In October 1990, Enterococcus faecium that was highly resistant to glycopeptides, penicillins, and aminoglycosides was isolated from the peritoneal dialysis fluid from a patient in an intensive care unit. Over the following 6 months, multiresistant E. faecium organisms were isolated from cultures of blood, urine, or surgical wound specimens from eight additional patients. Surveillance cultures of groin and/or rectal swabs were positive for eight of 37 patients and four of 62 employees at risk. Restriction endonuclease digestion of chromosomal DNA from outbreak isolates was consistent with dissemination of a single strain throughout the intensive care unit. Strict infection control interventions contained the outbreak after several weeks. Review of patient charts suggested that renal insufficiency, length of hospital stay, duration of antibiotic treatment, and prior treatment with vancomycin were risks for infection due to multiresistant E. faecium. The emergence of multiple-drug-resistant enterococci presents serious infection control and therapeutic dilemmas.

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In several strains of Enterococcus faecium isolated in Europe, the cluster of genes encoding high-level resistance to vancomycin (VanA phenotype) resides on a 10.85-kb transposon, Tn1546, or closely related elements. To determine whether Tn1546 was conserved in recent enterococcal isolates from the northeastern United States, seven strains were compared by restriction mapping and DNA hybridization with probes from within the van cluster. Two of the seven strains contained intact Tn1546-like sequences; however, in five of the strains, the organization of the van cluster differed from that of Tn1546. Three of the five strains with variations harbored a novel DNA segment within the van gene cluster. This 1,496-bp segment was similar to IS1165 of Leuconostoc mesenteroides and IS1181 of Staphylococcus aureus and was flanked by 24-and 23-bp imperfect inverted repeats and 8-bp direct repeats. On the basis of these findings, we propose that this element comprises a novel insertion-like sequence, IS1251. Multiple copies of IS1251 were also present at other sites in both resistant and susceptible clinical isolates. Our findings suggest that the van cluster in recent isolates from the northeastern United States differs from that present in the early European VanA phenotype strains.Glycopeptide antibiotics such as vancomycin act by binding to the D-alanyl-D-alanine terminus of peptidoglycan precursors, preventing cell wall synthesis (26). It had been widely assumed that this terminus was ubiquitous among eubacterial species producing peptidoglycan and that vancomycin resistance was therefore unlikely to emerge in the absence of a barrier to vancomycin binding, such as the outer membrane of gram-negative bacteria. Nonetheless, vancomycin-resistant isolates of Enterococcus faecium were identified in France in 1986 (22). Resistant enterococcal strains have subsequently been isolated worldwide, and in 1993 the estimated incidence of glycopeptide resistance among isolates of Enterococcus spp. from intensive care units in the United States was 14% (24).Vancomycin resistance in members of several gram-positive genera is due to the production of peptidoglycan precursors terminating in the depsipeptide D-alanyl-D-lactate, to which vancomycin does not bind (1,17,18,23). In highly resistant (VanA phenotype) E. faecium and Enterococcus faecalis strains, production of this altered precursor is encoded by a plasmid-borne cluster of genes. Insertional mutagenesis experiments with two vancomycin resistance plasmids, pIP816 and pHKK100, have shown that four genes in the cluster are required for resistance : vanR, vanH, vanA, and vanX (3, 4, 15). vanR and vanS act as a sensor-regulatory pair analogous to such previously characterized systems as ompR-envZ and are required for the induction of resistance (3, 29). VanH, a D-specific ␣-keto acid reductase (8), and VanA, a D-alanine-Dalanine ligase of altered specificity (7), act in concert to form the depsipeptide D-alanyl-D-lactate, which is added in place of D-alanyl-D-alanine to the UDP-muram...