Diagnosis Of Febrile Neutropenia Research Articles

Exploring Coagulation and Fibrinolysis Activation As Mechanisms of Sepsis-Related Tissue Damage in Patients with Severe Neutropenia and Thrombocytopenia Secondary to Hematological Malignancies

Sepsis is a life-threatening end-organ dysfunction resulting from dysregulated host responses to infection with physiopathology not fully understood. Yet, it has been long recognized that platelets and neutrophil extracellular traps collaborate to promote secondary tissue damage. Interestingly, patients with hematological malignancies and febrile neutropenia (FN) secondary to chemotherapy, with neutrophils and platelet counts frequently around zero, develop sepsis and septic shock, raising questions about which mechanisms are involved. Here, we show that extracellular vesicles (EVs) and activation of the fibrinolytic system are two potential mediators of tissue damage in sepsis among patients with very low platelets and neutrophil counts. The study population consisted of patients with hematologic malignancies who underwent antineoplastic treatment and that presented neutrophil counts < 500/μl and temperature ≥ 37.5 °C. Sepsis was defined as an increase of at least 2 points in the Sequential Organ Failure Assessment (SOFA) score and septic shock was defined by the need for vasoactive drugs after adequate volume infusion. Samples were obtained after FN diagnosis, at sepsis onset, and 72 h thereafter. A control group of patients with hematological malignancies and chemotherapy-induced neutropenia without fever was also included. Forty-two subjects, both genders, aged from 21 to 71 years were included and categorized into 4 groups, referred to: FN (n=18), FN + sepsis (n=10), FN + sepsis 72h (n=9), and the control group (n=18). The clinical and laboratory characteristics of these groups are described in Table 1. We first evaluated whether the release of EVs could be associated with the development of sepsis in these patients. EVs were characterized and enumerated from platelet-poor plasma (PPP) obtained from all groups and then separated through high-speed centrifugation (30 min, 20,000 g, 4ºC). EVs were marked with CD146 and 144 for endothelial cells; CD66b for granulocytes; CD14 and CD68 for monocytes, CD41 for platelets, and CD142 for tissue factor (TF) expression. Lactadherin and calcein were used to identify EVs according to size and integrity. Samples were acquired in a flow cytometer, Cytoflex S, with 30 μL/min flow rate and calibration microbeads were used to identify EV of specific sizes (Rosetta). The main findings are shown in Table 2. The main results were an increase in monocyte-derived EVs in patients with FN after sepsis onset (FN + sepsis 72h), compared to all other groups (p=0.01). Moreover, the expression of TF + was higher in these EVs (FN + sepsis 72h) when compared to EVs obtained at sepsis onset (FN + sepsis): 0.50 (IQR 0.29 - 1.10) events/μL versus 0.28 (IQR 0.12 - 0.56) in FN + Sepsis (p=0.03). Additionally, an increase in endothelial (CD146 +) and granulocyte-derived EVs were observed at the same time-point compared to FN and the control group. Of note, monocyte-derived EVs counts were not correlated with monocyte cell counts (Rs= 0.03; p=0.94). Given that coagulation activation plays a role in the immunothrombotic cascade known to mediate tissue damage in sepsis, we also explored whether thrombin and plasmin generation were increased in these patients. Briefly, the assay used PPP and two independent fluorometric substrates for thrombin (Boc-Val-Pro-Arg-MCA) and plasmin (Boc-Glu-Lys-Lys-MCA) in a 96-well plate, lately initiated by the addition of TF (10 pM). The plate was read in a fluorometric spectrophotometer for 4 h. Results are shown in Table 2, and no differences were observed in thrombin generation. However, the area under the curve of plasmin generation, which could be interpreted as a proxy of the plasma fibrinolytic potential, was lower in both FN + sepsis and FN + sepsis 72 h when compared to FN and the control group. Our findings reveal that EVs might present a role in the pathogenesis of sepsis in a scenario where cells known to be critical to this process are virtually absent. The increase of TF + EVs from monocytes, which has been demonstrated in classical sepsis, seems to be relevant even in this context, warranting additional studies using functional assays to further explore this mechanism of tissue damage. Our results also demonstrate that hypofibrinolysis is a characteristic of FN-associated sepsis, suggesting that deregulation of the fibrinolytic system is at least in part independent of the participation of granulocytes and platelets in these patients.

Yield of Repeat Blood Cultures in Acute Myeloid Leukemia Patients Following Allogeneic Hematopoietic Stem Cell Transplantation

