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

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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 β-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.

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