Febrile Neutropenia Mortality Research Articles

Serum Albumin as a Prognostic Biomarker for Febrile Neutropenia Outcome and Complications: A Prospective Observational Trial.

Febrile neutropenia (FN) poses a significant challenge in cancer treatment, with a high incidence among patients undergoing standard therapies. Predicting FN complications and outcomes remains crucial for improving patient management strategies. Biomarkers, including procalcitonin and albumin, have garnered attention for their potential prognostic value in FN. We conducted a prospective observational study at a tertiary hospital, enrolling 185 adult cancer patients experiencing FN episodes. We assessed serum albumin levels and incorporated them into the Multinational Association for Supportive Care in Cancer (MASCC) risk index to enhance risk stratification. Serum albumin levels displayed promising prognostic utility in febrile neutropenia (FN). They exhibited moderate specificity and sensitivity in predicting mortality during FN and 28-day mortality. Serum albumin levels were significantly associated with gastrointestinal infections, serving as an independent predictor. Integrating serum albumin into the MASCC risk index improved predictive accuracy for FN mortality by 50%, 28-day mortality by 66.67%, and respiratory tract infections by 62.50%, enhancing in this way risk stratification for FN-related complications. Serum albumin emerges as a promising biomarker for prognostication in FN, complementing existing risk assessment frameworks. Its incorporation into the MASCC risk index enhances predictive capabilities, aiding clinicians in identifying high-risk patients promptly. While albumin shows potential in predicting mortality and complications, further research is warranted to optimize sensitivity and specificity, ensuring its clinical utility.

Etiology and Factors Affecting Severe Complications and Mortality of Febrile Neutropenia in Children with Acute Leukemia

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. 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. 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. 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.

Evaluating the usefulness of the pediatric early warning system (PEWS) for predicting clinical deterioration and mortality in febrile neutropenia

Evaluating the usefulness of the pediatric early warning system (PEWS) for predicting clinical deterioration and mortality in febrile neutropenia

Approach to fever in patients with neutropenia: a review of diagnosis and management.

Febrile neutropenia (FN) is associated with mortality rates as high as 40%, highlighting the importance of appropriate clinical management in this patient population. The morbidity and mortality of FN can be attributed largely to infectious processes, with specific concern for infections caused by pathogens with antimicrobial resistance. Expeditious identification of responsible pathogens and subsequent initiation of empiric antimicrobial therapy is imperative. There are four commonly used guidelines, which have variable recommendations for empiric therapy in these populations. All agree that changes could be made once patients are stable and/or with an absolute neutrophil count (ANC) over 500 cells/mcL. Diagnostic advances have the potential to improve knowledge of pathogens responsible for FN and decrease time to results. In addition, more recent data show that rapid de-escalation or discontinuation of empiric therapy, regardless of ANC, may reduce days of therapy, adverse effects, and cost, without affecting clinical outcomes. Antimicrobial and diagnostic stewardship should be performed to identify, utilize, and respond to appropriate rapid diagnostic tests that will aid in the definitive management of this population.

Mortality-associated clinical risk factors in patients with febrile neutropenia: A retrospective study

ObjectivesTo determine the predictors for 30-day all-cause mortality in patients with febrile neutropenia (FN) and develop a prediction score. MethodsThe electronic medical records of patients undergoing chemotherapy with FN between 2018 and 2019 were reviewed. Multivariate logistic regression was performed to identify factors associated with 30-day all-cause mortality to develop a parsimonious model. A prediction score was developed from the model's coefficients of each predictor. ResultsThere were 273 FN episodes in 153 patients. The overall mortality rate was 12.5%. Pre-existing cardiovascular disease (OR 22.45), alteration of consciousness on admission (OR 18.50), anemia (OR 4.33), acute kidney injury (AKI) (OR 13.15), causative pathogen identified (OR 8.68), intensive care unit admission (OR 0.13), septic shock (OR 18.72), and the need for mechanical ventilation (OR 22.65) were associated with mortality. After exploring confounding effects between factors, septic shock, anemia, AKI, and the need for mechanical ventilation were selected to develop the prediction score which provided good sensitivity (87.88%) and specificity (90.91%) with an area under the ROC curve of 0.8939. ConclusionsSeptic shock, anemia, AKI, and the need for mechanical ventilation were associated with FN mortality. Our prediction score is effective in discriminating high and low-risk patients for mortality.