Introduction: Unnecessary repeat blood culture collection has been demonstrated to increase health care costs, length of stay, duration of antimicrobial exposure, and risk of anemia and result in unnecessary removal of vascular catheters. The aim of this study was to characterize the yield of new pathogen identification in acute myeloid leukemia (AML) patients with known bacteremia in the post-allogeneic hematopoietic stem cell transplant (HSCT) period. Methods: This was a retrospective study of AML patients who underwent allogeneic HSCT at Taussig Cancer Center from January 1 st 2019 to December 31 st 2022. Patients who experienced an occurrence of febrile neutropenia (FN) within 35 days of date of HSCT and had positive initial blood cultures within 24 hours of diagnosis of FN were included in the study. Patients who had at least 1 additional set of repeat cultures drawn following initial blood cultures were included in the study. Blood cultures were collected through a peripheral site via venipuncture or through a central line. The study was approved by the Institutional Review Board. Data were collected on baseline patient characteristics, AML disease characteristics, HSCT characteristics, and infection characteristics. Febrile neutropenia was defined as recorded temperature ≥ 100.4°F with concurrent ANC <1500 cells/uL. Each patient day with a recorded temperature ≥100.4°F and ANC <1500 cells/μL was considered as a day of FN. An episode of FN was considered to be resolved following 72 hours of defervescence. Cultures drawn within 24 hours of onset of FN were considered the initial blood cultures. All subsequent sets of blood cultures were considered repeat blood cultures. A positive set of blood culture was defined as >50% of all blood cultures in that set growing an organism. Cultures drawn from all peripheral and central sites on the same day of FN were considered as one set of blood cultures. All patients received post-HSCT anti-bacterial prophylaxis with bactrim or ciprofloxacin. Results: A total of 154 AML patients who underwent HSCT at Taussig Cancer Center were screened for the study. 50/154 (32.5%) of those patients met inclusion criteria and were included in the study. Among the 50 patients included in the study, there were 50 episodes of FN with positive initial blood cultures that were diagnosed within 35 days of HSCT. There were 120 total days of FN among the 50 episodes of FN with an average of 2.4 days per episode. 50 initial sets of blood cultures and 96 sets of repeat blood cultures were drawn between the 50 episodes of FN with an average of 2.9 total sets of blood cultures per episode. 12/96 (12.5%) of repeat blood cultures sets were positive for a pathogen. 3/96 (3.1%) of repeat blood cultures sets grew a pathogen that differed from the pathogen which grew in the preceding positive blood culture. The median duration of febrile neutropenia at time of repeat positive culture was 3.5 days. 30-day mortality rate from infection was 6.0% (3/50). Conclusion: Even amongst bacteremic AML patients in the post-HSCT period, the yield of repeat blood cultures was low for detecting new pathogen identification. Repeat blood cultures should be guided by thorough evaluation of emerging clinical signs and symptoms.

Can MASCC and CISNE scores predict delays of lung cancer chemotherapy after febrile neutropenia?

Febrile neutropenia (FN) during cancer chemotherapy can lead to morbidity and mortality. The Multinational Association of Supportive Care in Cancer (MASCC) and clinical index of stable febrile neutropenia (CISNE) scores have been widely used to predict the risk of severe medical complications in patients with FN; however, there are few tools for predicting chemotherapy delays or discontinuation after FN. Patients admitted to two university hospitals between 2014 and 2018 with a FN diagnosis during the first cycle of chemotherapy for lung cancer were reviewed retrospectively. Among 539 patients who received 813 courses of chemotherapy for lung cancer, 49 (9%) developed FN during the first treatment cycle. Although all the patients recovered from their primary infection, 19 patients (38.8%) developed serious medical complications, 11 (22.4%) were unable to resume chemotherapy and one (2.0%) declined to resume chemotherapy, and nine (18.4%) died within 90 days. Patients who failed to resume chemotherapy had a lower MASCC score (median 8.5 vs. 17, p < 0.01) and a higher CISNE score (median 3 vs. 1, p < 0.01) at the onset of FN. The specificity to predict the patient who failed to resume chemotherapy was 90% or more with MASCC score ≤9 or CISNE score ≥3, with the sensitivity of 61%. MASCC score ≤ 16 can also be a sensitive indicator with the sensitivity and specificity of 89 and 52%, respectively. The MASCC and CISNE scores are useful in identifying lung cancer patients who are unable to resume chemotherapy as scheduled after the onset of FN.

1600P The role of C-reactive protein/albumin ratio in predicting 90-day mortality in patients with febrile neutropenia

The MASCC score is widely used to predict the prognosis of febrile neutropenia after chemotherapy in cancer patients. The MASCC score does not use any laboratory data and has low sensitivity. Therefore, the search for markers to predict the prognosis of febrile neutropenia continues. Albumin(alb) and C-Reactive Protein(CRP) are acute phase reactants, besides albumin reflects nutritional status. In this study, we aimed to evaluate the effect of CRP/alb ratio on the prognosis of febrile neutropenia. The files of patients admitted with the diagnosis of febrile neutropenia between January 2018 and January 2022 were reviewed retrospectively, MASCC risk score, CRP and albumin levels at admission were collected. All patients who were followed up by the medical oncology department, received at least 1 course of chemotherapy and presented with the diagnosis of febrile neutropenia were included in the study. A total of one hundred and fifty-six (n=156) episodes of febrile neutropenia were included in the study, and 55 (35%) of these patients died within ninety days. While the 90-day mortality rate was 45% in the group of patients with MASCC <21, this rate was 26% in patients with MASCC >21 (p = 0.007). The median of the CRP/alb ratio was determined as 58 and the patients were divided into two groups according to the median value. The 90-day mortality rate was 24% in the group with a low CRP/alb ratio, and 45% in the group with a high CRP/Alb ratio (p = 0.004). In patients with a MASCC score of >21 and a CRP/alb score of <58 (n=47), the 90-day mortality rate was 21%, compared to 55% in patients with a MASCC <21 and CRP/alb >58 (p= 0.001). In conclusion, high CRP/Alb ratio worsens the prognosis of febrile neutropenia independently of other factors. The combined evaluation of MASCC risk score and CRP/Alb ratio is beneficial in predicting the prognosis of febrile neutropenia and increases the prognostic power of the MASCC risk score.

