Our goal is to create and implement an Antibacterial Resistance Leadership Group (ARLG) that will develop, design, implement, and manage a clinical research agenda that will increase knowledge of and mitigate the important factors that drive resistance. We will pair an unprecedented team of over two dozen of the world's top investigators with the organizational excellence of the Duke Clinical Research Institute (DCRI), one of the world's largest Academic Research Organizations. Because of the complexity of integrating multiple components of such a large-scale clinical research network, our submission features centralized leadership through an Executive Committee and a dual PI approach. One PI (Fowler) focuses primarily on operations and the other (Chambers) focuses largely on scientific agenda. The organizational structure, modeled after that of the ACTG, also features Scientific Subcommittees devoted to four priority areas: Gram-negative bacterial infections, Stewardship and infection prevention, Gram-positive bacterial infections, and Diagnostics and devices. These Subcommittees are supported by three Special Emphasis Panels (SEPs) (Pediatrics, Pharmacokinetics, and Special Populations) and a Mentoring Core. Each Subcommittee, SEP, and Core contains internationally recognized investigators, ensuring expertise. To complement the current research activities of both NIH and the pharmaceutical biotechnology industry, our ARLG has established collaborative ties with members of both communities. Our long-term goals are 1) to complete a superiority trial of new anti-infectives (either new agent or new dosing regimen of existing agent) for MDR-Gram negative bacterial infections;2) to define shorter course, narrow-spectrum therapeutic regimens for common infections as a principal means to support stewardship;3) to test a rapid diagnostic that identifies antimicrobial resistance based on genotypic markers in bacteria;and 4) to identify a more effective alternative to vancomycin for MRSA infections. The research agenda reflects our overall strategy of making realistic, incremental steps in early phase studies upon which to build toward more complex transformational trials that will change clinical practice and reduce the impact of antibacterial resistance.

Public Health Relevance

Antibacterial resistance (AR) is one of the world's top health threats. It is a complex, growing problem. Reducing the burden of AR requires a sustained program that simultaneously addresses critical issues from many perspectives. Our goal is to establish an Antibacterial Resistance Leadership Group (ARLG) that will develop, design, implement, and manage a clinical research agenda to increase knowledge of AR, and to reduce the factors that drive its emergence.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
5UM1AI104681-02
Application #
8667988
Study Section
Special Emphasis Panel (ZAI1-AWA-M (S1))
Program Officer
Zou, Lanling
Project Start
2013-06-01
Project End
2019-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
2
Fiscal Year
2014
Total Cost
$10,000,000
Indirect Cost
$3,124,102
Name
Duke University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Tamma, Pranita D; Pierce, Virginia M; Cosgrove, Sara E et al. (2018) Can the Ceftriaxone Breakpoints Be Increased Without Compromising Patient Outcomes? Open Forum Infect Dis 5:ofy139
Kanwar, Anubhav; Marshall, Steven H; Perez, Federico et al. (2018) Emergence of Resistance to Colistin During the Treatment of Bloodstream Infection Caused by Klebsiella pneumoniae Carbapenemase-Producing Klebsiella pneumoniae. Open Forum Infect Dis 5:ofy054
Springer, Jan; White, P Lewis; Kessel, Johanna et al. (2018) A Comparison of Aspergillus and Mucorales PCR Testing of Different Bronchoalveolar Lavage Fluid Fractions from Patients with Suspected Invasive Pulmonary Fungal Disease. J Clin Microbiol 56:
Huskins, W Charles; Fowler Jr, Vance G; Evans, Scott (2018) Adaptive Designs for Clinical Trials: Application to Healthcare Epidemiology Research. Clin Infect Dis 66:1140-1146
Tsalik, Ephraim L; Bonomo, Robert A; Fowler Jr, Vance G (2018) New Molecular Diagnostic Approaches to Bacterial Infections and Antibacterial Resistance. Annu Rev Med 69:379-394
Gopalsamy, Srinivasa Nithin; Sherman, Amy; Woodworth, Michael H et al. (2018) Fecal Microbiota Transplant for Multidrug-Resistant Organism Decolonization Administered During Septic Shock. Infect Control Hosp Epidemiol 39:490-492
Bassetti, Matteo; Righi, Elda; Montravers, Philippe et al. (2018) What has changed in the treatment of invasive candidiasis? A look at the past 10 years and ahead. J Antimicrob Chemother 73:i14-i25
van Duin, David; Lok, Judith J; Earley, Michelle et al. (2018) Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae. Clin Infect Dis 66:163-171
Wenzler, Eric; Bleasdale, Susan C; Sikka, Monica et al. (2018) Phase I Study To Evaluate the Pharmacokinetics, Safety, and Tolerability of Two Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Participants. Antimicrob Agents Chemother 62:
Chotiprasitsakul, Darunee; Han, Jennifer H; Cosgrove, Sara E et al. (2018) Comparing the Outcomes of Adults With Enterobacteriaceae Bacteremia Receiving Short-Course Versus Prolonged-Course Antibiotic Therapy in a Multicenter, Propensity Score-Matched Cohort. Clin Infect Dis 66:172-177

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