Review of studies of the impact on Gram-negative bacterial resistance on outcomes in the intensive care unit

Objective., To review studies addressing mortality, length of stay (LOS), and cost of resistant Gram-negative bacterial infections in the intensive care unit (ICU). Data Sources and Study Selection: A qualitative review of published studies identified through PubMed search was performed. Study exclusion criteria were population <40 adults or <39% of cases in the ICU. Criteria for judging study quality were prospective analysis, multicenter study, author-specified diagnostic criteria, appropriate control group defined as patients with infections caused by susceptible bacteria, adjustments for confounding factors, and use of cost. Data Extraction and Synthesis: Twenty-one original studies and a meta-analysis, which included three of the original studies, were identified. Infections caused by mixed resistant Gram-negative bacteria, extended-spectrum beta-lactamase-producing Enterobacteriaceae, multidrug-resistant Pseudomonas aeruginosa, and Acinetobacter species were generally associated with Increased mortality and LOS, especially in univariate analyses. Economic analyses performed in eight studies indicated that these resistant Gram-negative infections were also associated with increased patient charges or hospital costs. Associations sometimes disappeared in multivariate analyses after adjusting for variables significant in univariate analyses. Conclusion. The collective findings of the studies in this review suggested that Gram-negative bacterial resistance increases the burden in the ICU as measured by mortality, LOS, and charges. More prospective studies are needed to explore methods for combating Gram-negative resistance, including prevention, education, and better antimicrobial therapy. For example, well-designed research is needed to determine the cost-effectiveness of appropriate empiric therapy with broad-spectrum agents active against resistant Gram-negative bacteria followed by de-escalation. (Crit Care Med 2009; 37:1463-1469)