Antibiotic Overload: Antibiotic Stewardship in Febrile Patients with Hematologic Malignancies

Introduction: Febrile neutropenia (FN) is defined as a temperature >100.4°F in the setting of an absolute neutrophil count (ANC) less than 1000 cells/mm3. FN carries a mortality that has been variably reported between 2% and 20%. Monotherapy with cefepime, a carbapenem, or piperacillin-tazobactam are recommended as first-line therapy. The addition of vancomycin has not been shown to reduce mortality. Overuse/misuse of the aforementioned antibiotics has been reported to contribute to the rise of drug-resistant organisms causing life-threatening infections in febrile cancer patients (FCP). Our study aims to assess antibiotic stewardship in FCP at our institution and the outcomes of infections in this patient population.Methods: A retrospective chart review of 200 randomly selected patients with hematologic malignancies admitted with a diagnosis of fever from 1/2011 through 12/2016 was performed. Eleven patients were pediatric cases and therefore excluded. 189 adult patients were analyzed using univariate and bivariate statistics; Chi-square tests were performed to assess differences across groups.Results: Patient demographics and characteristics of infection are shown in Table 1. The in-hospital neutropenia-related mortality (NRM) for neutropenic patients was 16% while the all-cause mortality for neutropenic patients was 39%. Neutropenic patients with leukemia had higher NRM than neutropenic lymphoma patients (65% vs. 35%; P=0.01), those who received granulocyte colony stimulating factor had lower NRM compared to those who did not (11% vs. 24%; P=0.04), and neutropenic patients without an identified source of infection had lower NRM than those with a documented infection (36% vs. 64%; P=0.00). Neutropenic patients who had a resistant organism isolated were less likely to survive their episode of FN than those who did not (56.3% vs. 95.7%%; P=0.00). There was a non-significant trend towards lower NRM amongst neutropenic patients who were on prophylaxis with ciprofloxacin prior to admission compared to those who were not (10% vs. 18%; P=0.17). There were no NRM differences amongst neutropenic patients who developed FN as a complication of stem cell transplantation versus chemotherapy (P=0.31), ≥ 65 years of age compared to <65 years of age (P=0.69), infection with gram negative compared to gram positive organism (P=0.89) or those treated with cefepime alone compared to cefepime plus vancomycin (P=0.62). Of the patients with FN, 68.8% received a cefepime-containing regimen (22.7% cefepime alone, 46.1% cefepime plus vancomycin). Of the patients that had fever without neutropenia, 45.83% received a cefepime-containing regimen (14.6% cefepime alone, 31.23% cefepime plus vancomycin). 2.1% of the population had an identified infection with methicillin-resistant staphylococcus aureus (MRSA) and 3.7% had an infection with vancomycin-resistant enterococcus (VRE).Conclusion: Improved supportive care, including prompt administration of broad spectrum antibiotics and evidence-based sepsis guidelines, has reduced the morbidity and mortality of FN. This is evidenced by the lower in-hospital NMR compared to the all-cause mortality rate in our patient population. Nonetheless, patients infected with resistant organisms have higher NRM. The inappropriate use of cefepime in febrile, non-neutropenic patients and of vancomycin in febrile cancer patients with or without neutropenia suggests a greater need for antibiotic stewardship at our institution. As the addition of vancomycin offers no survival benefit, more judicious use of this antibiotic is warranted in FCP as its overuse is contributing to the rise of resistant organisms such as VRE. Implementation of methods such as placing holds in our institution's electronic medical record requiring calculation of ANC prior to administering antibiotics and education programs regarding the appropriate empiric antibiotic regimens in febrile cancer patients with or without neutropenia is merited. [Display omitted] DisclosuresLeslie:celgene: Speakers Bureau; KITE pharma: Speakers Bureau; seattle genetics: Speakers Bureau.

