Macrolides, Ketolides & Streptogramins

Introduction

• Macrolides are antibiotics built on a macrocyclic lactone ring bearing one or more glycosidically-linked deoxy sugars; ring size defines the subclass. Erythromycin (the prototype) carries two sugars — desosamine and cladinose — and was isolated in 1952 from Saccharopolyspora erythraea.
• Erythromycin is acid-labile and poorly water-soluble, losing activity rapidly at acid pH — driving development of acid-stable esters and the semisynthetic congeners clarithromycin (6-O-methyl) and azithromycin.
• Ketolides (telithromycin) are semisynthetic 14-membered erythromycin derivatives in which α-L-cladinose is replaced by a 3-keto group plus a C11–C12 carbamate — modifications that defeat several macrolide-resistance mechanisms.
• Streptogramins are used as the fixed combination quinupristin (streptogramin B) + dalfopristin (streptogramin A) in a 30:70 ratio — a reserve agent for multidrug-resistant gram-positives.
• All three classes are 50S ribosomal protein-synthesis inhibitors whose binding sites overlap with the lincosamides and chloramphenicol — the basis of the shared MLS_B resistance and mutual antagonism.