Priorities and Progress in Gram-negative Bacterial Infection Research by the Antibacterial Resistance Leadership Group

Michael J. Satlin, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA.
David van Duin, Division of Infectious Diseases, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
Pranita D. Tamma, Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Thomas P. Lodise, Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, Albany, New York, USA.
Daria Van Tyne, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Keith A. Rodvold, Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, USA.
Nadine Rouphael, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Scott R. Evans, Department of Biostatistics, George Washington University, Washington, DC, USA.
Vance G. Fowler, Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
Toshimitsu Hamasaki, George Washington University Biostatistics Center, Rockville, Maryland, USA.
Robin Patel, Division of Clinical Microbiology and Division of Public Health, Infectious Diseases, and Occupational Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Lauren Komarow, George Washington University Biostatistics Center, Rockville, Maryland, USA.
Keri Baum, Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Maria Souli, Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Nyssa Schwager, Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Robert A. Bonomo, Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA.
Yohei Doi, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

Document Type

Journal Article

Publication Date

10-16-2023

Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

Volume

77

Issue

Suppl 4

DOI

10.1093/cid/ciad547

Keywords

antimicrobial resistance; clinical trials; gram-negative; interventional studies; observational studies

Abstract

Addressing the treatment and prevention of antibacterial-resistant gram-negative bacterial infections is a priority area of the Antibacterial Resistance Leadership Group (ARLG). The ARLG has conducted a series of observational studies to define the clinical and molecular global epidemiology of carbapenem-resistant and ceftriaxone-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii, with the goal of optimizing the design and execution of interventional studies. One ongoing ARLG study aims to better understand the impact of fluoroquinolone-resistant gram-negative gut bacteria in neutropenic patients, which threatens to undermine the effectiveness of fluoroquinolone prophylaxis in these vulnerable patients. The ARLG has conducted pharmacokinetic studies to inform the optimal dosing of antibiotics that are important in the treatment of drug-resistant gram-negative bacteria, including oral fosfomycin, intravenous minocycline, and a combination of intravenous ceftazidime-avibactam and aztreonam. In addition, randomized clinical trials have assessed the safety and efficacy of step-down oral fosfomycin for complicated urinary tract infections and single-dose intravenous phage therapy for adult patients with cystic fibrosis who are chronically colonized with P. aeruginosa in their respiratory tract. Thus, the focus of investigation in the ARLG has evolved from improving understanding of drug-resistant gram-negative bacterial infections to positively affecting clinical care for affected patients through a combination of interventional pharmacokinetic and clinical studies, a focus that will be maintained moving forward.

Department

Biostatistics and Bioinformatics

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