Incidence and Clinical Outcomes of Febrile Neutropenia in Adult Cancer Patients with Chemotherapy Using Korean Nationwide Health Insurance Database

PurposeThe aim of this study was to evaluate the episodes of febrile neutropenia (FN) in patients with gastric cancer (GC), colorectal cancer (CRC), lung cancer (LC), and breast cancer (BC); and to identify the incidence and trends of admission rates, as well as factors affecting mortality.Materials and MethodsUsing nationwide claims data, all new admissions to hospitals for FN were selected. We evaluated the incidence of FN and mortality-related clinical factors in adult cancer patients who received cytotoxic chemotherapy from January 2004 to December 2013.ResultsWhile the incidence of FN increased, the length of hospitalization decreased in Korea. The incidence of FN was 19.8% in LC patients, 15.5% in GC patients, 13.3% in BC patients, and 9.5% in CRC patients. The overall in-hospital mortality of FN was 12.9% and showed a decreasing trend. Admission rates to intensive care units and in-hospital mortality were the highest for lung cancer (15.2% and 19.3%, respectively). Age and sepsis syndrome were risk factors for in-hospital mortality for all cancer types.ConclusionCareful observation and active prophylaxis should be considered for patients at high risk of FN.

Evaluation of Risk Factors for Mortality in Febrile Neutropenia.

We aimed to evaluate the epidemiology of infections and factors associated with mortality in patients with febrile neutropenia (FEN). The adult patients, who developed FEN after chemotherapy due to a hematologic malignancy or a solid tumor in a training and research hospital were evaluated, retrospectively. The demographic data of the patients, underlying malignancy, administered antimicrobial therapy, microbiological findings, and other risk factors associated with mortality were evaluated. A total of 135 FEN episodes of 115 patients, who comprised of 72 (63%) patients with 89 FEN episodes due to hematologic malignancies (hemato-group) and 43 (37%) patients with 46 FEN episodes due to solid organ cancers (onco-group), were evaluated in the study. The median age was 47 years (range: 17-75 years) and 66 (57%) patients were male. A total of 12 patients (8.8%) died during 135 episodes of FEN including nine cases from hemato-group and three cases from onco-group. Those factors including a presence of pneumonia, advanced age, persistent fever despite an antimicrobial treatment, and need for mechanical ventilation in intensive care unit (ICU) with were determined as risk factors associated with mortality. Morbidity and mortality are more common in patients with hematological malignancies compared to patients with solid organ cancers due to prolonged neutropenia. In case of persistent fever, an invasive fungal infection (IFI) should be kept in mind in patients with hematologic malignancies and then antifungal treatment should be initiated. Although a persistent fever is also common in patients with solid tumors, the necessity of antifungal therapy is rare due to the short duration of neutropenia.

Effect of serum uric acid level and Multinational Association for Supportive Care in Cancer risk score on febrile neutropenia mortality.

The study was aimed to evaluate the effect of uric acid (UA) on the 30-day mortality of patients admitted to the tertiary referral hospital with a complaint of febrile neutropenia (FEN). The secondary aim was to evaluate the use of combining serum UA levels with the Multinational Association for Supportive Care in Cancer (MASCC) risk score. A retrospective study in which the MASCC score and serum UA levels were used to evaluate the mortality risk within 30days among patients with FEN. A total of 118 FEN episodes were included in the study and 17 (14%) of these patients died. While this rate is 23% in the high-risk group according to the MASCC score, it is 7% in the low-risk group (p= 0.011). In multivariate analysis of the parameters that significantly affect the 30-day FEN mortality, MASCC risk score (OR, 4.28; CI 95% 1.19-15.39, p= 0.013) and having a level of serum UA > 7mg/dL (OR, 4.46; CI 95% 1.19-15.38, p= 0.032) was significantly increased the risk of in 30-day mortality of FEN. The rate of 30-day mortality of FEN was 0% in patients with a low MASCC risk score and UA level compared with 50% in the high MASCC risk score and high UA level group, and the difference was statistically significant (p< 0.001). Increased level of UA at the time of FEN diagnosis was independently associated with an increased rate of 30-day mortality of FEN. The combination of the MASCC risk score and serum UA level might thoroughly predict the 30-day mortality of FEN.

Impact of time to antibiotic on hospital stay, intensive care unit admission, and mortality in febrile neutropenia.

