Context Previous surveillance studies have documented increasing rates of antimicrobial resistance in US intensive care units (ICUs) in the early 1990s. Objectives To assess national rates of antimicrobial resistance among gramnegative aerobic isolates recovered from ICU patients and to compare these rates to antimicrobial use. Design and Setting Participating institutions, representing a total of 43 US states plus the District of Columbia, provided antibiotic susceptibility results for 35790 nonduplicate gram-negative aerobic isolates recovered from ICU patients between 1994 and 2000. Main Outcome Measures Each institution tested approximately 100 consecutive gram-negative aerobic isolates recovered from ICU patients. Organisms were identified to the species level. Susceptibility tests were performed, and national fluoroquinolone consumption data were obtained. Results The activity of most antimicrobial agents against gram-negative aerobic isolates showed an absolute decrease of 6% or less over the study period. The overall susceptibility to ciprofloxacin decreased steadily from 86% in 1994 to 76% in 2000 and was significantly associated with increased national use of fluoroquinolones. Conclusions This study documents the increasing incidence of ciprofloxacin resistance among gram-negative bacilli that has occurred coincident with increased use of fluoroquinolones. More judicious use of fluoroquinolones will be necessary to limit this downward trend.

The rapid emergence and dissemination of antibiotic-resistant microorganisms in ICUs worldwide threaten adequate antibiotic coverage of infected patients in this environment. The causes of this problem are multifactorial, but the core issues are clear: the emergence of antibiotic resistance is highly correlated with selective pressure resulting from inappropriate use of these drugs. Because a significant increase in mortality is observed when antibiotic therapy is delayed in infected ICU patients, initial therapy should be broad enough to cover all likely pathogens. Receipt of unnecessary prolonged broad-spectrum antibiotics, however, should be avoided. Local microbiologic data are extremely important to predict the type of resistance that may be present for specific causative bacteria, as is prior antibiotic exposure, and antibiotic choices should thus be made at an individual patient level.

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Infections occur frequently in critically ill patients and their management can be challenging for various reasons, including delayed diagnosis, difficulties identifying causative microorganisms, and the high prevalence of antibiotic-resistant strains. In this review, we briefly discuss the importance of early infection diagnosis, before considering in more detail some of the key issues related to antibiotic management in these patients, including controversies surrounding use of combination or monotherapy, duration of therapy, and de-escalation. Antibiotic pharmacodynamics and pharmacokinetics, notably volumes of distribution and clearance, can be altered by critical illness and can influence dosing regimens. Dosing decisions in different subgroups of patients, e.g., the obese, are also covered. We also briefly consider ventilator-associated pneumonia and the role of inhaled antibiotics. Finally, we mention antibiotics that are currently being developed and show promise for the future.