719. Cefiderocol Retains Anti-Biofilm Activity in MDR Gram-Negative Pathogens

Abstract

BackgroundCefiderocol is a siderophore cephalosporin with potent antibacterial activity against a broad range of Gram-negative pathogens. Microorganisms forming biofilm, e.g., cUTI, utilize bacterial siderophores to access free iron. A siderophore antibiotic may have unique antimicrobial properties in the setting of biofilm. In this study, we compared antimicrobial activity of cefiderocol to comparator antibiotics in well-characterized multi-drug-resistant pathogens. We determined the activity of cefiderocol and comparator antibiotics in the biofilm setting.MethodsMinimum inhibitory concentrations (MICs) in Mueller–Hinton II broth (MHII) and iron-depleted cation-adjusted MHII (ID-CAMHB) were determined for cefiderocol and seven comparator antibiotics in multidrug-resistant isolates of P. aeruginosa, Burkholderia cepacia complex (Bcc), Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii. MBEC (minimum biofilm eradication concentration) assays were used to test cefiderocol’s activity in biofilms formed on pegs. Total biofilm biomass and viable cell number were measured.ResultsThe MIC90 of cefiderocol ranged from 0.125 μg/mL (Bcc) to 1 μg/mL (P. aeruginosa) in ID-CAMHB. MIC90 values were consistently lower for cefiderocol in all strains tested compared with other agents (ceftolozane-tazobactam, ceftazidime–avibactam, ceftazidime, pipercallin-tazobactam, imipenem, tobramycin, clarithromycin). Twenty-four hour P. aeruginosa biofilms (strains ATCC 9027, MB640, MB771, MB580A, MB730) were treated every 12 hours with 4 μg/mL of cefiderocol or comparator antibiotics. Cefiderocol treatment displayed a superior reduction in biofilm based on colony counts ( >90%; P < 0.0001 vs. untreated control) compared with comparator drugs (50 to 80% reduction). Crystal violet staining revealed a dose-dependent response of cefiderocol in the reduction of biofilm. Reduction of biofilm was not significantly altered by the growth media that was used; however, P. aeruginosa strains form more biofilm in MHII.ConclusionCefiderocol effectively reduces biofilm in multidrug-resistant strains of P. aeruginosa and is a potent inhibitor of planktonic growth across a range of Gram-negative medically important pathogens.Disclosures All authors: No reported disclosures.