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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

PURPOSE: Febrile 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. METHODS: The 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. RESULTS: The 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). CONCLUSION: Mortality 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.

Incorporating Absolute Phagocyte Count With Absolute Neutrophil Count as a Measure for Safe Discharge for Pediatric Oncology Febrile Neutropenia: A Pilot Study.

Adequate bone marrow recovery is a discharge requirement after admission for febrile neutropenia in oncology patients, without specific threshold in consensus guidelines. In January 2016, our institution implemented count recovery criteria of absolute neutrophil count ≥100 cells/µL and absolute phagocyte count ≥300 cells/µL compared with prior criteria of absolute neutrophil count ≥500 cells/µL. Retrospective analysis comparing pre (July 2013 to December 2015, N=68) and post (January 2016 to June 2018, N=30) groups showed no difference in readmissions (P>0.9), no patient deaths, and decreased average length of stay in the post group (P<0.0001). Updated count recovery criteria seem feasible and safe.

Comparison of Different Doses of Granulocyte Colony-stimulating Factor in the Treatment of High-risk Febrile Neutropenia in Children With Cancer.

Febrile neutropenia (FEN) is a significant side effect after chemotherapy, and it is known that using granulocyte colony-stimulating factor (G-CSF) has positive effects on treatment results. In this study, the effects of different G-CSF doses (5 to 10 mcg/kg/day) on treatment results in patients with high-risk FEN were evaluated. A total of 124 high-risk FEN episodes of 62 patients were enrolled in the study between June 2017 and October 2018. The episodes were divided into 2 groups according to G-CSF treatment doses, they received from 5 to 10 mcg/kg/day. The clinical characteristics of the patients, the treatments they received, laboratory findings, microbiologic results, and cost analysis were recorded. No statistically significant difference was found between 2 groups in terms of the mean duration of recovery from neutropenia, duration of fever, total length of hospital stay, duration of FEN episode, duration of G-CSF use, costs, bacteremia frequency, and other treatments. In patients with solid tumors, the cost of filgrastim was significantly higher in the high-dose G-CSF group. Using different doses of G-CSF in high-risk FEN episodes did not show any different effects on clinical and treatment results. The dose of 5 mcg/kg/day would be more appropriate in FEN treatment.

The Feasibility of Host Transcriptome Profiling as a Diagnostic Tool for Microbial Etiology in Childhood Cancer Patients with Febrile Neutropenia.

Infection is a common and serious complication of cancer treatment in children that often presents as febrile neutropenia (FN). Gene-expression profiling techniques can reveal transcriptional signatures that discriminate between viral, bacterial and asymptomatic infections in otherwise healthy children. Here, we examined whether gene-expression profiling was feasible in children with FN who were undergoing cancer treatment. The blood transcriptome of the children (n = 63) was investigated at time of FN diagnosed as viral, bacterial, co-infection or unknown etiology, respectively, and compared to control samples derived from 12 of the patients following the FN episode. RNA sequencing was successful in 43 (68%) of the FN episodes. Only two genes were significantly differentially expressed in the bacterial versus the control group. Significantly up-regulated genes in patients with the other three etiologies versus the control group were enriched with cellular processes related to proliferation and cellular stress response, with no clear enrichment with innate responses to pathogens. Among the significantly down-regulated genes, a few clustered into pathways connected to responses to infection. In the present study of children during cancer treatment, the blood transcriptome was not suitable for determining the etiology of FN because of too few circulating immune cells for reliable gene expression analysis.

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

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Single-center risk factor analysis for FOLFIRINOX associated febrile neutropenia in patients with pancreatic cancer.

