Streptogramins: a new class of antibiotics

Streptogramin antibiotics represent a unique class of antibacterials in the each member of the class consists of at least 2 structurally unrelated molecules: group a streptogramins (macrolactones) and group B streptogramins (cyclic hexadepsipeptides). Both group A and group B streptogramins inhibit protein synthesis at the ribosomal level, and they act synergistically against many isolates their combination generating bactericidal activities and reducing the possibility of emergencies of resistant strains. The mechanisms of acquired resistance to group B streptogramins remain unaffected by target modifications and active efflux. The pharmacokinetic parameters of group A and group B streptogramins in blood are quite similar. In addition, both the A and B group penetrate and accumulate in macrophages and in the bacterial gegetations of experimental endocarditis. Until recently, the complex and irregular composition of naturally occurring pristinamycin and virginiamycin, as well as the unavailability of soluble forms, have limited the clinical development of streptogramins. The synthesis of water soluble derivatives of pristinamycin IA and IIB has now allowed the development of injectable streptogramins with fixed compositions. This unique class of antibacterials will have a significant clinical impact in a world of increasing multidrug resistance affecting the Gram-positive cocci, especially staphylococci and pneumococci. The absence of cross-resistance to macrolides in many of these isolates and the rapid antibacterial killing against these species bright future for this class of antibiotics.