Macrolides: present and future. An appraisal of in-vitro activity and pharmacokinetic behavior

Macrolides belong to a large family of drugs called macrocyclic antibiotics, that can be divided into four groups: macrolactamas or ansamycins, polyene macrolides, macrolide-like compounds and macrolide antibiotics. Macrolide antibiotics comprise a large group of drugs, which are very much alike, characterized by large lactonic cycle with 12, 14, 15 or 16 atoms, to which are bound sugar and/or aminosugar. Although there are very large structural differences, macrolides represent a homogeneous group of drugs for which both a spectrum and a mode of action are similar. Macrolide antibiotics bind to the large subunit of prokaryotic ribosomes and perturb protein synthesis. The antimicrobial activity of macrolides is broad spectrum, being exhibited against gram-positive and gram-negative bacteria, including actinomyces and mycobacteria, as well as against treponemes, mycoplasmas, chlamydiae, rickettsias and also against some protozoa. Depending on the drug concentrations, bacterial species and phase of growth, macrolides may be bacteriostatic or bactericidal. Macrolides show high tissue/serum rations and greater concentrations of antibiotics are though to be achieved at the presumed site of infection. Such findings are in agreement with the apparent volumes of distribution for all the macrolide drugs, which are generally large. The worldwide resurgence of interest in macrolide antibiotics has yielded several semisynthetic derivatives of 14- and 16-membered macrolides which have progressed to clinical trials.