To determine if time to antibiotics (TTA) improves outcomes of hospital length of stay, admission to the intensive care unit, and 30-day mortality in adult patients with febrile neutropenia. This retrospective cohort study evaluated the impact of time to antibiotic, in the treatment of febrile neutropenia, on hospital length of stay, admission to the intensive care unit, and 30-day mortality. Cases included were patients 18years or older hospitalized with febrile neutropenia from August 1, 2006 to July 31, 2016. To adjust for other characteristics associated with hospital length of stay, admission to the intensive care unit, and 30-day mortality, a multivariate analysis was performed. A total of 3219 cases of febrile neutropenia were included. The median hospital length of stay was 7.0days (IQR 4.1-13.3), rate of intensive care unit admission was 13.6%, and 30-day mortality was 6.6%. Multivariate analysis demonstrated time to antibiotics was not associated with hospital length of stay but was associated with admission to the intensive care unit admission and 30-day mortality. Delays in time to antibiotic of up to 3hours did not impact outcomes. A shorter time to antibiotic is important in treatment of febrile neutropenia; however, moderate delays in antibiotic administration did not impact outcomes. Further investigation is needed in order to determine if other indicators of infection, in addition to fever, or other supportive management, in addition to antibiotics, are indicated in the early identification and management of infection in patients with neutropenia.

Trends in the Incidence and Outcomes of Clostridium difficile Colitis in Hospitalized Patients of Febrile Neutropenia: Nationwide Analysis 2008-2014: 2017 Presidential Poster Award

Introduction: Clostridium difficile infection (CDI) has been attracting attention lately as the most common hospital acquired infection and increasing incidence, morbidity and mortality, and increasing healthcare costs. Patients with neutropenia due to malignancy appear to be at an increased risk for developing CDI. There is currently limited data that assesses the national disease burden and outcomes of patients with febrile neutropenia who have CDI.Table: Demographics & Basic Characteristics of Febrile Neutropenia patients with and without C diff colitis.Methods: We analyzed the National Inpatient Sample (NIS) database for all subjects with discharge diagnosis of febrile neutropenia with or without C. diff colitis (ICD-9 codes 288.00, 288.03,780.60 & 008.45) as primary or secondary diagnosis during the period from 2008-2014. All analyses were performed with the use of PROC SURVEYMEANS, FREQUENCY and SURVEYLOGISTIC procedures of SAS, version 9.4 (SAS Institute).Table: Univariate and Multivariate regression analysis for predictors of C. diff colitis in febrile Neutropenia & Mortality in Febrile neutropenia with C. diff colitis.Results: From 2008-2014 there were total 19422 discharges of Febrile neutropenia patients with C diff. colitis. Most of the patients were Caucasians (73.6%) with age above 50 (73.7%), majority had underlying hematological malignancy (64.7%) and 1 to 3 co-morbid conditions (95.1%). There was a rising incidence of C diff colitis in febrile neutropenia from 4.11 %(2008) to 5.83 % (2014). The In-hospital mortality showed a decreasing trend from 7.79%(2008) to 5.32%(2014), likely because of improvements in diagnostics and treatment. Similar trend was observed for median length of stay and the median hospital charges per stay. The overall mortality (6.37% vs 4.61%), Length of Stay >5 days (76.45% Vs 50.98%), Hospital charges >50000 dollars (64.43% Vs 40.29%), Colectomy and colostomy (0.35% vs 0.15%) and discharge to SNF (10.47% vs 6.43%) was significantly more in febrile neutropenia patients with C. Diff vs without C. Diff over 7 years (2008-14). Age above 65 years, Hispanic race, Hematological malignancies, urban hospital settings and sepsis were significant predictors of mortality in febrile neutropenia patients with C diff. colitis.Figure: Graph depicting trends in Mortality, incidence, Median Length of stay and Median cost of care.Conclusion: Despite the significant decrease in mortality, the incidence of C diff. colitis is rising in hospitalized febrile neutropenia patients with underlying hematological malignancies. The liberal and prolonged use of broad spectrum antibiotics in this cohort of patients is one explanation. Risk factor modification, with the best possible empiric antibiotic regimen that doesn't predispose to C. diff. is imperative for reducing mortality and healthcare costs in this cohort.

