|
Azithromycin
|
Azithromycin
- Macrolide antimicrobial
- Differs from erythromycin in having amino substituted expanded macrolide
nucleus
- Structural differences provide better pharmacokinetics
|
Mechanism
of Action
- Inhibits
protein synthesis by binding to
50S ribosomal subunit of bacteria
- Better gram negative coverage than erythromycin
|
Antimicrobial
activity
- Staphylococcus
aureus & Staph.epidermidis
- Streptococcus pyogenes, S.agalactiae, S.viridans, S.pneumoniae
- Bordetella pertussis, B.parapertussis
- Campylobacter jejuni
- Helicobacter pylori
- Haemophilus influenzae, H.parainfluenzae
- Moraxella catarrhalis
- Neisseria gonorrhoeae, N.meningitidis
- Gardnerella vaginalis
- Bacteroides melaninogenicus
- Clostridium perfringens
- Propionibacterium acnes
- Chlamydia trachomatis, C. pneumoniae
- Mycoplasma pneumoniae
- Ureaplasma urealyticum
|
Pharmacokinetics
- More stable
than erythromycin in gastric acid
- Pharmacokinetics characterised by rapid passage from circulation
into intracellular compartment, followed by slow release
- Concentration in tissues, organs, tissue fluids and cells is more
than in blood
- High intracellular penetration tackles difficult
-to-reach organisms proliferating intracellularly e.g., Chlamydia,
Mycobacterium, Legionella
- Metabolised in liver; unchanged drug excreted in urine and faeces
- Pharmacokinetics nor significantly altered in elderly or in patients
with mild renal or hepatic impairment
|
Indications
- Urogenital
infections & STD : Single dose covers C.trachomatis, N.gonorrhoeae,
U.urealyticum & H.ducreyi
- LRTI : Acute exacerbations of chronic bronchitis, pneumonia, other
RTI
- URTI & ENT Infections: pharyngitis, otitis media, sinusitis
- Skin & Soft Tissue Infections : dermatological infections & surgical
wound infection
- AIDS patients with M.avium infection 500 mg administered over 10-30
days reduces mycobacteraemia and clinical symptoms
|
Dosage
Usual
dose for otitis media, RTI and skin infections :
500 mg single dose daily for 3 days or 500 mg initially and 250 mg
daily for further 4 days
Chlamydia
trachomatis infection:
1 gm as a single dose
Gonorrhoea:
1 gm as a single dose
Children
10 mg/kg on first day;
5 mg/kg for next 2-5 days
|
Tolerability
- Well
tolerated; better tolerated than erythromycin
- Usual adverse effects are gastrointestinal (nausea, diarrhoea, abdominal
pain)
- No important drug interactions; though heavy meal may interfere
with absorption
|
Advantages
over Erythromycin
- Better stability
in gastric acid
- 37% bioavailability vs. 25% with erythromycin
- Higher and more sustained tissue/intracellular concentrations
- Once daily x 3 days dosing vs. q.i.d. x 5-10 days dosing with erythromycin
- Greater coverage of gram negative bacteria
|
Advantages
over Clarithromycin
- Greater coverage
of gram negative bacteria
- Once daily x 3 days dosing vs. b.i.d. x 10 days dosing with clarithromycin
- More economical than clarithromycin
|
