Combination Antibiotic Therapy for Empiric and Definitive Treatment of Gram‐Negative Infections: Insights from the Society of Infectious Diseases Pharmacists

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<jats:p>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 <jats:italic>Pseudomonas aeruginosa, Acinetobacter baumannii</jats:italic>, 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.</jats:p>

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