1252. In Vitro Activity of Cefiderocol Against Metallo-β-Lactamase-Producing Gram-Negative Bacteria Collected in North America and Europe Between 2014 and 2017: SIDERO-WT-2014–2016 Studies

Abstract

Background. Metallo-β-lactamases (MBLs; eg, NDM, VIM, and IMP) can inactivate most commonly-used β-lactam antibiotics, including carbapenems. Infections caused by MBL producers are difficult to treat due to their resistance to many antibiotics. Cefiderocol (CFDC) is a siderophore cephalosporin antibiotic approved in the USA in 2019, with potent activity against carbapenem-resistant Gram-negative bacteria (GNB), including both serine- and metallo-carbapenemase positive strains. We evaluated the in vitro activity of CFDC and comparator agents against MBL-producing strains of GNB from North America and Europe in 3 years' of consecutive surveillance studies (SIDERO-WT-2014-2016). Methods. Susceptibility testing for CFDC, ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), meropenem (MEM), cefepime (FEP), ciprofloxacin (CIP), and colistin (CST) was performed by broth microdilution according to CLSI guidance. CFDC was tested in iron-depleted medium. A total of 275 MBL-producing strains, consisting of 120 Enterobacterales (45 NDM; 75 VIM), 5 NDM-producing Acinetobacter baumannii, and 150 Pseudomonas aeruginosa (134 VIM; 16 IMP), identified among 4985 (654 Enterobacterales and 4331 non-fermenters) MEM non-susceptible (based on CLSI breakpoints) strains were used for the current analysis. Results. The minimum inhibitory concentration (MIC) range and MIC90 for CFDC and comparators for each MBL-producing organism group are shown in the Table. Against NDM-producing Enterobacterales, of which 42% and 33% were isolated in Turkey and Russia, respectively, CFDC inhibited the growth of 84% of isolates tested at ≤4 μg/mL. CFDC MIC90 was 4 μg/mL for VIM-producing Enterobacterales (41% and 31% isolated in Greece and Italy, respectively), 1 μg/mL for VIM-producing P. aeruginosa (50% isolated in Russia), and 4 μg/mL for IMP-producing P. aeruginosa (88% isolated in Czech Republic). Other comparators (except for CST) were not active against these MBL producers. Conclusion. CFDC inhibited the growth of 100% of MBL-positive GNB at ≤8 mg/mL and showed MIC90 of 4 μg/mL against all 275 MBL producers, indicating that CFDC has high potential for treating infections caused by these difficult-to-treat strains.