Azithromycin Information. Specificity, Antibacterial activity, Pharmacokinetics and Clinical application

Azithromycin: respiratory specificity and uniqueness.

Azithromycin is an azalide representative - a subclass of macrolide antibiotics. Chemically it differs from the presence of macrolide 15-membered lactone ring containing a nitrogen atom. In the arsenal of antibacterial agents for the treatment of respiratory infections, azithromycin always maintains a leading position: depending on the nosology of it is used as a first-line drug, an alternative agent or in combination with other antibiotics. This is due to a number of exceptional features of azithromycin, is what sets it apart from other antibacterial agents.

The spectrum of antibacterial activity.

Azithromycin has a broad spectrum of antibacterial activity, which covers the majority of bacterial species that cause respiratory tract infections. The drug is effective against Gram-positive organisms, including producing β-lactamase (streptococci, staphylococci) and Gram-negative bacteria (enterococci, Escherichia coli, Haemophilus influenzae, Shigella, Salmonella), atypical pathogens (Chlamydia pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae) , anaerobes and spirochetes. Azithromycin is 2-4 times less active against streptococci and staphylococci than erythromycin, but surpasses it in effects on Haemophilus influenzae and Gram negative cocci. A positive feature of azithromycin is a low level of resistance of microorganisms to it.

Pharmacokinetics.

Azithromycin has unique pharmacokinetic characteristics: first, a high degree of accumulation in tissues and in cells where its levels are 10-100 times higher than in blood plasma. This property is due to the highly lipophilic drug. The maximum concentration of azithromycin is determined in lung tissue (compared to erythromycin, had no marked differences in the level of blood plasma and in the lungs). Due to the accumulation of azithromycin in phagocytes drug is distributed in pockets of infectious inflammation. The concentration of azithromycin in the foci of infection was significantly higher than in unaffected tissues.

Azithromycin is inherent metabolic stability. He works for a long time (half-life 2-4 days.), With postantibioticski effect (maintenance of effective concentrations at the site of infection within 3-5 days after discontinuation of the drug) against S.pyogenes, S.pneumoniae, H.influenzae, L.pneumophila. Duration postantibioticski effect in relation to H.influenzae L.pneumophila and azithromycin in higher than that of clarithromycin. This exclusive feature makes the use of azithromycin in the treatment of respiratory tract infections - the effectiveness of 3-5-day course of treatment.

The blood-brain barrier drug does not penetrate. Elimination occurs in the urine in unchanged form with bile. In renal failure and hepatic elimination half-life is not changed. The drug has no effect on the liver microsomal system, therefore, there is no risk of unwanted effects specific to the interaction.

In the US, created and introduced into clinical practice of new oral dosage form of azithromycin - sustained-release microspheres (SG). Office of the Food and Drug US funds (FDA) approved the use of azithromycin for the treatment of pollutants CAP and light / moderate sinusitis in a single dose for the course. As compared with conventional dosage form azithromycin pollutants slowly absorbed in the intestine, the maximum plasma concentration is reached after 2.5 hours and the bioavailability was 82.8%. The use of azithromycin is characterized by SG lower incidence of dyspeptic disorders. Concurrent use of antacids has no significant effect on the pharmacokinetic parameters of azithromycin pollutants (maximum plasma concentration, area under the concentration-time curve). The introduction of azithromycin pollutants allowed not only to achieve high efficiency of antibiotic therapy, but also to increase compliance: drug is given once, has a favorable safety and tolerability profile.

Clinical application.

Azithromycin was widely justified in the treatment of respiratory system pathologies. This is due to favorable spectrum of antibacterial activity, low resistance thereto pathogens pharmacokinetic characteristics (high pulmonary depozitsiya) and good tolerability.

In a comparative study of azithromycin, amoxicillin / clavulanate and cefuroxime, erythromycin combination with community-acquired pneumonia set to the same clinical efficacy comparable conditions, but azithromycin characterized by better tolerability and a lower incidence of adverse effects (12%). In the group treated combined with cefuroxime erythromycin, frequency of adverse effects was 48% (mainly diarrhea symptoms). When comparing pharmacoeconomic empirical treatment with azithromycin or erythromycin combination with cefuroxime in sequential therapy set equivalent value of these modes of modes (while reducing costs in the azithromycin group was not taken into account due to the lower incidence of adverse effects, therapeutic process simplification and reduction of staff time).

Azithromycin in addition to other macrolide antibiotics is the drug of choice for treatment of atypical (Mycoplasma, Legionella, Chlamydia) pneumoniae. According to some data, the share of these intracellular pathogens account for over 30% of all cases of community-acquired pneumonia, and verification of these pathogens requires the use of expensive procedures. In this regard, the empirical use of azithromycin in the treatment of community-acquired pneumonia is reasonable. In severe pneumonia justified empiric combination with azithromycin ceftriaxone.

A new form of azithromycin (microspheres sustained release) was applied in a single dose of 2 g for the course for the empirical treatment of community-acquired pneumonia and bacterial sinusitis mild to moderate severity. A single dose of azithromycin was comparable in efficiency with the use of levofloxacin and clarithromycin for 7 days in community-acquired pneumonia or levofloxacin for 10 days with sinusitis. The use of a new form of azithromycin showed a high compliance and tolerability.

Justified the appointment of azithromycin as the drug of choice for treatment of exacerbations of chronic bronchitis, agents which are usually S.pneumoniae, M.catarrhalis, H.influenzae. The use of other macrolides considered inappropriate because of the absence of clinically significant activity against H.influenzae.

Long-term use of low-dose azithromycin in cystic fibrosis patients with chronic Pseudomonas aeruginosa infection was accompanied by a decrease in the number of exacerbations, the positive effect on pulmonary function, improvement in nutritional status and well-tolerated drug.

Interest are the data on the properties of organo azithromycin, which may be caused by non-specific anti-inflammatory activity and antioxidant activity of azithromycin. For example, one study demonstrated that azithromycin protects against lung injury induced by smoking. Azithromycin inhibits damage caused by tobacco smoke alveolocytes type II, the activation of nuclear factor k and an increase in the concentration of tumor necrosis factor a. This action, of course, is an advantage of the antibiotic in the treatment of bronchopulmonary diseases.

Is of independent interest data on the use of azithromycin for the treatment of infectious processes at other sites: urogenital chlamydia, syphilis, chronic bacterial prostatitis (in combination with ciprofloxacin), acne, Lyme disease, chronic periodontitis.

Conclusion.

The unique pharmacokinetic characteristics (tissue storage, metabolic stability, characteristic exclusively for azithromycin long half-life), a wide spectrum of antibacterial activity including atypical pathogens presence postantibiotic effect tolerability, high compliance, low resistance agents, the presence of organo properties (antiinflammatory and antioxidant activity) - all this gives grounds for the widespread use of azithromycin for respiratory infections. The clinical efficacy of azithromycin in empiric treatment of bronchopulmonary infections (alone or in combination with β-lactam) outpatient and inpatient demonstrated in several multicenter trials.



Comments:


Leave Your Comment Here!

Enter Username*:

Enter Your Comment*: