Table 1.
Antibacterial Resistance Leadership Group Research Agenda and Community Prioritization of Scientific Agenda Questions
| Gram-Positive | |||
|---|---|---|---|
| Question | ARLG Project | Status | Rank in Community Survey |
| Are there safe and effective alternatives to prolonged IV therapy for complicated Staphylococcus aureus bacteremia? | DOTS | Start-up | 1 |
| Are there safe and effective alternatives to prolonged IV therapy for complicated S. aureus infective endocarditis (including oral options)? | DOTS | Start-up | 2 |
| Are novel long-acting anti-MRSA agents (dalbavancin or oritavancin) noninferior to standard of care for therapy of MRSA osteomyelitis? | DOTS | Start-up | 3 |
| What is the role of combination antibiotic therapy for the treatment of complicated MRSA bacteremia and endocarditis? | 4 | ||
| What is the best therapy for vancomycin-resistant enterococci bacteremia? | VENOUS | Complete | 5 |
| Are there safe and effective alternatives to prolonged IV therapy for complicated strep infections (eg, Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci)? | 6 | ||
| Gram-Negative | |||
| Question | ARLG Project | Status | Rank in Community Survey |
| Are there safe and effective carbapenem-sparing regimens for extended-spectrum beta lactamase–positive Enterobacterales bloodstream infections? | CEF-BP FOCUS-PK ArROw PROOF MERINO-4 SHREC |
Complete Complete Complete Complete Planning Enrolling |
1 |
| What is the role of combination therapy vs monotherapy for the treatment of drug-resistant gram-negative bacilli? | COMBINE-HFIM COMBINE ACUMIN |
Complete Complete Complete |
2 |
| What is the role of oral step-down to complete therapy for gram-negative bacteremia? | TREAT-GNB MERINO-4 SHREC |
Planning Planning Enrolling |
3 |
| What should the duration of treatment be for gram-negative bacilli bacteremia and/or pneumonia? | SCOUT-CAP STAR TREAT-GNB MERINO-4 SHREC |
Complete Complete Planning Planning Enrolling |
4 |
| What is the role of innovative approaches (eg, phage products, microbiome alteration, immunotherapeutics) for the treatment of drug-resistant bacterial infections? | PHAGE PHAT |
Start-up Start-up |
5 |
| Are there safe and effective approaches to reduce the risk of bloodstream infections in neutropenic patients colonized with drug-resistant bacteria? | CREST RESISTOME SCENE |
Complete Complete Start-up |
6 |
| Diagnostics | |||
| Question | ARLG Project | Status | Rank in Community Survey |
| What is the role of rapid diagnostics that discriminate between bacterial and viral respiratory tract infections for optimizing management of and antibiotic use for acute respiratory illness? | RADICAL I/II, TRAP-LRTI |
Enrolling Enrollment complete |
1 |
| What is the role of rapid diagnostics for the management of bloodstream infection? | BCID RAPIDS-GN DISK FAST MASTERMIND-BSI |
Complete Complete Complete Start-up Planning |
2 |
| What is the role of rapid diagnostics for the management of community-acquired, hospital-acquired, and ventilator-associated pneumonia? | 3 | ||
| How do rapid qualitative and quantitative phenotypic susceptibility methods compare to genomic assessments of antibacterial resistant bacteria? | GENO-SMART | Planning | 4 |
| What is the role of rapid diagnostics for the management of urinary tract infections? | 5 | ||
| What is the role of shotgun metagenomics for the diagnosis of infection and detection of antimicrobial resistance? | GENO-SMART | Planning | 6 |
Abbreviations: ARLG, Antibacterial Resistance Leadership Group; IV, intravenous; MRSA; methicillin-resistant Staphylococcus aureus.
Project names: ACUMIN, Acute Care Unit tetracycline antibiotic; ArROw, Antibiotic Resistance in Organ Transplant; BCID, Film array Blood Culture ID panel; CEF-BP, CEFtriaxone BreakPoint; COMBINE, AVYCAZ® in COMBINation with aztreonam; COMBINE-HFIM, Combination regimen of ceftazidime-avibactam with aztreonam Hollow Fiber Infection Model against NDM-1-producing Enterobacteriaceae; CREST, Using novel molecular beacons to study the impact of Carbapenem Resistant Enterobacteriaceae carriage on the outcomes of Solid organ Transplant; DISK, DISK diffusion test method; DOTS, Dalbavancin as an Option for Treatment of S. aureus bacteremia; FAST, Fast Antibiotic Susceptibility for gram-negative bacteremia Trial; FOCUS-PK, Fosfomycin Oral for Complicated Urinary Syndromes study Pharmacokinetics and dynamics; GENO-SMART, GENOmics, Susceptibility, clinical epidemiology and Metagenomics of Antibiotic Resistance Tool; MASTERMIND BSI, MASTER protocol for evaluating Multiple INfection Diagnostics for rapid detection of BloodStream Infection; MERINO-4, Early oral step-down antibiotic therapy to tebipenem versus continued intravenous therapy with a carbapenem for bloodstream infection with Enterobacterales resistant to ceftazidime or ceftriaxone, ciprofloxacin or levofloxacin and trimethoprim/sulfamethoxazole; PHAGE, Study of the safety and microbiological activity of bacterioPHAGEs in persons with cystic fibrosis colonized with P. aeruginosa; PHAT, Isolation and characterization of lytic PHAges that Target MDR bacteria; PROOF, Phase I study to evaluate Pharmacokinetics, pharmacodynamics, and safety/tolerability of three dosing Regimens Of Oral Fosfomycin tromethamine in healthy adult participants; RADICAL, RApid Diagnostics In Categorizing Acute Lung infections; RAPIDS-GN, RAPID identification and Susceptibility testing for Gram-Negative bacteremia; RESISTOME, RESistance In Stem cell Transplant microbiOME; SCENE, Screening for Colonization with Resistant Enterobacterales in Neutropenic patients with hEmatologic malignancies; SCOUT-CAP, Standard Course Outpatient Therapy of Community Acquired Pneumonia in Children; SHREC, Study of Highly Resistant Escherichia coli; STAR, Short-course Therapy and the Antibiotic Resistome; TRAP-LRTI, Targeted Reduction of Antibiotics using Procalcitonin in a multi-center, randomized, blinded, placebo-controlled, non-inferiority study of azithromycin treatment in outpatient adults with suspect Lower Respiratory Tract Infections and a procalcitonin level of <0.1 ng/mL; TREAT-GNB, TRansition to Enteral versus intravenous Antibiotic Therapy for Gram-Negative Bacteremia; VENOUS, Prospective evaluation of clinical outcomes of cancer patients with Vancomycin-resistant ENterococcUS faecium bacteremia.