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Background: Gram-positive bacteria are frequently resistant to empirical beta-lactams in febrile neutropenic patients with cancer. As microbiology and antibiotic susceptibility changes, we reevaluated the risk factors for resistant Gram-positive bacteremia in febrile neutropenic patients with cancer., Methods: Episodes of bacteremic febrile neutropenia in Seoul National University Hospital from July 2019 to June 2022 were reviewed. Resistant Gram-positive bacteria were defined as a pathogen susceptible only to glycopeptide or linezolid in vitro (e.g., methicillin-resistant staphylococci, penicillin-resistant viridans streptococci, and ampicillin-resistant enterococci). Episodes were compared to identify independent risk factors for resistant Gram-positive bacteremia., Results: Of 225 episodes, 78 (34.7%) involved resistant Gram-positive bacteremia. Multivariate analysis revealed that breakthrough bacteremia while being administered antibiotics (adjusted odds ratio [aOR], 6.794; 95% confidence interval [95% CI], 3.130-14.749; P < 0.001) and catheter-related infection (aOR 4.039, 95% CI 1.366-11.946; P = 0.012) were associated with resistant Gram-positive bacteremia. Chronic liver disease (aOR 0.231, 95% CI 0.059-0.905; P = 0.035) and hypotension at bacteremia (aOR 0.454, 95% CI 0.218-0.945; P = 0.035) were inversely associated with resistant Gram-positive bacteremia., Conclusions: Resistant Gram-positive bacteria should be considered in breakthrough bacteremia and catheter-related infection in febrile neutropenic patients with cancer., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

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., Competing Interests: None of the authors identify a conflict of interest., (©Copyright 2024 by University Health Partners of Hawai‘i (UHP Hawai‘i).)

Background: Computed tomography (CT) imaging has become a first line investigation for most cases of febrile neutropenia (FN) which can be the only sign of infection in oncology patients undergoing active chemotherapy and bone marrow transplants. The utility of routine non-targeted imaging remains unclear., Objective: To assess and compare the diagnostic rate between targeted, non-targeted and pan-scan CT in identifying an acute source of infection in adult oncology patients with FN., Materials and Methods: A retrospective observational study was conducted between February 2019 and March 2023 on 417 consecutive CT examinations for the clinical indication of source identification in FN. Scans were noted for the anatomical regions that were imaged and reports were classified as positive, negative or equivocal for infection. Pre-existing pathology was also noted. Results were tabulated and statistical analyses for comparison between groups of scans was performed using chi-square test., Results: All targeted regional scans had statistically significant difference in positive rate compared to non-targeted scans of the respective region; chest (Χ²(1)=18.11, P<.001); sinus (Χ²(1)=15.36, P<.001); abdomen and pelvis (Χ²(1)=5.95, P=.01). Pneumonia (41.3 %) was much more likely to be the diagnosis compared to sinusitis (16.2 %) in concomitant CT chest to sinus examinations (Χ²(1)=45.3, P<.001). Pan-scans had a higher incidence of positive diagnosis compared to all-targeted scans (Χ²(1)=4.91, P=.03) but when compared to higher yield targeted scans (abdomen and chest), there was no statistical difference (Χ²(1)=2.43, P=.12). 20/54 patients had pan-scans despite having localising symptoms., Conclusion: Imaging guided by presenting signs and symptoms can help to reduce unnecessary imaging and promote more judicious use of non-targeted and pan-scan CT in current practices., Competing Interests: Declaration of competing interest Authors of this manuscript have are no conflicts of interest to disclose or declare relevant to this submission, (Copyright © 2024. Published by Elsevier Inc.)

Background: Several studies have suggested that short-course antibiotic therapy was effective in Pseudomonas aeruginosa (PA) bloodstream infections (BSI) in immunocompetent patients. But similar studies in patients with hematological malignancies were rare., Methods: This cohort study included onco-hematology patients at 2 hematology centers in China. Inverse probability of treatment weighting was used to balance the confounding factors. Multivariate regression model was used to evaluate the effect of short-course antibiotic therapy on clinical outcomes., Results: In total, 434 patients met eligibility criteria (short-course, 7-11 days, n = 229; prolonged, 12-21 days, n = 205). In the weighted cohort, the univariate and multivariate analysis indicated that short course antibiotic therapy had similar outcomes to the prolonged course. The recurrent PA infection at any site or mortality within 30 days of completing therapy occurred in 8 (3.9%) patients in the short-course group and in 10 (4.9%) in the prolonged-course group (P = .979). The recurrent infection within 90 days occurred in 20 (9.8%) patients in the short-course group and in 13 (6.3%) patients in the prolonged-course group (P = .139), and the recurrent fever within 7 days occurred in 17 (8.3%) patients in the short-course group and in 15 (7.4%) in the prolonged-course group (P = .957). On average, patients who received short-course antibiotic therapy spent 3.3 fewer days in the hospital (P < .001)., Conclusions: In the study, short-course therapy was non-inferior to prolonged-course therapy in terms of clinical outcomes. However, due to its biases and limitations, further prospective randomized controlled trials are needed to generalize our findings., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Many systemic treatments used in genitourinary oncology negatively affect haematopoiesis, thus leading to neutropenia. Neutropenic patients are vulnerable to bacterial, and other infections. Often fever is the only symptom in these patients. Neutropenic fever is a major threat for these patients, as it may lead to life-threatening therapy complications that significantly impair the patient's quality of life, Moreover, it may also worsen the prognosis due to therapy delays or necessary dose modifications. Granulocyte colony stimulating factors (GCSF), which can improve neutrophil granulocyte formation, are used both for supportive treatment in febrile neutropenia and for its prophylaxis. The correct indication for such GCSF support depends on the general risk of febrile neutropenia of the therapy used, as well as on individual patient factors and the treatment intent (palliative vs. curative). Based on the current recommendations both of the German and international guidelines, this article aims to provide an up-to-date and practice-oriented overview of the use of GCSF in uro-oncology., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Purpose: Febrile neutropenia (FN) in pediatric patients with cancer can cause severe infections, and prompt antibiotics are warranted. Extrapolated from other populations, a time-to-antibiotic (TTA) metric of <60 minutes after medical center presentation was established, with compliance data factoring into pediatric oncology program national rankings., Methods: All FN episodes occurring at Vanderbilt Children's Hospital (2007-February 2022) and a sample of episodes from Colorado Children's Hospital (2012-2019) were abstracted, capturing TTA and clinical outcomes including major complications (intensive care unit [ICU] admission, vasopressors, intubation, or infection-related mortality). Odds ratios (ORs) were adjusted for age, treatment center, absolute neutrophil count, hypotension presence, stem-cell transplant status, and central line type., Results: A total of 2,349 episodes were identified from Vanderbilt (1,920) and Colorado (429). Only 0.6% (n = 14) episodes required immediate ICU management, with a median TTA of 28 minutes (IQR, 20-37). For the remaining patients, the median TTA was 56 minutes (IQR, 37-90), and 54.3% received antibiotics in <60 minutes. There were no significant associations between TTA (<60 or ≥60 minutes) and major complications (adjusted OR, 0.99 [95% CI, 0.62 to 1.59]; P = .98), and a TTA ≥60 minutes was not associated with any type of complication. Similarly, TTA, when evaluated as a continuous variable, was not associated with a major (OR, 0.99 [95% CI, 0.94 to 1.04]; P = .69) nor any other complication in adjusted analysis., Conclusion: There is no clear evidence that a reduced TTA improves clinical outcomes in pediatric oncology FN and thus it should not be used as a primary quality measure.

