Zithromax azithromycin sale


General properties

Pharmacotherapeutic group: Antibacterials for systemic use. ATC code: J01FA10

Mode of action:

Zithromax is a macrolide antibiotic belonging to the azalide group. The molecule is constructed by adding a nitrogen atom to the lactone ring of erythromycin A. The chemical name of azithromycin is 9-deoxy-9a-aza-9a-methyl-9a-homoerythromycin A. The molecular weight is 749.0. Azithromycin binds to the 23S rRNA of the 50S ribosomal subunit. It blocks protein synthesis by inhibiting the transpeptidation/translocation step of protein synthesis and by inhibiting the assembly of the 50S ribosomal subunit.

Cardiac electrophysiology

QTc interval prolongation was studied in a randomized, placebo-controlled parallel trial in 116 healthy subjects who received either chloroquine (1000 mg) alone or in combination with azithromycin (500 mg, 1000 mg, and 1500 mg once daily). Co-administration of azithromycin increased the QTc interval in a dose- and concentration-dependent manner. In comparison to chloroquine alone, the maximum mean (95% upper confidence bound) increases in QTcF were 5 (10) ms, 7 (12) ms and 9 (14) ms with the co-administration of 500 mg, 1000 mg and 1500 mg azithromycin, respectively.

Mechanism of resistance

The two most frequently encountered mechanisms of resistance to macrolides, including azithromycin, are target modification (most often by methylation of 23S rRNA) and active efflux. The occurrence of these resistance mechanisms varies from species to species and, within a species, the frequency of resistance varies by geographical location.

The most important ribosomal modification that determines reduced binding of macrolides is post-transcriptional (N6) -dimethylation of adenine at nucleotide A2058 (Escherichia coli numbering system) of the 23S rRNA by methylases encoded by erm (erythromycin ribosome methylase) genes. Ribosomal modifications often determine cross resistance (MLSB phenotype) to other classes of antibiotics whose ribosomal binding sites overlap those of the macrolides: the lincosamides (including clindamycin), and the streptogramin B (which include, for example, the quinupristin component of quinupristin/dalfopristin). Different erm genes are present in different bacterial species, in particular streptococci and staphylococci. Susceptibility to macrolides can also be affected by less frequently encountered mutational changes in nucleotides A2058 and A2059, and at some other positions of 23S rRNA, or in the large subunit ribosomal proteins L4 and L22.

Efflux pumps occur in a number of species, including Gram-negatives, such as Haemophilus influenzae (where they may determine intrinsically higher minimal inhibitory concentrations [MICs]) and staphylococci. In streptococci and enterococci, an efflux pump that recognizes 14- and 15-membered macrolides (which include, respectively, erythromycin and azithromycin) is encoded by mef(A) genes.

Methodology for determining the in vitro susceptibility of bacteria to azithromycin

Susceptibility testing should be conducted using standardized laboratory methods, such as those described by the Clinical and Laboratory Standards Institute (CLSI). These include dilution methods (MIC determination) and disk susceptibility methods. Both CLSI and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) provide interpretive criteria for these methods.

Based on a number of studies, it is recommended that the in vitro activity of azithromycin be tested in ambient air, to ensure physiological pH of the growth medium. Elevated CO2 tensions, as often used for streptococci and anaerobes, and occasionally for other species, result in a reduction in the pH of the medium. This has a greater adverse effect on the apparent potency of azithromycin than on that of other macrolides.

The CLSI susceptibility breakpoints, based on broth microdilution or agar dilution testing, with incubation in ambient air, are given in the table below.

azithromycin
zithromax azithromycin sale

CLSI Dilution Susceptibility Interpretive Criteria

Organism

Broth microdilution MIC (mg/L)

Susceptible

Intermediate

Resistant

Haemophilus species

≤ 4

-

-b

Moraxella catarrhalis

≤ 0.25

-

-

Neisseria meningitidis

≤ 2

-

-b

Staphylococcus aureus

≤ 2

4

≥ 8

Streptococci a

≤ 0.5

1

≥ 2

a Includes Streptococcus pneumoniae, β-hemolytic streptococci and viridans streptococci.

b The current absence of data on resistant strains precludes defining any category other than susceptible. If strains yield MIC results other than susceptible, they should be submitted to a reference laboratory for further testing.

Incubation in ambient air.

CLSI = Clinical and Laboratory Standards Institute;.

Source: CLSI, 2012,; CLSI, 2010

Susceptibility can also be determined by the disk diffusion method, measuring inhibition zone diameters after incubation in ambient air. Susceptibility disks contain 15 μg of azithromycin. Interpretive criteria for inhibition zones, established by the CLSI on the basis of their correlation with MIC susceptibility categories, are listed in the table below.

CLSI Disk Zone Interpretive Criteria

Organism

Disk inhibition zone diameter (mm)

Susceptible

Intermediate

Resistant

Haemophilus species

≥ 12

-

-

Moraxella catarralis

≥ 26

-

-

Neisseria meningitidis

≥ 20

-

-

Staphylococcus aureus

≥ 18

14 - 17

≤ 13

Streptococci

≥ 18

14 - 17

≤ 13

a Includes Streptococcus pneumoniae, β-hemolytic streptococci and viridans streptococci.