Plasma presepsin level is an early diagnostic marker of severe febrile neutropenia in hematologic malignancy patients

BackgroundFebrile neutropenia (FN) is a common infectious complication in chemotherapy. The mortality of FN is higher in hematologic malignancy patients, and early diagnostic marker is needed. Presepsin is a prompt and specific marker for bacterial sepsis, but its efficacy in severe febrile neutropenia (FN) is not well confirmed. We tried to clarify whether it is a useful maker for early diagnosis of FN in patients during massive chemotherapy.MethodsWe measured plasma presepsin levels every 2–3 day in FN cases and evaluated its change during the course of massive chemotherapy. The patients had hematologic malignancy or bone marrow failure, and in all cases, neutropenia was severe during the episode. The baseline levels, onset levels, increase rate at FN onset, and onset / baseline ratio were evaluated for their efficacy of early FN diagnosis.ResultsEleven episodes of bacteremia (six gram negatives and five gram positives) in severe neutropenia were analyzed in detail. While plasma presepsin level was strongly associated to the CRP level (r = 0.61, p < 0.01), it was not associated with the absolute WBC count (r = −0.19, p = 0.19), absolute neutrophil count (r = −0.11, p = 0.41) or absolute monocyte count (r = −0.12, p = 0.40). The average of onset presepsin level was 638 ± 437 pg/mL and the cutoff value (314 pg/mL) has detected FN onset in 9 of 11 cases. The two cases undetected by presepsin were both Bacillus species bacteremia.ConclusionsPlasma presepsin level is a reliable marker of FN even in massive chemotherapy with very low white blood cell counts. Closer monitoring of this molecule could be a help for early diagnosis in FN. But bacteremia caused by Bacillus species was an exception in our study.

Cost-effectiveness of febrile neutropenia prevention with primary versus secondary G-CSF prophylaxis for adjuvant chemotherapy in breast cancer: a systematic review

The adoption of primary (PP) versus secondary prophylaxis (SP) of febrile neutropenia (FN), with granulocyte colony-stimulating factors (G-CSF), for adjuvant chemotherapy (AC) regimens in breast cancer (BC) could be affected by its "value for money". This systematic review examined (i) cost-effectiveness of PP versus SP, (ii) FN threshold at which PP is cost-effective including the guidelines 20% threshold and (iii) potential impact of G-CSF efficacy assumptions on outcomes. The systematic review identified all cost-effectiveness/cost-utility analyses (CEA/CUA) involving PP versus SP G-CSF for AC in BC that met predefined inclusion/exclusion criteria. Five relevant CEA/CUA were identified. These CEA/CUA examined different AC regimens (TAC=2; FEC-D=1; TC=2) and G-CSF formulations (filgrastim "F"=4; pegfilgrastim "P"=4) with varying baseline FN-risk (range 22-32%), mortality (range 1.4-6.0%) and utility (range 0.33-0.47). The potential G-CSF benefit, including FN risk reduction with P versus F, varied among models. Overall, relative to SP, PP was not associated with good value for money, as per commonly utilized CE thresholds, at the baseline FN rates examined, including the consensus 20% FN threshold, in most of these studies. The value for money associated with PP versus SP was primarily dependent on G-CSF benefit assumptions including reduced FN mortality and improved BC survival. PP G-CSF for FN prevention in BC patients undergoing AC may not be a cost-effective strategy at the guidelines 20% FN threshold.

Evaluation of malnutrition as a predictor of adverse outcomes in febrile neutropenia associated with paediatric haematological malignancies.

Malnutrition has been reported in the literature to be adversely associated with outcomes in paediatric malignancies. Our objective in this paper was to evaluate malnutrition as a potential predictor for adverse outcomes in febrile neutropenia associated with haematological malignancies. A prospective observational study was performed in a tertiary care teaching hospital of Kolkata, India. Forty-eight participants, suffering from haematological malignancy, were included. Participants were included if they experienced at least one episode of febrile neutropenia. For children aged <5 years, weight for height, height for age and weight for age were used as criteria for defining malnutrition, while body mass index for age was used in children ≥5 years. A total of 162 episodes of febrile neutropenia were studied. Thirty patients (30/48, 62.5%) included in the study had malnutrition. In bivariate analyses at patient level, there is a strong association between malnutrition and death (odds ratio (OR) 7.286, 95% confidence interval (CI) 0.838-63.345, one-tailed P = 0.044), and life-threatening complications show a moderate trend towards significance (OR 3.333, 95% CI 0.791-14.052, one-tailed P = 0.084). Survival functions were significantly different between malnourished and non-malnourished children (log rank test χ(2) = 4.609, degree of freedom = 1, P = 0.032). Wasting was associated with life-threatening complications in children aged <5 years (OR 14, 95% CI 1.135-172.642, one-tailed P = 0.036). Logistic regression analyses at episode level revealed that phase of treatment and respiratory system involvement were significant predictors of death, while malnutrition was not. Malnutrition may be a potential predictor of mortality in febrile neutropenia.

