NIAID announces four new contracts for clinical trials to address problem of antimicrobial resistance

Eight large NIH trials now seeking to preserve the usefulness of licensed antibiotics

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, today announced four new contracts for large-scale clinical trials that address the problem of antimicrobial resistance. Over the next five to six years, these new clinical trials will evaluate treatment alternatives for diseases for which antibiotics are prescribed most often, including acute otitis media (middle ear infections), community-acquired pneumonia and diseases caused by Gram-negative bacteria, which frequently are resistant to first-line antibiotics. Each trial will enroll at least 1,000 participants who have been diagnosed with these illnesses and diseases.

"Many infectious diseases are increasingly difficult to treat because bacteria and other microbes have developed resistance to commonly used antimicrobial drugs," says NIAID Director Anthony S. Fauci, M.D. "Research to preserve the effectiveness of licensed antibiotics is a critical priority for the Institute. With these new contracts, NIAID now supports a total of eight large clinical trials in this arena."

Antimicrobial research has changed significantly since many current drugs were developed, says Dennis M. Dixon, Ph.D., chief of NIAID's Bacteriology and Mycology Branch. "Years ago, we were not as focused on antimicrobial resistance because there was generally another class of drug in the research and development pipeline. Today, the development of new antimicrobials is moving much more slowly than the evolution of resistance to existing treatments, so we need to preserve the drugs we have."

These new trials are part of a two-pronged NIAID approach to antimicrobial research: learning how to make better use of the drugs we have today in order to protect their usefulness while simultaneously facilitating the development of new drugs.

Like the four large NIAID trials already in progress, the four new studies are designed to answer specific questions about how to improve treatment strategies. The investigators will conduct clinical trials of new regimens involving the use of already licensed, off-patent antimicrobial therapies to reduce the risk of antimicrobial resistance developing in the diseases of interest. For example, the dosage and duration of treatment will be evaluated.

"If one type of treatment proves to be just as safe and just as effective as one that is traditionally used, but less likely to induce antimicrobial resistance, then the new treatment could be preserved for a longer time," says Dr. Dixon. "These clinical trials look not only at effectiveness of various antimicrobial drugs in the individual patient, but also at how to preserve the most effective use of drugs in the overall population. The goal is to be more precise with what antimicrobial drugs a patient needs, at what dose, and for how long."

The awardees of the four new contracts include:

• Principal Investigator (PI): Alejandro Hoberman, M.D., University of Pittsburgh
• Determining the efficacy and impact on antimicrobial resistance of short-course antimicrobial therapy in young children with acute otitis media
• Initial award for fiscal year 2010: $772,863
• PI: Victor Yu, M.D., University of Pittsburgh
  • Comparing narrow-spectrum antimicrobial therapy to standard of care in patients with community-acquired pneumonia
  • Initial award for fiscal year 2010: $3.01 million
• PI: Keith Kaye, M.D., M.P.H., Wayne State University, Detroit
• Comparing combination antimicrobial therapy with monotherapy for the treatment of Acinetobacter baumannii, a major cause of bloodstream infection and pneumonia in health care settings
• Initial award for fiscal year 2010: $2.84 million
• PI: George Drusano, M.D., Ordway Research Institute, Albany, N. Y.
• Comparing pharmacodynamic guidance of therapy, based on the drug's effect on the body, versus standard of care for Gram-negative bacteremia
• Initial award for fiscal year 2010: 1.98 million