Use of Advanced Diagnostics for Timely Identification of Travel-associated Leptospira santarosai Infection in Four Adolescents Through Plasma Microbial Cell-free DNA Sequencing With the Karius Test.

BACKGROUND: Leptospirosis is an important zoonotic infection worldwide. Diagnosis of leptospirosis is challenging given its nonspecific clinical symptoms that overlap with other acute febrile illnesses and limitations with conventional diagnostic testing. Alternative advanced diagnostics, such as microbial cell-free DNA (mcfDNA), are increasingly being used to aid in the diagnosis of infections and can be applied to pathogens with public health importance such as Leptospira , a nationally notifiable disease. METHODS: The Karius Test uses plasma mcfDNA sequencing to detect and quantify DNA-based pathogens. This test offered through the Karius lab detected 4 cases of Leptospira santarosai during a 5-month period across the United States in 2021 and were clinically reviewed. RESULTS: In our case series, 4 adolescents with recent travel to Central America (Costa Rica, n = 3 and Belize, n = 1) from April to August 2021 were diagnosed with leptospirosis. While a large workup was performed in all cases, mcfDNA testing was the first test to detect L. santarosai as the microbiological diagnosis in all cases. CONCLUSIONS: Results of the Karius Test enabled rapid, noninvasive diagnosis of leptospirosis allowing for targeted therapy. Use of mcfDNA can be utilized for diagnosis of pathogens where conventional testing is challenging or limited. This in turn can enable quick diagnosis for targeted treatment and potentially aid in supporting case definitions of reportable diseases of public health concern.

Hospital-wide Description of Clinical Indications for Pediatric Anti-infective Use.

PURPOSE: This study is the first description of hospital-wide anti-infective use according to clinical indication for a pediatric hospital. Children's Hospital Colorado (CHCO) is uniquely poised to examine its anti-infective use after the implementation of provider-selected order indications (PSOIs), which are distinct from Diagnosis Related Group classifications in that they are used for clinical treatment as opposed to final diagnosis codes for billing and thus are more granular. METHODS: This study used our institution's mandatory PSOIs to describe overall clinical indications for anti-infective use. For 2016, all anti-infective orders were extracted from the electronic medical record (Epic), including drug name, route, prescribing unit, and PSOI. We calculated the number of times each drug was associated with each indication and the number of times an indication was attributed to each drug, and then analyzed these data in Excel. FINDINGS: There were 29,258 orders at CHCO in 2016 with at least 1 indication. The most common clinical indication was "prophylaxis-medical/surgical," accounting for 23% of all orders and commonly associated with cefazolin (42% of prophylaxis-medical/surgical orders). This was followed by the indications of "sepsis/bacteremia" and "pneumonia/sinusitis." The most commonly prescribed anti-infectives for nonprophylactic clinical indications were IV vancomycin (14%), ceftriaxone (11%), and ampicillin (6%). IMPLICATIONS: Knowledge of the clinical reasons for hospital-wide anti-infective use enables hospitals to identify targets for improved use through education and guideline and policy development. This description provides better details than billing codes about the clinical reasons anti-infectives are used and offers a useful template for implementation at other hospitals.