Decreased incidence of febrile neutropenia in Michigan following masking and social distancing orders for the COVID-19 pandemic: A population based cohort study.

BACKGROUNDIt has been theorized that 75%-80% of febrile neutropenia (FN) is caused by endogenous pathogens, while up to 20% of cases are thought to be caused by a viral infection. It is unknown if precautions such as masking and social distancing reduce the risk of FN in susceptible populations.AIMTo determine whether coronavirus disease 2019 (COVID-19) infection mitigation efforts, namely masking and social distancing, were associated with a reduction in the incidence of FN.METHODSThis was a retrospective population based cohort study comparing the incidence of FN in the 13 mo prior to (Year 0) and 13 mo following (Year 1) the public health executive orders (PHEO) in Michigan. Data was queried for all emergency department (ED) visits from April 1, 2019 to March 31, 2021 from the National Syndromic Surveillance Program, a program which collects data that is voluntarily submitted by approximately 89% of Michigan EDs. The primary study outcome was the incidence of FN as a proportion of ED visits in the 13-mo before and 13-mo after COVID-19 mitigations efforts, namely masking and social distancing. We hypothesized that there would be a significant decrease in the incidence of FN in the period following the PHEO aimed at reducing the spread of the severe acute respiratory syndrome coronavirus 2 virus.RESULTSThere was a total of 8979221 total ED visits captured during the study period. In Year 0 there were 5073081 recorded ED visits and 3906140 in Year 1. There was a significant reduction in the proportion of total ED visits with a diagnosis of FN, decreasing 13.3% across periods (0.15% vs 0.13%, P = 0.036). In patients with a hematologic malignancy a more impressive reduction in the incidence of FN was evident following PHEO (22% vs 17%, P = 0.02).CONCLUSIONWe found a significant association between social distancing and mask guidelines implemented on a large public scale with decreased rates of FN, particularly in those with a hematologic malignancy. These findings may be useful in the design of future research and recommendations regarding the prevention of FN.

Impact of weekend effect on neutropenic fever admissions associated with malignancy.

e18658 Background: The impact of the “weekend effect” (increased mortality rate during Saturday and/or Sunday admissions) on hospitalizations for various medical emergencies has been studied with results often showing adverse patient outcomes. Febrile neutropenia in cancer patients is an acute oncological emergency with significant mortality and morbidity. Here, we attempt to explore if the day of admission impacts outcomes and healthcare utilization in cancer patients admitted for neutropenic fever. Methods: We performed a retrospective analysis using the National Inpatient Sample (NIS) database from 2019, and identified all adult admissions with cancer (hematological and solid cancers) and a concomitant primary or secondary diagnosis of Febrile Neutropenia using ICD 10 codes. These patients were divided based on the day of admission (group 1: weekday vs. group 2: weekend). The groups were compared for demographic differences, inpatient mortality, length of stay (LOS), and hospital charges (TCHG). Secondary outcomes studied were complications like sepsis, septic shock (SS), and mechanical ventilation (MV). Statistics were performed using the t-test, chi-square test, multivariate logistic analysis. Results: A total of 136,895 cancer patients were admitted with febrile neutropenia, and of those, 28,559 patients were admitted during the weekend. Both groups had similar demographics (p = &gt; 0.05) with a mean age of 61 years, more males (52% vs. 51%), admitted in large-sized and urban teaching hospitals, and a majority had Medicare insurance (48% vs. 50%). 4.6% of weekday and 4.7 % of the weekend admissions died during hospitalization. Weekend admissions were likely to have a slightly lower mortality, although not statistically significant(aOR = 0.96,95% CI = 0.81-1.1, p = 0.72). The mean LOS was 9 days for group 1 and 8 days for group 2 (p &lt; 0.001*). TCHG was lower for the weekend by $ 15,770 per admission (p &lt; 0.001*). The rates and odds of having sepsis, SS, MV were similar between both groups (p &gt; 0.05). In addition, increasing age, Hispanic race, and comorbid chronic kidney disease, diabetes, congestive heart failure, acute kidney injury, acute respiratory failure resulted in higher mortality, LOS, and all complications (p = &lt; 0.001*) regardless of the day of the admission. Conclusions: The mortality rate and other outcomes in neutropenic fever did not statistically change between weekday and weekend admissions. Interestingly, the healthcare resource utilization (LOS and TCHG) was higher on weekdays. It is encouraging to note that the “weekend effect” has not impacted the in-hospital outcomes. However, patients admitted with febrile neutropenia have a high mortality rate and increased risk of serious complications. Therefore, utmost vigilance and close follow-up are necessary when treating these patients. *p = &lt; 0.05 was considered significant; aOR = Adjusted Odds Ratio.

Smaller but more frequent dosing of cefepime in the treatment of febrile neutropenia.

