Chapter 18 : Macrolides

Abstract:

The natural macrolides of importance in human pathology are the 14- and 16-membered-ring macrolides; the semisynthetic derivatives of importance in human pathology are the 15-membered-ring macrolides (azalides). A characteristic of new molecules is the increased acid stability of the macrolides. This can be fully achieved with roxithromycin and azithromycin. The principal physicochemical properties of the macrolides are listed in this chapter. The natural antibacterial spectrum of the macrolides, irrespective of their structure, includes gram-positive bacteria; gram-negative cocci; fastidious gram-negative bacilli, such as Haemophilus influenzae, Moraxella catarrhalis, Pasteurella spp., and Bordetella spp.; anaerobic bacteria; intracellular bacteria; mycoplasmas and related species; spirochetes; bacteria responsible for gastrointestinal infections (V. cholerae and other Vibrio spp. and Campylobacter spp.); and H. pylori. Roxithromycin and azithromycin are very effective in experimental infection in rabbits with Treponema pallidum strain Nichols, whereas these molecules have cross-resistance with erythromycin A, as has been demonstrated with an erythromycin A-resistant strain of T. pallidum. The macrolides inhibit protein synthesis by binding to the 50S subunit of the bacterial ribosomes. The absorption and bioavailability of macrolides vary according to the molecule, partly explaining the difference in unit and dosage rhythm of the different macrolides. Many publications have shown that macrolides have nonantibiotic pharmacological effects. Some of these effects have been studied for their therapeutic potential (motilide) or are the subject of important basic research: anti-inflammatory or cardiological effects.