Time to defervescence evaluation for extended- vs. standard-infusion cefepime in patients with acute leukemia and febrile neutropenia.

BACKGROUND/OBJECTIVES: Febrile neutropenia (FN) occurs in up to 80% of patients with hematologic malignancies. Evidence suggests using extended infusions (EI) of beta-lactams can improve outcomes in some populations, but there is limited clinical literature comparing cefepime standard infusion (SI) versus EI for FN. The FDA-approved regimen for FN was used at a large community teaching hospital for patients with FN until a hospital-wide EI beta-lactam protocol was introduced that allowed for EI cefepime in FN at the physicians' discretion. We sought to compare outcomes between patients with FN who received SI and EI cefepime. METHODS: Patients with acute myeloid or lymphocytic leukemia who developed FN between April 2014 and January 2021 were included in this single-center, retrospective study. The primary outcome was to compare mean time to defervescence after the initiation of cefepime SI or EI regimens. SI regimens consisted of IV cefepime 2G q8h/0.5 h, and EI regimens as IV cefepime 1G q8h/4 h. Secondary outcomes included 30-day all-cause mortality, hospital length of stay (LOS), duration of cefepime, and need to escalate therapy. RESULTS: Overall, 193 patients were included. Baseline characteristics were similar between groups. Time to defervescence was significantly shorter with EI compared with the SI group (median 48 h [48-100.5] vs. 70 h [48-113], p = 0.005). Cefepime duration of therapy was significantly shorter in the EI compared with the SI group (median 6.0 days vs. 8.0 days, p = 0.002). There was no difference between other secondary outcomes including LOS, mortality, and antibiotic escalation. CONCLUSION: Despite reduced total daily dose of cefepime, EI cefepime administered as a 1G/0.5 h LD followed 2 h later by 1G q8h/4 h for FN acutely achieves more rapid defervescence than the FDA-approved SI regimen and ultimately attains comparable patient outcomes.

Association of Elevated Amyloid and Tau Positron Emission Tomography Signal With Near-Term Development of Alzheimer Disease Symptoms in Older Adults Without Cognitive Impairment.

Importance: National Institute on Aging-Alzheimer's Association (NIA-AA) workgroups have proposed biological research criteria intended to identify individuals with preclinical Alzheimer disease (AD). Objective: To assess the clinical value of these biological criteria to identify older individuals without cognitive impairment who are at near-term risk of developing symptomatic AD. Design, Setting, and Participants: This longitudinal cohort study used data from 4 independent population-based cohorts (PREVENT-AD, HABS, AIBL, and Knight ADRC) collected between 2003 and 2021. Participants were older adults without cognitive impairment with 1 year or more of clinical observation after amyloid ß and tau positron emission tomography (PET). Median clinical follow-up after PET ranged from 1.94 to 3.66 years. Exposures: Based on binary assessment of global amyloid burden (A) and a composite temporal region of tau PET uptake (T), participants were stratified into 4 groups (A+T+, A+T-, A-T+, A-T-). Presence (+) or absence (-) of neurodegeneration (N) was assessed using temporal cortical thickness. Main Outcomes and Measures: Each cohort was analyzed separately. Primary outcome was clinical progression to mild cognitive impairment (MCI), identified by a Clinical Dementia Rating score of 0.5 or greater in Knight ADRC and by consensus committee review in the other cohorts. Clinical raters were blind to imaging, genetic, and fluid biomarker data. A secondary outcome was cognitive decline, based on a slope greater than 1.5 SD below the mean of an independent subsample of individuals without cognitive impairment. Outcomes were compared across the biomarker groups. Results: Among 580 participants (PREVENT-AD, 128; HABS, 153; AIBL, 48; Knight ADRC, 251), mean (SD) age ranged from 67 (5) to 76 (6) years across cohorts, with between 55% (137/251) and 74% (95/128) female participants. Across cohorts, 33% to 83% of A+T+ participants progressed to MCI during follow-up (mean progression time, 2-2.72 years), compared with less than 20% of participants in other biomarker groups. Progression further increased to 43% to 100% when restricted to A+T+(N+) individuals. Cox proportional hazard ratios for progression to MCI in the A+T+ group vs other biomarker groups were all 5 or greater. Many A+T+ nonprogressors also showed longitudinal cognitive decline, while cognitive trajectories in other groups remained predominantly stable. Conclusions and Relevance: The clinical prognostic value of NIA-AA research criteria was confirmed in 4 independent cohorts, with most A+T+(N+) older individuals without cognitive impairment developing AD symptoms within 2 to 3 years.