Table 1.
Antibacterial Resistance Leadership Group Priority Studies and Key Advancements
| Study | Description | Status | Scientific Area |
|---|---|---|---|
| Optimize administration and repurpose existing antibacterial agents | |||
| ACUMIN | Phase 4 open-label PK study of tetracycline antibiotic for injection following a single infusion in critically ill adults | Published [1] | GN, PK |
| COMBINE HFIM | Hollow fiber infection model studies to determine the optimal dosing of the combination of ceftazidime-avibactam with aztreonam against NDM-1–producing Enterobacterales | Published [2] | GN, PK |
| COMBINE | Phase 1 open-label study in healthy adults to evaluate the safety and PK of ceftazidime-avibactam in combination with aztreonam | Published [3, 4] | GN, PK |
| PROOF | Phase 1 study to evaluate PK, safety, and tolerability of 2 dosing regimens of oral fosfomycin tromethamine in healthy adults | Published [5] | GN, PK |
| FOCUS | Phase 4 randomized, double-blinded trial to evaluate the efficacy of oral fosfomycin versus levofloxacin in complicated urinary tract infections | Manuscript submitted | GN |
| PROVIDE | Prospective observational evaluation of the association between the day 2 vancomycin exposure and failure rates among adult hospitalized patients with methicillin-resistant Staphylococcus aureus bloodstream infections | Published [6] | GP, PK |
| OPTIMIZE-GNI | Phase 4 prospective, multicenter, interventional PK study to develop individualized meropenem and cefepime dosing algorithms for critically ill patients with suspected or documented antimicrobial-resistant gram-negative infections and varying degrees of renal function based on observed cystatin C serum concentrations | Study design | GN, PK |
| Evaluate the effectiveness of antibacterial agents alone or in combination | |||
| DOTS | Multicenter, randomized, open-label, assessor-blinded, superiority trial to compare dalbavancin to the standard-of-care treatment for the completion of therapy in participants who have complicated S. aureus bacteremia or right-sided native valve infective endocarditis and who have cleared their baseline bacteremia | Enrollment complete [7] | GP |
| Colistin versus Ceftazidime-Avibactam | Prospective, multicenter, observational study to compare the efficacy and safety of colistin to ceftazidime-avibactam for the treatment of infections due to carbapenem-resistant Enterobacterales | Published [8] | GN |
| Identify and evaluate novel antiinfective agents and treatment strategies for bacterial infections | |||
| PHAGE | Phase 1b/2, multicenter, randomized, double-blind, placebo-controlled trial of the safety and microbiological activity of a single dose of bacteriophage therapy in cystic fibrosis patients colonized with Pseudomonas aeruginosa | Enrolling [9] | GN |
| PHAT | Isolation and characterization of lytic phages that target multidrug-resistant bacteria to generate species-specific panels of phages | Published [10, 11] | GN |
| SCOUT-CAP | Phase 4 double-blind, placebo-controlled, randomized trial to evaluate short-course versus standard-course outpatient therapy of community-acquired pneumonia and microbiome analysis | Published [12, 13] | GP |
| MeChaTeBla | Mechanistic and structural characterization of the interaction of a novel antibiotic with clinically relevant beta-lactamases | Data analysis | GN |
| ARGONAUT | Series of studies for the characterization of the in vitro activity of novel agents against genetically defined clinical isolates of carbapenem-resistant gram-negative bacteria | Data analysis | GN |
| STEP FMT | Study to determine strain temporal engraftment and persistence after FMT by identifying the specific taxa that may confer long-term multidrug-resistant colonization resistance among FMT-treated individuals in a clinical trial of renal transplant recipients undergoing FMT | Data analysis | GN, GP |
| TRAP-LRTI | Multicenter, randomized, placebo-controlled, noninferiority study of azithromycin treatment versus placebo in adults with suspect lower respiratory tract infection and a procalcitonin level of <0.1 ng/mL | Published [14] | GP, Dx |
| Global clinical and molecular epidemiology of MDROs | |||
| CRACKLE | Multicenter, prospective cohort study to define the clinical and molecular epidemiology of carbapenem-resistant Enterobacterales in the United States | Published [15] | GN |
| CRACKLE-2 | International prospective cohort study to define the global clinical and molecular epidemiology of carbapenem-resistant Enterobacterales | Published [16, 17] | GN |
| POP | International prospective cohort study to define the global clinical and molecular epidemiology of carbapenem-resistant P. aeruginosa | Published [18] | GN |
| SNAP | International prospective cohort study to define the global clinical and molecular epidemiology of carbapenem-resistant Acinetobacter baumannii | Manuscript submitted | GN |
| SHREC | Multicenter prospective cohort study that uses the MDRO network to study the clinical and molecular epidemiology of ceftriaxone-resistant Escherichia coli in the United States | Published [19] | GN |