PURPOSE: FOLFIRINOX is the standard therapy in patients with unresectable pancreatic cancer (PC). However, FOLFIRINOX frequently induces febrile neutropenia (FN) and neutropenia. The purpose of this study was to explore risk factors for FN and grade 4 neutropenia (NP G4) in patients receiving FOLFIRINOX for PC. METHODS: We collected data on 106 patients with PC treated with first-line FOLFIRINOX between 2015 and 2017 using the Pancreatic Cancer Cohort Registry of Severance Hospital in Seoul, Korea. RESULTS: Multivariate logistic regression analysis showed that female (OR, 3.24; P = 0.023), Eastern Cooperative Oncology Group performance status (OR, 3.70; P = 0.024), overweight (OR, 4.25; P = 0.022), and initial biliary stent insertion (OR, 4.22; P = 0.008) were significantly related to a high risk of FN. Time-dependent bias was reduced using Cox regression analysis, which revealed that female (OR, 2.29; P = 0.041), overweight (OR, 2.67; P = 0.022), and initial biliary stent insertion (OR, 2.59; P = 0.016) were statistically significant predictors. Regarding NP G4, female sex (OR, 2.90; P = 0.016) and overweight (OR, 4.07; P = 0.033) were identified as risk factors in multivariate analysis; however, in Cox regression analysis, tumor in the head of the pancreas (OR, 1.96; P = 0.027) and hemoglobin (g/dL < 12) (OR, 1.87; P = 0.049) were also identified as risk factors. CONCLUSION: Female sex, overweight, and initial biliary stent insertion were independent risk factors for the occurrence of FN in patients with unresectable PC treated with FOLFIRINOX.

Safety and efficacy of step-down to oral outpatient treatment versus inpatient antimicrobial treatment in pediatric cancer patients with febrile neutropenia: A noninferiority multicenter randomized clinical trial.

BACKGROUND: It has been suggested that low-risk febrile neutropenia (FN) episodes can be treated in a step-down manner in the outpatient setting. This recommendation has been limited to implementation in middle-income countries due to concerns about infrastructure and lack of trained personnel. We aimed to determine whether early step-down to oral antimicrobial outpatient treatment is not inferior in safety and efficacy to inpatient intravenous treatment in children with low-risk FN. PROCEDURE: A noninferiority randomized controlled clinical trial was conducted in three hospitals in Mexico City. Low-risk FN was identified in children younger than 18 years. After 48 to 72 hours of intravenous treatment, children were randomly allocated to receive outpatient oral treatment (experimental arm, cefixime) or to continue inpatient treatment (standard of care, cefepime). Daily monitoring was performed until neutropenia resolution. The presence of any unfavorable clinical outcome was the endpoint of interest. We performed a noninferiority test for comparison of proportions. RESULTS: We identified 1237 FN episodes; 117 cases were randomized: 60 to the outpatient group and 57 for continued inpatient treatment. Of the FN episodes, 100% in the outpatient group and 93% in the inpatient group had a favorable outcome (P < 0.001). The mean duration of antibiotics was 4.1 days (SD 2.5; 95% CI, 3.4-4.8 days) in the outpatient group and 4.4 days (SD 2.5; 95% CI, 3.7-5.0 days) in the inpatient group (P = 0.70). CONCLUSIONS: In our population, step-down oral outpatient treatment of low-risk FN was as safe and effective as inpatient intravenous treatment. Clinical Trials Identifier: NCT04000711.

Mortality and admission to intensive care units after febrile neutropenia in patients with cancer.

Febrile neutropenia (FN) is a critical complication of chemotherapy associated with increased in-hospital mortality. However, associations with increased mortality and intensive care unit (ICU) admissions during longer follow-up are not established. Patients treated with standard first-line chemotherapy for solid cancers at Rigshospitalet, Denmark in 2010-2016 were included. Incidence rate ratios (IRR) of all-cause, infectious and cardiovascular mortality, and ICU admissions after FN were analyzed by Poisson regression. Risk factors at the time of FN were analyzed in the subpopulation of patients with FN; all-cause mortality was further stratified by the time periods 0-30, 31-365, and 366+ days after FN. We included 9018 patients with gastric (14.4%) and breast (13.1%) cancer being the most common, 51.2% had locally advanced or disseminated disease and the patients had a median Charlson Comorbidity Index score of 0 (interquartile range, 0-0). During follow-up, 845 (9.4%) experienced FN and 4483 (49.7%) died during 18 775 person-years of follow-up. After adjustment, FN was associated with increased risk of all-cause mortality, infectious mortality, and ICU admissions with IRRs of 1.39 (95% CI, 1.24-1.56), 1.94 (95% CI, 1.43-2.62), and 2.28 (95% CI, 1.60-3.24). Among those with FN, having a positive blood culture and low lymphocytes were associated with excess risk of death and ICU admissions (predominantly the first 30 days after FN), while elevated C-reactive protein and low hemoglobin predicted mortality the first year after FN. The risk of death varied according to the time since FN; adjusted IRR per additional risk factor present for the time periods 0-30, 31-365, and 366+ days after FN were 2.00 (95% CI, 1.45-2.75), 1.36 (95% CI, 1.17-1.57), and 1.17 (95% CI, 0.98-1.41). FN was associated with increased mortality and risk of ICU admissions. An objectively identifiable subgroup of patients among those with FN carried this excess risk.

