Mechanism of action
Azithromycin is a second-generation macrolide antibiotic from the group of azalides.
Inhibits protein synthesis in bacteria by binding to 50Sthe subunit of ribosomes and preventing the translocation of peptides.
The mechanism of resistance
There are three mechanisms of resistance for different species of bacteria to macrolides: due to modification of the target of the action, modification of the antibiotic or due to active release of the antibiotic from the microbial cell by means of transport systems (efflux). For bacteria, various efflux systems are described. An important efflux system for streptococci is coded / neogen and results in resistance to bounded macrolides (M-phenotype). Modification of the target of action, controlled erm coded methylase (MLSB-phenotype), leads to cross-resistance to different classes of antibiotics (see below).
Cases of cross-resistance to erythromycin, azithromycin, other macrolides and lincosamide and streptogrammin B for Streptococcus pneumoniae, P-hemolytic group streptococci A, Enterococcus spp. and Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). Constitutive mutants in the disease-resistant strains with erm (A) or erm (FROM) can be distinguished in vitro at low frequencies ~ 10 '7 CFU in the presence of azithromycin.
Boundary value
Below are the minimum inhibitory concentrations (MICs) for microorganisms at these indications (see section "Indications for use").
It should be noted that the boundary values of the MIC and the spectrum of action presented below refer to systemic application. MIC data can not be used in the case of topical treatment with an eye drop preparation due to other concentrations and physicochemical conditions that may affect the overall activity of the drug at its site of action.
In accordance with EUCAST (European Committee for the Determination of Antibiotic Sensitivity) for azithromycin, the following MIC boundary values were determined, mg / l:
- Haemophilus influenzae: S < 0.12 mg/l and R > 4 mg/l
- Moraxella catarrhalis: S < 0,5 mg/l and R > 0,5 mg/l
- Neisseria gonorrhoeae: S < 0,25 mg/l and R > 0,5 mg/l
- Staphylococcus spp *: S < 1,0 mg/l and R > 2,0 mg/l
- Streptococcus pneumoniae: S < 0,25 mg/l and R > 0,5 mg/l
- Streptococcus A, B, C, G: S < 0.25 mg / l and R > 0,5 mg / l
* spp includes all species of the genus
EUCAST allows the use of erythromycin to determine the sensitivity of other species of these bacteria to azithromycin.
The frequency of acquired resistance for individual species may vary depending on the geographical region and time. In this regard, it is desirable to have local information on resistance, especially when treating severe infections. If necessary, seek the advice of a specialist when the local frequency of resistance is such that the effectiveness of the drug, at least for some types of infection, is questionable.
Table: Antimicrobial spectrum of azithromycin by types of bacteria for the duration of these indications
Species that are traditionally sensitive to the drug
Aerobic Gram-negative bacteria
Moraxella (Branhamella) catarrhalis
Neisseria gonorrhoeae1
Haemophilus influenzaes
Haemophilus parainfluenzathes
Other microorganisms
Chlamydia trachomatis*
Irregularly sensitive species
Aerobic Gram-positive bacteria
Staphylococcus aureus (methicillin-resistant and methicillin-sensitive)
Staphylococcus, Coagulase-releasing (methicillin-resistant and methicillin-sensitive)
Streptococcus pneumoniae
Streptococcus pyogenes
Streptococci viridans
Streptococcus agalactiae
Streptococcus group G
Kinds from natural resistance
Aerobic Gram-positive bacteria
Corynebacterium spp.
Enterococcus faecium
Aerobic Gram-negative bacteria
Pseudomonas aeruginosa
Acinetobacter
Enterobacteriaceae
* Clinical efficacy is demonstrated in sensitive isolated strains for approved indications.
$ Natural intermediate sensitivity.
1 Conjunctivitis caused by Neisseria gonorrhoeae, requires systemic treatment (see section "Special instructions").
Information on clinical trials
- Trachomatous conjunctivitis caused by Chlamydia trachomatis.
A randomized, double-blind, 2-month study comparing Azidrop with oral administration of a single dose of azithromycin for the treatment of active trachoma in 670 children aged 1-10 years. The main variable efficacy was a clinical cure for 60 days, i.e. absence of active trachoma TF0 (according to the simplified classification of severity of trachoma according to WHO). On the 60th day, the frequency of clinical cure with Azidrop, applied 1 drop 2 times a day for 3 days, was not lower (96.3%) than when taking azithromycin inwards (96.6%).
The clinical efficacy of Azidrop applied 1 drop 2 times a day for 3 days, for treatment and prevention of trachoma of the whole population (since birth) in Northern Cameroon (112,000 subjects) was assessed in a multicentre, open, non-comparative phase IV study. The treatment was carried out for 3 periods of 1 year. The primary criterion of effectiveness was the predominance of active trachoma, i.e. trachomatous follicular inflammation or severe trachomatous inflammation (TF+TI0 or TF+TI+). For the analysis, a clinical evaluation of trachoma was performed every year in 2,400 children aged> 1 and <10 years, selected by random cluster sampling. The prevalence of active trachoma (TF+TI0 or TF+TI+) was observed in 31.1% of cases before the instillation of Azidrop in the "year 0" and decreased to 6.3% (1 st year), 3.1% (2 nd year) and 3.1% (3 rd year). In general, the population did not observe any serious adverse reactions to the study drug.
- Purulent bacterial conjunctivitis
A randomized, blind comparative study of Azidrop was performed, applied 1 drop 2 times daily for 3 days, with tobramycin, ophthalmic drops, 0.3%, applied 1 drop every 2 hours for 2 days, and then 4 times in day for 5 days, for treatment of purulent bacterial conjunctivitis in 1043 patients (group ITT), including 109 children under the age of 11 years, 5 of whom were newborns (0 to 27 days), 38 infants and toddlers (from 28 days to 23 months). According to the protocol, the population (n = 471) (PP group) included 16 infants and toddlers and did not include newborns. The clinical study was conducted in different regions of Europe, North Africa and India. The primary efficacy variable was a clinical cure for day 9 in the PP group and was defined as 0 for bulbar conjunctiva injection and for purulent discharge. On the 9th day the frequency of clinical cure with Azidrop (87.8%) was not lower than with tobramycin (89.4%). The microbiological efficacy of azithromycin was comparable to that of tobramycin.
Children's population
The efficacy and safety of Azidrop in children under 18 years of age were shown in a randomized study with masking of the investigator compared to tobramycin in 282 patients under study with purulent bacterial conjunctivitis (including 148 patients in the subgroup of 0 days - <24 months). Patients received either Azidrop (1 drop 2 times a day for 3 days), or tobramycin, eye drops, 0.3% (1 drop every 2 hours for 2 days, and then 4 times a day for 5 days). The main efficacy criterion was the clinical cure of the more affected eye on day 3 in patients with positive bacteriological analysis at day 0. In patients using Azidrop, the clinical cure of the more affected eye on day 3 exceeded (47%) this value in comparison with patients who used tobramycin (28%). On the 7th day, 89% of the patients treated with Azidrope were completely cured, whereas among the patients who applied tobramycin, a complete cure was noted in 78% of cases. There were no statistical differences between treated groups with regard to bacteriological resolution on day 7. Azidrop, applied 1 drop 2 times a day for 3 days, was well tolerated in all age groups in the study of a large group of children. Undesirable reactions noted in children have also been found in adults; no new adverse reactions in children have been identified. Moreover, no age-related clinical problems were noted. Short duration of therapy with azithromycin, eye drops, 1.5%, a small number of necessary instillations,and ease of instillation of drops to children were taken into account by both children and parents.