Purpose: This study aimed to identify the patient characteristics of children with febrile neutropenia, the associated bacterial organisms, and their sensitivity patterns., Materials and Methods: A descriptive cross-sectional study was conducted at the Moi Teaching and Referral Hospital (MTRH) pediatric oncology ward, from June 2021 to April 2022. A total of 110 children who developed fever and neutropenia during chemotherapy were enrolled. Blood samples for culture were collected aseptically. Patient characteristics were presented in frequency tables. Antimicrobial sensitivity patterns were plotted in tables against the bacterial isolates cultured. Chi-square/Fisher's exact test was used to determine any association between patient characteristics, bacterial growth, and antimicrobial sensitivity., Results: The majority (n = 66; 60%) were males. The median age was 6.3 years (standard deviation, 3.7). The majority of patients 71 (64.5%) had hematologic malignancies, the most common being AML. There was a significant association between severity of neutropenia and hematologic malignancies ( P = .028). In total, 31/110 (28.2%) blood cultures were positive for bacterial growth. Gram-positive bacteria were more frequent (n = 20; 58.1%). The most common organism was Escherichia coli (n = 6; 18.2%), followed by Staphylococcus aureus (n = 5; 15.2%). All the isolates were sensitive to linezolid and vancomycin and also showed good sensitivity toward meropenem (n = 10/11; 90.9%). High resistance to cephalosporins was noted with ceftriaxone (n = 5/6; 83.3%), cefepime (n = 4/7; 57.1%), and ceftazidime (n = 3/4; 75%)., Conclusion: The most common malignancy associated with febrile neutropenia was AML. Gram-positive bacteria were the most common isolates. There was high resistance to cephalosporins.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Recent clinical practice guidelines have recommended ambulatory management of febrile neutropenia in patients with low risk of complications. Although some centers have begun developing management protocols for these patients, there appears to be a certain reluctance to implement them in clinical practice. Our aim is to evaluate the strengths and weaknesses of this strategy according to available evidence and to propose new lines of research., Methods: Systematic review using a triple aim approach (efficacy, cost-effectiveness, and quality of life), drawing from literature in MEDLINE (PubMed), Embase, and Cochrane Library databases. The review includes studies that assess ambulatory management for efficacy, cost-efficiency, and quality of life., Results: The search yielded 27 articles that met our inclusion criteria., Conclusion: In conclusion, based on current evidence, ambulatory management of febrile neutropenia is safe, more cost-effective than inpatient care, and capable of improving quality of life in oncological patients with this complication. Ambulatory care seems to be an effective alternative to hospitalization in these patients., (© 2023. The Author(s).)

Tigecycline has been used to treat patients with febrile neutropenia (FN). This study aims to analyse the effectiveness of tigecycline as salvage treatment of FN. Patients records from 09/2004 to 04/2019 were reviewed. Cases were eligible if fever persisted/recurred (p/r-FN) after 3 days of second-line treatment with a carbapenem, and were divided into three groups: switch to tigecycline (TGC group), switch to other antibiotics (OAB group), and no switch (W&W group). The primary endpoint was response rate (defervescence for ≥ 7 days or at least until discharge); the key secondary endpoint was 30-day mortality rate. Two hundred cases from 176 patients (median 59 years; 53.5% men) treated were included, mostly acute myeloid leukaemias (61.0%). 45.5% of cases were in the TGC group (in combination with an anti-pseudomonal antibiotic, mostly ceftazidime [95.6%]); 35.5% were in the OAB and 19.0% in the W&W group. There was no significant difference in response rates (TGC, 73.6%; OAB, 62.0%; W&W, 78.9%; p = 0.12) or 30-day mortality rates (TGC, 7.7%; OAB, 7.0%; W&W, 5.3%; p = 0.94). Tigecycline plus an anti-pseudomonal antibiotic does not improve response or 30-day mortality rate compared to other antibiotics in patients with p/r-FN. Also, in some cases, no switch in antibiotics may be necessary at all., (© 2023. The Author(s).)

Objective: Febrile neutropenia (FN) is an important complication that causes high rates of morbidity and mortality in patients with malignancies. We aimed to investigate the etiology, epidemiological distribution and its change over the years, clinical courses, and outcomes of FN in children with acute leukemia., Materials and Methods: We retrospectively analyzed the demographic data, clinical characteristics, laboratory results, severe complications, and mortality rates of pediatric patients with FN between January 2010 and December 2020., Results: In 153 patients, a total of 450 FN episodes (FNEs) occurred. Eighty-four (54.9%) of these patients were male, the median age of the patients was 6.5 (range: 3-12.2) years, and 127 patients (83%) were diagnosed with acute lymphoblastic leukemia. Fever with a focus was found in approximately half of the patients, and an etiology was identified for 38.7% of the patients. The most common fever focus was bloodstream infection (n=74, 16.5%). Etiologically, a bacterial infection was identified in 22.7% (n=102), a viral infection in 13.3% (n=60), and a fungal infection in 5.8% (n=26) of the episodes. Twenty-six (23.2%) of a total of 112 bacteria were multidrug resistant (MDR) The rate of severe complications was 7.8% (n=35) and the mortality rate was 2% (n=9). In logistic regression analysis, refractory/relapsed malignancies and high C-reactive protein (CRP) at first admission were found to be the most important independent risk factors for mortality. Prolonged neutropenia after chemotherapy, diagnosis of acute myeloid leukemia, identification of fever focus or etiological agents, invasive fungal infections, polymicrobial infections, and need for intravenous immunoglobulin treatment increased the frequency of severe complications., Conclusion: We found that there was no significant change in the epidemiological distribution or frequency of resistant bacteria in our center in the last 10 years compared to previous years. Prolonged duration of fever, relapsed/refractory malignancies, presence of fever focus, and high CRP level were significant risk factors for poor clinical course and outcome., (©Copyright 2023 by Turkish Society of Hematology Turkish Journal of Hematology, Published by Galenos Publishing House.)

Background: Early evaluation of symptoms and taking appropriate preventive measures can improve outcomes for patients with lymphoma undergoing hematopoietic stem cell transplantation (HSCT). This study aimed to examine the treatment and outcomes of patients with lymphoma undergoing HSCT., Methods: Patients with lymphoma undergoing SCT at a university hospital between 15.06.2018 and 15.06.2020, were selected for a retrospective study. The medical treatments of patients were obtained from the records on the Hospital Information Management System (HIMS) database. The study was reported following the STROBE checklist., Results: Sixty-four patients were analyzed. The mean age of the patients was 48.25 ± 16.93 (p = 0.76). Although relapse developed in 26 (40.6%) patients with lymphoma, remission was achieved in 38 (59.4%) patients. The incidence of skin graft-versus-host disease (GVHD) symptoms in patients with relapse [14(53.8%)] was found to be significantly higher than in patients in remission [4(10.5%)] (p < 0.001). The most common symptoms seen in patients undergoing HSCT were oral mucositis (78.1%), febrile neutropenia (68.8%), and anemia (56.3%). In the treatments applied after SCT, the administration of antifungal (p = 0.033), analgesic (p = 0.001), and anticoagulant (p = 0.008) treatments to the patients who were in remission compared with the relapsed patients was significant. Less courses (OR: 0.446; 95% CI: 0.22-0.907; p = 0.026), analgesic therapy (OR:6.22; 95% CI: 1.61-24.027; p = 0.008), and anticoagulant treatment (OR:7.13; %) 95 CI: 1.374-37.1; p = 0.019) were found to increase the risk of relapse. Because of the increase in the number of cures in SCT, the incidence of diarrhea (p = 0.016) and GIS GVHD (p = 0.022) was high. It was determined that the hospitalization period was shorter in patients with febrile neutropenia (p = 0.021), thrombocytopenia/bleeding (p = 0.031), and secretion (p = 0.036) symptoms., Conclusions: Patients experienced severe symptoms such as oral mucositis, febrile neutropenia, and anemia due to HSCT, and necessary treatment was applied for the symptoms. Further clinical studies must determine the symptoms and patient outcomes associated with SCT. It is predicted that patients will benefit from regular follow-up of their symptoms and planning of appropriate evidence-based nursing interventions and that this will improve the quality of care to be offered to them and increase their life span., Competing Interests: Declaration of Competing Interest The authors have no funding conflicts of interest to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: In this retrospective study, we evaluated the effect of ferritin levels on the outcomes of autologous stem cell transplantation in patients with MM or lymphoma., Methods: In this study, 170 patients with measured ferritin levels within one month before transplantation who underwent ASCT with the diagnosis of MM or lymphoma were evaluated. The cut-off value of ferritin was determined as 500 ng/mL to evaluate the transplant outcomes in both groups. The hematological recovery status/duration, febrile neutropenia rate, hospitalization time, transplant-related mortality (TRM) in the first 100 days, and OS were evaluated according to the ferritin level RESULTS: Of all patients, 105 (61,8%) were diagnosed with MM and 65 (38.2%) with lymphoma. Ferritin levels had no statistically significant effect on the engraftment status/times, the febrile neutropenia rates, and hospitalization times of both lymphoma and myeloma patients (p > .05). Ferritin level was not significantly associated with TRM in MM (p = .224). However, in lymphoma, ferritin level was significantly associated with TRM (33.3% for ferritin level ≥500 ng/L vs. 5.3% for ferritin level ng/mL, p = .005). There was no statistically significant correlation between ferritin value and OS in MM group [ferritin level ≥ 500 ng/L: 39.9 months (95% CI: 33.7-46.1) and ferritin level 500 ng/mL: 39.4 months (95% CI: 36.5-42.2), p = .446]. Ferritin level was significantly associated with OS in patients with lymphoma [ferritin level ≥ 500 ng/L: 22.1 months 95% CI: 14.7-29.5), ferritin level 500 ng/mL: 27.3 months (95% CI: 22.4-32.2), p = .038] CONCLUSION: High ferritin level is important prognostic factor on survival after ASCT in patients with lymphoma., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Abstract: Febrile neutropenia is a serious complication of chemotherapy treatment and may present as the only clinical sign of infection. If not addressed in a timely manner, it may progress to multisystem organ failure and may be fatal. Initial assessment of fever in those receiving chemotherapy requires prompt administration of antibiotics, ideally within one hour of presentation. Depending on the clinical status of the patient, antibiotic treatment may occur in the inpatient or outpatient setting. Nurses play an important role in the identification and treatment of patients at high risk for febrile neutropenia through assessment and adherence to clinical practice guidelines. In addition, nurses play an active role in patient education regarding risk factors, protective measures, and signs and symptoms of infection in the immunocompromised oncology patient., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Hyperthyreoidism is a clinical manifestation of excessive production of thyroid hormones. In most cases pacient ´s condition allows ambulant treatment. Rarely, it can develop into an acute, life- threatening thyrotoxic crisis which has to be treated in the intensive care unit. Main therapy includes antithyroid medication, corticosteroids, beta- blockers and rehydratation, mostly parenteral. If initial treatment fails, plasmapheresis provides effective strategy. Antithyroid medication may come with side effects as rash, digestive issues, joint pain.Agranulocystosis or acute liver lesion which leads to liver failure belong among the most severe ones. In this case we report a pacient with thyrotoxic crisis, atrial fibrilation which led to ventricular fibrilation, cor thyreotoxicum. The treatment was complicated by febrile neutropenia.