Generally national guidelines for febrile neutropenia recommend treatment with cefepime 2 g every 8 h. Due to beta-lactam's time dependent killing effects, it is hypothesized smaller doses given more frequently might be non-inferior. The objective of this study is to retrospectively evaluate the efficacy of cefepime 1 g every 6 h versus 2 g every 8 h in cancer patients with febrile neutropenia. This retrospective, single-center, cohort study included patients with a diagnosis of febrile neutropenia treated with cefepime during an inpatient encounter. Patients were grouped based on receipt of cefepime 2 g every 8 h (high dose cohort) versus cefepime 1 g every 6 h (low dose cohort). The primary outcome compared the time to defervescence after cefepime initiation between the two dosing strategies. A subgroup analysis of the primary endpoint was conducted in patients who received both cefepime and vancomycin. Ninety-seven patients were included in the high dose cohort, and seventy-six patients were included in the low dose cohort. Baseline characteristics were similar between cohorts with the exception of race. The time to defervescence between the high dose cohort and low dose cohort were comparable between groups (49.2 vs. 46.7 h). The time to defervescence in subgroup analysis of patients who received empiric vancomycin and cefepime was 65.7 versus 59.7. Patients who received cefepime 1 g every 6 h were found to have similar trends in achieving time to defervescence compared to 2 g every 8 h.

Emergency department management of chemotherapy related febrile neutropenia: An opportunity to improve care.

Febrile neutropenia (FN) is an important oncological emergency seen in the emergency department (ED), and the American Society of Clinical Oncology recommends risk stratification of patients with febrile neutropenia using the Multinational Association for Supportive Care in Cancer (MASCC) Index, with ED discharge on oral antibiotics recommended for low-risk patients. To determine the prevalence of FN neutropenia and medical system wide ED treatment guideline adherence. We performed a retrospective chart review of all patients with an ICD-10 confirmed diagnosis of FN from January 2016-2019at 13 affiliated EDs within one medical system. Only cancer/chemotherapy related FN were included. Following the MASCC guidelines, we used post-hoc calculations to classify patients as low/high-risk, and compared key clinical variables (mortality, blood culture positivity, interventions). 203 patients were found to have FN. 97.9% (184/203) received broad spectrum antibiotics, including 92% of the low-risk group (60/65). All patients were admitted, and no observed in-hospital mortality was noted in the low-risk group, meanwhile 5.1% (7/138) of the high-risk group died. 14/203 patients had positive blood cultures, none in the low-risk group. The prevalence of FN is low among 13 EDs that had almost 1.7 million ED visits over a 3-year period. Guideline compliance for low-risk FN was poor. All patients were admitted, and nearly all patients received IV fluids and IV antibiotics. Improving FN management to align with national guidelines represents an opportunity to improved ED care of patients with cancer by reducing unnecessary hospitalizations.

Clinical Characteristics and Predictive Factors of Invasive Fungal Disease in Pediatric Oncology Patients with Febrile Neutropenia in a Country with Limited Resources.

BackgroundThe most common complication among pediatric oncology patients is febrile neutropenia (FN). Invasive fungal disease (IFD) is suspected when fever persists >4–7 days after empirical antibiotics. Its clinical characteristics and predictive factors associated with IFD among pediatric oncology patients with FN were thus explored.MethodsPediatric oncology patients with FN between January 1, 2012 and December 31, 2016 were enrolled in this study. Clinical characteristics, including laboratory investigations, treatment modalities, and final outcomes of IFD were retrospectively reviewed and analyzed.ResultsIn all, 73 patients with 180 episodes of confirmed diagnosis of FN were studied. Median age at diagnosis was 6.2 years, with equal sex distribution. The most common diagnosis was acute lymphoblastic leukemia (n=91, 51%), followed by acute myeloid leukemia (n=47, 26%), Burkitt’s lymphoma (n=7, 4%) and neuroblastoma (n=7, 4%). Median absolute neutrophil count at FN diagnosis was 0 (0–806) cells/mm3. IFD was diagnosed for 25 (14%) episodes. Mortality rates for FN and IFD were 4% and 20%, respectively. Respiratory compromise, oxygen requirement, hypotension, prolonged hospitalization, duration of fever and neutropenia, bacteremia, bacteriuria, funguria, abnormal liver-function results, and prolonged broad-spectrum antibiotic administration were factors associated with IFD (P<0.05). Prolonged duration between initiation of fever and antifungal administration for nearly 10 days was an independent factor in prediction of IFD occurrence (P=0.014).ConclusionRespiratory compromise, oxygen requirement, hypotension, prolonged hospitalization, duration of fever and neutropenia, bacteremia, bacteriuria, funguria, abnormal liver-function results and prolonged broad-spectrum antibiotic administration were factors associated with IFD. Duration between initiation of fever and antifungal administration of nearly 10 days were considered a risk factors of IFD among patients with FN.IRB Reference NumberIRBRTA 825/2560.

Pediatric Invasive Fungal Risk Score in Cancer and Hematopoietic Stem Cell Transplantation Patients With Febrile Neutropenia.

