Journal
PHARMACOTHERAPY
Volume 31, Issue 11, Pages 1073-1084Publisher
WILEY
DOI: 10.1592/phco.31.11.1073
Keywords
combination therapy; gram-negative organisms; Pseudomonas aeruginosa; colistin; multidrug resistance
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The widespread emergence of antibiotic-resistant gram-negative organisms has compromised the utility of current treatment options for severe infections caused by these pathogens. The rate of gram-negative multidrug resistance is worsening, threatening the effectiveness of newer broad-spectrum antibiotic agents. Infections associated with multidrug-resistant Pseudomonas aeruginosa, Acinetobacter battmannii, and Enterobacteriaceae are having a substantial impact on hospital costs and mortality rates. The potential for these resistant gram-negative nosocomial pathogens must always be a primary consideration when selecting antibiotic therapy for critically ill patients. Empiric combination therapy directed at gram-negative pathogens is a logical approach for patients with suspected health care associated infections, particularly those with risk factors for infections caused by multidrug-resistant pathogens. Although in vitro synergy tests have shown potential benefits of continued combination therapy, convincing clinical data that demonstrate a need for combination therapy once susceptibilities are known are lacking. Thus, deescalation to a single agent once susceptibilities are known is recommended for most patients and pathogens. Use of polymyxins, often in combination with other antimicrobials, may be necessary for salvage therapy.
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