Introduction: Infectious complications, particularly invasive bacterial and fungal infections, are still a major cause of morbidity in pediatric cancer patients and are associated with significant mortality. Over the last few years, there has been much effort in defining risk groups to tailor antimicrobial therapy, and in establishing pediatric-specific guidelines for antimicrobial strategies., Areas Covered: This review provides a critical overview of defining risk groups for infection, diagnostic work-up, antimicrobial prophylaxis, empirical therapy, and treatment of established infections., Expert Opinion: To date, no generalizable risk prediction model has been established for pediatric cancer patients. There is growing interest in defining the impact of the individual genetic background on infectious complications. New diagnostic tools have been developed over the last few years, but they need to be validated in pediatric cancer patients. International, pediatric-specific guidelines for antimicrobial prophylaxis, empirical therapy, and treatment of established infections have recently been published and will harmonize antimicrobial strategies in the future.

Background: Febrile neutropenia (FN) is a life-threatening complication that predisposes cancer patients to serious infections. This study aims to describe the epidemiology and source of infection in cancer patients with FN in a tertiary care hospital., Methods: A hospital-based retrospective study was conducted in a large tertiary care hospital from January 2020 to December 2021. Data on cancer patients with FN were collected from the hospital information system., Results: 150 cancer patients with FN were identified during the study period. Most patients were males (98; 65.3%), and the mean age of participants was 42.2 ± 16.0 years. Most patients (127; 84.7%) had hematologic malignancies, and acute myeloid leukemia was the most common diagnosis (42; 28%), followed by acute lymphocytic leukemia (28; 18.7%) and Hodgkin's lymphoma (20; 13.3%). Fifty-four (36%) patients had a median Multinational Association for Supportive Care in Cancer (MASCC) scores greater than 21. Regarding the outcome, nine (6%) died, and 141(94%) were discharged. The focus of fever was unknown in most patients (108; 72%). Among the known origins of fever were colitis (12; 8%), pneumonia (8; 5.3%), cellulitis (6; 4%), bloodstream infections (7; 4.6%), perianal abscess (2; 1.3%) and others. The median duration of fever was two days, and the median duration of neutropenia was seven days. Sixty-three (42%) patients had infections: 56 (73.3%) were bacterial, four (2.6%) were viral, two (1%) were fungal and 1 (0.7%) was parasitic. Among the bacterial causes, 50 cases (89.2%) were culture-positive. Among the culture-positive cases, 34 (68%) were gram-positive and 22 (44%) were gram-negative. The most frequent gram-positive bacteria were E. faecalis (9; 18% of culture-positive cases), and the most frequent gram-negative organisms were Klebsiella pneumoniae (5; 10%). Levofloxacin was the most commonly used prophylactic antibiotic (23; 15.33%), followed by acyclovir (1610.7%) and fluconazole in 15 patients (10%). Amikacin was the most popular empiric therapy, followed by piperacillin/tazobactam (74; 49.3%), ceftazidime (70; 46.7%), and vancomycin (63; 42%). One-third of E. faecalis isolates were resistant to ampicillin. Approximately two-thirds of Klebsiella pneumoniae isolates were resistant to piperacillin/tazobactam and ceftazidime. Amikacin resistance was proven in 20% of isolates., Conclusions: The majority of patients suffered from hematologic malignancies. Less than half of the patients had infections, and the majority were bacterial. Gram-positive bacteria comprised two-thirds of cases. Therefore, empiric therapy was appropriate and in accordance with the antibiogram of the isolated bacteria., (© 2023. The Author(s).)

Background and objectives : Patients admitted to the intensive care unit (ICU) have an increased risk of hospital-acquired infection (HAI). A diagnosis of cancer alone increases the risk of sepsis three-five-fold, which further increases the risk of nosocomial infection, subsequently deteriorates results, and leads to high mortality. In this study, we aimed to assess the mortality rate among hematologic oncologic patients with suspected infection who were subsequently admitted to the ICU and the predictive factors that are associated with high ICU mortality. Materials and Methods : This retrospective cohort study was conducted in the hematological oncology critical care unit of a tertiary care hospital between November 2017 and February 2021. We analyzed anonymized medical records of hospitalized hematologic oncologic patients who were suspected or proven to have infection in the hematology-oncology department and were subsequently transferred to the ICU. Results : Both shorter hospitalization and shorter ICU stay length were observed in survivors [9.2 (7.7-10.4)] vs. non-survivors [10 (9.1-12.9), p = 0.004]. Sepsis had the highest hazard ratio (7.38) among all other factors, as patients with sepsis had higher mortality rates (98% among ICU non-survivors and 57% among ICU survivors) than those who had febrile neutropenia. Conclusions : The overall ICU mortality in patients with hematologic malignancies was 66%. Sepsis had the highest hazard ratio among all other predictive factors, as patients with sepsis had higher mortality rates than those who had febrile neutropenia. Chronic hepatitis (HBV and HCV) was significantly associated with higher ICU mortality.