Invasive fungal diseases (IFDs) are opportunistic infections that result in significant morbidity and mortality in pediatric oncology patients. Predictive risk tools for IFD in pediatric cancer are not available. We conducted a 7-year retrospective study of pediatric oncology patients with a diagnosis of febrile neutropenia at UCM Comer Children's Hospitals. Fourteen clinical, laboratory, and treatment-related risk factors for IFD were analyzed. Stepwise variable selection for multiple logistic regression was used to develop a risk prediction model for IFD. Two comparative analyses have been conducted: (i) all suspected IFD cases and (ii) all proven and probable IFD cases. A total of 667 febrile neutropenia episodes were identified in 265 patients. IFD was diagnosed in 62 episodes: 13 proven, 27 probable, and 22 possible. In the final multiple logistic regression models, 5 variables were independently significant for both analyses: fever days, neutropenia days, hypotension, and absolute lymphocyte count <250 at the time of diagnosis. The odds ratio and a relative weight for each factor were then calculated and summed to calculate a predictive score. A risk score of ≤4 and ≤5 (10/11 maximum) for each model signifies low risk, respectively (<1.2% incidence). Model discrimination was evaluated by the area under the receiver operator characteristics curve with an area under the curve of 0.95/0.94 for each model. Our prediction IFD risk models perform well, are easy-to-use, and are based on readily available clinical data. Profound lymphopenia absolute lymphocyte count <250 mm3 could serve as a new important prognostic marker for the development of IFD in pediatric cancer and hematopoietic stem cell transplant patients.

Febrile Neutropenia Syndromes in Children: Risk Factors and Outcomes of Primary, Prolonged, and Recurrent Fever.

The approach to recurrent febrile neutropenia (FN) in children with cancer has not been sufficiently addressed and was cited as a research gap in the International Pediatric Fever and Neutropenia (IPFNP) Guideline 2017. Retrospective medical record review for all pediatric cancer patients with a diagnosis of FN was performed. Variables were collected at 2 different time sets (at day 1 and day 4 of presentation). Three FN syndromes have been defined based on the duration and time course of the fever: (1) primary: fever resolved before 96 hours and did not follow with recurrent fever; (2) prolonged fever: episodes failing to defervesce after at least 96 hours of antibacterial therapy; (3) recurrent fever: a new episode of fever >72 hours after resolution of the initial fever when a patient remained neutropenic and on antibiotics or if a fever developed within 1 week after antibiotic discontinuation. These entities were compared with define risk factors and adverse outcomes associated with recurrent fever. A total of 633 FN episodes (FNEs) were identified in 268 patients. Each FNE was classified as primary (n=453, 71.5%), prolonged (n=119, 18.7%), or recurrent (n=61, 9.7%). In multivariable analysis, acute myelogenous leukemia (odds ratio [OR]=4.6, 95% confidence interval [CI]: 2.95-7.24), allogeneic stem cell transplant (SCT) (OR=4.9, 95% CI: 2.61-7.35), absolute lymphocyte count <300/mm3 (OR=3.8, 95% CI: 1.30-5.02), prior neutropenia of ≥10 days, (OR=3.95, 95% CI: 1.70-5.93) and hypotension (OR=3.65, 95% CI: 1.30-5.86) on day 1 of presentation were all associated with an increased risk of recurrent fever when compared with primary fever. In subset analysis for only the high-risk FN group, hypotension (OR=3.2, 95% CI: 1.80-4.96), prior neutropenia ≥10 days (OR=2.55, 95% CI: 1.40-6.22), and absolute lymphocyte count <300/mm3 at presentation (OR=2.6, P=0.03, 95% CI: 2.65-7.12) were associated with an increased risk of recurrent fever when compared with high-risk FN not developing recurrent fever. Allogeneic SCT (OR=5.9, 95% CI: 2.65-7.12) and prior neutropenia ≥10 days (OR=2.11, 95% CI: 1.25-9.32) were significantly associated with recurrent fever when compared with prolonged fever. Invasive fungal disease was a more common etiology with recurrent fever compared with primary and prolonged fever (P=0.001 and 0.01, respectively). Recurrent fever episodes were more likely to be admitted to the pediatric intensive care unit (OR=3, 95% CI: 1.27-6.23) and had a higher 30-day mortality (OR=8, 95% CI: 1.87-71.85) when compared with primary fever. Knowledge of risk factors for recurrent fever may enable the early detection infection-related complications of this high-risk group, and possible improved approaches to treatment resulting in decreased morbidity and mortality.

Plasma Microbial Cell-free DNA Next-generation Sequencing in the Diagnosis and Management of Febrile Neutropenia.

BackgroundStandard testing fails to identify a pathogen in most patients with febrile neutropenia (FN). We evaluated the ability of the Karius microbial cell-free DNA sequencing test (KT) to identify infectious etiologies of FN and its impact on antimicrobial management.MethodsThis prospective study (ClinicalTrials.gov; NCT02912117) enrolled and analyzed 55 patients with FN. Up to 5 blood samples were collected per subject within 24 hours of fever onset (T1) and every 2 to 3 days. KT results were compared with blood culture (BC) and standard microbiological testing (SMT) results.ResultsPositive agreement was defined as KT identification of ≥1 isolate also detected by BC. At T1, positive and negative agreement were 90% (9/10) and 31% (14/45), respectively; 61% of KT detections were polymicrobial. Clinical adjudication by 3 independent infectious diseases specialists categorized Karius results as: unlikely to cause FN (N = 0); definite (N = 12): KT identified ≥1 organism also found by SMT within 7 days; probable (N = 19): KT result was compatible with a clinical diagnosis; possible (N = 10): KT result was consistent with infection but not considered a common cause of FN. Definite, probable, and possible cases were deemed true positives. Following adjudication, KT sensitivity and specificity were 85% (41/48) and 100% (14/14), respectively. Calculated time to diagnosis was generally shorter with KT (87%). Adjudicators determined real-time KT results could have allowed early optimization of antimicrobials in 47% of patients, by addition of antibacterials (20%) (mostly against anaerobes [12.7%]), antivirals (14.5%), and/or antifungals (3.6%); and antimicrobial narrowing in 27.3% of cases.Clinical Trials RegistrationNCT02912117ConclusionKT shows promise in the diagnosis and treatment optimization of FN.

