Review article
Occurrence and spread of antibiotic resistances in Enterococcus faecium

https://doi.org/10.1016/S0168-1605(03)00190-9Get rights and content

Abstract

Enterococci are the second to third most important bacterial genus in hospital infections. Especially Enterococcus (E.) faecium possesses a broad spectrum of natural and acquired antibiotic resistances which are presented in detail in this paper. From medical point of view, the transferable resistances to glycopeptides (e.g., vancomycin, VAN, or teicoplanin, TPL) and streptogramins (e.g., quinupristin/dalfopristin, Q/D) in enterococci are of special interest.

The VanA type of enterococcal glycopeptide resistance is the most important one (VAN-r, TPL-r); its main reservoir is E. faecium. Glycopeptide-resistant E. faecium (GREF) can be found in hospitals and outside of them, namely in European commercial animal husbandry in which the glycopeptide avoparcin (AVO) was used as growth promoter in the past. There are identical types of the vanA gene clusters in enterococci from different ecological origins (faecal samples of animals, animal feed, patients in hospitals, persons in the community, waste water samples). Obviously, across the food chain (by GREF-contaminated meat products), these multiple-resistant bacteria or their vanA gene clusters can reach humans. In hospital infections, widespread epidemic-virulent E. faecium isolates of the same clone with or without glycopeptide resistance can occur; these strains often harbour different plasmids and the esp gene. This indicates that hospital-adapted epidemic-virulent E. faecium strains have picked up the vanA gene cluster after they were already widely spread. The streptogramin virginiamycin was also used as feed additive in commercial animal husbandry in Europe for more than 20 years, and it created reservoirs for streptogramin-resistant E. faecium (SREF). In 1998/1999, SREF could be isolated in Germany from waste water of sewage treatment plants, from faecal samples and meat products of animals that were fed virginiamycin (cross resistance to Q/D), from stools of humans in the community, and from clinical samples. These isolations of SREF occurred in a time before the streptogramin combination Q/D was introduced for therapeutic purposes in German hospitals in May 2000, while other streptogramins were not used in German clinics. This seems to indicate that the origin of these SREF or their streptogramin resistance gene(s) originated from other sources outside the hospitals, probably from commercial animal husbandry. In order to prevent the dissemination of multiple antibiotic-resistant enterococci or their transferable resistance genes, a prudent use of antibiotics is necessary in human and veterinary medicine, and in animal husbandry.

Introduction

Enterococci are Gram-positive, facultative anaerobic bacteria that live as part of the natural flora in the intestinal tract of animals and humans. Enterococci are normally considered as bacteria of low pathogenicity that only infect persons with special predispositions (e.g., immunocompromised patients in oncology, hematology, nephrology, or transplantation units). They can cause different infections, e.g., of the urinary tract and the bile trays, in wounds, and also life-threatening infections such as bacteremia or endocarditis. With about 12% frequency, they are the second to third most important bacterial genus in hospital infections Woodford, 1998, Linden and Miller, 1999. Of the 24 enterococcal species known until now, E. faecalis and E. faecium are the most important ones for infections in humans (Facklam et al., 2002).

Section snippets

Natural and acquired antibiotic resistances in enterococci

Apart from several insusceptibilities to physico-chemical and environmental factors Murray, 1990, Devriese et al., 1993, Facklam et al., 2002, enterococci (especially E. faecium) possess a broad spectrum of natural and acquired antibiotic resistances Brunton, 1984, Murray, 1990, Woodford et al., 1995, Gold and Moellering, 1996, Rice and Bonomo, 1996, Klare and Witte, 1997, Quintiliani et al., 1999, Kak and Chow, 2002, Klare et al., 2002.

Spread of microbial antibiotic resistance genes

Resistance genes can be disseminated by two different ways: (i) by clonal dissemination of resistant isolates or (ii) by spread of resistance genes between different strains of the same or other species or genera (horizontal gene transfer).

Glycopeptide resistance genes

The first indication of a reservoir for GREF outside the hospital was the isolation of VanA-type E. faecium strains from waste water of a sewage treatment plant in a small German town which had no hospital (Klare et al., 1993). The assumption that the use of AVO as growth promoter in commercial animal husbandry could be responsible for this observation was emphasised by the isolation of VanA-type E. faecium strains from faecal samples of animals (pigs, chicken) in farms in which AVO was used.

Role of antibiotic selective pressure in dissemination of resistance in enterococci

As shown in this paper, different reservoirs exist for antibiotic-resistant enterococci.

First, the hospitals with their broad use of antibiotics, especially in medical intensive care units, appear to be important reservoirs. Because of the broad spectrum of natural and acquired antibiotic resistances, enterococci (and especially E. faecium) can be selected in these ecological niches. In parallel, there is a change in the types of the hospitalised patients during recent years; in connection with

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