Background: Chemotherapy-induced febrile neutropenia (FN) is one of the more common oncological emergencies. Despite evidence in the oncology literature suggesting that low-risk cases of FN can be managed safely at home, most patients with FN who present to the emergency department (ED) are admitted. FN risk stratification methods, such as Multinational Association for Supportive Care in Cancer (MASCC) and Clinical Index of Stable Febrile Neutropenia (CISNE) scores, may be useful when considering patient disposition. We sought to address whether the existing body of literature is adequate to support the use of these methods when treating patients with FN in the ED., Methods: A PubMed search from January 1, 2016 to March 19, 2021 was performed using the following search strategy: "febrile neutropenia" OR (fever AND neutropenia)) AND (emerg* OR outpatient) AND (admit OR admission OR hospitalization). General review articles and case reports were omitted. Each of the articles selected underwent a structured review., Results: The search yielded 371 articles, which were independently screened for relevance by two authors, and 23 articles were selected for inclusion. MASCC score was used in 10 of the identified studies and each of these studies concluded that the score was useful in the ED. Most of the identified studies found that CISNE score had a higher sensitivity than MASCC score (96.7% vs. 32.9%, respectively), but a lower specificity (22.2% vs. 89.5%)., Conclusions: FN risk stratifications tools, such as MASCC and CISNE scores, are supported by the existing literature and may be included as part of the decision-making process when considering patient disposition., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Febrile neutropenia is a prevalent oncologic complication. Initiating rapid treatment with empirical antimicrobials in febrile neutropenia patients reduces mortality due to infections., Objectives: The study aims to evaluate antimicrobial utilization among FN patients in Lebanon in terms of drug choice, dose, and duration of the treatment. This is a retrospective, multicenter, observational study conducted at three different Lebanese university hospitals (in which the Infectious Diseases Society of America (IDSA) guidelines are adopted), between February 2014 and May 2017., Methods: Adult cancer patients aged 18 years and older with febrile neutropenia were included in the study. Using the IDSA guidelines as a reference, patients were assessed whether they received the antimicrobial regimen inconsistent with the IDSA reference or not. Statistical analysis was performed using the Statistical Package for the Social Science software (SPSS version 22.0). The adherence to guidelines for the indication and doses of antibiotics and anti-fungal in patients with febrile neutropenia., Results: A total of 124 patients with a mean age of 54.43 ± 17.86 years were enrolled in the study. Leukemia (29.7%) was the most prevalent cancer and the most common infection was sepsis (20.2%). Combination antibiotic lactams are the most prescribed antibiotics (86.8%). Only 94 (86.23%) patients were given the antibiotic therapy appropriate for choice, dose, and duration. Empirical antifungal therapy was initiated in 63.7% of the patients and fluconazole was the most used antifungal (36.3%). In contrast to antibiotics, the majority of antifungal choices were not selected according to the recommendations and they were considered inappropriate for doses and the required treatment duration as proposed by (IDSA). Fifty-eight percent of patients received antivirals, even though it is not recommended as empirical treatment., Conclusion: In conclusion, this study reveals a non-consistent antimicrobial utilization practice at the involved sites concerning FN treatment. Inappropriateness was encountered in drug selection, dose, and duration of treatment with antifungals and antivirals., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Reliable and rapid medical diagnosis is the cornerstone for improving the survival rate and quality of life of cancer patients. The problem of clinical decision-making pertaining to the management of patients with hematologic cancer is multifaceted and intricate due to the risk of therapy-induced myelosuppression, multiple infections, and febrile neutropenia (FN). Myelosuppression due to treatment increases the risk of sepsis and mortality in hematological cancer patients with febrile neutropenia. A high prevalence of multidrug-resistant organisms is also noted in such patients, which implies that these patients are left with limited or no-treatment options amidst severe health complications. Hence, early screening of patients for such organisms in their bodies is vital to enable hospital preparedness, curtail the spread to other weak patients in hospitals, and limit community outbreaks. Even though predictive models for sepsis and mortality exist, no model has been suggested for the prediction of multidrug-resistant organisms in hematological cancer patients with febrile neutropenia. Hence, for predicting three critical clinical complications, such as sepsis, the presence of multidrug-resistant organisms, and mortality, from the data available from medical records, we used 1166 febrile neutropenia episodes reported in 513 patients. The XGboost algorithm is suggested from 10-fold cross-validation on 6 candidate models. Other highlights are (1) a novel set of easily available features for the prediction of the aforementioned clinical complications and (2) the use of data augmentation methods and model-scoring-based hyperparameter tuning to address the problem of class disproportionality, a common challenge in medical datasets and often the reason behind poor event prediction rate of various predictive models reported so far. The proposed model depicts improved recall and AUC (area under the curve) for sepsis (recall = 98%, AUC = 0.85), multidrug-resistant organism (recall = 96%, AUC = 0.91), and mortality (recall = 86%, AUC = 0.88) prediction. Our results encourage the need to popularize artificial intelligence-based devices to support clinical decision-making.

Endoscopic biliary drainage is the recommended 1st-line treatment for malignant biliary obstruction. Although a high incidence of febrile neutropenia has been reported in patients treated with FOLFIRINOX and a biliary stent, it remains unknown whether the biliary stent contributes to patient survival. Thus, we aimed to elucidate the effects of biliary stents on the survival of patients with advanced pancreatic cancer treated with modified FOLFIRINOX (mFFX). We retrospectively reviewed medical charts of patients with advanced pancreatic cancer treated with mFFX between January 2014 and April 2020. We compared the overall survival (OS) of patients with and without biliary stent during mFFX treatment and examined the independent effect on mortality using propensity score matching. Overall, we included 89 patients (stent group, n = 24; non-stent group, n = 65). The proportion of patients with pancreatic head cancer was significantly higher in the stent group than in the non-stent group (P < .01). Stratification analysis in patients with pancreatic head cancer revealed that OS was significantly shorter in the stent group than in the non-stent group (P = .03). After propensity score matching, 19 pairs of patients in each group were analyzed. The stent group revealed a significantly shorter survival than the non-stent group (median OS, 10.3 vs 24.9 months; P < .01). The incidences of febrile neutropenia (P = .01) and biliary tract-related events that required biliary stenting or stent replacement (P < .01) were significantly higher in the stent group than in the non-stent group. Stent insertion was an independent risk factor for overall mortality. Biliary stents may reduce survival in patients with advanced pancreatic cancer. The rate of febrile neutropenia was higher in the stent group than in the non-stent group. There is a need to assess the patient's condition with discretion and develop a treatment strategy with short prognosis in mind after stent insertion., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Febrile neutropenia (FN) is one of the major complications with high mortality rates in cancer patients undergoing chemotherapy. The Multinational Association for Supportive Care in Cancer (MASCC) risk-index score has limited applicability for routine use in the emergency department (ED). This study aimed to develop simplified new nomograms that can predict 28-day mortality and the development of serious medical complications in patients with FN by using a combination of complete blood count (CBC) parameters with quick Sequential Organ Failure Assessment (qSOFA)., Methods: In this retrospective observational study, various models comprising qSOFA score and individual CBC parameters (red cell distribution width, delta neutrophil index, mean platelet volume (MPV)) were evaluated for association with outcomes by a multivariate logistic analysis. Subsequently, nomograms were developed for outcome prediction. The primary outcome was mortality at 28 days from ED presentation; the secondary outcome was the development of serious medical complications., Results: A total of 378 patients were included. Among the CBC parameters, only MPV was significantly associated with 28-day mortality and serious medical complications in patients with FN. The nomogram developed to predict 28-day mortality and serious medical complications showed good discrimination with area under the receiver-operating characteristic curve (AUC) values of 0.729 and 0.862 (95% CI, 0.780-0.943), respectively, which were not different from those of the MASCC score (0.814, 95% CI, 0.705-0.922; p  = .07 and 0.921, 95% CI, 0.863-0.979; p  = .11, respectively) in the validation set. The calibration of both nomograms demonstrated good agreement in the validation set., Conclusion: In this study, a novel prognostic nomogram using qSOFA score and MPV to identify cancer patients with FN with high risk of 28-day mortality and serious medical complications was verified and validated. Prompt management of fatal complications of FN can be possible through early prediction of poor outcomes with these new nomograms.KEY MESSAGESAmong the evaluated CBC parameters, only mean platelet volume was associated with 28-day mortality and serious medical complications in cancer patients with febrile neutropenia.A novel and rapid prognostic nomogram was developed using quick Sequential Organ Failure Assessment score and mean platelet volume to identify cancer patients with febrile neutropenia having high risk of 28-day mortality and serious medical complications.The nomogram developed to predict 28-day mortality and serious medical complications in patients with febrile neutropenia showed good discrimination and provides rapid patient evaluation that is especially applicable in the emergency department.

Introduction Invasive fungal infections have been attracting attention as significant fatal complications in patients with febrile neutropenia (FN) who undergo intensive chemotherapy or hematopoietic stem cell transplantation to treat hematological malignancies. Although clinical trials are already underway in other countries, evidence supporting the use of caspofungin (CAS) in FN patients in Japan is still insufficient. Methods A retrospective study of patients treated with CAS for FN associated with hematological diseases between April 2015 and March 2018 was conducted to determine the treatment efficacy and safety. The study was conducted as a multicenter collaboration, and the data of 52 patients who met all of the inclusion criteria were analyzed. A five-composite-endpoint method was used, and the treatment was judged to be effective when all five endpoints (defervescence during neutropenia; no breakthrough fungal infections; resolution of baseline fungal infections; a survival for seven days or more after the completion of therapy; and no discontinuation of therapy due to side effects or invalidity) were met. Results The efficacy rate was 53.8% (28/52), which is close to the average reported efficacy rate. Adverse events included liver dysfunction and electrolyte abnormalities, but no renal dysfunction or serious events were seen. Conclusion These results suggest that the use of CAS in FN patients with hematological diseases is effective and well-tolerated, and we believe that the use of CAS could become a significant treatment in Japan.

