streptogramin

Streptogramins are a class of antibiotics produced by Streptomyces species. They are traditionally grouped into two major classes, streptogramin A and streptogramin B, which act synergistically when used together. The best known clinical formulation is a combination of dalfopristin (A) and quinupristin (B), marketed as Synercid for intravenous use. A related agent, pristinamycin, is used in some regions as an oral therapy and contains components corresponding to the A and B classes.

Mechanism of action relates to inhibition of protein synthesis on the 50S ribosomal subunit. Dalfopristin binding (class A) induces a conformational change that enhances the binding of quinupristin (class B) at a separate site. Together, the two agents block peptide chain elongation, leading to inhibition of protein synthesis. In many organisms, the combination is bactericidal, whereas in others it remains bacteriostatic.

Spectrum and clinical use are focused on Gram-positive bacteria. Streptogramins have activity against many staphylococci, including some methicillin-resistant strains, and against streptococci, including penicillin-resistant pneumococci. They have limited activity against Gram-negative bacteria and variable activity against Enterococcus species; some Enterococcus faecium strains may be susceptible, whereas Enterococcus faecalis is often resistant. Clinically, intravenous dalfopristin-quinupristin is used for complex skin and soft tissue infections, bacteremia, intra-abdominal infections, and endocarditis caused by susceptible Gram-positive organisms. Pristinamycin is used orally in other regions for similar indications.

Resistance mechanisms include ribosomal target modification (erm-mediated methylation conferring MLS_B resistance) and enzymatic inactivation or efflux, which can reduce activity. Pharmacokinetics differ by formulation, with oral pristinamycin having good absorption, while intravenous dalfopristin-quinupristin has limited distribution and is subject to hepatic metabolism and biliary excretion. Adverse effects commonly observed with IV therapy include infusion-related pain, arthralgia and myalgia, nausea, and potential hepatic effects.