The diagnostic value of soluble urokinase plasminogen activator receptor compared with C-reactive protein and procalcitonin in children with febrile neutropenia

ABSTRACTThe aim of the present study was to determine the diagnostic value of soluble urokinase plasminogen activator receptor (suPAR) in pediatric patients with febrile neutropenia. A prospective case-control study was performed. Patients included 29 children with febrile neutropenia (FN) and 27 control subjects without any infection or immunosuppressive condition. Blood samples were obtained on the day of admission and on the 4th to 7th days of the hospital stay. The median (minimum–maximum) serum levels of suPAR obtained on the first day of the admission were 2.08 (0.93–9.42) and 2.22 (1.08–5.13) ng/mL for the FN group and the control group, respectively. The median serum levels of suPAR in the FN and control groups were not significantly different (P = .053). The mean serum suPAR level was significantly higher in nonsurvivors than in survivors in the FN group (P < .05). In the FN group, the area under the receiver operating characteristics curve (AUCROC) for suPAR was 0.546, but no optimum cutoff value, sensitivity, specificity, negative predictive value (NPV), or positive predictive value (PPV) was obtained. We conclude that suPAR is not useful as a diagnostic biomarker in children with febrile neutropenia; however, persistent high serum suPAR level may predict mortality in FN in children.

Meropenem versus piperacillin-tazobactam as empiric therapy for febrile neutropenia in pediatric oncology patients.

Infection is a serious cause of mortality in febrile neutropenia of pediatric cancer patients. Recently, monotherapy has replaced the combination therapy in empirical treatment of febrile neutropenia. Since there has been no reported trial comparing the efficacy of meropenem and piperacillin-tazobactam (PIP/ TAZ) monotherapies, the present retrospective study was conducted to compare safety and efficacy in febrile neutropenic children with cancer. Charts of febrile, neutropenic children hospitalized at our center between March 2008 and April 2011 for hemato-oncological malignancies were reviewed. Patients received PIP/TAZ 360 mg/kg/day or meropenem 60 mg/kg/day intravenously in three divided doses. Duration of fever and neutropenia, absolute neutrophil count, modification, and success rate were compared between the two groups. Resolution of fever without antibiotic change was defined as success and resolution of fever with antibiotic change or death of a patient was defined as failure. Modification was defined as changing the empirical antimicrobial agent during a febrile episode. Two hundred eighty four febrile neutropenic episodes were documented in 136 patients with a median age of 5 years. In 198 episodes meropenem and in 86 episodes PIP/ TAZ were used. Duration of fever and neutropenia, neutrophil count, sex, and primary disease were not different between two groups. Success rates and modification rate between two groups showed no significant differences (p>0.05). Overall success rate in the meropenem and PIP/TAZ groups were 92.4% and 91.9% respectively. No serious adverse effects occurred in either of the groups. Meropenem and PIP/TAZ monotherapy are equally safe and effective in the initial treatment of febrile neutropenia in children with cancer.

Características demográficas, morbilidad y mortalidad de los pacientes adultos con neutropenia febril tratados con cefepima

Cefepime efficacy for treatment of febrile neutropenia (FN) in cancer adult patients is a controversial issue. To describe the demographic characteristics and general mortality of patients suffering from febrile neutropenia treated with cefepime in a fourth-level Latin American hospital. A cross-sectional observational study was performed. Study settled at San Ignacio of Bogotá, Colombia. University Hospital from January 2004 to December 2008. A total of 333 patients were treated with cefepime, of whom 125 had suffered FN and met pre established inclusion and exclusion criteria. The general mortality was 14.4%, which was similar to the overall mortality in FN in other reports. Although there is still no clarity regarding the efficacy of cefepime in FN, its use has not been restricted. This study did not identify an excess risk of mortality in patients treated with cefepime.

3D index calculated from duration and severity of neutropenia and a degree of fever as prognostic factors predicting mortality of chemotherapy-induced febrile neutropenia in hematologic malignancies.

