Objective: To determine the impact of the rotation of antimicrobial agents on the rates of infection, intestinal colonization, and acquisition with antimicrobial-resistant Gram-negative bacteria.
Design: Pre- and postintervention design.
Setting: A 19-bed, medical intensive care unit.
Patients: Individuals admitted to the study unit for >48 hrs.
Interventions: After a 5-month baseline observation period, four classes of antimicrobial agents with Gram-negative activity were cycled at 3- to 4-month intervals for 24 months.
Measurements and Main Results: The primary outcome was the acquisition rate of antimicrobial resistance among Enterobacteriaceae and Pseudomonas aeruginosa obtained from rectal swab cultures performed on admission, weekly during the patients' stay, and at discharge. Rates and microbiology of nosocomial bloodstream infections and ventilator-associated pneumonia were also compared between baseline and cycling periods. The cycling program resulted in a significant change in prescribing practices; the predominant agent used changed with each cycle. Among study patients who were not already colonized with a resistant organism, the rate of acquisition of enteric colonization with bacteria resistant to any of the target drugs remained stable during the cycling period for P. aeruginosa (relative rate, 0.96; 95% confidence Interval, 0.47-2.16) and Enterobacteriaceae (relative rate, 1.57; 95% confidence interval, 0.80-3.43). Hospital-wide, P. aeruginosa from routine clinical cultures resistant to the target drugs increased during the cycling period. The proportion of Gram-negative bacteria isolated from cases of nosocomial bloodstream infection (29% baseline vs. 26% cycling; p = .11) and ventilator-associated pneumonia (80% vs. 41%; p = .06) did not significantly differ.
Conclusions: In this study, antimicrobial cycling did not result in a significant change in enteric acquisition of resistant Gram-negative bacteria among intensive care unit patients.
Critically ill patients are at increased risk for hospital-acquired infections. The unique nature of the intensive care unit (ICU) environment makes it a focus for the emergence and spread of antimicrobial-resistant bacterium. Antimicrobial resistance among ICU-related pathogens has consistently increased over the last decade. The emergence of antimicrobial-resistant bacteria in ICUs has made treating nosocomial infections increasingly difficult, particularly multi-drug-resistant Gram-negative bacterial infections, which have been associated with increased morbidity and mortality rates.
Excessive use of broad-spectrum antimicrobials in ICUs has been directly correlated with the emergence of antimicrobial-resistant Gram-negative bacteria. Antimicrobial cycling, which is the systematic rotation of available antimicrobials for use in empirical and directed therapy, is one proposed method to control broad-spectrum antimicrobial use. The routine and systematic cycling of the predominantly used antimicrobial agents will, in theory, reduce the selective pressure driving pathogens to become resistant to any single class of antimicrobials, thereby reducing the emergence of antimicrobial-resistant bacteria.
Several previous studies have examined the impact of cycling of empirical antimicrobial therapy within individual ICUs. The interventions tested varied from a simple switch from one predominant antimicrobial drug class to another, to the rotation of several different classes of antimicrobials on a regular basis. These studies reported reductions in the occurrence of nosocomial infections and favorable alterations in the antimicrobial susceptibility of clinical isolates of Gram-negative bacteria.
Although previous studies suggest that antimicrobial cycling can be effective in reducing the prevalence of antimicrobial resistant Gram-negative bacteria associated with infections acquired within ICUs, several limitations of these studies leave questions regarding the effectiveness of antimicrobial cycling programs. None of these studies consistently differentiated organisms acquired during a patient's ICU stay from organisms present at admission. Therefore, it is possible that any observed changes in the prevalence of antimicrobial resistance among clinical specimens can be due to changes in prevalence of colonizing flora among patients at admission. Also, most previous studies determined the prevalence of antimicrobial resistance by relying on clinical cultures alone. Since enteric colonization with antimicrobial-resistant Gram-negative bacteria usually precedes infection with the same organism, demonstrating a decrease in the rate of colonization or infection with these organisms would strengthen the hypothesis that antimicrobial cycling creates a less favorable environment for the dissemination of resistant strains of Gram-negative bacterium within an ICU.
The objective of this study was to evaluate the impact of a program of systematic rotation of available antimicrobial classes used for empirical and targeted treatment of Gram-negative infections on the acquisition of intestinal colonization or infection with antimicrobial-resistant Gram-negative bacteria among patients admitted to a medical ICU. In addition, we hoped to measure the impact on other health outcomes and the relative importance of measuring gastrointestinal colonization of antimicrobial-resistant bacteria in this type of study.