title: Gram-Negative Bacterial Infections: Research Priorities, Accomplishments, and Future Directions of the Antibacterial Resistance Leadership Group.
abstract: Antimicrobial resistance in pathogenic gram-negative bacteria is one of the most pressing challenges in the field of infectious diseases and is one of 4 key areas of unmet medical need identified by the Antibacterial Resistance Leadership Group (ARLG). The mission of the Gram-Negative Committee is to advance our knowledge of these challenging infections and implement studies to improve patient outcomes. Studies have fallen primarily into 2 broad categories: prospective cohort studies and interventional trials. Among the observational studies, CRACKLE (Consortium on Resistance Against Carbapenems in Klebsiella pneumoniae and Other Enterobacteriaceae) has contributed seminal multicenter data describing risk factors and clinical outcomes of carbapenem-resistant Enterobacteriaceae (CRE) in sentinel US hospitals. Building on this success, CRACKLE II will expand the network to hospitals across the United States and Colombia. Similar protocols have been proposed to include Acinetobacter baumannii and Pseudomonas aeruginosa (SNAP and POP studies). In addition, the CREST study (Carbapenem-Resistant Enterobacteriaceae in Solid Organ Transplant Patients) has provided pivotal data on extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and CRE carriage among solid organ transplant recipients to inform management of this vulnerable patient population. Two clinical trials to define novel ways of using an existing antibiotic, fosfomycin, to treat ESBL-producing Enterobacteriaceae (one that has completed enrollment and the other in late protocol development) will determine the clinical efficacy of fosfomycin as step-down oral therapy to treat complicated urinary tract infections. Additional clinical studies and trials using immunotherapeutic or newly approved agents are also in the planning stage, with the main goals of generating actionable data that will inform clinical decision making and facilitate development of new treatment options for highly resistant gram-negative bacterial infections.
authors.affiliation: Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pennsylvania.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Doi
authors.affiliation: Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Departments of Medicine, Pharmacology, Biochemistry and Molecular Biology, and Microbiology, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bonomo
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Boston.
authors.forename: David C
authors.initials: DC
authors.lastname: Hooper
authors.affiliation: Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor.
authors.forename: Keith S
authors.initials: KS
authors.lastname: Kaye
authors.affiliation: Minneapolis Veterans Health Care System, Minnesota.
authors.forename: James R
authors.initials: JR
authors.lastname: Johnson
authors.affiliation: Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pennsylvania.
authors.forename: Cornelius J
authors.initials: CJ
authors.lastname: Clancy
authors.affiliation: Division of Infectious Diseases, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Thaden
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno," Ciudad Autónoma de Buenos Aires, Argentina; and.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Stryjewski
authors.affiliation: Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill.
authors.forename: David
authors.initials: D
authors.lastname: van Duin
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D000068456:Clinical Studies as Topic; D024881:Drug Resistance, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000175:diagnosis* / Q000382:microbiology / Q000628:therapy*; D006801:Humans; D007857:Leadership; D012106:Research / Q000458:organization & administration / Q000639:trends
chemical_list: D000900:Anti-Bacterial Agents
keywords: antimicrobial resistance; clinical trials.; gram-negative; interventional studies; observational studies