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Enterococci Resistant to Multiple Antimicrobial Agents, Including Vancomycin: Establishment of Endemicity in a University Medical Center

J. Glenn Morris; David K. Shay; Joan N. Hebden; Robert J. McCarter; Beulah E. Perdue; William Jarvis; Judith A. Johnson; Thomas C. Dowling; Louis B. Polish; and Richard S. Schwalbe
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From the University of Maryland School of Medicine and Veterans Affairs Medical Center, Baltimore, Maryland. The Centers for Disease Control and Prevention, Atlanta, Georgia. Requests for Reprints: J. Glenn Morris Jr., MD, Infectious Diseases Section, Baltimore Veterans Affairs Medical Center, 10 North Greene Street, Baltimore, MD 21201. Acknowledgments: The authors thank Sadaf Qaiyumi, Teheri Laskerwala, Marcia Fullem, Punam R. Verma, Tracy Harrison, Michael Ann Priess, and the staff of the University of Maryland School of Medicine Clinical Microbiology Laboratory for their technical assistance in this study; Kim Homes for assistance with chart review and collection of epidemiologic data; Michael J. Orsini and Drs. Paul J. Weidle and Joseph Gallina for establishing and monitoring compliance with the vancomycin restrictions and for collecting pharmacy data; Sonia Aguero and Dr. Matthew Arduino for hand-culturing studies; and Drs. Harold Standiford and Steve Schimpff for their thoughtful comments on the manuscript.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1995;123(4):250-259. doi:10.7326/0003-4819-123-4-199508150-00002
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Objectives: To determine the distribution of and risk factors for colonization and infection with vancomycin-resistant enterococci; to evaluate the molecular epidemiology of these strains; and to assess the effect of interventions, including 1) strict adherence to infection control procedures and 2) restricted use of vancomycin.

Design: Problem identification based on descriptive studies, point-prevalence surveys, and case–control studies and followed by specific interventions and evaluation of the response to these interventions.

Setting: University medical center.

Participants: All patients hospitalized between May 1992 and June 1994 (59 196 admissions).

Main Results: 75 active infections attributed to vancomycin-resistant enterococci were identified. Thirty-one patients (41%) had bloodstream infections and 6 (8%) died. The incidence of active infection was highest in the organ transplantation unit (13.2 infections/1000 admissions). In the point-prevalence studies, vancomycin-resistant enterococci were isolated from 20% of a random sample of hospitalized patients in July, August, and September 1993 [adjusted prevalence, 16.9%]. Case-control studies showed significant associations between colonization and infection and 1) receipt of antimicrobial agents, particularly vancomycin, and 2) severity of illness. Although several small case clusters had isolates with identical banding patterns on pulsed-field gel electrophoresis, at least 45 different banding patterns were noted among medical center isolates. Interventions took place in November and December 1993. Vancomycin restriction policies resulted in a 59% decrease in intravenous vancomycin use and an 85% decrease in oral vancomycin use. Point-prevalence surveys done in April, May, and June 1994 showed a consistent 20% level of colonization with vancomycin-resistant enterococci strains (adjusted prevalence, 18.7%). No significant changes were seen in rates of vancomycin-resistant enterococci infection.

Conclusions: Vancomycin-resistant enterococci are an important cause of illness and death in the study institution, particularly among organ transplant recipients and other seriously ill persons; they have also become a common intestinal colonizer among hospitalized patients. The diversity of isolates (based on molecular typing studies) suggests that resistant organisms have been introduced from multiple sources. Interventions that effectively lower the overall level of colonization with vancomycin-resistant enterococci must still be identified.


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Figure 1.

Patients with active vancomycin-resistant enterococci infections, May 1992 to June 1994.

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Figure 2.

Administration of oral and intravenous vancomycin from January 1993 to June 1994 (restrictions on vancomycin use were imposed on 1 December 1993). Administration of ceftazidime, ceftriaxone, and ciprofloxacin from January 1993 to June 1994.

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Figure 3.
Contour-clamped homogeneous electric field electrophoresis fibroblast (CHEF) banding patterns of chromosomal DNA prepared from enterococci recovered from the initial point-prevalence study.

Twelve electrophoretically distinct patterns from 12 patient samples are shown. Deoxyribonucleic acid was digested with SmaI and was subjected to electrophoresis with the CHEF DRII system. The running conditions included a pulse time of 5 to 25 seconds at 200 V for 25 hours. Lane 1: λ ladder molecular size standards. Numeric values are equivalent to kilobase pairs.

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