title: Activity of temocillin, mecillinam, ceftazidime, and ceftazidime/avibactam against carbapenem-non-susceptible Enterobacteriaceae without carbapenemase production.
abstract: Treatment options for multidrug-resistant Gram-negative infections are scarce and therefore alternatives with a narrow spectrum or new agents are sought. Antimicrobial susceptibility to temocillin, mecillinam, ceftazidime, and ceftazidime/avibactam was determined using Etest and disk diffusion according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) methodology. A total of 77 carbapenem-nonsusceptible Enterobacteriaceae were studied, including Klebsiella pneumoniae (26%), Escherichia coli (26%), Enterobacter cloacae (26%), and Enterobacter aerogenes (22%). Several phenotypic tests, PCRs followed by sequencing and a microbiological bioassay excluded carbapenemase production in all isolates. Antimicrobial susceptibility rates were low for temocillin (15.6%, minimum inhibitory concentration [MIC] range 2 to >1,024 μg/ml), moderate for mecillinam (59.7%, MIC range 0.25 to >256 μg/ml), and excellent for ceftazidime/avibactam (100%, zone diameter range 19 to 32 mm, median 25 mm). 5.2% of the isolates were susceptible to ceftazidime alone (zone diameter range 6 to 32 mm). In this study, mecillinam exhibited moderate and ceftazidime/avibactam excellent in vitro antimicrobial activity against carbapenem-nonsusceptible Enterobacteriaceae without carbapenemase production. Ceftazidime/avibactam was able to restore previously reduced susceptibility to ceftazidime in all isolates, thus potentiating its activity. Temocillin only exhibited low in vitro antimicrobial activity against the isolates. Further evaluation of mecillinam and ceftazidime/avibactam with regard to the potential clinical utility against infections caused by these pathogens has to be performed.
authors.affiliation: Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, 69120, Heidelberg, Germany.
authors.forename: N T
authors.initials: NT
authors.lastname: Mutters
authors.affiliation: Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, 69120, Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Zimmermann
authors.affiliation: National Reference Laboratory for Multidrug-Resistant Gram-Negative Bacteria, Department of Medical Microbiology, Ruhr University Bochum, 44801, Bochum, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kaase
authors.affiliation: Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, 69120, Heidelberg, Germany. alexander.mischnik@uniklinik-freiburg.de.|Division of Infectious Diseases, Department of Medicine, University Medical Center Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany. alexander.mischnik@uniklinik-freiburg.de.
authors.forename: A
authors.initials: A
authors.lastname: Mischnik
mesh_terms: D001426:Bacterial Proteins / Q000032:analysis / Q000235:genetics; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D016972:Enterobacter cloacae / Q000187:drug effects* / Q000235:genetics; D004755:Enterobacteriaceae / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000235:genetics; D008826:Microbial Sensitivity Tests; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000032:analysis / Q000235:genetics; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D047090:beta-Lactams; D001618:beta-Lactamases; C063912:carbapenemase