MACROLIDES - NEW THERAPEUTIC PRESPECTIVES

The aim of the development of semisynthetic derivatives was to overcom e the problem of chemical stability of erythromycin A in acid medium, with less variability in gastro-intestinal absorption and leading to r enewed interest in macrolides. The new macrolides have the same antiba cterial spectrum as erythromycin A including Gram-positive and Gram-ne gative cocci, intracellular bacteria, mycoplasma, Campylobacter sp., H elicobacter pylori, mycobacteria spp., Gram-negative bacilli including Haemophilus influenzae, Bordetella pertussis, Pasteurella multocida, Gram-positive bacilli including Corynebacterium diphtheriae and anaero bic species. In vitro activity against Haemophilus influenzae is still a controversial subject. Macrolides are among the best tolerated anti bacterial agents. Theoretically, macrolides could be given to a large range of patients even those suffering from underlying diseases. The n ew macrolides, roxithromycin, azithromycin, clarithromycin, dirithromy cin, rokitamycin and miokamycin, are indicated for the treatment of up per respiratory tract infections and lower respiratory tract infection s due to intracellular bacteria or Mycoplasma pneumoniae. Macrolides c ould be used as first line therapy for non-gonococcal urethritis, espe cially those due to Chlamydia trachomatis or Ureaplasma urealyticum. I n pelvic inflammatory infections in which Chlamydia trachomatis is inv olved macrolides could also be used. Other non-conventional indication s under discussion are H. pylori and Lyme's disease. Macrolides in com bination with other antibacterials could be an alternative for Mycobac terium avium-intracellulare infections. The antiparasite effect of ery thromycin has been known since ther 1950's. Extensive experimental wor k is currently underway to determine the potential use of these drugs in this setting. Research during the 80's in the macrolide field, led to enhanced pharmacokinetic properties. Current research is focused on expanding the antibacterial spectrum and to overcome cross-resistance among 14-membered-ring macrolides.