Pharmacology and Toxicology of Azithromycin Tablets

Pharmacological action Azithromycin is one of the subclasses of macrolide antibiotics, that is, the first drug of azalide antibiotics. The mechanism of azithromycin is to block the process of bacterial peptide transfer by binding with 50s ribosome subunit, thus inhibiting the synthesis of bacterial protein. In vitro tests have proved that azithromycin is effective against a variety of pathogenic bacteria. Including [u] Gram-positive aerobic bacteria: [/u] Staphylococcus aureus, Streptococcus pyogenes (Group A, b- hemolytic Streptococcus), Streptococcus pneumoniae, Streptococcus A, other Streptococcus and Corynebacterium diphtheriae. Azithromycin is cross-resistant to erythromycin-resistant Gram-positive bacteria including Streptococcus faecalis (Enterococcus) and most methicillin-resistant Staphylococcus strains. [u] Gram-negative aerobic bacteria: [/u] Haemophilus influenzae, haemophilus parainfluenzae, Moraxella catarrhalis, Acinetobacter, Yersinia, Legionella pneumophila, Bordetella pertussis, Parapertussis, Shigella, Pasteurella, Vibrio cholerae, Vibrio parahaemolyticus and Shigella-like bacteria. The activities of Escherichia coli, Salmonella enteritidis, Salmonella typhi, Enterobacter, Aeromonas hydrophila and Klebsiella pneumoniae are different, so sensitivity tests are needed. Usually resistant to Proteus, Serratia, Morgan and Pseudomonas. [u] Anaerobic bacteria: [/u] Bacteroides fragilis, Bacteroides, Clostridium perfringens, Streptococcus digestion, Fusobacterium necrophorum and Propionibacterium acne. [u] STD microorganisms: [/u] Chlamydia trachomatis, Treponema pallidum, Neisseria gonorrhoeae and Haemophilus Duke. [u] Other microorganisms: [/u] Borrelia Borrelia Borrelia (pathogen of Lyme disease), Chlamydia pneumoniae, Mycoplasma pneumoniae, Mycoplasma hominis, Ureaplasma urealyticum, Campylobacter, Listeria monocytogenes. [U] Conditional pathogens related to HIV infection: Mycobacterium avium, Pneumocystis carinii and Toxoplasma gondii. There are two main determinants of drug resistance in clinical isolates of Streptococcus pneumoniae and Streptococcus pyogenes: mef and erm. Mef-encoded discharge pump only caused bacteria to develop resistance to macrolide antibiotics of 14 and 15 yuan ring. Mef is also found in many other genera. Erm gene encodes 23S-rRNA methyltransferase, and methyl is added to adenine 2058 of 23S rRNA (Escherichia coli rRNA numbering system). Methylated nucleotide in V region can interact with macrolide antibiotics, linconamide antibiotics and streptomycin B to form MLSB drug-resistant phenotype. Erm(B) erm(A) genotype was detected in clinical isolates of Streptococcus pneumoniae and Streptococcus pyogenes. Haemophilus influenzae AcrAB-TolC pump leads to the increase of MIC value of macrolide antibiotics. 23S rRNA mutation, especially nucleotide mutation at position 2611in V region, or ribosomal protein L4 or L22 mutation are rare in clinical isolates. Sensitive Breakpoint The MIC value of azithromycin (unit: μg/ml) is recommended as (NCCLS recommended standard): Haemophilus: S≤4, and no drug-resistant breakpoint is recommended [sup]*[/sup] Streptococcus includes Streptococcus pneumoniae and Streptococcus pyogenes: S≤0.5, R≥2[sup]*[/sup] In view of the current situation, if the MIC value of the strain, The epidemic trend of acquired drug resistance of specific strains of bacteria may be different in region and time, and the information of local drug resistance is very important, especially for the treatment of serious infections. If local drug resistance will cause concern about the use of this drug in at least some infections, you should consult an expert in time. In vitro sensitivity data are not always consistent with clinical results. Usually sensitive strains [u] are gram-positive aerobic bacteria: [/u] Staphylococcus aureus, Streptococcus agalactiae, Streptococcus (groups C, F and G) and Streptococcus viridis. [u] Gram-negative aerobic bacteria: [/u] Bordetella pertussis, Haemophilus ducreyi, Haemophilus influenzae [sup]*$[/sup], haemophilus parainfluenzae, Legionella pneumophila, Moraxella catarrhalis [sup]*[/sup] and Neisseria gonorrhoeae. [u] Other [/u] Chlamydia pneumoniae [sup]*[/sup], Chlamydia trachomatis, Mycoplasma pneumoniae [sup]*[/sup] and Ureaplasma urealyticum. Acquired drug-resistant strains have been reported: Gram-positive aerobic bacteria: Streptococcus pneumoniae [sup]*[/sup] Streptococcus pyogenes [sup]*[/sup] Note: Azithromycin is cross-resistant to erythromycin-resistant Gram-positive strains. Inherent drug-resistant strain: the efficacy of Pseudomonas enterobacteriaceae [sup]*[/sup] has been confirmed in clinical trials [sup]$[/sup] Toxicological study of natural strain with moderate sensitivity [u] Genotoxicity [/u]: The results of human lymphocyte test in vitro, mouse bone marrow micronucleus test and mouse lymphoma cell test all confirmed that this product has no mutagenic effect. [u] Reproductive toxicity [/u]: The reproductive toxicity test of rats and mice showed that no teratogenic effect was found when the dose reached the level of moderate maternal toxicity (that is, 200mg/kg/ day, about 2-4 times of the human dose of 500mg/kg/ day). No damage to fertility and fetus was found. [u] Carcinogenicity [/u]: There is no data on the carcinogenicity of this product in animals for a long time. Animal high-dose drug tolerance test found that when the dose of azithromycin is 40 times of the clinical dose, it can cause reversible phospholipid deposition, but usually it will not produce the observed toxic reaction. At present, there is no evidence that similar events will occur when azithromycin is used in humans at normal doses. Pre-clinical safety data After azithromycin is administered in multiple doses, phospholipid damage (intracellular phospholipid accumulation) can be found in various tissues of mice, rats and dogs (such as eyes, dorsal root ganglion of spinal cord, liver, gallbladder, kidney, spleen and/or pancreas) through microscopic examination. Phospholipid lesions can also be seen in similar tissues of young rats and puppies. This effect can be reversed after azithromycin treatment is stopped. The significance of this discovery to animals and humans is still unclear.