Molecular analysis of streptogramin resistance in enterococci.
The new semi-synthetic streptogramin antibiotic combination quinupristin/dalfopristin (Synercid) is a promising alternative for a treatment of infections with multiple resistant gram-positive pathogens, e.g. glycopeptide- and multi-resistant Enterococcus faecium. Streptogramins consist of two unrelated compounds, a streptogramin A and B, which act synergistically when given in combination. Mechanisms conferring resistance against both components are essential for resistance against the combination in E. faecium. In this species resistance to streptogramin A compounds is mediated via related acetyltransferases VatD and VatE. Resistance against streptogramins B is either encoded by the widespread ermB gene cluster conferring resistance to macrolide-lincosamide-streptogramin B antibiotics or via expression of the vgbA gene, which encodes a staphylococcal-type lactonase. E. faecalis is intrinsically resistant to streptogramins. Due to a wide use of streptogramins (virginiamycins S/M) in commercial animal farming a reservoir of streptogramin-resistant E. faecium isolates had already been selected. Determinants for streptogramin resistance are localized on plasmids that can be transferred into an E. faecium recipient both in vitro in filter-matings and in vivo in the digestive tracts of rats. Hybridization and sequencing experiments revealed a linkage of resistance determinants for streptogramins A and B on definite plasmid fragments.
Robert Koch Institute, Wernigerode Branch, Burgstr. 37, D-38855 Wernigerode, Germany. wernerg@rki.de
Guido
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Werner
Ingo
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Klare
Wolfgang
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Witte
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D016984:Enterococcus faecium / Q000235:genetics* / Q000378:metabolism; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy; D006801:Humans; D025361:Streptogramins / Q000494:pharmacology*; D014769:Virginiamycin / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D025361:Streptogramins; D014769:Virginiamycin; C062940:quinupristin-dalfopristin