Cardiologia

The

n e w e ng l a n d j o u r na l

of

m e dic i n e

review article
Current Concepts

Hospital-Acquired Infections Due to Gram-Negative Bacteria
Anton Y. Peleg, M.B., B.S., M.P.H., and David C. Hooper, M.D.

From the Division of Infectious Diseases, Massachusetts General Hospital (A.Y.P., D.C.H.), the Division of Infectious Disease, Beth Israel Deaconess Medical Center (A.Y.P.),and Harvard Medical School (A.Y.P., D.C.H.) — all in Boston; and the Department of Infectious Diseases, Alfred Hospital, and the Department of Microbiology, Monash University (A.Y.P.) — both in Melbourne, Australia. Address reprint requests to Dr. Peleg at the Division of Infectious Disease, Beth Israel Deaconess Medical Center, 110 Francis St., Boston, MA 02215, or at apeleg@ bidmc.harvard.edu.N Engl J Med 2010;362:1804-13.
Copyright © 2010 Massachusetts Medical Society.

ospital-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 infectionsthe 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 highlyefficient 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 ofantimicrobial-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 aboutreduced 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.

H

T y pe s of Infec t ions
Hospital-acquired infections are most commonly associated with invasive medical devices or surgical procedures. Lower respiratory tract and bloodstreaminfections are the most lethal; however, urinary tract infections are the most common. Recent data from the U.S. National Healthcare Safety Network indicate that gramnegative bacteria are responsible for more than 30% of hospital-acquired infections, and these bacteria predominate in cases of ventilator-associated pneumonia (47%) and urinary tract infections (45%).7 In intensive care units (ICUs) inthe United States, gram-negative bacteria account for about 70% of these types of infections, and similar data are reported from other parts of the world.8 A range of gramnegative organisms are responsible for hospital-acquired infections, the Enterobacteriaceae family being the most commonly identified group overall (see the table in the Supplementary Appendix, available with the full text ofthis article at NEJM.org). Unfortunately, multidrug-resistant organisms, including Pseudomonas aeruginosa, Acineto­ bacter baumannii, and extended-spectrum β-lactamase (ESBL)–producing or carba1804

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