Chapter 38 : Orthosomycins

Abstract:

The family of orthosomycins includes the everninomicins, which are oligosaccharide antibiotics containing two orthodiester bonds and a dichloroeverninic acid residue. The everninomicins are original antibiotics that belong structurally to the oligosaccharide antibacterial agents. They are characterized by an oligosaccharide structure with the presence of one or more orthodiester-type bonds. This type of bond is unusual in nature but has been described for a series of molecules grouped together in a family known as orthosomycins. Avilamycin is an orthosomycin complex extracted from Streptomyces viridochromogenes Tü 57 in 1965. An approach to the structure and activity of everninomicins has been undertaken by means of chemical modifications, particularly of evernimicin. The configuration of the two orthoester bonds at C-49 and C-16 is important for the antibacterial activity. Mechanisms of resistance to evernimicin are complex phenomena which include mainly mutations, methylation, and efflux. Recently it was shown that avilamycin A and evernimicin share common mechanisms of resistance. The rplP gene mutations have been also reported for enterococcal isolates resistant to avilamycin A. The steady-state apparent volume of distribution is on the order of 22 liters, indicating that evernimicin is distributed in the extravascular media. Evernimicin was thought to be an alternative in severe pneumococcal infections for which no other treatment is possible because of a multiresistant strain.