Meropenem to Children With Febrile Neutropenia Induces Monoresistant Pseudomonas aeruginosa.

Antimicrobial resistance in Pseudomonas aeruginosa is a threat to children with cancer. We explored the association between P. aeruginosa resistance and previous antibiotic exposure. All children with cancer and P. aeruginosa bacteremia in 2007 to 2016 in Denmark, a country with an overall resistance rate of ∼3%, were included. Twenty percent (10/49) of isolates from children previously exposed to meropenem were meropenem nonsusceptible. The only significant risk factor of meropenem nonsusceptibility was previous meropenem therapy (P=0.03). On the basis of these results, we suggest that meropenem should be reserved as a last resort for children with febrile neutropenia in countries with low antimicrobial resistance.

PROGNOSIS OF THE COURSE OF CHORNOBYL-ORIGINATED ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDREN IN UKRAINE DEPENDING ON THE REASON OF STANDARD CHEMOTHERAPY INTERRUPTION. / PROGNOZ PEREBIGU GOSTRYKh LIMFOBLASTNYKh LEY̆KEMIY̆ ChORNOBYL'S'KOGO POKhODZhENNIa U DITEY̆ UKRAÏNY ZALEZhNO VID PRYChYN PERERV PRY PROVEDENNI STANDARTNOÏ KhIMIOTERAPIÏ.

OBJECTIVE: Estimation of the bone marrow haemopoietic status depending on the reasons and duration of breaks in a standard chemotherapy (BFM-ALL protocol) to predict the course of acute lymphoblastic leukemia (ALL) in chil- dren exposed to low doses of ionizing radiation after the Chornobyl accident. MATERIALS AND METHODS: The ALL patients (n = 34) were examined within 5 stages of a program chemotherapy. The clinical symptoms, hemogram and myelogram data were analyzed. The radiation dose on bone marrow, initial leuko- cyte count, variants and prognosis of ALL course were accounted. Days of the stopped chemotherapy, type and fre- quency of complications (septic processes, febrile neutropenia, toxic hepatitis, granulocytopenia degree), and the prognosis of disease course (child living status, i.e. alive or died) were estimated. RESULTS: There were abnormal differentiation processes and high percentage of lymphoblasts (86.2 ± 3.3) % in bone marrow in the 1st acute period. Hematological remission was established in all patients on the 33rd day of chemothe- rapy. In a half of cases the haematopoietic recovery occurred by a granulocyte-monocyte type. One third of patients presenting an erythroid type of haemopoiesis died later. The inverse correlation was found between the number of myelocaryocytes and disease prognosis (rs = -0.49). Breaks in chemotherapy for various reasons were recorded. The number of patients with granulocytopenia was greater at the phase 1 and 2 of protocol I and protocol M application, coinciding with a higher incidence of complications. An inverse correlations between the prediction of ALL course and sum of days of breaks between the protocol M and phase 1 of protocol II (rs = -0.56), as well as the duration of the phase 2 of protocol II (rs = -0.62) were found. The radiation dose on bone marrow was (5.37 ± 1.23) mSv. No relationship was found between the radiation doses, ALL variants and disease course. CONCLUSIONS: Prognosis of ALL course in children depends on the type of haemopoietic recovery and reasons of breaks in a standard chemotherapy. Interaction between the haemopoiesis functioning and microenvironment and that of their regulation are the key mechanisms of above-mentioned abnormalities, which is the basis for further research.

A Randomized, Open-Labeled, Prospective Controlled Study to Assess the Efficacy of Frontline Empirical Intravenous Piperacillin/Tazobactam Monotherapy in Comparison with Ceftazidime Plus Amikacin for Febrile Neutropenia in Pediatric Oncology Patients.

