Zithrolide Mechanism of Action

Pharmacology: Pharmacodynamics: Azithromycin is a nitrogen-containing macrolide or azalide with actions and uses similar to those of erythromycin.
Mechanism of Action: Inhibition of protein synthesis in bacteria binding in 50s ribosomal subunit and preventing translocation of peptides.
Pharmacokinetics: Following oral administration in human, about 40% of a dose of azithromycin is bioavailable. Absorption from the capsule formulation, but not the tablet formulation, is reduced by food. Peak plasma concentrations are achieved 2-3 hrs after a dose but azithromycin is extensively distributed to the tissues and tissue concentrations subsequently remain much higher than those in the blood; in contrast to most other antibacterials, plasma concentrations are of little value as a guide to efficacy. High concentrations are taken up into white blood cells.
There is little diffusion into the cerebrospinal fluid when the meninges are not inflamed. Small amounts of azithromycin are demethylated in the liver, and is excreted in the bile as unchanged drug and metabolites. About 6% of an oral dose (representing about 20% of the amount in the system circulation) is excreted in the urine. The terminal excretion half-life is probably in excess of 40 hrs.
Microbiology: Azithromycin demonstrates activity in in vitro against a wide range of bacteria including: Gram-Positive Aerobic Bacteria: Staphylococcus aureus, Streptococcus pyogenes (group A β-hemolytic streptococci), Streptococcus pneumoniae, α-hemolytic streptococci (viridans group) and other streptococci and Corynebacterium diphtheriae. Azithromycin demonstrates cross-resistance with erythromycin-resistant gram-positive strains, including Streptococcus faecalis (enterococcus) and most strains of methicillin-resistant staphylococci.
Gram-Negative Aerobic Bacteria: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Acinetobacter spp, Yersinia spp, Legionella pneumophila, Bordetella pertussis, Bordetella parapertussis, Shigella spp, Pasteurella spp, Vibrio cholera and shigelloides. Activities against Escherichia coli, Salmonella enteritidis, Salmonella typhi, Enterobacter spp, Aeromonas hydrophilla and Klebsiella spp are variable and susceptibility tests should be performed. Proteus spp, Serratia spp, Morganella spp and Pseudomonas aeruginosa are usually resistant.
Anaerobic Bacteria: Bacteroides fragilis and Bacteroides spp, Clostridium perfringens, Peptococcus spp and Peptostreptococcus spp, Fusobacterium necrophorum and Propionibacterium acnes.
Organisms of Sexually Transmitted Diseases: Azithromycin is active against Chlamydia trachomatis and also shows good activity against Treponema pallidum, Neisseria gonorrhoeae and Haemophilus ducreyi.
Other Organisms: Borrelia burgdorferi (Lyme disease agent), Chlamydia pneumoniae, Mycoplasma pneumoniae, Mycoplasma hominis, Ureaplasma urealyticum, Campylobacter spp and Listeria monocytogenes.
Opportunistic Pathogens Associated with Human Immunodeficiency Virus (HIV) Infections: Mycobacterium avium-intracellulare complex, Pneumocystis carinii and Toxoplasma gondii.