title: New β-Lactamase Inhibitors in the Clinic.
abstract: Given the serious medical burden of β-lactamases, many approaches are being used identify candidate agents for β-lactamase inhibition. Here, we review two β-lactam-β-lactamase inhibitor (BL-BLI) combinations, ceftolozane-tazobactam and ceftazidime-avibactam that recently entered the clinic. In addition, we focus on BL-BLI combinations in preclinical development that have demonstrated activity in clinical isolates via susceptibility testing and/or in in vivo models of infection. We highlight only the BLIs that are able to reduce the Clinical Laboratory Standards Institute (CLSI) breakpoints for the BL partner into the susceptible range. Our analysis includes the primary literature, meeting abstracts, as well as the patent literature.
authors.affiliation: Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, 10701 East Boulevard, Cleveland, OH 44106, USA; Department of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors.forename: Krisztina M
authors.initials: KM
authors.lastname: Papp-Wallace
authors.affiliation: Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, 10701 East Boulevard, Cleveland, OH 44106, USA; Department of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA; Department of Biochemistry, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA; Department of Pharmacology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA; Department of Molecular Biology and Microbiology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA. Electronic address: robert.bonomo@va.gov.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bonomo
mesh_terms: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D001897:Boronic Acids; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000201:enzymology / Q000472:pathogenicity; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D013450:Sulfones; D018440:beta-Lactam Resistance; D065093:beta-Lactamase Inhibitors
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D001897:Boronic Acids; D013450:Sulfones; D065093:beta-Lactamase Inhibitors
keywords: Boronic acids; Carbapenems; Diazabicyclooctanones; Inhibitor; Metallo-beta-lactamases; Monobactams; Sulfones; β-Lactamases