9053 Background: Risk stratification of patients with febrile neutropenia (FN) is important to select the suitable therapeutic option. Although the MASCC scoring system is used as a reliable risk-discriminator, the objective evaluation of “burden of illness” has been difficult to be pointed-out. The latest IDSA Guidelines on FN proposes a set of risk factors based on the expert’s recommendations. The present study demonstrates usefulness of newly proposed 3D-index on predicting mortality of chemotherapy-induced FN in hematologic malignancies (HM). Methods: Patients with HM admitted to our hospital between Jan 2008 and Dec 2011 were enrolled, and data from 282 FN episodes in 129 FN patients including 20 infection-associated deaths were retrospectively analyzed to determine useful prognostic factors on the mortality of FN. Correlation between mortality and 59 characteristics including 3D-index were examined by univariate analysis and receiver operating characteristic curve analysis. 3D-index is a duration and severity of neutropenia and degree of fever. Total duration of days during neutropenia was not calculate at the time of risk evaluation. 3D-indexes after three and five days from the start of FN were also analyzed. Results: 32 out of 59 characteristics were significantly correlated with mortality by univariate analysis. Among them, 3D-index and 3D-indexes after three and five days were demonstrated as more useful factors (3D-index, p=0.0015; 3D-index after three days, p=0.0030; 3D-index after five days, p=0.0044). And 3D-index after three days over 4000 indicates patients' mortality above 20%, index 2600-4000 15-20% , index 900-2600 10-15%, and index below 900 below 10%, respectively. Conclusions: 3D-indexes after three days were suggested as useful predictors for infection-related mortality during FN. It was suggested that FN patients were categorized into four risk groups according to the value.

Microbiology and Mortality of Pediatric Febrile Neutropenia in El Salvador

Febrile neutropenia (FN) and infection-related mortality are major problems for children with cancer in low-income countries. Identifying predictors for adverse outcome of FN in low-income countries permits targeted interventions. We describe the nature and predictors of microbiologically documented infection (MDI) and mortality of FN in children with cancer in El Salvador. We examined Salvadoran pediatric oncology patients admitted with FN over a 1-year period. Data were collected prospectively. Demographic, treatment, and admission-related variables were examined as predictors of outcomes. Hundred six FN episodes among 85 patients were included. Twenty-three of 106 episodes (22%) were microbiologically documented; 13 of 106 episodes (12%) resulted in death. Gram-positive and gram-negative organisms were isolated in 14 of 23 and 11 of 23 specimens; polymicrobial infections were common (11 of 23 episodes of MDI). Older age decreased the MDI risk [odds ratio (OR) per year=0.87, 95% confidence interval (CI), 0.75-0.99; P=0.04] while increasing number of days since the last chemotherapy increased the risk (OR=1.03 per day, 95% CI, 1.01-1.04; P=0.002). Pneumonia diagnosed either clinically (OR=6.6, 95% CI, 1.8-30.0; P=0.005) or radiographically (OR=5.5, 95% CI, 1.7-18.1; P=0.005) was the only predictor of mortality. In El Salvador, polymicrobial infections were common. Pneumonia at admission identified children with FN at high risk of death; these children may benefit from targeted interventions.

Imbalances in serum angiopoietin concentrations are early predictors of septic shock development in patients with post chemotherapy febrile neutropenia

BackgroundFebrile neutropenia carries a high risk of sepsis complications, and the identification of biomarkers capable to identify high risk patients is a great challenge. Angiopoietins (Ang -) are cytokines involved in the control microvascular permeability. It is accepted that Ang-1 expression maintains endothelial barrier integrity, and that Ang-2 acts as an antagonizing cytokine with barrier-disrupting functions in inflammatory situations. Ang-2 levels have been recently correlated with sepsis mortality in intensive care units.MethodsWe prospectively evaluated concentrations of Ang-1 and Ang-2 at different time-points during febrile neutropenia, and explored the diagnostic accuracy of these mediators as potential predictors of poor outcome in this clinical setting before the development of sepsis complications.ResultsPatients that evolved with septic shock (n = 10) presented higher levels of Ang-2 measured 48 hours after fever onset, and of the Ang-2/Ang-1 ratio at the time of fever onset compared to patients with non-complicated sepsis (n = 31). These levels correlated with sepsis severity scores.ConclusionsOur data suggest that imbalances in the concentrations of Ang-1 and Ang-2 are independent and early markers of the risk of developing septic shock and of sepsis mortality in febrile neutropenia, and larger studies are warranted to validate their clinical usefulness. Therapeutic strategies that manipulate this Ang-2/Ang-1 imbalance can potentially offer new and promising treatments for sepsis in febrile neutropenia.