We report a case of brucellosis-induced severe neutropenia in a 2-year-old girl who presented with a 2-week history of fever. On clinical examination, the patient was febrile with mild aphthous stomatitis. However, her general condition was stable, and systemic examination did not show involvement of any other organ. Laboratory test results revealed severe neutropenia, mild anemia, and an elevated serum C-reactive protein level. Flow cytometry of peripheral blood leukocytes revealed no malignancy, and blood film morphology was unremarkable except for mild microcytosis and hypochromia. Antineutrophil antibody and Coombs test results were negative. We administered intravenous cefuroxime; however, therapy was switched to meropenem plus clarithromycin because fever persisted for 5 days, despite treatment. On the 10th day after admission, Brucella serology tests showed positive results, and trimethoprim-sulfamethoxazole plus rifampicin therapy was prescribed for 8 weeks. The fever defervesced, and the child was discharged in a good state of health. Neutropenia persisted for several months but gradually resolved. Neutropenia, defined as an absolute neutrophil count (ANC) < 1.5 cells × 10 9 /L beyond the first year of life, is a benign transient condition associated with an intercurrent infection (usually viral illnesses or infections) in immunocompetent children. However, severe neutropenia (ANC < 0.5 × 10 9 /L) associated with fever necessitates hospitalization and administration of broad-spectrum antibiotics to avoid the high risk of sepsis, particularly in children. Brucellosis is rarely associated with hematologic abnormalities such as neutropenia. Early diagnosis of hematologic complications of brucellosis is essential for prompt initiation of specific and aggressive treatment., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

We present a case series of three febrile episodes in neutropenic pediatric cancer patients who wore a Food and Drug Administration approved high-frequency temperature monitoring (HFTM) wearable device (WD) at home. The WD detected fever events when temperature monitoring by thermometer did not detect fever or was not feasible to perform. Two of the episodes were associated with bloodstream infections and the WD detected fevers 5 and 12 h prior to fevers detected by thermometer, triggering earlier medical evaluation and more prompt administration of antibiotics. These observations provide a basis for future investigation of home-based HFTM to improve infection-related outcomes in pediatric oncology., (© 2022 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Despite diagnostic advances in microbiology, the etiology of neutropenic fever remains elusive in most cases. In this study, we evaluated the utility of a metagenomic shotgun sequencing based assay for detection of bacteria and viruses in blood samples of patients with febrile neutropenia. We prospectively enrolled 20 acute leukemia patients and obtained blood from these patients at three time points: 1) anytime from onset of neutropenia until before development of neutropenic fever, 2) within 24 hours of onset of neutropenic fever, 3) 5-7 days after onset of neutropenic fever. Blood samples underwent sample preparation, sequencing and analysis using the iDTECT® Dx Blood v1® platform (PathoQuest, Paris, France). Clinically relevant viruses or bacteria were detected in three cases each by metagenomic shotgun sequencing and blood cultures, albeit with no concordance between the two. Further optimization of sample preparation methods and sequencing platforms is needed before widespread adoption of this technology into clinical practice., Competing Interests: M.M., C.R., S.C. and P.B. are employed by PathoQuest and own shares of PathoQuest. A.F. is a former employee of PathoQuest. M.R.S. reports receiving funds from TYRX Inc. and Medtronic for prior research unrelated to this study administered according to a sponsored research agreement between Mayo Clinic and study sponsor that prospectively defined the scope of the research effort and corresponding budget; and honoraria/consulting fees from Medtronic Inc. and Aziyo Biologics, Inc. Research Grant: Medtronic (significant - $40K), Honoraria: Medtronic (significant $20K), and Aziyo Biologics (modest $5K). M.M.P. serves on the Advisory Board for Kura Oncology. R.P reports grants from ContraFect, TenNor Therapeutics Limited, and BioFire. R.P. is or has been a consultant to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Torus Biosystems, Day Zero Diagnostics, Mammoth Biosciences, CARB-X, and Qvella; monies are paid to Mayo Clinic. R.P. is also a consultant to Netflix. In addition, R.P. has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued. R.P. receives travel reimbursement from ASM and IDSA and an editor’s stipend from IDSA, and honoraria from the NBME, Up-to-Date and the Infectious Diseases Board Review Course. All other authors report no potential conflicts of interest. this does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: Chest and sinus CT imaging among cancer patients undergoing chemotherapy and bone marrow transplant in the setting of neutropenic fever is not uncommon, yet the utility of routine imaging surveillance remains unclear. We aim to compare the rates of acute infection detected on CT chest and CT sinus exams performed in this clinical setting., Methods: Reports of 1059 consecutive CT chest and sinus examinations for the clinical indication of neutropenic fever on 262 patients performed between January through June 2017 were retrospectively reviewed. Infection as reported was characterized as acute or worsening, improving, stable, indeterminate or negative. Results were tabulated and Pearson's chi-square test was used for comparison analysis., Results: Absence of infection on CT sinus was significantly higher than CT chest (86.1% vs. 58.5%; P<0.001). Conversely, CT chest had significantly higher incidence of acute or worsening infection than CT sinus (28.7% vs. 11.6%; P<0.001). CT chest also showed significantly higher incidence of improving infection compared to CT sinus (6.2% vs. 1.1%; P<0.001). There was no significant difference between incidence of stable infection on CT chest and CT sinus (1.1% vs. 0.2%; P=0.059). Infection was indeterminate in 5.5% of CT chest vs. 1% on CT sinus (P<0.001)., Conclusions: CT chest showed significantly higher diagnostic yield for acute infection than CT sinus, suggesting that sinusitis is less likely to be the source of fever than chest infections in febrile neutropenic patients. The majority of CT studies showed absence of infection, raising the question of the overall utility of routine surveillance CT imaging among this subset of patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: In 2017, international guidelines proposed new management of febrile neutropenia in children with cancer, adapted to the risk of severe infection by clinical decision rules (CDRs). Until now, none of the proposed CDRs has performed well enough in high-income countries for use in clinical practice. Our study aimed to build and validate a new CDR (DISCERN-FN) to predict the risk of severe infection in children with febrile neutropenia., Methods: We did two prospective studies. First, a prospective derivation study included all episodes of febrile neutropenia in children (aged <18 years) with a cancer diagnosis and receiving treatment for it who were admitted for an episode of febrile neutropenia, excluding patients already treated with antibiotics for this episode, febrile neutropenia not induced by chemotherapy, those receiving palliative care, and those with a stem cell allograft for less than 1 year, from April 1, 2007, to Dec 31, 2011 from two paediatric cancer centres in France. We collected the children's medical history, and clinical and laboratory data, and analysed their associations with severe infection. Sipina software was used to derive the CDR as a decision tree. Second, a prospective, national, external validation study was done in 23 centres from Jan 1, 2012, to May 31, 2016. The primary outcome was severe infection, defined by bacteraemia, a positive bacterial culture from a usually sterile site, a local infection with a high potential for extension, or an invasive fungal infection. The CDR was applied a posteriori to all episodes to evaluate its sensitivity, specificity, and negative likelihood ratio., Findings: The derivation set included 539 febrile neutropenia episodes (270 episodes in patients with blood cancer [median age 7·5 years, IQR 3·7-11·2; 158 (59 %) boys and 112 (41%) girls] and 269 in patients with solid tumours [median age 6·6 years, IQR 2·9-14·2; 140 (52 %) boys and 129 (48%) girls]). Significant variables introduced into the decision tree were cancer type (solid tumour vs blood cancer), age, high-risk chemotherapy, level of fever, C-reactive protein concentration (at 24-48 h after admission), and leucocyte and platelet counts and procalcitonin (at admission and at 24-48 h after admission). For the derivation set, the CDR sensitivity was 98% (95% CI 93-100), its specificity 56% (51-61), and the negative likelihood ratio 0·04 (0·01-0·15). 1806 febrile neutropenia episodes were analysed in the validation set (mean age 8·1 years [SD 4·8], 1014 (56%) boys and 792 (44%) girls), of which 332 (18%, 95% CI 17-20) were linked with severe infection. For the validation set, the CDR had a sensitivity of 95% (95% CI 91-97), a specificity of 38% (36-41), and a negative likelihood ratio of 0·13 (0·08-0·21). Our CDR reduced the risk of severe infection to a post-test probability of 0·8% (95% CI 0·2-2·9) in the derivation set and 2·4% (1·5-3·9) in the validation set. The validation study is registered at ClinicalTrials.gov, NCT03434795., Interpretation: The use of our CDR substantially reduced the risk of severe infection after testing in both the derivation and validation groups, which suggests that this CDR would improve clinical practice enough to be introduced in appropriate settings., Funding: Ligue Nationale Contre le Cancer., Competing Interests: Declaration of interests AM declares paid appointments for lectures, consultancy, or advice, and invitations to European Society for Paediatric Infectious Diseases meetings from GlaxoSmithKline and Pfizer. FD received expenses from Sanofi-Pasteur and Takeda for scientific experts' meetings in 2020 and 2021. MD, FG, HB, AT, HS-B, AL, SA, SP, ST-D, IP, LM, CPi, CPa, LB, ET, DP, PB, PSc, CG, PSi, CD, HP, MLM, CPl, CV, GP, and AD declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Acute myeloid leukemia (AML) often requires long-term intensive chemotherapy for its cure. During chemotherapy, the patient always experiences neutropenia with readings below 500 cells/μL; this is often accompanied by pyrexia with a temperature of more than 101°F. This combination of neutropenia and fever is called febrile neutropenia (FN). A tool to sum up the daily severity of a patient's neutropenia, the "D-index," has been validated in some specific clinical settings. In this study, we examined whether the D-index is a useful predictor of the onset of FN. We recruited consecutive patients treated with induction and consolidation chemotherapy for newly diagnosed AML. We gathered all the FN events and their clinical background data retrospectively. Patients' background, such as pre-existing conditions and disease status before the treatment, were analyzed using multivariate methods. All FN events during chemotherapy were evaluated for infection focus and causative organism. A total cohort of 51 cases (25 women, 26 men; median age 51 years, range 18-74) was analyzed. They displayed 171 neutropenic events (115 FN and 56 afebrile episodes) during chemotherapy, and complete neutropenic events were used in this study. Sensitivity and specificity analysis showed that the most useful cutoff value to predict the onset of FN was a cumulative D-index at day 11 (c-D11-index) of 718. The cumulative incidence of FN during chemotherapy was significantly higher in the group with c-D11-index ≥710 (80%) than in the group with c-D11-index <710 (39%) (P < 0.0001). Through multivariate analysis, the presence of diabetes mellitus and the c-D11-index were extracted as contributing factors to the onset of FN (P = 0.0087 and 0.0002, respectively). In conclusion, we can predict that AML patients receiving chemotherapy will experience the complication of FN when the c-D-index at day 11 is >710, with an odds ratio of 2.1., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Febrile neutropenia (FN) is the most frequent hemato-oncological emergency, with high morbidi ty and mortality in pediatrics. The objective of the study was the microbiological characterization and antimicrobial susceptibility of infections associated with FN in pediatric hemato-oncological patients., Patients and Method: Retrospective cohort study with patients aged between 1 month and 18 years, with onco-hematological pathology according to ICD-10 codes, hospitalized in a tertiary healthcare center in Bucaramanga, Colombia. Based on the medical records of the period 2013-2017, the episodes of FN were identified, and the isolated microorganisms and their susceptibility pattern were described. Biochemical identification and antimicrobial susceptibility testing were performed with the Dade Behring Microscan« automated system. The resistant microorganism classification was performed based on the Minimum Inhibitory Concentration (MIC) and the interpretation of the laboratory according to the cut-off points of the Clinical and Laboratory Standards Institute recommendations., Results: Of 130 patients, 14.7% of the cultures obtained were positive. Bloods tream infection was observed in 17.5% of the episodes. The isolated microorganisms were mainly Gram-negative bacteria (75.8%). Enterobacteriaceae (EB) were the most frequent, led by Klebsiella pneumoniae, Escherichia coli, followed by Pseudomonas aeruginosa and coagulase-negative Staphylo cocci. Of the EBs, 40.5% showed resistance to Piperacillin/Tazobactam, 33.3% to Cefepime, and 8.2% to Meropenem. According to the antimicrobial resistance pattern, it was observed that 16.4% of the positive EB cultures had an extended-spectrum beta-lactamase pattern and 5% a pattern suggestive of carbapenemases. All Gram-positive cocci were sensitive to Vancomycin., Conclusion: In the studied patients, the predominant pathogenic microorganisms were Gram-negative ones with resistance in dices similar to those of developing countries.

