Of 3,052 Staphylococcus aureus strains collected by the European SENTRY surveillance study, 35 were found to be nonsusceptible to quinupristin-dalfopristin (MIC of >2 mg/liter). These isolates originated from four hospitals in France and one in Spain. In isolates from two Parisian hospitals exhibiting the same SmaI macrorestriction pattern, streptogramin resistance was based on vatA and vgbA. One isolate from a hospital in Lyon and 22 from a hospital in Lille were of the vatB vgaB streptogramin A resistance genotype and possessed ermA and/or ermC. As deduced from the loss of either streptogramin A or streptogramin B resistance determinants in particular isolates, resistance to quinupristin-dalfopristin requires mechanisms conferring resistance to both compounds. The SmaI macrorestriction patterns of strains from hospitals in Lille and Lyon were different; however, similarity analysis suggested a relatedness of 20 methicillin-resistant S. aureus strains from the Lille hospital, a finding confirmed by PCR typing based on three different genomic polymorphisms. These groups of isolates were found to be hetero-glycopeptide-intermediate susceptible S. aureus. Information about the failure of glycopeptide chemotherapy has not been available.Methicillin-resistant Staphylococcus aureus (MRSA) has become an important nosocomial pathogen in many countries. Glycopeptides have been the drugs of choice for treating MRSA infections. However, with the emergence of intermediate susceptibility to glycopeptides, first reported from sporadic cases in many countries (12, 20) and more recently also from an outbreak of infections (11), other treatment alternatives such as quinupristin-dalfopristin and linezolid have become important. Quinupristin-dalfopristin is a combination of streptogramin B and A compounds with a synergistic activity against most gram-positive bacteria (8,14).Resistance to the B component is mediated by methylation of 23S rRNA which confers macrolide-lincosamide-streptogramin B (MLS B ) resistance when the erm genes are expressed constitutively (7). A second mechanism is hydrolysis of the drug by a lactonase encoded by the vgbA and the vgbB genes, respectively (1, 6). Two kinds of mechanisms are known to mediate resistance to the A compound: inactivation of the drug by acetylation and efflux. In staphylococci, three acetyltransferase genes, vatA, vatB, and vatC (3, 4, 6) and two genes for efflux pumps (ABC porters), vgaA and vgaB (2, 5), have been described. These streptogramin A and B resistance genes are often located on the same plasmids (6).In this study we describe quinupristin-dalfopristin-resistant S. aureus strains collected during the course of the European SENTRY surveillance study in European countries (18). These strains were characterized in our laboratory with regard to streptogramin resistance genes, phenotypic resistance to other antibiotics, and genotype.
MATERIALS AND METHODS
Bacterial isolates.A total of 35 isolates of S. aureus exhibiting insensitivity to quinupristin-dalfopristin originated f...