A comprehensive assessment of the prolonged febrile neutropenia evaluation in pediatric oncology patients.

BACKGROUND: Pediatric oncology patients with prolonged (≥96 hours) febrile neutropenia (absolute neutrophil count < 500/µL) often undergo an evaluation for invasive fungal disease (IFD) and other infections. Current literature suggests that beta-D-glucan (BDG), galactomannan, bronchoalveolar lavage (BAL), and computed tomography (CT) scans (sinus, chest, and abdomen/pelvis) may help determine a diagnosis in this population. METHODS: In a retrospective cohort study of all cancer/stem cell transplant patients (diagnosed 2005-2019) from one pediatric hospital, all episodes with prolonged febrile neutropenia or IFD evaluations (defined as sending a fungal biomarker or performing a CT scan to assess for infection) were identified. RESULTS: In total, 503 episodes met inclusion criteria and 64% underwent IFD evaluations. In total, 36.4% of episodes documented an infection after initiation of prolonged febrile evaluation, most commonly Clostridioides difficile colitis (6.4%) followed by a true bacterial bloodstream infection (BSI) (5.2%), proven/probable IFD (4.8%), and positive respiratory pathogen panel (3.6%). There was no difference in sinus CTs showing sinusitis (74% vs 63%, p = 0.46), whereas 32% of abdomen/pelvis CTs led to a non-IFD diagnosis, and 25% of chest CTs showed possible pneumonia. On chest CT, the positive predictive value (PPV) for IFD was 19% for nodules and 14% for tree and bud lesions. BDG had a PPV of 25% for IFD and GM 50%. BAL diagnosed IFD once and pneumocystis jirovecii pneumonia twice. CONCLUSIONS: Chest CTs and abdomen/pelvis CTs provide clinically relevant information during the prolonged febrile neutropenia evaluation, whereas BDG, galactomannan, BAL, and sinus CTs have less certain utility.

Potential reduction of hospital stay length with outpatient management of low-risk febrile neutropenia in a regional cancer center.

BACKGROUND: Febrile neutropenia is a serious complication of chemotherapy. The Multinational Association for Supportive Care in Cancer (MASCC) risk index score identifies patients at low risk of serious complications. Outpatient management programs have been successfully piloted in other Australian metropolitan cancer centers. AIM: To assess current management of febrile neutropenia at our regional cancer center and determine potential impacts of an outpatient management program. METHOD: We performed a retrospective review of medical records for all patients admitted at our regional institution with febrile neutropenia between 1 January 2016, and 31 December 2018. We collected information regarding patient characteristics, determined the MASCC risk index score, and if low risk, we determined the eligibility for outpatient care and potential reduction in length of stay and cost benefit. RESULTS: A total of 98 hospital admissions were identified. Of these, 66 had a MASCC low-risk index score. Fifty-eight patients met the eligibility criteria for outpatient management. Seventy-one percent were female. The most common tumor type was breast cancer. Forty-eight percent were treated with curative intent. The median length of stay was 3 days. The median potential reduction in length of stay for each admission was 2 days. The total potential reduction in length of stay was 198 days. No admission resulted in serious complications. CONCLUSION: This review demonstrates a significant number of hospital admission days can be avoided. We intend to conduct a prospective pilot study at our center to institute an outpatient management program for such low-risk patients with potential reduction in hospital length of stay. This will have significant implications on health resource usage, service provision planning, and patient quality of life.

Performance and economic evaluation of the molecular detection of pathogens for patients with severe infections: the EVAMICA open-label, cluster-randomised, interventional crossover trial.

