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Old is New Again: Multicenter Study Led by Pitt Determines Dosing for 1950s Drug Now Being Used to Treat Drug-Resistant Infections

PITTSBURGH, June 29, 2011 – An ongoing study led by a University of Pittsburgh researcher has established the first scientifically-based dosing guidelines for a more than 50-year-old drug that has re-emerged as the best, and often only, treatment for some bacterial infections that are resistant to modern therapies. The study appears in the July issue of the journal Antimicrobial Agents and Chemotherapy.

Researchers say preliminary results of the study are important because the drug, called colistin, was introduced in the 1950s before the inception of modern drug development protocols so there is little information available to determine the correct dose for patients. With no new drugs in development, physicians have increasingly turned to colistin as the number of drug-resistant infections have risen, researchers say.

“These infections are associated with a high morbidity and mortality due to the lack of adequate antibiotics and also due to the fact that they normally occur in hospitalized patients, especially those who already are critically ill,” said Fernanda P. Silveira, M.D., M.S., associate director of education, Division of Infectious Diseases, University of Pittsburgh School of Medicine. She led the study along with Roger Nation, Ph.C., M.S., Ph.D., professor, Monash University in Melbourne, Australia and Jian Li, Ph.D., M.Sc., senior research fellow, Monash University.

Because the drug was developed so many years ago, there are no dosing recommendations for critically ill patients, including those on renal replacement therapy or those who are critically ill, both populations that increasingly require this antibiotic, Dr. Silveira said.

Colistin is administered as an injection. Researchers determined dosages using a complex formula after testing the blood of 105 critically ill patients at various times prior to and after receiving colistin. The participants tested at sites in the United States and Thailand were all adults who were already receiving colistin for either bacterial bloodstream infection or pneumonia. Researchers hope to refine the dosages after data is analyzed from all 238 participants who will eventually be recruited for the study.

Dr. Nation and Dr. Li, who have been working on colistin for the past 12 years, said they are delighted to see these much-needed dosing guidelines finally developed which will allow physicians to better use this important antibiotic of last resort and minimize the emergence of resistance.

Other collaborators on the study include David Paterson, M.D., Ph.D., University of Queensland; Visanu Thamlikitkul, M.D., Mahidol University;  and Alan Forrest, Pharm.D., State University of New York at Buffalo.

The study was funded by the National Institutes of Health.

About the University of Pittsburgh School of Medicine

As one of the nation’s leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1997.

Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region’s economy. For more information about the School of Medicine, see www.medschool.pitt.edu.

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