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EBBING LAUTENBACH, MD, MPH, MSCE, Associate Professor of Medicine and Epidemiology, University of Pennsylvania School of Medicine, 825 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021 (ebbing{at}mail.med.upenn.edu), and RON E. POLK, PHARM.D., FIDSA, Professor of Pharmacy and Medicine, Chairman, Department of Pharmacy, School of Pharmacy, Virginia Commonwealth University/Medical College of Virginia Campus, 410 North 12th Street, PO Box 980533, Richmond, VA 23298-0533 (rpolk{at}vcu.edu).

Purpose. Infections caused by drug-resistant gram-negative bacteria are a growing threat to the healthcare community and clinicians are encouraged to employ a combination of strategies for effective prevention and treatment of these difficult infections. Summary. Recent epidemiological studies suggest an increase in healthcare- associated infections caused by gram-negative bacteria, particularly Klebsiella spp., Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter spp. The rising incidence of drug resistance of these pathogens presents a challenge given the few novel antimicrobial agents under development that specifically target these organisms. To combat this trend, recent guidelines promote Antimicrobial Stewardship Programs (ASP) as an effective means to possibly control the emergence and spread of antimicrobial resistance. Two key ASPs strategies include prospective audit, intervention, and feedback, and formulary restriction and preauthorization. The best methods to measure antimicrobial use and antimicrobial resistance are still being developed. In addition, using pharmacokinetics and pharmacodynamics priniciples to guide antimicrobial dosing regimens may have a role in controlling development of resistance. Finally, enforcing rigorous infection control practices can reduce the transmission of problematic pathogens within the healthcare setting. Conclusion. With a limited number of antimicrobial agents in development, clinicians cannot rely on new drugs alone to treat infections due to drug-resistant gram-negative bacteria but must also incorporate strategies that reduce the emergence of resistance and prevent the spread of problematic bacteria. Potentially effective interventions include antimicrobial stewardship tactics that advocate optimal use of currently available antimicrobial agents and rigorous infection control measures. Infectious diseases trained pharmacists are in a unique position to play a key role in helping control the spread of nosocomial pathogens. Index terms: Antiinfective agents; Control; Dosage; Epidemiology; Gram-negative bacteria; Gram-negative bacterial infections; Protocols; Resistance