Table 1.
Research Priorities for the Gram-negative Committee in the Antibacterial Resistance Leadership Group
| Research Priority/Study Title | Study Description | Status |
|---|---|---|
| 1. Define the global epidemiology of multidrug-resistant gram-negative bacterial infections to optimize the design and execution of interventional studies | ||
| Multi-Drug Resistant Organism (MDRO) Network | Observational cohort studies of hospitalized patients with resistant gram-negative bacteria | … |
| CRACKLE-2 (Consortium on Resistance Against Carbapenems in Klebsiella and Other Enterobacterales) | International cohort of patients with carbapenem-resistant Enterobacterales | Analysis partially completed [4–7] |
| POP (Prospective Observational Pseudomonas Study) | International cohort of patients with carbapenem-resistant Pseudomonas aeruginosa | Analysis partially completed [8] |
| SNAP (Study Network of Acinetobacter as a Carbapenem-Resistant Pathogen) | International cohort of patients with carbapenem-resistant Acinetobacter baumannii | Analysis partially completed [9] |
| SHREC (Study of Highly Resistant Escherichia coli) | Domestic cohort of patients with ceftriaxone-resistant and ceftriaxone-susceptible E. coli bloodstream infections | Analysis partially completed [10] |
| 2. Evaluate novel strategies to prevent multidrug-resistant gram-negative bacterial infections in immunocompromised hosts | ||
| SCENE (Screening for Colonization with Resistant Enterobacterales in Neutropenic Patients with Hematologic Malignancies) | Multicenter cohort study to assess the prevalence and clinical impact of colonization with fluoroquinolone-resistant Enterobacterales in neutropenic patients with hematologic cancers | Ongoing |
| 3. Identify strategies to optimize the administration of antibiotics for the treatment of gram-negative bacterial infections | ||
| PROOF (Pharmacokinetics, Pharmacodynamics and Safety/Tolerability of Two Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Participants) | Phase 1 clinical trial to evaluate the pharmacokinetics, pharmacodynamics, and safety/tolerability of different dosing regimens of oral fosfomycin | Completed [11, 12] |
| FOCUS (The Fosfomycin Oral for Complicated Urinary Syndromes Study) | Randomized clinical trial to assess the safety and efficacy of fosfomycin versus levofloxacin oral step-down therapy for complicated urinary tract infections | Data analysis underway |
| ACUMIN (Acute Care Unit Minocycline) | Phase 4 clinical trial to evaluate the pharmacokinetics of intravenous minocycline in critically ill patients | Completed [13] |
| COMBINE (Ceftazidime-Avibactam in Combination with Aztreonam) | Phase 1 clinical trial to evaluate the safety and pharmacokinetics of ceftazidime-avibactam in combination with aztreonam | Completed [14, 15] |
| 4. Identify and evaluate novel antimicrobial agents or treatment strategies for multidrug-resistant gram-negative bacterial infections | ||
| ARGONAUT III, IV, and V (ARLG Reference Group for the Testing of Novel Therapeutics) | Characterization of the in vitro activity of novel agents against genetically defined clinical isolates of carbapenem-resistant gram-negative bacteria | Analysis partially completed |
| PHAT (Phages That Target MDR Bacteria) | Isolation and characterization of lytic bacteriophages that target P. aeruginosa and Enterobacter species | Completed [16, 17] |
| PHAGE (Study of the Safety and Microbiologic Activity of Bacteriophages) | Phase 1b/2 randomized, placebo-controlled trial of the safety and microbiologic activity of a single intravenous dose of bacteriophage therapy in patients with cystic fibrosis who are colonized with P. aeruginosa | Ongoing [18] |
Abbreviations: ARLG, Antibacterial Resistance Leadership Group; MDR, multidrug-resistant.