Zarkotou, Olympia

Importance Novel blood culture diagnostics provide rapid antimicrobial susceptibility testing (AST) results for bacteria causing bloodstream infections (BSIs) but have unclear clinical impact. Objective To evaluate clinical outcomes of blood culture testing using a rapid AST method compared with standard AST in patients with BSIs caused by gram-negative bacilli in regions with high prevalence of antimicrobial resistance. Design, Setting, and Participants Open-label randomized clinical trial that enrolled participants from December 2023 to May 2025 (final follow-up, June 18, 2025) at 7 medical centers in Greece (n = 2), India (n = 1), Israel (n = 3), and Spain (n = 1). Hospitalized patients (adults and children) with BSIs caused by gram-negative bacilli were eligible. Statistical analysis was conducted from August 2025 to January 2026. Intervention Patients were randomized to undergo blood culture evaluation using rapid, phenotypic AST directly from positive blood cultures plus standard susceptibility testing (n = 413) vs standard susceptibility testing alone (n = 437). Local antimicrobial stewardship teams reviewed all patients and provided treatment recommendations. Main Outcomes and Measures The primary outcome was a desirability of outcome ranking (DOOR) at day 30, with 3 categories (alive without deleterious events, alive with deleterious events, and death). The difference between rapid and standard testing was summarized as the probability that the DOOR outcomes were more desirable in the rapid testing group. Superiority was concluded if the lower limit of the 95% CI exceeded 50%. Secondary outcomes included 30-day mortality, length of hospitalization, intensive care unit admission, acquisition of hospital-acquired infections, time to effective antibiotic therapy within 3 days, and time to antibiotic escalation or deescalation within 3 days. Results Of the 899 patients randomized, 850 were included in the primary outcome analysis (median [IQR] age, 72 [21] years; 43% female). The probability that DOOR outcomes were more favorable in the rapid testing group was 48.8% (95% CI, 45.3%-52.4%). Median time to effective antibiotic therapy was not different between the groups in the as-randomized population. Median time to antibiotic escalation or deescalation was faster in the rapid testing group by 14 hours (95% CI, 6-22) in the as-randomized population. There were no differences between the groups in other secondary outcomes. In the prespecified subgroup with carbapenem-resistant infections, median time to effective therapy was 9.5 hours in the rapid testing group vs 28 hours in the standard testing group (difference, −18 hours [95% CI, −42 to 6]). Conclusions and Relevance Among patients with gram-negative bacilli BSIs, rapid blood culture AST was not superior to standard testing by DOOR. When considered with other efficacy and safety outcomes, these findings may help inform the use of rapid susceptibility testing in clinical practice. Trial Registration ClinicalTrials.gov Identifier: NCT06174649

Abstract Background Intestinal colonization with carbapenem-resistant organisms (CRO) may be considered to inform empiric antibiotic selection for symptomatic infection. However, it is unclear how often gut colonizing CRE isolates are related to bloodstream isolates in hospitalized patients with bacteremia, especially in areas with high CRO prevalence. Minimum spanning tree of isolate relatedness Isolates and corresponding patient number (P1-P6) and rectal (R) or blood (B) specimen are noted within circles and allelic differences are numerated on linking lines between the circles. Group 1 and 3 isolates are possibly related to each other. Created with BioRender.com. Methods Patients with paired K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates cultured from surveillance rectal specimens and clinically collected blood specimens collected within 1-8 days of each other between 2019-2023 were identified at 3 Greek hospitals. Isolates were frozen and shipped to a reference laboratory in the U.S for whole genome sequencing (WGS) using Illumina MiSeq. Assembly and core genome multilocus sequence typing (cgMLST) analysis were performed with Ridom SeqSphere+ software. Isolate relatedness was based on the total number of allelic differences between each isolate: < 15, related; 16-50, possibly related; ≥ 51, unrelated. Results One hundred eight paired isolates were identified from 54 unique patients; 6 pairs and 12 total isolates underwent cgMLST. In 5 of 6 pairs (83%), the rectal isolate was collected prior to the bloodstream isolate. Rectal and bloodstream isolates were related to one another in 5 of 6 (83%) pairs and were unrelated in 1 pair. Two pairs collected from 2 distinct patients admitted to the same intensive care unit (patients 2 and 3, Figure) were possibly related (16-50 allelic differences) to each other. Conclusion In this pilot evaluation conducted in a setting of high CRO prevalence, KPC-producing K. pneumoniae isolated from paired rectal and blood specimens from individual patients were often related to each other, suggesting that intestinal colonization by this organism could inform empiric antibiotic treatment for bacteremia. Two patients from the same hospital unit had isolates that were possibly related, suggesting within hospital transmission. WGS is a powerful tool that can inform clinical and infection control practices. WGS of the remaining K. pneumoniae pairs and additional Acinetobacter baumannii pairs is ongoing. Disclosures Robin Patel, MD, I already disclosed so please pull from disclosure for other abstracts: Advisor/Consultant|I already disclosed so please pull from disclosure for other abstracts: Grant/Research Support|I already disclosed so please pull from disclosure for other abstracts: Honoraria