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In vitro activity of cefiderocol and comparators against isolates of Gram-negative pathogens from a range of infection sources: SIDERO-WT-2014-2018 studies in Italy. 2021

Stefano Stracquadanio, and Eleonora Torti, and Christopher Longshaw, and Anne Santerre Henriksen, and Stefania Stefani
Department of Biomedical and Biotechnological Sciences, Università di Catania, Via Santa Sofia 97, I-95123 Catania, Italy. Electronic address: s.stracquadanio@unict.it.

Antimicrobial resistance, particularly carbapenem resistance, in Gram-negative pathogens poses a significant healthcare threat. Carbapenem resistance rates in Italy are among the highest in Europe. We report the in vitro activity of cefiderocol, a novel siderophore cephalosporin, and comparator antibiotics against Gram-negative isolates from Italy as part of the SIDERO-WT studies. Isolates were collected between 2014 and 2018. Minimum inhibitory concentrations (MICs) were determined using International Organization for Standardization and EUCAST guidelines. Antimicrobial susceptibilities were interpreted using EUCAST breakpoints; pharmacodynamic/pharmacokinetic breakpoints were used if EUCAST breakpoints were not specified. The 2472 isolates [1545 (62.5%) Enterobacterales and 927 (37.5%) non-fermenters] represented a range of infection sources, including nosocomial pneumonia (902; 36.5%), complicated urinary tract infection (374; 15.1%), bloodstream infection (596; 24.1%), complicated intra-abdominal infection (257; 10.4%) and other infection sources (343; 13.9%). Cefiderocol was active against the majority of isolates, regardless of infection source (susceptibility, 94.2-97.3%). A high proportion of non-fermenters (97.6%) and Enterobacterales (95.6%) were cefiderocol-susceptible, although susceptibility was lower in Klebsiella pneumoniae (88.1%). Susceptibility to cefiderocol was significantly (P < 0.01) greater than comparators overall (96.4% vs. 71.3-81.6%) and in non-fermenters (97.6% vs. 44.3-90.3%) across infection sources. Overall 612/2472 isolates (24.8%) were meropenem-resistant (MIC > 8 mg/L), comprising 516/927 (55.7%) non-fermenters and 96/1545 (6.2%) Enterobacterales. Cefiderocol (499/516; 96.7%) activity was greater than colistin (440/516; 85.3%), ceftazidime/avibactam (123/516; 23.8%) and ceftolozane/tazobactam (89/516; 17.2%) in meropenem-resistant non-fermenter isolates. Susceptibility to cefiderocol was significantly greater than meropenem, colistin, ceftazidime/avibactam and ceftolozane/tazobactam overall, regardless of infection source.

UI MeSH Term Description Entries
D007558 Italy A country in southern Europe, a peninsula extending into the central Mediterranean Sea, northeast of Tunisia. The capital is Rome. Sardinia
D011550 Pseudomonas aeruginosa A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. aeruginosa is a major agent of nosocomial infection. Bacillus aeruginosus,Bacillus pyocyaneus,Bacterium aeruginosum,Bacterium pyocyaneum,Micrococcus pyocyaneus,Pseudomonas polycolor,Pseudomonas pyocyanea
D002511 Cephalosporins A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus ACREMONIUM. They contain the beta-lactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid. Antibiotics, Cephalosporin,Cephalosporanic Acid,Cephalosporin,Cephalosporin Antibiotic,Cephalosporanic Acids,Acid, Cephalosporanic,Acids, Cephalosporanic,Antibiotic, Cephalosporin,Cephalosporin Antibiotics
D005060 Europe The continent north of AFRICA, west of ASIA and east of the ATLANTIC OCEAN. Northern Europe,Southern Europe,Western Europe
D000097602 Cefiderocol A siderophore cephalosporin with enhanced activity against GRAM-NEGATIVE AEROBIC BACTERIA. Cefiderocol Sulfate Tosylate,Fetroja,S-649266,S 649266,S649266
D024901 Drug Resistance, Multiple, Bacterial The ability of bacteria to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS). Drug Resistance, Extensive, Bacterial,Drug Resistance, Extensively, Bacterial,Extensive Antibacterial Drug Resistance,Extensively Antibacterial Drug Resistance,Multidrug Resistance, Bacterial,Multiple Antibacterial Drug Resistance,Bacterial Multidrug Resistance,Bacterial Multidrug Resistances,Resistance, Bacterial Multidrug

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