PURPOSE: Microbiological diagnosis (MD) of infections remains insufficient. The resulting empirical antimicrobial therapy leads to multidrug resistance and inappropriate treatments. We therefore evaluated the cost-effectiveness of direct molecular detection of pathogens in blood for patients with severe sepsis (SES), febrile neutropenia (FN) and suspected infective endocarditis (SIE). METHODS: Patients were enrolled in a multicentre, open-label, cluster-randomised crossover trial conducted during two consecutive periods, randomly assigned as control period (CP; standard diagnostic workup) or intervention period (IP; additional testing with LightCycler®SeptiFast). Multilevel models used to account for clustering were stratified by clinical setting (SES, FN, SIE). RESULTS: A total of 1416 patients (907 SES, 440 FN, 69 SIE) were evaluated for the primary endpoint (rate of blood MD). For SES patients, the MD rate was higher during IP than during CP [42.6% (198/465) vs. 28.1% (125/442), odds ratio (OR) 1.89, 95% confidence interval (CI) 1.43-2.50; P < 0.001], with an absolute increase of 14.5% (95% CI 8.4-20.7). A trend towards an association was observed for SIE [35.4% (17/48) vs. 9.5% (2/21); OR 6.22 (0.98-39.6)], but not for FN [32.1% (70/218) vs. 30.2% (67/222), P = 0.66]. Overall, turn-around time was shorter during IP than during CP (22.9 vs. 49.5 h, P < 0.001) and hospital costs were similar (median, mean ± SD: IP €14,826, €18,118 ± 17,775; CP €17,828, €18,653 ± 15,966). Bootstrap analysis of the incremental cost-effectiveness ratio showed weak dominance of intervention in SES patients. CONCLUSION: Addition of molecular detection to standard care improves MD and thus efficiency of healthcare resource usage in patients with SES. ClinicalTrials.gov registration number: NCT00709358.

Asymmetric dimethylarginine in the assessment of febrile neutropenia in hematological patients.

Asymmetric dimethylarginine (ADMA) has been recognized as an independent prognostic factor for sepsis mortality in intensive care units. No data are available on kinetics or prognostic value of ADMA in hematological patients. We evaluated the ability of ADMA to act as a predictor for complicated course of febrile neutropenia, defined as bacteremia and/or septic shock in adult hematological patients receiving intensive chemotherapy. This prospective study included 87 adult hematological patients with febrile neutropenia after an intensive chemotherapy for acute myeloid leukemia (AML) or after an autologous stem cell transplantation (ASCT). Plasma ADMA and serum C-reactive protein (CRP) levels were measured from the onset of fever (d0) and for 2 days (d1-d2) thereafter. The levels of ADMA were stable or had only minimal changes during the study period. There was no difference between the levels at any time-point in patients having complicated course compared to those without it. On the other hand, CRP levels were significantly higher on d1 (p = 0.016) in patients with bacteremia and/or septic shock than in those without. ADMA was not able to differentiate hematological patients with a complicated course from those without complications. Elevated ADMA levels are probably associated with organ dysfunction, which is rare in this group of patients, of whom about 95% can be successfully managed at the hematology ward.

Predictive performance of the quick Sequential Organ Failure Assessment score as a screening tool for sepsis, mortality, and intensive care unit admission in patients with febrile neutropenia.

PURPOSE: In Sepsis-3, the quick Sequential Organ Failure Assessment (qSOFA) score was developed as criteria to use for recognizing patients who may have poor outcomes. This study was performed to evaluate the predictive performance of the qSOFA score as a screening tool for sepsis, mortality, and intensive care unit (ICU) admission in patients with febrile neutropenia (FN). We also tried to compare its performance with that of the systemic inflammatory response syndrome (SIRS) criteria and Multinational Association of Supportive Care in Cancer (MASCC) score for FN. METHODS: We used a prospectively collected adult FN data registry. The qSOFA and SIRS scores were calculated retrospectively using the preexisting data. The primary outcome was the development of sepsis. The secondary outcomes were ICU admission and 28-day mortality. RESULTS: Of the 615 patients, 100 developed sepsis, 20 died, and 38 were admitted to ICUs. In multivariate analysis, qSOFA was an independent factor predicting sepsis and ICU admission. However, compared to the MASCC score, the area under the receiver operating curve of qSOFA was lower. qSOFA showed a low sensitivity (0.14, 0.2, and 0.23) but high specificity (0.98, 0.97, and 0.97) in predicting sepsis, 28-day mortality, and ICU admission. CONCLUSIONS: Performance of the qSOFA score was inferior to that of the MASCC score. The preexisting risk stratification tool is more useful for predicting outcomes in patients with FN.

Utility of the Multinational Association for Supportive Care in Cancer (MASCC) Risk Index Score as a Criterion for Nonadmission in Febrile Neutropenic Patients with Solid Tumors.

Febrile neutropenic episodes in patients with solid tumors were identified electronically from 10/1/2008 to 11/15/2010. Inclusion criteria were met in 198 episodes. Sensitivity, specificity, and positive and negative predictive values of the MASCC risk index score vs complications were, respectively, 94%, 29.6%, 57.7%, and 82.9%. An MASCC risk index score of 21 or greater could not be used as a criterion for "no complication/ do not admit." Inability to eat should be an admission criterion.