µg/l versus 0.78µg/l, p=0.002) and PCT level >2µg/l was significantly associated with bacteremia. The median CRP levels in the bacteremia and without-bacteremia patients were 137.4mg/L and 54.17mg/L, respectively (p=0.036). In direct comparisons, PCT showed better overall performance than CRP with the AUC being 0.797 (95% CI 0.651-0.943) for PCT and 0.697 (95% CI 0.54-0.855) for CRP in predicting the bacterial infection. PCT and CRP both are useful biomarkers for the prediction of bacteremia, but PCT may be a superior early biomarker as compared to CRP to predict bacterial infection in children with febrile neutropenia in acute leukemia.
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Bacteriemia , Neutropenia Febril , Leucemia Mieloide Aguda , Humanos , Masculino , Niño , Preescolar , Femenino , Proteína C-Reactiva/análisis , Polipéptido alfa Relacionado con Calcitonina , Escherichia coli , Biomarcadores , Bacteriemia/diagnóstico , Enfermedad Aguda , Neutropenia Febril/diagnóstico , Neutropenia Febril/microbiologíaRESUMEN
BACKGROUND/AIM: Febrile neutropenia (FN) is a potentially life-threatening complication of chemotherapy. In this study, we evaluated the predictors for FN according to neoadjuvant chemotherapy (NAC) in all breast cancer subtypes. PATIENTS AND METHODS: We examined 327 patients with breast cancer treated with NAC. The correlation between the development of FN and clinicopathological features, including systemic inflammatory markers, and prognosis was evaluated retrospectively. RESULTS: There were no significant differences between patients with and without FN in terms of disease-free survival or overall survival (p=0.562, p=0.149, log-rank, respectively). Low body mass index (BMI) (p<0.001), white blood cells (WBC) at baseline (p=0.008), and NAC regimen (p=0.026) significantly related with FN in all patients with breast cancer. Moreover, among patients with hormone receptor-positive/human epidermal growth factor receptor 2-positive breast cancer, low WBC (p=0.007) and low absolute lymphocyte counts (ALC) at baseline (p=0.039) were significantly associated with FN, and overall survival was significantly worse in patients with FN development (p=0.039, log-rank). CONCLUSION: Poor immune activity-related factors, low ALC or BMI, may be useful to predict the development of FN in patients with breast cancer.
Asunto(s)
Neoplasias de la Mama , Neutropenia Febril , Terapia Neoadyuvante , Femenino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neutropenia Febril/inducido químicamente , Neutropenia Febril/diagnóstico , Factor Estimulante de Colonias de Granulocitos , Terapia Neoadyuvante/efectos adversos , Pronóstico , Estudios RetrospectivosRESUMEN
Risk stratification of pediatric febrile neutropenia (FN) is an established concept, yet clinical risk tools misclassify nearly 5% of clinical standard-risk episodes with severe outcomes. The internal evaluation of a clinical risk tool before implementation has not been well-described. In this noninterventional cohort study, we evaluated a study decision rules (SDR) tool; a clinical risk tool with serial procalcitonin. The study standard-risk (SSR) group met clinical standard-risk criteria with two serial procalcitonin <0.4 ng/mL. The study high-risk (SHR) group met clinical high-risk criteria or clinical standard-risk with a procalcitonin ≥0.4 ng/mL. Descriptive and bivariate statistics compared the groups and outcomes. Clinical criteria alone identified 39.1% (238/608) standard-risk episodes; 5.9% (14/238) had severe events. Prospectively using the SDR, the SHR group encompassed 76.6% (92/120) of episodes; severe events occurred in 20% (3/15) of standard-risk episodes included due to elevated procalcitonin ≥0.4 ng/mL. The SHR group had more blood stream infections [21.7% (20/92) vs. 0% (0/28); P = 0.007] and intensive care admissions [13% (12/92) vs. 3.6% (1/28); P = 0.158]. In conclusion, the SDR with serial procalcitonin aided in identifying severe events in clinical standard-risk episodes, but analysis was limited. Institutions may consider similar internal evaluation methodology before FN episode risk stratification.