Scientists are addressing the threat of antimicrobial drug resistance by launching two new clinical trials aimed at prolonging the effectiveness of currently available antibacterial drugs. The concept underlying both studies: Less is more.

The six-year contracts from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, are part of an initiative intended to help answer key questions about proper antimicrobial doses, treatment duration and whether antimicrobial treatment is necessary in all cases. NIAID has made an initial award of $1.5 million to the Children's Hospital of Philadelphia with further funding of up to a total of $13.8 million available over the six-year course of the contract if clinical trial milestones are met. Duke University, Durham, N.C., has received an initial award of $1.4 million. If milestones are met, the total award from NIAID to the Duke team could total up to $11 million over six years.

Many infectious diseases are increasingly difficult to treat because bacteria and other microbes have developed resistance to commonly used antimicrobial drugs. Microbial drug resistance is driven by a variety of forces, including expanded use of antimicrobial drugs in human and animal healthcare. According to one estimate, between 5 and 10 percent of all hospitalized patients in the United States develop a drug-resistant infection of some kind, leading to an added $5 billion in annual healthcare costs.

"The clinical trials supported by this important initiative will provide vital information on the optimal use of antimicrobial drugs in a variety of clinical settings," says NIAID Director Anthony S. Fauci, M.D. "This information is critical to improving patient care and slowing the development of drug resistance."

Reducing the risk of antimicrobial resistance is a priority for NIAID, as exemplified by these new trials and two similar studies now under way. NIAID also intends to fund additional innovative proposals aimed at slowing the development of antimicrobial resistance through targeted clinical trials.

"Historically, development of new antimicrobials has moved at a much slower pace than the evolution of resistance to those treatments, so we need to look at preserving the usefulness of the drugs we have," says Dennis M. Dixon, Ph.D., chief of the Bacteriology and Mycology Branch within NIAID's Division of Microbiology and Infectious Diseases. "One way to reduce the risk of resistance, and therefore to preserve antimicrobials, is to reduce unnecessary use of these drugs."

In the new round of research, investigators at Children's Hospital of Philadelphia will study children with urinary tract infections to determine if treatment with antimicrobials can be shortened from the standard length of up to two weeks and still be effective. The study will enroll as many as 1,000 children.

The Duke study also will test the effectiveness of shorter duration of antimicrobial treatment. This project will focus on hospitalized patients who acquire staphylococcal infections in the bloodstream after use of an intravenous catheter. This study could lead to reduced drug exposure in patients with such infections, which in turn lowers the chance that bacteria will develop resistance to the drugs. The conditions studied in these trials — infections in the urinary tract or the bloodstream — are ones where development of antimicrobial resistance is of particular concern.

Christine Chiou, M.D., is the NIAID program officer overseeing the projects at Children's Hospital of Philadelphia and at Duke. The projects are part of a second round of funding to support research on optimal ways to treat bacterial infections while minimizing development of antimicrobial resistance. The first awards were made in 2007 (http://www3.niaid.nih.gov/news/newsreleases/2007/ca-mrsa_contracts.htm) to the University of California, Los Angeles, and the University of California, San Francisco.

NIAID is soliciting additional proposals for new projects to minimize the development of antibiotic resistance, including ones focused on acute ear infections in children, pneumonia and bloodstream infections caused by Gram-negative bacteria. For more information about this new research initiative, see Targeted Clinical Trials to Reduce the Risk of Antimicrobial Resistance (https://www.fbo.gov/index?s=opportunity&mode=form&tab=core&id=58d549166da1779f976c6ecc4c2b67bd&_cview=1).

To learn more about NIAID research on this topic, visit the Antimicrobial Resistance portal (http://www3.niaid.nih.gov/topics/antimicrobialResistance/).

NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.