A University of Washington bioengineer led a team that has created a ciprofloxacin- containing polymer that releases antibiotic slowly onto the surface of hospital devices, such as catheters and prostheses, to reduce the risk of biofilm-related infections.  Such infections may account for thousands of hospital deaths each year in the United States.
       "Rather than massively dosing the patient with high levels of released antibiotic, this strategy allows the release of extremely low levels of this very potent antibiotic over long periods of time," explained Buddy Ratner, PhD, Professor and Director of the Engineered Biomaterials Program at the University of Washington, Seattle.  "We calculated the amount released at the surface that would kill 100% of the bacteria entering the surface zone."
         Bacteria in biofilms have a different physiology than liquid-phase bacterial populations and are less susceptible to most antibiotics; thus, a delay of even a day or two in administering antibiotics may result in bacterial colonization.  A study published in the December issue of the Journal of Controlled Release (1999;62: 289-299) describes this new approach to providing antibiotics immediately after prosthesis or catheter implantation at the site where the antibiotics are most needed.
         Dr. Ratner, PhD candidate Connie Kwok, and other collaborators at the University of Washington, Montana State University, Bozeman, and the University of Connecticut Health Center, Farmington, combined ciprofloxacin (Cipro, Bayer) with polyethylene glycol and a form of polyurethane used to make medical products.  Ciprofloxacin was chosen because of its wide antimicrobial spectrum and extremely low minimum inhibitory concentration for Pseudomonas aeruginosa.  The researchers found that the efficacy of the released ciprofloxacin against P. aeruginosa was fourfold greater than  that of a control polymer containing no antibiotic.
         Leonard Mermel, DO, ScM, AM (Hon), Associate Professor of Medicine, Brown University School of Medicine, Providence, R.I., and the author of an article in the March 7 issue of Annals of Internal Medicine (2000; 132:391-402) on the problems associated with coating catheters with antibiotics, noted that this method is not optimal for preventing infections.
         "The study shows that this coating could thwart device-related infections due to such a difficult-to-treat pathogens as  Pseudomonas,"  Dr. Mermel told Pharmacy Practice News.  "However, I have a grave concern with using an invaluable therapeutic antimicrobial agent to prevent infections.  We know from recently published research that the increased use of quinolone antibiotics, such as ciprofloxacin, have been associated with increased resistance of bacteria such as pneumococcus.  And, although this organism is not a common cause of device-related infections, it seems clear that excessive use of antimicrobial agents relates to the development of resistance."
           "Dr. Mermel's concerns are, in fact, why we developed this system for ciprofloxacin release."  Dr. Ratner responded.  "Bacteria that live through antibiotic dosing can go on to produce resistant strains.  If 100% of the bacteria approaching the surface are killed, they can't produce resistant offspring.  The classical physician approach, dosing the patient systemically and heavily to rid the patient of a persistent bacteria, can lead to those resistant strains.  Our approach releases miniscule doses compared to what a physician would use, but releases the antibiotic where it will be optimally effective and lest likely to leave ciprofloxacin-resistant survivors."

         Republished with permission
Pharmacy Practice News, May 2000, pg 24
Written by Rosemary Frei, MSc

Based on articles in the Journal of Controlled Release (1999; 62:289-299) and Annals of Internal Medicine (2000; 132:391-402), and interviews with Buddy Ratner, PhD, and Leonard Mermel, DO, ScM, AM (Hon).