| Identify and evaluate novel diagnostic strategies | |||
| RADICAL | Series of studies to develop and evaluate a host-based assay to distinguish among bacterial, viral, and non-infectious etiologies of acute respiratory tract infections, which could help reduce inappropriate antimicrobial use | Published [20–22] | Dx |
| RADICAL-3 | Prospective, randomized, interventional, pilot study to estimate the clinical utility of the host response-bacterial/viral test run on a novel platform in emergency department patients with acute, febrile respiratory infection | Study design | Dx |
| MASTER RADICAL | MASTER protocol to advance the validation of platforms measuring the RADICAL test, including an evaluation of the impact of specimen type and specimen storage conditions | Data analysis | Dx |
| RADICAL 510(k) | Prospective, multicenter study to assess the performance of host gene expression signature in blood specimens to discriminate between bacterial and viral infections | Study design | Dx |
| MASTERMIND-GC | Cross-sectional study to evaluate the diagnostic accuracy of multiple commercially available NAATs for detection of Neisseria gonorrhoeae and Chlamydia trachomatis from oropharyngeal and rectal sites | Published [23] | Dx |
| MASTERMIND-BSI | MASTER protocol for evaluating multiple rapid diagnostics for identification of bacteria directly from blood samples | Start-up | Dx |
| MASTERMIND-RING | MASTER protocol for evaluating multiple diagnostics for direct-from-specimen NAATs for detection of ciprofloxacin resistance in N. gonorrhoeae | Protocol development | Dx |
| BCID | Prospective, randomized, controlled trial to evaluate the clinical and economic impact of rapid identification and susceptibility testing of pathogens growing in blood culture bottles | Published [24] | Dx |
| RAPIDS-GN | Multicenter, prospective, randomized, controlled trial to evaluate standard culture and AST versus rapid identification and AST for patients with confirmed gram-negative bacteremia | Published [25] | Dx, GN |
| FAST | International, prospective, randomized trial to evaluate clinical outcomes among patients with gram-negative bacteremia who have blood culture evaluation using standard methods versus rapid antibiotic susceptibility testing | Start-up | Dx, GN |
| DIFFR | Study to optimize a novel molecular diagnostic to detect Clostridioides difficile toxin mRNA expression in stool, determine its analytical performance characteristics, and evaluate the clinical sensitivity and specificity relative to gold-standard methods | Data analysis | Dx, GP |
| PNEUMONIA DIRECT PILOT | Prospective, observational, diagnostic feasibility study to determine the accuracy of pathogen- and host-directed testing for the diagnosis of ventilator-associated pneumonia | Protocol development | Dx, GN, GP |
| GENO-STELLAR | Web-based genomic-epidemiological tool for antimicrobial resistance prediction | Platform launched [26] | Dx, GN |
| REPORT-ABC | Study evaluating laboratory reporting practices of rapid testing performed on positive blood cultures | Published [27] | Dx |
| PST | Comparative evaluation of 2 assays for PST to assess reproducibility of PST methods needed to support clinical trials of phage therapy | Manuscript submitted | Dx, GN |
| Create innovations in clinical trial design [28] | |||
| DOOR | Desirability of outcome ranking: patient-centric benefit-risk evaluation paradigm for the design, analysis, and interpretation of clinical trials of bacterial infection syndromes | … | … |
| QOL | Quality of life: incorporate the patient perspective as an outcome in clinical trials of bacterial infection syndromes | … | … |
| DOOR MAT | Desirability of outcome ranking for the management of antimicrobial therapy: framework for assessing antibiotic selection strategies in the presence of drug resistance | … | … |
| SMART-COMPASS | Sequential, multiple-assignment, randomized trials for comparing personalized antibiotic strategies: a trial design to compare strategies | … | … |
| MASTERMIND | MASTER protocol for simultaneously evaluating multiple infection diagnostics with a single patient’s sample(s), providing efficiencies of specimen collection and characterization | … | … |
| BED-FRAME/AWA | Benefit-risk evaluation of diagnostics: a FRAMEwork and average weighted accuracy: systematic and pragmatic approach to evaluate and compare diagnostic alternatives to aid in clinical decision-making | … | … |
| Clinically adjudicated reference standards | Approach to use clinically adjudicated reference standards for evaluation of diagnostic test accuracy when a predefined gold standard is lacking or the test’s accuracy potentially exceeds that of its predecessors [29] | … | … |
Abbreviations: AST, antimicrobial susceptibility testing; Dx, diagnostics; BSI, bloodstream infection; FMT, fecal microbiota transplantation; GN, gram-negatives; GP, gram-positives; MDRO, multidrug-resistant organism; NAAT, nucleic acid amplification test; NDM, New Delhi metallo-β-lactamase; PK, pharmacokinetic(s); PST, phage susceptibility testing.