Background: Febrile neutropenia (FN) is the most common complication in pediatric oncology patients. Appropriate empirical antibiotics treatment is essential for treatment outcome. Methods: This study was a randomized prospective controlled study to demonstrate the efficacy of piperacillin/tazobactam (PIP/TZO) monotherapy compared with ceftazidime/amikacin in children with FN. Pediatric oncology patients at Chiang Mai University Hospital, diagnosed with FN, were randomized to receive either PIP/TZO 320 mg/kg/day divided every 8 hours or ceftazidime 100 mg/kg/ day divided every 8 hours plus amikacin 15 mg/kg/day once daily. Treatment responses were compared between the two groups. Results: One-hundred and eighteen febrile neutropenic episodes in 70 patients (42 males and 28 females) were enrolled. The median age was 7 (3-10) years. The early response and complete response to initial treatment were achieved in 48/59 (81.4%) episodes and 41/59 (69.5%) episodes in PIP/TZO group compared with 40/59 (67.8%) episodes and 33/59 (55.9%) episodes in ceftazidime/amikacin group (p-value 0.091 and 0.128, respectively). Treatment modification in PIP/TZO group was required in 18/59 (30.5%) compared with 26/59 (44.1%) patients in ceftazidime/amikacin group (p-value 0.128). Similarly, the duration of fever, duration of neutropenia and duration of antibiotics treatment were not significantly different between two groups. No serious adverse events were observed. Conclusion: The treatment responses of PIP/TZO monotherapy and ceftazidime/amikacin therapy were not significantly different. Both therapies were effective for FN in pediatric oncology patients.

Prevalence and clinical outcome of respiratory viral infections among children with cancer and febrile neutropenia.

Background: The role of respiratory viruses (RV) in children with cancer having febrile neutropenic episodes has not been well studied. The objectives of our study were to investigate the prevalence and clinical outcomes of Respiratory viral infection (RVI). Methods: Children with cancer and febrile neutropenia (FN) having acute respiratory infections (ARI) were considered as cases and febrile neutropenic cancer patients without ARI were considered as controls. A throat swab sample was obtained for the detection of 21-respiratory pathogens. Results: A total of 81 episodes of FN in cases and 37 episodes of FN in controls were included. Prevalence of RVI (at least 1 RV) was seen in 76.5% of cases and 48.6% of controls (p = 0.005). The mixed-respiratory viruses (co-infections of ≥2 viruses) were seen only in cases (26%) (p = 0.00). Rhinovirus (36.8%) and respiratory syncytial virus (13.6%) were the most frequently detected viruses. Median duration of fever before presentation was more in cases with RVI compared to without RVI [2 (1-5) days vs 1 (1-5) day (p = 0.012)]. The median total duration of febrile period was 4 (IQR, 3-6) days in cases with RVI and 3 (IQR, 1-4) days in cases without RVI (p = 0.005). The median duration of antibiotic days were longer in cases with RVI as compared to patients without RVI [9 (IQR, 7-17) days vs 7 (IQR, 6-10) days (p = 0.046)] respectively. Conclusion: There was high prevalence of RVI in children with cancer and FN; more in association with ARI. The RVI were associated with prolonged febrile period and days of antibiotics therapy.

Risk factors for neutropenia and febrile neutropenia following prophylactic pegfilgrastim.

AIM: Neutropenia is a common side effect of myelosuppressive chemotherapy. Administration of granulocyte colony-stimulating factor is being used for neutropenia prophylaxis, but there are patients who develop neutropenia or febrile neutropenia despite prophylaxis. We attempted to identify potential risk factors for chemotherapy-induced neutropenia in patients with pegfilgrastim prophylaxis. METHODS: This was a single-center, retrospective, observational study of patients with breast cancer or diffuse large B-cell lymphoma. We obtained patients' data from electronic medical records, including baseline demographics and clinical characteristics regarding diseases, treatments and laboratory values. The outcome measures assessed were the incidence of neutropenia and febrile neutropenia. RESULTS: There were a total of 127 patients, including 77 patients with diffuse large B-cell lymphoma (DLBCL) and 50 patients with breast cancer, and we analyzed 722 chemotherapy cycles. We found 88 cases (12.2%) of grade 3 or 4 neutropenia and 39 cases of febrile neutropenia (5.4%). In the univariate analysis, variables associated with both grade 3 or 4 neutropenia and febrile neutropenia were age, cancer type, cancer stage, radiotherapy and platelet count. A multivariate logistic regression model revealed that age, radiotherapy and platelet count were significant factors in severe neutropenia, whereas platelet count was the only statistically significant factor in febrile neutropenia. Platelet counts of less than 150 000/mm3 increased the risk of neutropenia and febrile neutropenia approximately fourfold. In the subgroup analysis of patients with DLBCL, it was found that platelet count was a significant factor for both neutropenia and febrile neutropenia. CONCLUSION: Among cancer patients with pegfilgrastim prophylaxis, advanced age, absence of radiation therapy and low platelet count were independent predictors of neutropenia, and low platelet count was the predictor of febrile neutropenia.

