In June 2013, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), provided $2 million in funding to establish an Antibacterial Resistance Leadership Group (ARLG) to develop, prioritize and implement a clinical research agenda to address the growing public health threat of antibiotic resistance. A new series of articles appearing in the March 15th issue of the journal Clinical Infectious Diseases details the group’s progress and outlines its ongoing and future efforts.
Antimicrobial-resistant bacteria cause more than 2 million infections and about 23,000 deaths each year in the United States, resulting in approximately $20 billion in excess medical spending and $35 billion in lost productivity. NIAID created the ARLG to address key clinical research questions of the antibacterial resistance problem in a well-coordinated manner.
Since its inception, the group has focused on four key areas
- Infections caused by gram-negative bacteria, such as Escherichia coli, Klebsiella pneumoniae and other carbapenem-resistant Enterobacteriaceae (CRE)
- Infections caused by gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci
- Antimicrobial stewardship and infection prevention
To date, the ARLG has reviewed more than 70 study proposals and initiated more than 30 clinical studies to address these issues. Many of these studies have involved innovative approaches, including adaptive designs to optimize enrollment in therapeutic trials, master protocols to simultaneously evaluate multiple diagnostic tests using specimens from a single patient and novel trial designs that increase clinical trial efficiencies and enable use of improved clinical trial designs.
One of the group’s key accomplishments is the launch of the CRACKLE (Consortium on Resistance Against Carbapenems in Klebsiella pneumoniae and Other Enterobacteriaceae) study, a prospective multicenter, cohort study designed to characterize the risk factors for and outcomes of infections caused by CRE and to identify barriers to enrollment that will inform future clinical trials. The study has enrolled more than 1,000 patients with CRE infection or bacterial colonization in the United States and South America.
There are encouraging signs in the fight against antibacterial resistance, the authors write, but the regulatory and approval processes for antibiotics and diagnostics need to allow more innovative clinical trial designs that could improve efficiencies, enrollment and overall study quality. Additionally, there must be an ongoing federal financial commitment to incentivize drug discovery and development, the authors note.
The ARLG supplement of articles appears in Clinical Infectious Diseases, Vol. 64.
NIAID Director Anthony S. Fauci, M.D., and Dennis Dixon, Ph.D., chief of the Bacteriology and Mycology Branch in NIAID’s Division of Microbiology and Infectious Diseases, are available to comment on the article series.