Determination of the relationship between mortality and SOFA, qSOFA, MASCC scores in febrile neutropenic patients monitored in the intensive care unit.

PurposeFebrile neutropenia (FN) is a hematological emergency. It is challenging and confusing for the clinicians to make the decision of the febrile neutropenic patients under chemotherapy to be monitored at intensive care unit (ICU). The aim of this study was to define the factors supporting decision-making for the critical patients with febrile neutropenia.MethodsThe data of 60 patients, who were taken to the ICU while they were under treatment in the Hematology Clinic with a diagnosis of febrile neutropenia, were analyzed retrospectively, in order to identify clinically useful prognostic parameters.ResultsThe ICU mortality rate was 80%. Mortality was significantly associated with higher sequential organ failure assessment score (SOFA), quick sequential organ failure assessment score (qSOFA), and hematological SOFA (SOFAhem) scores on admission. All cases having SOFA score 10 and above and qSOFA score 2 and above died. In multivariate analysis, qSOFA score was found to be statistically significant in predicting mortality in regard to ICU admission (p = 0.004).ConclusionMortality of febrile neutropenic patients admitted to ICU is high. It would be appropriate to determine the extent of organ dysfunction instead of underlying disease, for making the decision of ICU admission. It should be noticed that the risk mortality is high for the FN cases with SOFA score 10 or above, qSOFA score 2 or above, and in need of mechanical ventilation and positive inotropic support; hence, early intervention is recommended. In our study, the most significant parameter in predicting ICU mortality was found to be qSOFA.

Thrombin generation in children with febrile neutropenia.

Febrile neutropenia (FN) is a common and serious complication in patients with leukemia. Hemostasis and inflammation are two interrelated systems in response to infection. We aimed to investigate the course of thrombin formation in febrile neutropenia attack of children with acute lymphoblastic leukemia (ALL). Thrombin generation was monitored in children treated for ALL at diagnosis of febrile neutropenia (FN) (t < sub > 0 < /sub > ), at 48 < sup > th < /sup > hour of FN (t1) and after recovery from neutropenia (t < sub > 2 < /sub > ). Twenty-nine patients and 50 healthy children as control were enrolled into the study. Mean endogenous thrombin potential (ETP) and mean peak value of thrombin results at t < sub > 1 < /sub > were significantly higher than at t < sub > 0 < /sub > , t < sub > 2 < /sub > and control groups, respectively. A positive but statistically nonsignificant correlation between ETP values at t < sub > 1 < /sub > and duration of neutropenia was observed. Although thrombin generation is enhanced both due to chemotherapy or malignancy itself, our results revealed that thrombin formation also increased in neutropenic infection of children with leukemia.

1162. Engraftment fever (EF) in Pediatric stem cell transplantation (SCT): Risk Factors, Etiology and Outcomes

BackgroundEngraftment fever (EF) during stem cell transplantation (SCT) is likely due to non infectious causes like immune reconstitution syndrome (IRS) or engraftment syndrome (ES). Few studies have looked at the rate of infection causing fever during engraftment. There is no good evidence to guide the approach to evaluation and empiric treatment of infections during EF.MethodsRetrospective record review of pediatric SCT (autologous and allogenic) patients with a diagnosis of febrile neutropenia (FN) during engraftment period (days +7 to +30 post transplant). FN episodes classified as either EF or non-engraftment fever (NEF). EF = new onset fever in temporal relationship to neutrophil recovery (4 days before through 1 day after neutrophil engraftment (ANC >500/mm3). NEF = fever without signs of neutrophil recovery (ANC < 100/mm3 without significant rise ±4 days of fever onset). Only first FN during engraftment was included. Episodes meeting neither criteria were excluded.Results112 patients had 115 FN episodes (FNEs) identified: NEF 81 (71.5%); EF 34 (29.5%). In multivariable analysis: Neuroblastoma as underlying diagnosis (odds ratio [OR]=3.2, 95% CI 2.31-6.54, P< 0.01), G-CSF administration before day +7 (OR=2.8, 95% CI 1.92-4.65, P=0.03), absolute monocyte count (AMC) >100/mm3 at FN presentation (OR=2.9, 95% CI, 1.11 to 7.55, P=0.02), were associated with an increased risk of EF compared with NEF. Most EF episodes (26/34, 76%) had no specific infectious etiology identified; 8 had IFIs (24%) [3 proven, 2 probable, 3 possible). IFI rate was higher in EF than NEF group (24% vs 5%) (OR=4.5, 95% CI, 2.11 to 9.55, P< 0.01. EF episodes were more likely to be admitted to the intensive care unit (OR=2.3, 95% CI, 1.88 to 6.35) and had higher 30-day mortality (OR =4.52, 95% CI, 0.37 to 6.55) than NEF.Table 3 table 2 ConclusionEngraftment fever may have an infectious component. Work-up to exclude IFI and empirical antifungal therapy should be considered especially with prolonged fever and supportive clinical or radiological data. Large multi-center prospective studies are needed to further define infectious complications and determine the approach to engraftment fever. Early detection of IFI in this high-risk group may lead to improved morbidity and mortality.Disclosures All Authors: No reported disclosures

