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Background Ceftazidime-avibactam (caz-avi), a novel β-lactam/β-lactamase inhibitor, is commonly utilized for carbapenem-resistant gram-negative infections (CR-GNI). However, the benefits vs risks of combining caz-avi with other agents are unclear. Methods In this retrospective cohort study, inpatients with CR-GNI treated with caz-avi were identified at 9 U.S. hospitals. The impact of caz-avi monotherapy (MT) or combination therapy (CT; i.e., any concomitant use of gram-negative-active antibiotics) was studied using logistic regression, controlling for baseline patient and hospital factors. The primary outcome was in-hospital mortality or discharge to hospice (death), and secondary outcomes were length of stay (LOS), resolution of infectious signs and symptoms (clinical response), 90-day recurrent infection and future caz-avi–resistant organism. An adjusted odds ratio (aOR) with 95% confidence interval (CI) was used to assess the primary and secondary outcomes. Results 328/499 (65.7%) patients received caz-avi as targeted therapy for a CR-GNI. Overall patients treated with MT and CT were similar at baseline and had comparable baseline demographics although patients treated with CT were more likely to be in the ICU and receive a concomitant empiric in vitro-concordant antibiotic (table 1). The most common organism was Klebsiella spp. (44.6%) followed by Pseudomonas aeruginosa (27.7%) (table 2). Concomitant gram-negative agents are shown in table 3. Overall, 92 (28.1%) patients died and CT (vs MT) displayed similar adjusted mortality risk (27.7% vs 28.7%; aOR [95%CI]: 0.67 [0.34-1.33]) and LOS (19 [9, 37] and 20 [9, 42.5] days). CT (vs MT) was associated with greater odds of clinical response (aOR: 2.25 [95%CI:1.15-4.41]). Among survivors, similar rates of 90-day recurrent infection (50/154 (32.5%) were observed in CT vs 18/82 (22.0%) in MT group (p=0.09) and 5 (2.19%) patients had future infection with a caz-avi–resistant pathogen (3 in CT and 2 in MT group). Conclusion Compared to patients with CR-GNI treated with caz-avi alone, those who received CT including caz-avy had similar survival and LOS but higher clinical response. The role of CT in the era of novel antibiotics warrants additional study. Disclosures Helen W. Boucher, MD, American Society of Microbiology: Honoraria|Elsevier: Honoraria|Sanford Guide: Honoraria.

Determining the causative etiology of culture-negative endocarditis can be challenging. We performed next-generation sequencing of plasma microbial cell-free DNA to facilitate rapid diagnosis and genotyping of Coxiella burnetii in a patient with culture-negative endocarditis of a prosthetic pulmonary valve, enabling early targeted treatment prior to valve replacement surgery.

Determining the causative etiology of culture-negative endocarditis can be challenging. We performed next-generation sequencing of plasma microbial cell-free DNA to facilitate rapid diagnosis and genotyping of Coxiella burnetii in a patient with culture-negative endocarditis of a prosthetic pulmonary valve, enabling early targeted treatment prior to valve replacement surgery.

Background Identification of Coxiella burnetii, the etiologic agent of Q Fever, in culture-negative endocarditis (CNE) remains challenging, and strain-level information is typically unavailable through conventional testing. We used a novel next-generation sequencing (NGS) assay on plasma cell-free DNA to facilitate rapid diagnosis and genotyping in a patient with C. burnetii CNE. Methods NGS was performed on plasma by Karius, Inc. (Redwood City, California). Human reads were removed and remaining sequences were aligned to a curated database of over 1,000 pathogens. Organisms present above a predefined significance threshold were reported. For C. burnetti strain-typing, alignments to different Coxiella strains in the pathogen database were compared by BLAST bit-score to determine the most closely related strain to the infecting organism. C. burnetii genotype group was also determined by in silico analysis of polymorphic ORF deletion markers known to distinguish groups I–VI. Results Twenty-nine-year-old male with history of Tetralogy of Fallot, multiple pulmonary valve replacement (PVR), and 18 months of intermittent fever and night sweats were admitted. Relevant history included travel in South and South East Asia, the use of a LivaNova 3T Heater-Cooler device during surgery (i.e., at risk for Mycobacterium chimaera), and drinking unpasteurized milk. Cardiac CT showed 2 pulmonary opacities concerning for septic emboli and echocardiography showed echodensity on pulmonic valve. Blood cultures were negative. NGS detected C. burnetii within 48 hours of sample receipt. On the basis of these results, hydroxychloroquine and doxycycline were initiated with symptomatic improvement. Strain-typing demonstrated highest relatedness to the CbuK_Q154 (group IV) strain typically seen in North America. Genotype group was independently confirmed by inference of a pattern of ORF deletion most similar to group IV (and highly related group VII). Serologic testing for C. burnetii confirmed the diagnosis. After 4 weeks of antibiotics, the patient underwent successful PVR with graft exchange. Conclusion NGS testing aided in diagnosis of C. burnetii CNE, enabling early targeted antimicrobial therapy. It also allowed inference of strain-level information, supporting further investigations regarding epidemiologic origins of this pathogen. Disclosures S. Dalai, Karius, Inc.: Consultant, Consulting fee. S. Venkatasubrahmanyam, Karius, Inc.: Employee, Salary.