CURRENT CONCEPTS Hospital-Acquired Infections Due to Gram-Negative Bacteria

Hospital-acquired infections are a major challenge to patient safety. It is estimated that in 2002, a total of 1.7 million hospital-acquired infections occurred (4.5 per 100 admissions),1 and almost 99,000 deaths resulted from or were associated with a hospital-acquired infection,1 making hospital-acquired infections the sixth leading cause of death in the United States2; similar data have been reported from Europe.3 The estimated costs to the U.S. health care budget are $5 billion to $10 billion annually.4 Approximately one third or more of hospital-acquired infections are preventable.5 Infections caused by gram-negative bacteria have features that are of particular concern. These organisms are highly efficient at up-regulating or acquiring genes that code for mechanisms of antibiotic drug resistance, especially in the presence of antibiotic selection pressure. Furthermore, they have available to them a plethora of resistance mechanisms, often using multiple mechanisms against the same antibiotic or using a single mechanism to affect multiple antibiotics (Fig. 1). Compounding the problem of antimicrobial-drug resistance is the immediate threat of a reduction in the discovery and development of new antibiotics. 6 Several factors have contributed to this decline, including the increasing challenges of screening for new compounds, the high capital costs and long time required for drug development, the growing complexity of designing and performing definitive clinical trials, and the concern about reduced drug longevity due to the emergence of resistance. As a consequence, a perfect storm has been created with regard to these infections: increasing drug resistance in the absence of new drug development. Copyright © 2010 Massachusetts Medical Society. All rights reserved.