676. Synergistic Bacteriostatic and Bactericidal Activity of Fosfomycin Plus Trimethoprim-Sulfamethoxazole Combination Against Carbapenem-Resistant Enterobacteriales, Multidrug-Resistant <i>P. aeruginosa</i>, Carbapenem-Colistin-Resistant <i>A. baumannii,</i> MRSA, and <i>Enterococcus spp.</i>

Abstract Background Fosfomycin (F) inhibits the first committed step of peptidoglycan biosynthesis catalyzed by MurA enzyme which uses phosphoenolpyruvate as a substrate. Trimethoprim and sulfamethoxazole (TS) inhibit successive steps in folate are commonly used fixed combination (co-trimoxazole). In this study we explored (FTS) F with TS several gram-negative gram-positive bacteria increasing concern. Methods We synergy-checkerboard variant agar minimal inhibitory concentration (MIC) assay Mueller-Hinton Agar (glucose-6-phosphate supplemented; CLSI) against selection Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus spp. clinical isolates to characterize an FTS combination. Component antibiotics, TS, variety other antibacterial comparators were evaluated method or broth microdilution. Bactericidal assays conducted broth. Results Antibacterial synergy was exhibited all E. coli (20/20) at concentrations below individual breakpoints for TS. Against K. pneumoniae isolates, (12/12) that resistant F, many (10/13) both susceptible FTS. All P. aeruginosa (18/18) dually Extrapolating Enterobacteriales, clinically-relevant exerted 11/18 susceptibility achievable one component 7/18 isolates. A. values extrapolated achieved most (17/19), few (2/19), observed active MRSA regardless susceptibility. Conclusion The unique synergistic bactericidal activity not impacted resistance tested species any agent including carbapenem-resistant carbapenem-colistin-resistant MRSA, Disclosures John L. Pace, PhD, FleurirABX, LLC: Board Member|FleurirABX, Inventor company patents|FleurirABX, Ownership Interest.