Antimicrobial Use and Resistance in Eight US Hospitals: Complexities of Analysis and Modeling

OBJECTIVE: To evaluate the relation between antimicrobial use and resistance in intensive-care unit (ICU) and non-ICU inpatient areas in eight US hospitals. METHODS: We determined antimicrobial use in terms of defined daily doses, antimicrobial-use density (defined daily doses/1,000 patient days), and percentage resistance for five antimicrobial-organism combinations in the ICU and non-ICU inpatient areas of eight US hospitals participating in project Intensive Care Antimicrobial Resistance Epidemiology. RESULTS: Antimicrobial resistance and use varied tremendously among the eight hospitals. Antimicrobial resistance among these five nosocomial pathogens was significantly higher within the inpatient setting of these hospitals, compared with the outpatient setting. One hospital consistently ranked highest for use of all classes of antimicrobials examined. High antimicrobial use was not associated necessarily with high resistance for a particular antimicrobial-organism pair. CONCLUSION: Antimicrobial use varied significantly across these hospitals, but generally was higher in ICUs. These results suggest that concomitant surveillance of both antimicrobial resistance and antimicrobial use is helpful in interpreting antimicrobial resistance in a hospital or ICU and that further analysis is required to determine the role of variables other than antimicrobial use in a statistical model for predicting antimicrobial resistance (Infect Control Hosp Epidemiol 1998;19:388-394). Antimicrobial-resistant pathogens are challenges to progress in controlling infections, especially those acquired in the hospital. Increases in antimicrobial resistance are resulting in the use of much more expensive drugs, more prolonged hospitalizations, higher death rates, and higher healthcare costs.1 Resistance is increasing among certain gram-positive and gram-negative organisms. For example, resistance among enterococci now presents a serious challenge for physicians.2 From 1993 to 1996, the percentage of intensivecare unit (ICU) nosocomial infections reported to the National Nosocomial Infections Surveillance (NNIS) System that were caused by vancomycin-resistant Enterococcus (VRE) increased from 0.4% to nearly 13%. However, during 1994 to 1996, while there was little increase in VRE rates in ICU areas, there were relatively higher increases in non-ICU inpatient areas. This resulted in a significant narrowing of the gap between the prevalence of VRE in ICU and non-ICU areas in NNIS hospitals during 1994 to 1996. Reports from the NNIS System and other sources clearly highlight the association of the ICU with increasing resistance among nosocomial isolates of Enterobacter species, Enterococcus species, Pseudomonas aeruginosa, and Staphylococcus aureus.2' Among these same patients, the percentage of ICU Enterobacter species isolates resistant to ceftazidime increased 15% during 1987 to 1991.6 Most, but not all,9 studies have found a higher prevalence of antimicrobial resistance in ICUs compared with non-ICU areas within hospitals.10-13 An association between antimicrobial use and antimicrobial resistance has been recognized among hospital organisms.14,15 Moreover, multicenter studies in the United States and worldwide have reported large variations in antimicrobial resistance between institutions.4,6,16-18 Because antimicrobial prescribing practices vary in hospitals throughout the United States, selective pressure for antimicrobial resistance as a result of antimicrobial use also will be likely to vary from hospital to hospital. From the Hospital Infections Program, Centers for Disease Control and Prevention, Atlanta, Georgia. The authors thank Linda Waller for assistance with graphics. This work was supported in part by grants to the Rollins School of Public Health of Emory University by Zeneca Pharmaceuticals and the National Foundation for Infectious Diseases. Dr Monnet was supported in part by grants from Fondation Marcel-Merieux and Agence Nationale pour le Developpement de l'Evaluation en Medicine in France. Domimique L. Monnet currently is affiliated with Statens Serum Institut in Copenhagen, Denmark. Address reprint requests to Robert P Gaynes, MD, Hospital Infections Program, Centers for Disease Control and Prevention, Mailstop E-55, 1600 Clifton Rd NE, Atlanta, GA 30333. 96-0A-237. Monnet DL, Archibald IX, Phillips L, Tenover FC, McGowan JE Jr, Gaynes RP, the Intensive Care Antimicrobial Resistance Epidemiology Project and the National Nosocomial Infections Surveillance System hospitals. Antimicrobial use and resistance in eight US hospitals: complexities of analysis and modeling. Infect Control Hosp Epidemiol 1998;19:388-394. This content downloaded from 207.46.13.176 on Mon, 20 Jun 2016 07:31:14 UTC All use subject to http://about.jstor.org/terms Vol. 19 No. 6 ANTIMICROBIAL USE AND RESISTANCE IN US HOSPITALS 389 In 1994, the Hospital Infections Program, Centers for Disease Control and Prevention (CDC), and the Rollins School of Public Health of Emory University began project Intensive Care Antimicrobial Resistance Epidemiology (ICARE), a multiphase study designed to evaluate the relation between antimicrobial use and resistance in hospitals and to compare antimicrobial resistance in the hospital setting with resistance in the community. In addition, project ICARE seeks to clarify the role played by ICUs in the occurrence of antimicrobial resistance by establishing a nationwide network of sentinel hospitals and microbiology laboratories to enable surveillance of antimicrobial use, in order to study in more depth the antimicrobial-resistant organisms responsible for the majority of nosocomial infections in US hospitals. This is one of several reports of data from the first phase in project ICARE. Prior reports focused on the higher frequency of resistance in ICUs compared with other inpatients and outpatients, and on the dramatic differences in antimicrobial-use patterns in participating hospitals.19,20 This report focuses on differences in antimicrobial use in ICU versus non-ICU inpatient areas and correlation between antimicrobial use and resistance for selected antimicrobial-organism pairs.