Incubation in ambient air.

CLSI = Clinical and Laboratory Standards Institute; mm = Millimeters.

Source: CLSI, 2012; CLSI, 2010

The validity of both the dilution and disk diffusion test methods should be verified using quality control (QC) strains, as indicated by the CLSI. Acceptable limits when testing azithromycin against these organisms are listed in the table below.

Quality Control Ranges for Azithromycin Susceptibility Tests (CLSI)

Broth microdilution MIC

Organism

Quality control range (mg/L azithromycin)

Haemophilus influenzae ATCC 49247

1 - 4

Staphylococcus aureus ATCC 29213

0.5 - 2

Streptococcus pneumoniae ATCC 49619

0.06 - 0.25

Disk inhibition zone diameter (15 μg disk)

Organism

Quality control range (mm)

Haemophilus influenzae ATCC 49247

13 - 21

Staphylococcus aureus ATCC 25923

21 - 26

Streptococcus pneumoniae ATCC 49619

19 - 25

Incubation in ambient air.

CLSI = Clinical and Laboratory Standards Institute; MIC = Minimal inhibitory concentration; mm = Millimeters.

Source: CLSI, 2012.

The EUCAST has also established susceptibility breakpoints for azithromycin based on MIC determination. The EUCAST susceptibility criteria are listed in the table below.

EUCAST Susceptibility Breakpoints for Azithromycin

MIC (mg/L)

Susceptible

Resistant

Staphylococcus species

≤ 1

> 2

Streptococcus pneumoniae

≤ 0.25

> 0.5

β-hemolytic streptococci a

≤ 0.25

> 0.5

Haemophilus influenzae

≤ 0.12

> 4

Moraxella catarrhalis

≤ 0.25

> 0.5

Neisseria gonorrhoeae

≤ 0.25

> 0.5

Includes Groups A, B, C, G.

EUCAST = European Committee on Antimicrobial Susceptibility Testing; MIC = Minimal inhibitory concentration.Source: EUCAST Website.

EUCAST Clinical Breakpoint Table v. 2.0, valid from 2012-01-01 www.eucast.org/.../EUCAST.../Breakpoint_table_v_2.0_120221.pdf

Antibacterial Spectrum

The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.

Azithromycin demonstrates cross resistance with erythromycin-resistant gram-positive isolates. As discussed above, some ribosomal modifications determine cross resistance with other classes of antibiotics whose ribosomal binding sites overlap those of the macrolides: the lincosamides (including clindamycin), and the streptogramins B (which include, for example, the quinupristin component of quinupristin/dalfopristin). A decrease in macrolide susceptibility over time has been noted in particular in Streptococcus pneumoniae and Staphylococcus aureus, and has also been observed in viridans streptococci and Streptococcus agalactiae.

Organisms that are commonly susceptible to azithromycin include:

Aerobic and facultative Gram-positive bacteria (erythromycin-susceptible isolates): S aureus, Streptococcus agalactiae, S. pneumoniae, Streptococcus pyogenes, other β-hemolytic streptococci (Groups C, F, G), and viridans streptococci. Macrolide-resistant isolates are encountered relatively frequently among aerobic and facultative Gram-positive bacteria, in particular among methicillin-resistant S. aureus (MRSA) and penicillin-resistant S. pneumoniae (PRSP).

Aerobic and facultative Gram-negative bacteria: Bordetella pertussis, Campylobacter jejuni, Haemophilus ducreyi, Haemophilus influenzae, Haemophilus parainfluenzae, Legionella pneumophila, Moraxella catarrhalis, and Neisseria gonorrhoeae. Pseudomonas spp. and most Enterobacteriaceae are inherently resistant to azithromycin, although azithromycin has been used to treat Salmonella enterica infections.

Anaerobes: Clostridium perfringens, Peptostreptococcus spp. and Prevotella bivia.

Other bacterial species: Borrelia burgdorferi, Chlamydia trachomatis, Chlamydophila pneumoniae, Mycoplasma pneumoniae, Treponema pallidum, and Ureaplasma urealyticum.

Opportunistic pathogens associated with HIV infection: MAC, and the eukaryotic microorganisms Pneumocystis jirovecii and Toxoplasma gondii.

∗The efficacy of azithromycin against the indicated species has been demonstrated in clinical trials.


Source: http://www.medicines.ie/medicine/5557/SPC/ZITHROMAX+CAPSULES+250MG/


///

Multi-use antibiotic for stockpiling: azithromycin Azithromycin drug indications


Zithromax azithromycin sale Zithromax Azithromycin Ppt : Save On Discount
Zithromax azithromycin sale Uk Part of the easy family of brands
Zithromax azithromycin sale Azithromycin (Zithromax) - m
Zithromax azithromycin sale ZITHROMAX CAPSULES 250MG
Zithromax azithromycin sale Cached
Zithromax azithromycin sale AZITHROMYCIN DIHYDRATE C38H76N2O14 - PubChem
Zithromax azithromycin sale Antibiotics for Strep Throat: Benefits, Side Effects
Zithromax azithromycin sale At Least 75 Of Patients Who Test Negative For Gonorrhea

///
Дата: 31.08.2017, 18:22 / Просмотров: 92451