The study aim was to determine the benefit of the measurement of serum caspase-cleaved cytokeratin-18 (CK-18) fragment as a prognostic marker of febrile neutropenia (FN) in hematological patients. The study population consisted of 86 consecutive patients with FN who received intensive chemotherapy for hematological malignancy at the adult hematology ward of Kuopio University Hospital. Twenty-three patients (27%) had acute myeloid leukemia, and 63 patients (73%) were autologous stem cell transplant recipients. Serum caspase-cleaved CK-18 fragment M30, C-reactive protein (CRP) and procalcitonin (PCT) were measured at the onset of FN (d0), on day 1 (d1), and on day 2 (d2). Eight patients (9%) developed severe sepsis, including three patients with septic shock. Eighteen patients (21%) had a blood culture-positive infection. Serum CK-18 fragment peaked on the first day after fever onset in patients with severe sepsis. Higher CK-18 level was associated with severe sepsis, intensive care unit treatment, and fatal outcome, but not with blood culture positivity. In ROC curve analysis, d1 serum CK-18 fragment predicted severe sepsis with an area under the curve (AUC) of 0.767, CRP with an AUC of 0.764, and PCT with an AUC of 0.731. On d2, the best predictive capacity was observed for CRP with an AUC of 0.832. The optimal cutoff of caspase-cleaved CK-18 fragment M30 for predicting severe sepsis was 205 U/L on d1. In hematological patients, serum CK-18 fragment was found to be a potential prognostic marker of severe sepsis at early stages of FN., (© 2021. The Author(s).)

Objectives: There is no specific recommendation about antimicrobial treatment length for documented infections in chemotherapy induced febrile neutropenia (FN). Practices have changed along time in our center regarding length of antibiotic treatment. The aim of this study was to compare long versus short antibiotic course for bloodstream infection (BSI) treatment in acute myeloid leukemia (AML) patients during FN., Methods: This monocentric retrospective comparative study included all consecutive BSI episodes among AML patients with FN for 3 years (2017-2019). Episodes were classified regarding the length of antibiotic treatment, considered as short course if the treatment lasted ≤ 7 days, except for nonfermenting bacteria and Staphylococcus aureus or lugdunensis for which the threshold was ≤ 10 days and ≤ 14 days, respectively. The primary outcome was the number of BSI relapses in both groups within 30 days of antibiotic discontinuation., Results: Among 71 AML patients, 104 BSI episodes were included; 48 (46%) received short course treatment. Only 8 (7.6%) BSI episodes relapsed within 30 days of antibiotic discontinuation, 5 having received short course treatment. No association was found between risk of relapse and short course of antibiotic treatment (p = 0.37). The only risk factor significantly associated with BSI relapse was neutropenia duration (p = 0.005)., Conclusion: Antibiotic short course seemed as effective as prolonged treatment for BSI in AML patients during FN, with very few relapses at day 30. These encouraging findings should be confirmed through prospective studies., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Earlier initial antibiotic treatment for febrile neutropenia is associated with improved clinical outcomes. This study was conducted to evaluate the association of an emergency department (ED) intervention protocol with time to initial antibiotic treatment for febrile neutropenia patients., Methods: We conducted a cohort study of adult ED febrile neutropenia patients before and after implementation of an intervention protocol. Analyses included comparison of means and medians, Kaplan-Meier estimates, multivariable regression analyses, interrupted time-series analyses, and causal mediation analyses. The intervention protocol included specific triage and process-of-care actions to reduce the primary outcome of time to initial antibiotic treatment., Results: There were 69 patients in the 12-month preintervention period and 52 patients in the 8-month postintervention period. The mean (±SD) times to initial antibiotics were 197.6 (±85.4) min for the preintervention group and 97.7 (±51.0) min for the postintervention group (difference of 99.9 min with 95% confidence interval [CI] = 73.5 to 126.4, p < 0.001). The patients' probability for receiving initial antibiotics within 90 min was severalfold greater (adjusted risk ratio = 10.31, 95% CI = 4.99 to 21.30, p < 0.001) for the postintervention group versus preintervention group. ED length of stay, hospital length of stay, 30-day readmissions, and 30-day all-cause mortality were not different between the study groups. The association of the intervention protocol with time to initial antibiotics appeared to be mediated through times to treatment room placement, report of absolute neutrophil count, and initial antibiotic order., Conclusions: The intervention protocol was associated with a significant reduction in time to initial antibiotics for ED patients with febrile neutropenia. This association appears to be facilitated through specific intermediate process-of-care variables. A larger multicenter study is needed to assess the potential effects of an ED febrile neutropenia protocol on patient-centered clinical outcomes and resource utilization., (© 2021 Society for Academic Emergency Medicine.)

