1721. In Vitro Activity of Cefiderocol against IMP-Producing Enterobacterales Isolated in Japan

Abstract

Abstract Background Beta-lactam resistance is a major worldwide concern. Metallo-β-lactamases (MBLs) are a group of enzymes that can inactivate most commonly used β-lactam antibiotics including carbapenems and are not affected by new β-lactamase inhibitors. Therefore, treating infections caused by MBL producing strains is difficult. Imipenemase (IMP) type MBL is a rare family of acquired carbapenemases detected from Enterobacterales globally, however, it has been detected and become a major therapeutic concern in clinical settings mainly in East Asia including Japan [1]. Cefiderocol (CFDC) is a novel injectable siderophore cephalosporin antibiotic with potent activity against a wide variety of carbapenem resistant strains including both serine- and metallo-type carbapenemase-producers. We evaluated in vitro activity of CFDC and comparator agents against IMP-producing Enterobacterales isolated in Japan. Methods A total of 150 IMP-producing strains consisting of 48 Escherichia coli, 34 Klebsiella pneumoniae, 29 Klebsiella oxytoca, 21 Enterobacter cloacae, 7 Citrobacter freundii, 7 Serratia marcescens, 2 Providencia rettgeri, 1 Klebsiella aerogenes, and 1 Morganella morganii were tested. The minimum inhibitory concentrations (MICs) were determined for CFDC, ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), imipenem-relebactam (I-R), meropenem (MEM), and amikacin (AMK) by broth microdilution according to CLSI guidelines. CFDC was tested in iron-depleted cation-adjusted Mueller-Hinton broth. Results MIC50 and MIC90 of CFDC were 0.25 and 1 µg/mL, respectively. MICs of CFDC for all tested strains ranged from ≤ 0.03 to 4 µg/mL, which showed all strains were susceptible to CFDC based on the CLSI breakpoint (≤ 4 µg/mL). On the other hand, MIC90s of CZA, C/T, I-R, MEM, and AMK were > 32/4, > 32/4, 8/4, > 32, and 4 µg/mL, respectively. The susceptibilities were 98.0% for AMK, 66.0% for I-R, and < 10% for CZA, C/T and MEM. Conclusion CFDC had potent in vitro activity against IMP-producing Enterobacterales collected from Japan, indicating CFDC has high potential for treating infections caused by these difficult-to-treat strains. Reference: 1. Logan, LK. et al., J Infect Dis. 2017 Feb 15;215(suppl 1):S28-S36. Disclosures Hidenori Yamashiro, Shionogi & Co., Ltd.: Employee Ryuichiro Nakai, n/a, Shionogi TechnoAdvance Research CO., LTD.: Employee Miki Takemura, n/a, Shionogi: Employee Yoshinori Yamano, PhD, Shionogi: Employee.