Clonal Diversity among Streptogramin A-Resistant Staphylococcus aureus Isolates Collected in French Hospitals

Abstract

We analyzed 62 clinical isolates of streptogramin A-resistant (SGA r ) Staphylococcus aureus collected between 1981 and 2001 in 14 hospitals located in seven French cities. These isolates, including five with decreased susceptibility to glycopeptides, were distributed into 45 antibiotypes and 38 SmaI genotypes. Each of these genotypes included between 1 and 11 isolates, the SmaI patterns of which differed by no more than three bands. Although numerous clones were identified, we observed the spread of monoclonal isolates either within the same hospital or within hospitals in distinct cities and at large time intervals. Hybridization with probes directed against 10 SGA r genes (vatA, vatB, vatC, vatD, vatE, vgaA, vgaB, vgaAv, vgbA, and vgbB) revealed six patterns: vgaAv (21 isolates), vatA-vgbA (24 isolates), vgaAv-vatB-vgaB (14 isolates), vgaAv-vatA-vgbA (1 isolate), vgaAv-vatA-vgbA-vatB-vgaB (1 isolate), and vgaA (1 isolate). We detected at least one SGA r determinant in all of the tested isolates. vgaAv, which is part of the recently characterized transposon Tn5406, was found in 59.7% of the tested isolates. Of the 16 streptogramin B-susceptible isolates, 14 carried vgaAv alone and were susceptible to the mixtures of streptogramins, whereas the 2 isolates carrying vgaAv-vatB-vgaB were resistant to these mixtures. vatA-vgbA was found on plasmids of the same apparent size in 26 (42%) of the tested clinical isolates from 18 unrelated SmaI genotypes. The possible dissemination of some of the multiple clones characterized in the present study with an expected increased selective pressure of streptogramins following the recent licensing of Synercid (quinupristin-dalfopristin) must be carefully monitored.Methicillin-resistant Staphylococcus aureus (MRSA) has become a major nosocomial pathogen worldwide. Glycopeptides have been the reference drugs for the treatment of MRSA infections (16,21,30). After the emergence of clones with decreased susceptibility to these antibiotics, first reported as sporadic cases in several countries and more recently also as outbreaks, alternative treatments such as quinupristin-dalfopristin (Synercid) have been promoted (17,21,33). Quinupristin and dalfopristin are derivatives of pristinamycins IA and IIA, respectively (10). Quinupristin-dalfopristin is an injectable, semisynthetic, mixture with a synergistic activity against most gram-positive pathogens. Since 1999, quinupristin-dalfopristin has been available for use in hospitals for the treatment of infections caused by gram-positive cocci that are resistant to other antibiotics.Quinupristin-dalfopristin and the natural antibiotics produced by streptomycetes, such as streptogramin, pristinamycin, synergistin, mikamycin, and virginiamycin, are mixtures of two classes of compounds, A and B, with distinct primary structures (10, 14). The A compounds are polyunsaturated cyclic macrolactones, and the B compounds are cyclic hexadepsipeptides. Both types of compounds bind different targets in the peptidyltransferase domain of the 23S ribosoma...

Molecular Analysis of Resistance to Streptogramin A Compounds Conferred by the Vga Proteins of Staphylococci

“…This phenotype is similar to that conferred by the lsa gene in Enterococcus faecalis, although the levels of resistance to lincosamides were much lower for staphylococci with the vga(A) and the vga(A)v genes (38). We suggest, therefore, that vga(A) or its variant, vga(A)v, is involved in the LSA phenotype occasionally found among staphylococcal isolates (14,17,24).…”

“…To the best of our knowledge, this has never been described. The detection of this gene in clinical strains might therefore be of importance for prediction of the in vivo activity of quinupristin-dalfopristin (2,11,17,24).…”

DNA Microarray for Detection of Macrolide Resistance Genes

“…and has never been found in gram-negative bacteria. In S. aureus strain BM12235, carrying the major facilitator streptogramin efflux gene vga(B) and the streptogramin acetyltransferase gene vat(B), it was possible to identify also the presence of vga(A)v, an ATP-binding transporter gene which is commonly associated with vga(B) and vat(B) (11,12). DNA sequence analysis showed that vga(A)v of BM12235 was essentially identical (99% identity at the DNA level) to vga(A)v of S. aureus BM3327 (GenBank accession no.…”

Staphylococcus research

“…There is little prospect of eradicating staphylococcal disease in the short term so effective antibiotics are of great importance. Fortunately, both linezolid and Synercid (a streptogramin A/B combination) are newly licensed for use against staphylococci but resistance to streptogramins is already present among hospital staphylococci and its prevalence can be expected to increase with the widespread use of Synercid (Haroche et al, 2003).…”