Resistance Challenges Threatening the Treatment of Pseudomonas aeruginosa Infections with Levofloxacin: The Role of a Levofloxacin-Imipenem Combination for Prevention of Resistance
Philip D. Lister, PhD
Daniel J. Wolter, PhD
Center for Research in Anti-Infectives and Biotechnology,
Department of Medical Microbiology and Immunology,
Creighton University School of Medicine, Omaha, Nebraska, USA
Pseudomonas aeruginosa is an important nosocomial pathogen that exhibits the impressive ability to acquire antibacterial resistance, even during the course of therapy. When antibacterial resistance complicates therapy, morbidity and mortality increase significantly. Levofloxacin remains one of the drugs of choice for treatment of serious P. aeruginosa infections, but the overexpression of multi-drug efflux pumps and mutational changes in target enzymes are limiting its efficacy. Over the past decade, most global surveillance programs report that 20 to 30% of P. aeruginosa are resistant to levofloxacin and ciprofloxacin, with even higher rates being reported from some regions.
Historically, a combination of antibacterial agents has been the strategy to treat multi-drug resistant P. aeruginosa and to prevent the emergence of resistance during therapy. Unfortunately, the standard combination of an anti-pseudomonal β-lactam with an aminoglycoside is not always effective in achieving this goal. Therefore, the search for more effective mechanism-based combinations must be a priority. This review focuses on the resistance problems (global trends and molecular mechanisms) challenging the use of levofloxacin for treatment of P. aeruginosa and the potential role of a levofloxacin-imipenem combination for preventing emergence of resistance during therapy, even when the P. aeruginosa already lacks susceptibility to one or both drugs.