Gram-negative antibiotic resistance: there is a price to pay

Abstract

Resistance rates are increasing among several problematic Gram-negative pathogens that are often responsible for serious nosocomial infections, including Acinetobacter spp., Pseudomonas aeruginosa, and (because of their production of extended-spectrum beta-lactamase) Enterobacteriaceae. The presence of multiresistant strains of these organisms has been associated with prolonged hospital stays, higher health care costs, and increased mortality, particularly when initial antibiotic therapy does not provide coverage of the causative pathogen. Conversely, with high rates of appropriate initial antibiotic therapy, infections caused by multiresistant Gram-negative pathogens do not negatively influence patient outcomes or costs. Taken together, these observations underscore the importance of a 'hit hard and hit fast' approach to treating serious nosocomial infections, particularly when it is suspected that multiresistant pathogens are responsible. They also point to the need for a multidisciplinary effort to combat resistance, which should include improved antimicrobial stewardship, increased resources for infection control, and development of new antimicrobial agents with activity against multiresistant Gram-negative pathogens.

Figure 1

Acinetobacter spp. and Pseudomonas aeruginosa isolates: 1975 and 2003. Shown are the percentages of bacterial isolates associated with (a) Acinetobacter spp. and (b) P. aeruginosa by infection type in the National Nosocomial Infections Surveillance System for 1975 and 2003. Data from 1975 are from hospital-wide surveillance whereas those from 2003 are from intensive care unit surveillance [8].

Figure 2

Impact of imipenem resistance on mortality of patients with Acinetobacter bacteremia. Reprinted with permission from Kwon and coworkers [12]. Copyright ^© 2007 Oxford University Press.

Figure 3

Impact of high rates of appropriate antibiotic therapy on mortality in patients with Gram-negative bacteremia. Antibiotic resistance was defined as in vitro resistance to ceftazidime [27]. Reprinted with permission. Copyright ^© 2002 Infectious Diseases Society of America.