Search

Background Standard 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. Methods This 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. Results Positive 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 Registration NCT02912117 Conclusion KT shows promise in the diagnosis and treatment optimization of FN. [ABSTRACT FROM AUTHOR]

Background Metagenomic next-generation sequencing (mNGS) of plasma cell-free DNA has emerged as an attractive diagnostic modality allowing broad-range pathogen detection, noninvasive sampling, and earlier diagnosis. However, little is known about its real-world clinical impact as used in routine practice. Methods We performed a retrospective cohort study of all patients for whom plasma mNGS (Karius test) was performed for all indications at 5 United States institutions over 1.5 years. Comprehensive records review was performed, and standardized assessment of clinical impact of the mNGS based on the treating team's interpretation of Karius results and patient management was established. Results A total of 82 Karius tests were evaluated from 39 (47.6%) adults and 43 (52.4%) children and a total of 53 (64.6%) immunocompromised patients. Karius positivity rate was 50 of 82 (61.0%), with 25 (50.0%) showing 2 or more organisms (range, 2–8). The Karius test results led to positive impact in 6 (7.3%), negative impact in 3 (3.7%), and no impact in 71 (86.6%), and was indeterminate in 2 (2.4%). Cases with positive Karius result and clinical impact involved bacteria and/or fungi but not DNA viruses or parasites. In 10 patients who underwent 16 additional repeated tests, only 1 was associated with clinical impact. Conclusions The real-world impact of the Karius test as currently used in routine clinical practice is limited. Further studies are needed to identify high-yield patient populations, define the complementary role of mNGS to conventional microbiological methods, and discern how best to integrate mNGS into current testing algorithms. [ABSTRACT FROM AUTHOR]

Objective: to assess the role of oropharyngeal dysphagia (OD) as a risk factor for malnutrition and/or lower respiratory tract infection (LRTI) in the independently-living population of 70 years and over.Design: a population-based cohort study.Subjects and setting: persons 70 years and over in the community (non-institutionalised) were randomly selected from primary care databases.Measurements: the volume-viscosity swallow test (V-VST) was administered by trained physicians at baseline to identify subjects with clinical signs of OD and impaired safety or efficacy of swallow. At the one year follow-up visit, hand grip, functional capacity (Barthel score), nutritional status (mini nutritional assessment, MNA) and LRTI (clinical notes) were assessed.Results: two hundred and fifty-four subjects were recruited (46.5% female; mean age, 78 years) and 90% of them (227) were re-evaluated one year later. Annual incidence of ‘malnutrition or at risk of malnutrition’ (MNA <23.5) was 18.6% in those with basal signs of OD and 12.3% in those without basal signs of OD (P = 0.296). However, prevalent cases of ‘malnutrition or at risk of malnutrition’ at follow up were associated with basal OD (OR = 2.72; P = 0.010), as well as with basal signs of impaired efficacy of swallow (OR = 2.73; P = 0.015). Otherwise, LRTI's annual incidence was higher in subjects with basal signs of impaired safety of swallow in comparison with subjects without such signs (40.0 versus 21.8%; P = 0.030; OR = 2.39).Conclusions: OD is a risk factor for malnutrition and LRTI in independently living older subjects. These results suggest that older persons should be routinely screened and treated for OD to avoid nutritional and respiratory complications. [ABSTRACT FROM AUTHOR]