Priorities and Progress in Gram-negative Bacterial Infection Research by the Antibacterial Resistance Leadership Group
Michael J. Satlin, David van Duin, Pranita D. Tamma, Thomas P. Lodise, Daria Van Tyne, Keith A. Rodvold, Nadine Rouphael, Scott Evans, Vance G. Fowler, Toshimitsu Hamasaki, Robin Patel, Lauren Komarow, Keri Baum, Maria Souli, Nyssa Schwager, Robert A. Bonomo, Yohei Doi, for the Antibacterial Resistance Leadership Group, Minggui Wang, Eric Wenzler, Robert T. Schooley, Beth Evans, D. E. Hopkins, F Cathcart, Elizabeth Mocka, Carl Schuler, Zoë Sund, Smitha Zaharoff, Cathy Wickward, Leslie Estes, Donald Mau, Grant Booth, Erin Abbenante, Minal Bhojani, Hirra Zahir, Lizhao Ge, Abhigya Giri, Weixiao Dai, Guoqing Diao, Tamara Fidler, Wanying Shao, Yixuan Li, Lijuan Zeng, Shanshan Zhang, Kerryl E. Greenwood‐Quaintance, Suzannah Schmidt Malan, Krupa Parmar, Scott A. Cunningham, Varduhi Ghazaryan, Erica L. Raterman, Tamika Samuel, Marina S. Lee, Seema Nayak
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.