1828P Effect of serum albumin/globulin ratio in combination with MASCC and CISNE risk score on febrile neutropenia mortality

The aim of this study was to evaluate the effect of the serum albumin/globulin (ALG) ratio on the 30-day mortality of febrile neutropenia (FEN). The second aim of the study was to evaluate the effect of combination of the ALG ratio with the MASCC and CISNE risk indexes on 30-day mortality of FEN. Between January 2016 and May 2020, the files of patients with a diagnosis of febrile neutropenia were retrospectively evaluated, the data of MASCC and CISNE risk indexes and serum ALG ratios at the time of admission were recorded. The patients who were received at least one cycle of chemotherapy and diagnosed with FEN were screened. Patients with diseases that may affect serum albumin and globulin levels were not included in the study (e.g. chronic liver disease, multiple myeloma, nephrotic syndrome). Patients with MASCC score < 21 and CISNE score ≥ 3 were identified as a high-risk group. The median ALG ratio value was 1.13 and patients were divided into two groups according to this value. Patients with ALG ratio value ≤1.13 were identified as a high-risk group. One hundred and thirty-seven FEN episodes were included in the study. Nineteen patients (14%) had exitus within the first 30 days. The 30-day mortality rate was 96% in patients with high ALG ratios and 77% in patients with low ALG ratios (p = 0.002). According to the MASCC and CISNE risk scores, the mortality rates were 92% and 94%, respectively, in low-risk patients and 78% and 71%, respectively, in the high-risk group (p = 0.026 vs p < 0.001). A multivariate analysis with parameters that affect 30-day mortality revealed that CISNE scores ≥ 3 (OR: 4.55, CI 95% 1.61 – 12.86, p = 0.004) and ALG ratios <1.13 (OR:3.94, CI 95% 1.11 – 13.93, p = 0.033) were associated with increased 30-day mortality. In patients with MASCC<21 and CISNE >3 scores group if the ALG ratio was > 1.13, 30-day mortality rate was 93% and in those with ALG ratios ≤ 1.13 mortality rate decreased to 50% (p = 0.012). A low ALG ratio in a patient with FEN associated with an increased risk of 30-day mortality. Combining the ALG ratio with MASCC and CISNE risk indexes might increase the predictive value of the scores on mortality.

Optimizing the febrile neutropenia care process in cancer patients in a third level Spanish hospital.

e14034 Background: Cancer patients under cytotoxic treatment with fever used to have an average time of antibiotics administration of 11h (median 3h43min) when admitted and identified at the Emergency Room Service in the third level Central University Hospital of Asturias. International guidelines recommend antibiotic administration in the first hour: the so called “Golden Hour”. This delay implies an increase in patient morbidity as well as the cost of managing this complication. Methods: Data was collected from our electronic registry after proper authorization and corresponding anonymization. Pareto and fishbone diagrams were built to point out the possible causes and to stratify them in related subgroups. We measured: Number of visits to ER with fever and Number of inpatients with Febrile Neutropenia diagnosis, Time from the admission to antibiotic administration, Average stay of inpatients with Febrile Neutropenia diagnosis. A protocol associated to electronic tools and validated international scores was designed for patients at Febrile Neutropenia risk and launched on March 2019. Results: 66 patients were included since January 2018. Baseline data showed that the median time to antibiotics indication was 3h50min (average 4h38min) with a median delay of 18min to the administration (average 1h06min), a median of 3h54min (average 10h09min) time to antibiotic administration. When the protocol was activated, median time to antibiotic indication was 30min (average (1h08min) with a median 41min (average 40min) delay in administration, and a median of 1h30min (average 1h42min) time to antibiotic administration. Those with activation of the protocol had average length of stay of 1d13h40min vs. 5d11h18min in those to whom this protocol was not applied. Conclusions: A continuous evaluation effort and the design of appropriate protocols and interventions will increase the efficiency of the oncology patient care process with febrile neutropenia, by reducing unnecessary variability and costs.

Pediatric Febrile Neutropenia: Change in Etiology of Bacteremia, Empiric Choice of Therapy and Clinical Outcomes.

