B107-15 AtbFinder: A Novel Diagnostic Test That Improves Antibiotic Selection and Outcomes in Cystic Fibrosis Patients With Multidrug-Resistant Pathogens

Abstract Introduction and objective Even the most resistant bacteria are rarely resistant to all antibiotics, leaving potential treatment options. However, existing antibiotic susceptibility tests (AST) often fail to identify them. AtbFinder is a next-generation, phenotypic but culture-independent diagnostic test designed to guide antibiotic selection for hard-to-treat respiratory infections. The AtbFinder test-kit consists of four 48-well plates, each containing a novel agar supplemented with one or more antibiotics, and antibiotic-free control wells. Antibiotics are added to the agar at concentration achievable in the lungs allowing AtbFinder to select drugs based on site-specific efficacy rather than plasma-based MIC-breakpoints used in standard AST methods. Clinical samples (sputum/BAL) are plated to the agar, and for each patient, the AtbFinder tests up to 184 antibiotics within 4-8 hours. AtbFinder is the first test to select antibiotics based on (1) the response of the entire polymicrobial biofilm from the site of infection to (2) antibiotics at lung-achievable concentrations. Materials and Methods Prospective, nonrandomized, open-label study utilizing AtbFinder to formulate an individualized antibiotic regimen in 35-patients with CF. Study participants served as their own controls. The study included 2-years before implementing antibiotic therapy selected using AtbFinder (antibiotics were selected using standard AST methods (Vitek-2,MALDI-TOF,disk-diffusion, or microbroth-dilution), and 2 years after antibiotics were selected with AtbFinder (ClinicalTrials.gov identifier, NCT00437580). None of the patients were on gene-modifying drugs. Results Antibiotics selected using AtbFinder resulted in clearance of P. aeruginosa in 81.8% of subsequent cultures, arrested pulmonary exacerbations, and increased FEV1% up to 28.4% from baseline. We enrolled 35 persons with CF (33 with chronic P. aeruginosa colonization) aged 18-63. Antibiotics selected using AtbFinder resulted in clearance of P. aeruginosa in 81.8% of subsequent cultures, decreased pulmonary exacerbations from 1.21 per patient per annum to 0, and an increase in predicted percent predicted forced expiratory volume in 1 s up to 28.4% from baseline (p 0.001 for all). The number of systemic antibiotic courses used in patients after switching to the AtbFinder-selected therapy was reduced from 355 to 178. The total number of broad-spectrum antibiotic courses decreased by 55%. The number of ICU and ventilator days reduced by 95% and 100%, respectively during the 1st-year. Conclusion AtbFinder addresses a critical clinical question: Can the antibiotic concentrations actually achieved in the lungs eliminate bacterial biofilms? This approach demonstrated clear superiority over standard AST methods, enabling more effective, targeted, and rapid antibiotic selection for MDR respiratory infections in patients with CF. This abstract is funded by: None