Streptogramin combination

Hydrolysis of macrolides by products of the ere genes detected in enterobacteria is only of scientific interest, while esterases VGB-A and VGB-B encoded by the vgb type genes mediate clinically relevant resistance in staphylococci to the B compound (quinupristin) of the streptogramin combination quinu-pristin-dalfopristin. 

Resistance to the A compound of streptogramins is mediated by products of the vat genes (virginiamycin acetyliransferase), of which at least five molecular classes are known (vatA-E). These genes are located on plasmids of Enterococcus faecium and frequently in combination with a gene encoding a streptogramin hydrolase (vga/vgb) in staphylococci. 

Macrolides, lincosamides and streptogramins are protein biosynthesis inhibitors that bind to 50S subunit of the ribosome and inhibit peptidyl tRNA translocation from the A-site to the P-site." Macrolides have a glycosylated 14-, 15- or 16-membered lactone ring structure and are produced by several species of Streptomyces. Lincosamide antibiotics were isolated initially from Streptomyces lincolnensis but later isolated from different species of Streptomcyces. Streptogramins were also isolated from Streptomycesgraminofaciens and subsequently from several different Streptomyces species. There are two structurally different streptogramins, A and B they are bacteriostatic individually and can be bactericidal when combined. 

Overall, however, the immensity of temperate land corresponds to a most various secondary metabolic production, different from that of tropical land. The most renowned alkaloids belong to the morphine class (Chart 6.2.A1), and, in combination with isoprenoids, to the ergot and triterpene classes (Chart 6.2. A2). Prominent in the peptides are the cyclosporins (the first of which was isolated from a fiingus collected in Norway), streptogramins, and P-lactams (Chart 6.2.P). The isoprenoids are represented by pyrethrin monoterpenes, cedrane sesquiterpenes, ginkgolide and taxane diterpenes, ophiobolane sesterterpenes, and arborane and amyrin-like triterpenes (Chart 6.2.1). In the polyketides, epothilones, recently discovered from Myxobacteria, and the long known rapamycin, are two prominent classes of macrolides (Chart 6.2.FA/PO/C). 

Pristinamycin (rlNN) is a synergistic combination of streptogramin A (pristinamycin llA) and streptogramin B (pristinamycin IB). It is active against the main bacteria that cause respiratory tract infections and could be useful in the treatment of acute or recurrent sinusitis, community-acquired pneumonia, or periodontal infection with Actinobacillus actinomycetemcomitans (1-5). 

Quinuprtstin/Dalfopristin. Quinupristin/dalfopristin iSynercid) is a combination of the streptogramin B quinu-irittin with the streptogramin A dalfopristin in a 30 70 ratio. 

Two important new streptogramins are quinu-pristin (Fig. 10.15A) and dalfopristin (Fig. 10.15B), which are derivatives of pristinamycin I and IIA, respectively. Individually, the two components are bacteristatic but in combination they act synergistically to produce a bactericidal effect by inhibiting early (dalfopristin) and late (quinupristin) phases of bacterial protein synthesis. These two antibiotics are used intravenously in combination (ratio 30 70) for the treatment of serious or life-threatening infections associated with vancomycin-resistant Enterococcus faecium bacteraemia, although the effect against this organism is bacteristatic. 

The MLS (macrolides, lincosamides, streptogramins) group of antibiotics all inhibit protein synthesis by binding to the 50S ribosomal subunit. Resistance mechanisms specific to individual members occur but resistance to all may be conferred by a single mechanism that involves 23S rRNA. However, it is claimed that the quinupristin-dalfopristin combination does not demonstrate cross-resistance to other antibiotics within the MLS group or to other antibiotics. 

The two unrelated streptogramins, quinupristin and dalfopristin, are used in combination (in a 30 70 ratio) to treat infections caused by staphylococci and enterococci (including MRSA and VRE). Their action is synergistic, and is generally bacteri-... 

Quinuptistin/dalfopristin (synercid) combines quinuptistin, a streptogramin B, with dalfopristin, a streptogramin A, in a 30 70 ratio. These compounds are more soluble derivatives of piistinamycin and thus are suitable for intravenous administration. 

The streptogramins are a group of natural occurring antibiotics isolated from Streptomyces pristinasprialis. The streptogramin antibiotics consist of A-type molecules and B-type molecules, which when combined have a synergistic activity. The mechanism of action of the two different types of molecules appear to be quite different. 

A drug combination of the streptogramins, quinupristin and dalfopristin was approved for IV use in the treatment of infections caused by vancomycin-resistant Enterococcus faecium bacteremia as well as skin/skin structure infections caused by MRSAand methicillin-sensitive Streptococcus pyogenes. Certain strains of E. faecium are resistant to essentially all... 

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