The optimal choice of initial antibiotic therapy for patients with high-risk febrile neutropenia (FN) in children is unclear and varies by the institution on the basis of local antibiograms and epidemiology of specific pathogens. The authors evaluated the appropriateness of antibiotics for the empiric treatment of FN in pediatric patients with cancer in our institution on the basis of changes in the epidemiology of organisms isolated from blood cultures (BCx). The authors conducted a retrospective medical record review of pediatric patients who received any oncology care (including patients with cancer and patients who had stem cell transplant) at University of Chicago Medicine Comer Children's Hospitals (March 2009 to December 2016) with a diagnosis of FN who had at least 1 BCx obtained. They reviewed pathogens isolated from BCx and determined whether they were pathogens or contaminants using the Infectious Diseases Society of America (IDSA) guidelines and the team's decision to treat. They investigated the microbiologic spectrum and susceptibility patterns of pathogens causing bacteremia in pediatric FN and whether the empiric therapy chosen may have affected clinical outcomes. A total of 667 FN episodes were identified in 268 patients. BCx were negative in 497 (74.5%) and were determined to be contaminants in 27 (4%). In 143 episodes (21.5%), the BCx were positive for a pathogenic species. Polymicrobial bacteremia was identified in 25 episodes; a total of 176 pathogens were isolated. The majority of pathogens (95/176, 54%) were Gram-positive (GP), whereas 64 of 162 (36%) were Gram-negative (GN), 5 were fungal, and 4 were mycobacterial. The most common GP pathogens were viridans group streptococci (VGS) (n=34, 19.3%), coagulase-negative staphylococci (n=25, 14%), and methicillin-susceptible Staphylococcus aureus (n=12, 6.8%). Of aerobic GN bacilli, 15 (8.5%) were AmpC producers and 3 (1.7%) carried extended-spectrum beta-lactamases. There was no increase in the prevalence of multidrug-resistant GN isolates during the study period. Patients with VGS and multidrug-resistant GN bacteremia were more likely to be admitted to the pediatric intensive care unit [odds ratio (OR), 3.24; P=0.017; and OR, 2.8; P=0.07, respectively]. There were trends toward a higher prevalence of GP pathogens causing bacteremia and the emergence of VGS with decreased penicillin sensitivity. The prevalence of bacteremia with VGS was higher in acute myelogenous leukemia and neuroblastoma (OR, 2.3; P<0.01) than in patients with other solid tumors. Empiric antibiotic treatment should be tailored to patients' risk for VGS and multidrug-resistant organisms. Individual hospitals should monitor the pathogens causing FN among patients with cancer to guide choice of empiric therapy.

PCN365 CLINICAL CHARACTERISTICS AND MANAGEMENT COSTS OF FEBRILE NEUTROPENIA IN ONCOLOGY PATIENTS IN A HEALTH CARE INSTITUTION IN COLOMBIA

To describe the clinical characteristics, resource utilization and cost of management (COM) of febrile neutropenia (FN) in oncology inpatients. This is a descriptive and retrospective study of a cohort of patients hospitalized due to FN in Clínica SOMA - a health care institution in Medellín (Colombia) - from 2017 to 2019. The costs were extracted from the review of medical records from diagnosis of FN until discharge or death. Costs were classified as laboratories, medications, hospital length-of-stay (LOS), and specialist physician fees. FN episodes were classified as high-risk or low-risk according to the MASCC-scale. Official government manual and drug price information system were used to estimate the cost, which were expressed in 2019 US dollars (US$). The exchange rate applied was 3,278 colombian pesos per US$. Forty-four FN episodes were included. Median age was 61 years (IQR: 53-72), female (52.3%). Solid tumors accounted for 68.8%. The most frequent cancer diagnoses were colorectal (13.6%), breast (11.4%) and lung (9.1%). In terms of oncology treatments, 14 (31.8%) patients were in first-line; 14 (31.8%) in the adjuvant/neoadjuvant setting; and 5 (11.4%), in second-line (2L); 15 (34.0%) episodes occurred in the high-risk setting. Mean LOS per episode was 5.7 ±2.9 days. All patients were discharged alive. Highest COM was found in the 2L group (mean +/- sd: US$1,382±610). COM was higher in high-risk patients ($1,192 ± 1,025) as compared to low-risk (US$770 ± 581). The median overall COM was $633 (range:US US$262- US$3,376) per episode, being hospital LOS the main driver cost. Febrile neutropenia occurred mainly in advanced-stage solid tumors and in MASCC low-risk patients. Higher costs in this cohort were found in long hospital length of stay, and 2L or high-risk patients.

Incidence of febrile neutropenia with commonly used chemotherapy regimen in localized breast cancer.

Introduction:Breast cancer is the most frequently diagnosed cancer among the women. Most commonly used chemotherapy regimen is Doxorubicin and Cyclophosphamide (AC) which carries significant risk of febrile neutropenia. The aim of the study is to identify the incidence of febrile neutropenia and its effects on the delivery of chemotherapy in patients receiving following AC chemoregimen without primary prophylaxis.Materials and Methods:We retrospectively analyzed the case records of the localized breast cancer patients who were treated with AC chemoregimen without primary prophylaxis for febrile neutropenia.Results:Between 2013 and 2017, a total of 231 cases received AC chemoregimen. A total of 14 (6.1%) patients were found to have febrile neutropenia. All patients were recovered by day 19 and no deaths were observed. Except for ECOG performance status (P = 0.001) no significant association was found with age, co-morbidities, menopausal status, body surface area and stage of the cancer. There were no treatment delays or dose reductions because of febrile neutropenia.Conclusion:The incidence of FN with AC chemotherapy in breast cancer patients is relatively less in the present study. Routine primary prophylaxis is not recommended as this chemotherapy falls in to low risk category for FN but can be considered for patients with ECOG PS > 1. If the diagnosis of febrile neutropenia and institution of appropriate measures are prompt, FN did not affect the delivery of chemotherapy and thus compromise survival.