Objective: Febrile neutropenia (FN) represents a life-threatening complication in hematological malignancies. We aimed to analyze the utility of soluble vascular cell adhesion molecule 1 (sVCAM-1), intercellular adhesion molecule 1 (sICAM-1), vascular endothelial growth factor (VEGF) levels compared with C-reactive protein (CRP) and procalcitonin (PCT) during febrile neutropenia episodes of pediatric patients with leukemia., Methods: Two plasma samples, on day 0 (initial of episode) and day 3 (48-72 h after episode), for VCAM-1, ICAM-1 and VEGF, CRP and PCT were prospectively collected concomitantly during each febrile neutropenic episode between December 2016 and December 2017. The primary outcome was bacteremia and the secondary outcome was intensive care unit (ICU) admission., Results: Twenty-two (28.6%) acute lymphoblastic lymphoma (ALL), seventeen (22.1%) acute myeloblastic lymphoma (AML) patients and thirty-eight (49.3%) control patients with no known underlying disease or fever were included in this study. Of the 39 patients; 16 (41%) had bacteremia. Mean serum sVCAM1 and sICAM1 levels were significantly higher in control group, compared to FN patients (p < 0.001). Mean serum sVCAM2 level was significantly higher in FN patients with bacteremia compared to FN patients without bacteremia (144.97 ± 70.35 pg/mL vs 85.45 ± 53.76 pg/mL, p = 0.022). Mean sVCAM1 and 2 levels were higher in FN patients with ICU admission. In this study, we found that sVCAM-1 and VEGF, when combined to CRP and PCT, could predict gram-negative bacteremia in FN episodes of pediatric hematological malignancy., Conclusion: Serum endothelial adhesion molecules, excluding sVCAM-1, cannot predict bacteremia and ICU admission alone in FN patients; but may be associated with clinical outcome when used with PCT and CRP., (Copyright © 2021. Published by Elsevier Ltd.)

Patients treated for adult T-Cell leukemia/lymphoma (ATL) have a poor prognosis and are prone to infectious complications which are poorly described. As the French reference center for ATL, we retrospectively analyzed 47 consecutive ATL (acute, n = 23; lymphoma, n = 14; chronic, n = 8; smoldering, n = 2) patients between 2006 and 2016 (median age 51 years, 96% Afro-Caribbean origin). The 3-year overall survival (OS) was 15.8%, 11.3%, and 85.7% for acute, lymphoma, and indolent (chronic and smoldering) forms respectively. Among aggressive subtypes, 20 patients received, as frontline therapy, high dose of zidovudine and interferon alfa (AZT-IFN⍺) resulting in an overall response rate (ORR) of 39% (complete response [CR] 33%) and 17 chemotherapy resulting of an ORR of 59% (CR 50%). Ninety-five infections occurred in 38 patients, most of whom had an acute subtype (n = 73/95; 77%). During their follow-up, patients receiving frontline chemotherapy or frontline AZT-IFNα developed infections in 74% (n = 14/19) and 89% (n = 24/27) of the cases respectively. Sixty-four (67%) of infections were microbiologically documented. Among them, invasive fungal infections (IFI, n = 11) included 2 Pneumocystis jirovecii pneumonia, 5 invasive aspergillosis, and 4 yeast fungemia. IFI exclusively occurred in patients with acute subtype mostly exposed to AZT-IFNα (n = 10/11) and experiencing prolonged (> 10 days) grade 4 neutropenia. Patients with aggressive subtype experiencing IFI had a lower OS than those who did not (median OS 5.4 months versus 18.4 months, p = 0.0048). ATL patients have a poor prognosis even in the modern era. Moreover, the high rate of infections impacts their management especially those exposed to AZT-IFNα., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To evaluate ceftazidime/avibactam (C/A) and ceftolozane/tazobactam (C/T) use in haematological patients with febrile neutropenia receiving high-dose chemotherapy and haematopoietic stem cell transplantation (HSCT)., Methods: A retrospective study was conducted to assess C/A and C/T efficacy through infection-related mortality (IRM) and bacteraemia clearance for carbapenem-resistant Gram-negative bacteria (CR-GNB) pre-engraftment blood-stream infections (PE-BSIs) between January-December 2018., Results: Seventy patients underwent allogeneic HSCT: C/A and C/T were dispensed in 13% and 3%, respectively. C/A was administered as definite therapy for carbapenem-resistant Klebsiella pneumoniae (CR-Kp) PE-BSI in four carriers (bacteraemia clearance in 5 days), empirical therapy for a clinically documented infection in two patients (one carrier with pneumonia and one non-carrier with shock) and empirical therapy for fever of unknown origin in three CR-Kp carriers. C/T was administered as definite therapy for carbapenem-resistant Pseudomonas aeruginosa (CR-Pa) intra-abdominal infection in one carrier and empirical therapy for a clinically documented infection (pneumonia) in one non-carrier. Among patients without PE-BSIs and with Gram-positive bacteria PE-BSIs, IRM was 0% at +30 days; conversely, it was 30% in GNB PE-BSIs (two CR-Kp and one CR-Pa C/T-resistant). Thirty-nine patients underwent autologous HSCT: C/A and C/T were administered, respectively, as definite therapy for CR-Kp PE-BSI in one carrier (bacteraemia clearance in 3 days) and for Pa PE-BSI (three strains, one CR-Pa) in one non-carrier (bacteraemia clearance in 2 days). Overall, IRM at +30 days was 0%., Conclusions: Monitoring multidrug-resistant GNB colonisation enabled selection of carriers who benefit from prompt administration of new antibiotics, improving HSCT outcomes in a high-risk population. C/A and C/T were effective in bacteraemia clearance; unfortunately, multidrug-resistant GNB PE-BSIs were still a burden to IRM., (Copyright © 2021 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Background: Early diagnosis of sepsis in children with febrile neutropenia remains difficult owing to non-specific clinical and laboratory signs of infection. There is a need to assess the utility of inflammatory markers in clinical risk assessment for their ability to discriminate between low-risk and high-risk neutropenic patients since presently there is insufficient data to recommend their routine use., Methods: This is a prospective study of children on therapy admitted with febrile neutropenia and sampled for serum procalcitonin (PCT), interleukin-6 (IL-6), and interleukin-8 (IL-8) at admission. The febrile neutropenia episodes were categorized into two groups - Group I: no focus of infection and Group II: clinically/microbiologically documented infection. Statistical analyses for comparison were performed using Z-test and receiver operating curves at various cut-off levels., Results: A total of 46 episodes of febrile neutropenia in 33 children were analyzed. In total, 76% were categorized as group I and 24% as group II. The mean value of PCT in group II was higher (28.07 ng/mL) than group I (1.03 ng/mL) though there was no significant statistical difference. At a cut-off level of 2 ng/mL for PCT, sensitivity of 63%, specificity of 91%, positive predictive values (PPV) of 70%, and negative predictive value (NPV) of 88% were observed. There was no significant difference in the IL-6 and IL-8 levels between both the groups. However, at an optimal cut-off value of 50 pg/mL, IL-6 had an NPV of 80% and at a cut-off level of 130 pg/mL, IL-8 had an NPV of 73%, however, with low sensitivity and specificity., Conclusion: IL-6, IL-8, and PCT can be utilized to define a group of patients with a low risk of sepsis in view of their favorable NPV. The use of these biomarkers together can facilitate early discharge from the hospital, and the use of oral antimicrobial therapy, in turn, reducing the cost of supportive therapy in a developing country., Competing Interests: None

Introduction: Patients with hematological and advanced solid malignancies have acquired immune dysfunction, often exacerbated by treatment, posing a significant risk for the development of infections. This review evaluates the utility of current clinical and treatment guidelines, in the setting of management of infections in cancer patients., Areas Covered: These include causes of infection in cancer patients, management of patients with high-risk and low-risk febrile neutropenia, management of low-risk patients in an outpatient setting, the role of granulocyte colony-stimulating factor (G-CSF) in the prevention and treatment of neutropenia-related infections, management of lung infections in various clinical settings, and emerging challenges surrounding the risk of infection in cancer patients treated with novel treatments. The literature search was performed by accessing PubMed and other databases, focusing on published clinical trials of relevant anti-cancer agents and diseases, primarily covering the recent past, but also including several key studies published during the last decade and, somewhat earlier in a few cases., Expert Review: Notwithstanding the promise of gene therapy/gene editing in hematological malignancies and some types of solid cancers, innovations introduced in clinical practice include more discerning clinical management such as the generalized use of biosimilar formulations of G-CSF and the implementation of novel, innovative immunotherapies.

