title: Novel β-lactamase inhibitors: a therapeutic hope against the scourge of multidrug resistance.
abstract: The increasing incidence and prevalence of multi-drug resistance (MDR) among contemporary Gram-negative bacteria represents a significant threat to human health. Since their discovery, β-lactam antibiotics have been a major component of the armamentarium against these serious pathogens. Unfortunately, a wide range of β-lactamase enzymes have emerged that are capable of inactivating these powerful drugs. In the past 30 years, a major advancement in the battle against microbes has been the development of β-lactamase inhibitors, which restore the efficacy of β-lactam antibiotics (e.g., ampicillin/sulbactam, amoxicillin/clavulanate, ticarcillin/clavulanate, and piperacillin/tazobactam). Unfortunately, many newly discovered β-lactamases are not inactivated by currently available inhibitors. Is there hope? For the first time in many years, we can anticipate the development and introduction into clinical practice of novel inhibitors. Although these inhibitors may still not be effective for all β-lactamases, their introduction is still welcome. This review focuses on the novel β-lactamase inhibitors that are closest to being introduced in the clinic.
authors.affiliation: Department of Internal Medicine, Northeast Ohio Medical University Rootstown, OH, USA ; Division of Infectious Diseases, Akron General Medical Center Akron, OH, USA.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Watkins
authors.affiliation: Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center Cleveland, OH, USA ; Department of Medicine, Case Western Reserve University Cleveland, OH, USA.
authors.forename: Krisztina M
authors.initials: KM
authors.lastname: Papp-Wallace
authors.affiliation: Department of Lab Medicine and Pathology, University of Minnesota Minneapolis, MN, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Drawz
authors.affiliation: Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center Cleveland, OH, USA ; Department of Medicine, Case Western Reserve University Cleveland, OH, USA ; Pharmacology, Case Western Reserve University Cleveland, OH, USA ; Molecular Biology and Microbiology, Case Western Reserve University Cleveland, OH, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bonomo
keywords: antibiotic resistance; β-lactamase inhibitors