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We review the hospital-acquired gram-negative organisms commonly encountered among patients in the intensive care unit and discuss pertinent surveillance data, resistance mechanisms and patterns, and optimal treatment regimens for these pathogens.There has been a notable increase in antibiotic resistance among gram-negative intensive care unit pathogens. Data from surveillance programs such as National Nosocomial Infections Surveillance System, Intensive Care Antimicrobial Resistance Epidemiology, and others have documented undesirable trends in antibiotic resistance, indicating decreasing efficacy of antibiotic classes such as third-generation cephalosporins, carbapenems, and fluoroquinolones, The increased prevalence of extended-spectrum β-lactamases has contributed to the finding of multidrug resistance among bacteria such as Klebsiella and Escherichia coli. Furthermore, organisms such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia display intrinsic resistance to many antibiotics, making selection of optimal therapy difficult. Studies have correlated infection by these organisms with prior antibiotic exposure, and containment of the spread of infection can be achieved by careful antibiotic use and infection control practices.Antibiotic resistance continues to rise among hospital-acquired gram-negative pathogens. Optimal management of these infections requires knowledge of local epidemiology and practices to control their spread.