Although survival of children with hematological diseases and cancer has increased dramatically, febrile neutropenia (FN) is a frequently observed complication and is sometimes life-threatening in pediatric cancer patients. A prospective, randomized study was performed to clarify the usefulness of meropenem (MEPM) and piperacillin/tazobactam (PIPC/TAZ) for pediatric patients with FN. Ninety-nine patients with 394 episodes were randomly assigned to receive MEPM or PIPC/TAZ. MEPM was administered at 120 mg/kg/day as a 1-h drip infusion 3 times a day. On the other hand, PIPC/TAZ was administered at 360 mg/kg/day as a 1-h drip infusion 4 times a day. MEPM was effective in 69.5% of the 200 episodes, and PIPC/TAZ was effective in 77.2% of the 193 episodes. Compared with our previous study of MEPM 120 mg/kg/day as a 1-h drip infusion 3 times a day versus PIPC/TAZ 337.5 mg/kg/day as a 1-h drip infusion 3 times a day, the success rate of the MEPM group was not different. However, the success rate of the PIPC/TAZ group was higher than in the previous study (p = 0.001). In particular, the success rate in patients ≥ 15 years of age was improved in the PIPC/TAZ group of the present study compared with the previous study (p = 0.005).

Objective: Febrile neutropenia (FN) is a hematological emergency requiring urgent investigations to exclude infection and treatment with broad-spectrum antibiotics. Despite frequent blood cultures (BCs) being taking during episodes of FN, in the current literature BC positivity rates remain low in FN. This study aims to determine the BC positivity rate in FN hematology patients and determine the utility of collecting BCs beyond 24 h of commencing broad-spectrum antibiotics., Materials and Methods: BC results between 2014 and 2016 from all FN hematology patients were analyzed. Patient episodes of FN (PEFNs) were defined as a continuous period of FN where the interval between BC samples was a maximum of two days. In total from 2014 to 2016, 379 patients experienced 914 PEFNs and had 4267 BCs collected., Results: Overall BC positivity rates and BC-positive PEFN rates were 8.16% and 13.35%, respectively. Within the first 24 h, the positivity rate of the first BCs was 3.49%, while subsequent BC positivity within the first 24 h was 11.96%. BC positivity rates declined after 24 h to 2.18%., Conclusion: It is likely that BCs beyond 24 h of commencing broad-spectrum antibiotics will rarely identify relevant microorganisms. Not collecting BCs after 24 h would likely reduce laboratory test costs, patient discomfort, and iatrogenic anemia.

Background: Fever in neutropenia (FN) is a potentially life-threatening complication of chemotherapy in pediatric cancer patients. The current standard of care at most institutions is emergency hospitalization and empirical initiation of broad-spectrum antibiotic therapy., Methods: We analyzed in retrospect FN episodes with bacteremia in pediatric cancer patients in a single center cohort from 1993 to 2012. We assessed the distribution of pathogens, the in vitro antibiotic susceptibility patterns, and their trends over time., Results: From a total of 703 FN episodes reported, we assessed 134 FN episodes with bacteremia with 195 pathogens isolated in 102 patients. Gram-positive pathogens (124, 64%) were more common than Gram-negative (71, 36%). This proportion did not change over time (p = 0.26). Coagulase-negative staphylococci (64, 32%), viridans group streptococci (42, 22%), Escherichia coli (33, 17%), Klebsiella spp. (10, 5%) and Pseudomonas aeruginosa (nine, 5%) were the most common pathogens. Comparing the in vitro antibiotic susceptibility patterns, the antimicrobial activity of ceftriaxone plus amikacin (64%; 95%CI: 56%-72%), cefepime (64%; 95%CI 56%-72%), meropenem (64%; 95%CI 56%-72), and piperacillin/tazobactam (62%; 95%CI 54%-70%), respectively, did not differ significantly. The addition of vancomycin to those regimens would have increased significantly in vitro activity to 99% for ceftriaxone plus amikacin, cefepime, meropenem, and 96% for piperacillin/tazobactam (p < 0.001)., Conclusions: Over two decades, we detected a relative stable pathogen distribution and found no relevant trend in the antibiotic susceptibility patterns. Different recommended antibiotic regimens showed comparable in vitro antimicrobial activity., Competing Interests: The authors have declared that no competing interests exist.

The natural history of COVID-19 infection in children is still evolving as the pandemic unfolds. Few cases of severe and often fatal COVID-19 have been reported although the infection is mild in the large majority. Children with cancers are recognised as a high risk group for all infections. Since there aren't any definite treatment guidelines established in children with severe COVID, treatment is guided by adult recommendations which too are often not evidence based. We report the case of a 4-year-old girl with severe COVID-19 associated pneumonia who presented to us as febrile neutropenia. The use of convalescent plasma along with steroids and IVIG showed dramatic results in this child and she recovered without the need for any specific treatment. This is highlighted as one of the earliest cases that is reporting the use of convalescent plasma in a child; the first ever in a child with underlying malignancy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: Vancomycin-resistant enterococcus infections impact mortality in oncology patients. Given the low rate of vancomycin-resistant enterococcus bacteremia, low virulence of vancomycin-resistant enterococcus, and advent of rapid diagnostic systems, vancomycin-resistant enterococcus-directed empiric therapy in vancomycin-resistant enterococcus-colonized patients with neutropenic fever may be unnecessary, promoting increased antimicrobial resistance, drug-related toxicity, and cost., Methods: Vancomycin-resistant enterococcus-colonized adults admitted for hematopoietic stem cell transplantation or induction therapy for acute leukemia/myeloid sarcoma with neutropenic fever were stratified by vancomycin-resistant enterococcus bacteremia development and empiric vancomycin-resistant enterococcus-directed antimicrobial strategy for first neutropenic fever (Empiric Therapy vs. non-Empiric Therapy). Primary endpoints included vancomycin-resistant enterococcus-related, in-hospital, and 100-day mortality rates. Secondary outcomes included vancomycin-resistant enterococcus bacteremia incidence for first neutropenic fever and the entire hospitalization, length of stay, Clostridioides difficile infection rate, and duration and cost of vancomycin-resistant enterococcus-directed therapy., Results: During first neutropenic fever, 3 of 70 eligible patients (4%) developed vancomycin-resistant enterococcus bacteremia. Although all 3 (100%) were non-Empiric Therapy, no mortality (0%) occurred. Of 67 patients not developing vancomycin-resistant enterococcus bacteremia, 42 (63%) received Empiric Therapy and 25 (37%) non-Empiric Therapy. Empiric Therapy had significantly greater median duration (3 days vs. 0 days; P<.001) and cost ($1604 vs. $0; P<.001) of vancomycin-resistant enterococcus-directed therapy but demonstrated no significant differences in clinical outcomes., Conclusion: Available data suggest Empiric Therapy may offer no clinical benefit to this population, regardless of whether vancomycin-resistant enterococcus is identified in blood culture or no pathogen is found. Such an approach may only expose the majority of patients to unnecessary vancomycin-resistant enterococcus-directed therapy and drug-related toxicities while increasing institutional drug and monitoring costs. Even in the few patients developing vancomycin-resistant enterococcus bacteremia, waiting until the organism is identified in culture to start directed therapy likely makes no difference in mortality. This lack of benefit warrants consideration to potentially omit empiric vancomycin-resistant enterococcus-directed therapy in first neutropenic fever in many of these patients.