Despite its large distribution in nature, P. aeruginosa is primarily a problem among hospitalized patients and patients with cystic fibrosis, where it can cause severe and life-threatening infections. Our research focuses on preventing resistance from developing among Pseudomonas. These studies were performed by Daniel Wolter and Dr. Philip Lister, Associate Professor of Medical Microbiology and Immunology at Creighton University School of Medicine in Omaha, Nebraska. Fluoroquinolones and carbapenems are two classes of antibiotics that have demonstrated potent activity against P. aeruginosa . However, resistance to both agents has been identified in clinical isolates.
Efflux pumps are one mechanism used by Pseudomonas aeruginosa for fluoroquinolone resistance.
Some fluoroquinolones preferentially select mutants that overproduce a specific efflux pump that causes the bacterium to become significantly more susceptible to an unrelated drug, imipenem. Conversely, resistant mutants that emerge during therapy with imipenem remain susceptible to fluoroquinolones. Therefore, a combination of fluoroquinolones and imipenem may prevent the development of resistance. We used an In Vitro Pharmacokinetic Model that simulates the kinetics of antibiotics in humans to evaluate the antibacterial properties of fluoroquinolone-imipenem combinations against clinical isolates of Pseudomonas aeruginosa. In all experiments when either the fluoroquinolone or imipenem were dosed alone, we observed the emergence of resistance.