Evaluation of a Carbapenem-Saving Strategy Using Empirical Combination Regimen of Piperacillin-Tazobactam and Amikacin in Hemato-Oncology Patients.

We implemented a carbapenem-saving strategy in hemato-oncology patients from 2013, using an empirical combination of piperacillin-tazobactam and amikacin for high-risk hemato-oncology patients with febrile neutropenia, who remain hemodynamically unstable > 72 hours despite initial cefepime treatment. All-cause mortality was not different between the two periods (6.54 and 6.57 deaths per 1,000 person-day, P = 0.926). Group 2 carbapenem use significantly decreased after strategy implementation (78.43 vs. 67.43 monthly days of therapy, P = 0.018), while carbapenem-resistant gram-negative bacilli did not show meaningful changes during the study period. Our carbapenem-saving strategy could effectively suppress carbapenem use without an increase of overall mortality.

Associated factors and clinical outcomes of bloodstream infection due to extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae during febrile neutropenia.

Patients with neutropenia are vulnerable to serious infections. During the last decade, increased prevalence of extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae has affected immunocompromised patients. We conducted a single-center case-control study to evaluate factors associated with ESBL-positive bacteremia among neutropenic patients, and its clinical impact. The study included adult patients with hematologic or oncologic diseases diagnosed with ESBL-positive and ESBL-negative Escherichia coli or Klebsiella pneumoniae bacteremia during febrile neutropenia between January 2010 and October 2017 at the Shaare Zedek Medical Center, Jerusalem, Israel. Analyses included risk factors for ESBL-positive bacteremia, appropriateness of empiric antibiotics, mortality, length of stay, and intensive care unit (ICU) admission. Univariate and multivariate models were constructed. The cohort (80 patients), consisted of 54 ESBL-negative and 26 ESBL-positive Gram-negative bacteremia. Multivariate analysis suggested ESBL-positive bacteremia to be associated with long-term central venous catheter (CVC) (odds ratio (OR), 8.7; 95% confidence interval (CI), 1.6-48.1; P=0.01], index culture obtained 48 h post-admission (OR, 3.6; 95% CI, 1-12.3; P=0.04), and exposure to previous antimicrobial therapy (OR, 12.6; 95% CI, 2.1-74; P<0.01). There were no significant differences between groups with regard to length of stay, ICU admission, or mortality rates. Mortality was associated with high Pitt bacteremia score but not inappropriate empirical therapy. Previous antimicrobial therapy, long-term CVC, and hospital-acquired bacteremia were associated with ESBL bacteremia. Neutropenic patients with ESBL bacteremia have increased morality due to other factors than ESBL status. These findings should be validated in other centers and with larger populations.

Prospective study of a web-mediated management of febrile neutropenia related to chemotherapy (Bioconnect).

BACKGROUND: We aimed to investigate whether patient self-evaluated symptoms transmitted via Internet is feasible between planned visits to provide an early management of fever and neutropenia induced by chemotherapy, and if it can reduce hospitalizations for severe neutropenia. METHODS: Patients who received a chemotherapy regimen with an overall risk of febrile neutropenia ≥ 20% had to report daily temperature between physician planned visits using a web application. Fever and clinical signs of seriousness were reported to the physician (if some criteria were fulfilled in a specific algorithm) via automatic email notifications by the web application. Patients could be hospitalized quickly or could take over at home, make blood count, and take predefined oral antibiotics if indicated. Primary outcome was patient's compliance and satisfaction. The number and the cost of hospitalization were also assessed and compared with an historical cohort of patients with similar clinical conditions and treatment. RESULTS: Among the 41 patients included, 36 (87.8%) used the web application with 88% of daily compliance and 90% (28/33) of satisfaction. One patient (2.7%) had planned hospitalization after the web application alert. In the historical cohort, the rate of unplanned hospitalization for febrile neutropenia was 17% (6 patients) and 2.7% (1 patient) in users of the web application cohort. The cumulative cost of hospitalization for neutropenia was USD 28,827 in the historical cohort and USD 6563 in the web application cohort. CONCLUSION: Web-mediated follow-up of febrile neutropenia is feasible. It led to high patient satisfaction, high compliance, and a possible reduction of the number and the cost of hospitalizations.