Therapeutic Review Azithromycin

Azithromycin is a semisynthetic macrolide antibiotic representing the first of a subclass of macrolides classified as azalides. A relative newcomer to veterinary medicine azithromycin was first described in the late 1980s and differs from erythromycin by the insertion of a methyl-substituted nitrogen on the lactone ring at position 9a.1 This addition creates a 15-membered macrolide. The alteration of the lactone ring provides a more stable compound in acidic environments and provides a larger spectrum of activity against Gram-negative bacteria.2,3 Azithromycin, like other macrolides, is a bacteriostatic antibiotic that inhibits protein synthesis by binding to the 50s ribosome. This drug has been found to be effective against a variety of different Gram-positive and Gram-negative bacterial pathogens, and has some activity against anaerobic bacteria.2 In addition to its activity against bacteria, azithromycin has also been found to be effective against rickettsial organisms, spirochetes, and protozoa (eg, Toxoplasma gondii, Giardia spp., and Cryptosporidium spp.). Azithromycin is highly bioavailable after being administered per os (PO) in dogs (97%), and only moderately bioavailable in cats (58%) and humans (37%).4-7 In dogs, a single oral dose of 10 to 40 mg/kg provided tissue levels that were proportional to the dose.4 Fourto 7-fold increases in tissue concentration were observed in dogs after being dosed with 20 mg/kg for 7 days.4 In dogs, the elimination half-life after a 5-day treatment (30 mg/kg PO) for the liver was approximately 90 hours. More than 50% of the drug is excreted from mammals unchanged in the bile.4,5 Azithromycin can be concentrated in both polymorphonuclear cells and macrophages.8 The ability of these cells to transport the antibiotic directly to a site of infection is an example of an endogenous system, the immune system, and an exogenous compound, the azithromycin, working together to control an infection. The direct delivery of the antibiotic by leukocytes undergoing diapedesis would also be expected to