Azithromycin in Brief
- Generic name: Azithromycin
- Brand names: Zithromax, Sumamed, TRI-PAK®, Z-PAK®, Zmax®
- Therapeutic class: Antibiotic
- Pharmacologic class: Macrolide, Azalide group
- Pregnancy Category: B
- FDA Approved: November, 1991
- Originally discovered: 1981, Pliva, Croatia
Azithromycin is the first macrolide antibiotic belonging to the azalide
group. Azithromycin is derived from erythromycin by adding a nitrogen
atom into the lactone ring of erythromycin A. Azithromycin is sold under
the brand names Zithromax and Sumamed, and is one of the world's best-selling antibiotics.
Since the 1970s, PLIVA's (Croatian pharmaceutical company, based in
Zagreb, Croatia) research team, led by Dr Slobodan Dokic, had been working
in the area of macrolide antibiotics1.
In 1981, his team of researchers, Gabrijela Kobrehel, Zrinka Tamburasev
and Gorjana Radobolja-Lazarevski, synthesised a novel antibiotic named
azithromycin, the first member of a new class of macrolide antibiotics,
termed azalides. Azithromycin dihydrate was obtained from the erythromycin
molecule and demonstrated superior properties.
It was patented in 1981, and was later found by Pfizer's scientists
while going through patent documents. In 1986 Pliva and Pfizer signed
a licensing agreement which gave Pfizer exclusive rights for the sale
of azithromycin in Western Europe and the United States. Pliva brought
their azithromycin on the market in Central and Eastern Europe under
the brand name of Sumamed in 1988, and Pfizer under the brand name Zithromax in 1991.
Because of its exceptional therapeutic properties, azithromycin revolutionised
antibiotic treatment and became one of the most successful drugs worldwide.
From its early trials, it proved to be an extremely efficient antibiotic
with expanded and enhanced antibacterial activity (particularly against
gram-negative pathogens), prolonged and higher tissue concentration
and a low incidence of gastrointestinal side effects compared to other similar antibiotics.
FDA approved uses
Azithromycin is indicated for the treatment of the following infections
due to susceptible strains of sensitive organisms:
- Upper respiratory tract infections: pharyngitis/tonsillitis, sinusitis, otitis media
- Lower respiratory tract infections: bronchitis, acute exacerbation
of chronic bronchitis, community acquired pneumonia of mild severity.
- Sexually transmitted diseases: uncomplicated urethritis,
uncomplicated cervicitis due to Neisseria gonorrhoeae or Chlamydia trachomatis.
- Chancroid (genital ulcer disease in men).
- Skin and soft tissue infections: erysipelas, impetigo, secondary pyoderma, erythema migrans.
- Mycobacterial Infections.
Off-label & Investigational uses
Off-label and investigational uses of Azithromycin include:
- Pelvic inflammatory disease (PID)
PID comprises a spectrum of inflammatory disorders of the upper female
genital tract, including any combination of endometritis, salpingitis,
tubo-ovarian abscess, and pelvic peritonitis. Sexually transmitted
organisms, Neisseria gonorrhoeae and Chlamydia trachomatis are the
major pathogens causing PID. Azithromycin provides a short simple
treatment option for PID 3.
- Traveler's Diarrhea
Acute diarrhea is the most common illness among travelers.
Azithromycin has the broadest activity against the bacteria causing traveler's diarrhea13.(including Salmonella and Shigella species, as well as other diarrheal pathogens such as Yersinia and Campylobacter). It is a good choice for pregnant women, children, and for other patients who cannot take or tolerate fluoroquinolones 4. Azithromycin is also recommended in areas with quinolone-resistant Campylobacter (e.g., Thailand and surrounding areas of Southeast Asia).
Azithromycin 500 mg per day for 1 - 3 days appears to be effective in most cases of traveler's diarrhea.
- Dental infections
Azithromycin is given to people allergic to penicillins and those
who have abscesses and other dental infections, especially those extending
into the sinuses, gums and bone, and for whom other antibiotics have proved ineffective.
- Periodontal therapy
Azithromycin seems to have a triple role in the treatment and resolution of periodontal diseases: suppressing periodontal opathogens, anti-inflammatory activity, and healing through persistence at low levels in macrophages and fibroblasts in periodontal tissues15.
However, recent data suggests that azithromycin provides no additional benefit over nonsurgical periodontal treatment in patients with generalized aggressive periodontitis16.
Acne vulgaris is a common inflammatory disorder of the skin. Azithromycin
is a safe and effective alternative in the treatment of inflammatory
acne with few side effects and good compliance, even in adolescents.
In 2004, researchers studied azithromycin in patients with moderate to severe papulopustular acne
vulgaris 6. The researchers found that 83% of patients showed at least a 60%
improvement in only 4 weeks and the majority achieved 80% clearance in 12 weeks.
Azithromycin is as effective as and better tolerated than erythromycin
for the treatment of pertussis7.
Azithromycin is used in the treatment of chronic prostatitis caused
by Chlamydia trachomatis and Neisseria gonorrhoeae.
Azithromycin has been successfully used as a multidose treatment in
persons who have early syphilis8. However, CDC cautions against use of azithromycin for treating syphilis among men who have sex with men (MSM).
- Mediterranean spotted fever (Rickettsiosis)
Mediterranean spotted fever, also known as boutonneuse fever, is transmitted
by the dog tick Rhipicephalus sanguineus and has a characteristic
rash and a distinct mark, a tache noire (black spot) at the site of
the tick bite. Azithromycin is effective treatment in children and
can be used as alternatives to doxycycline in adults9.
Azithromycin is used for prophylaxis of bacterial endocarditis in
persons who are allergic to penicillin and undergoing surgical or
- Non-cystic fibrosis bronchiectasis 14
Gastroparesis (delayed gastric emptying)12
Azithromycin has been shown to increase gastrointestinal motility.
Azithromycin appears to reduce the risk of Chlamydia pneumoniae-induced
According to the studies2,
azithromycin significantly improves quality of life, reduces the number
of respiratory exacerbations, and reduces the rate of decline in lung
function in persons with cystic fibrosis. Azithromycin is considered an appropriate choice for patients with chronic P. aeruginosa infection, in whom maintaining respiratory condition has been difficult17.
While the exact mechanisms are unknown, anti-inflammatory rather than
antimicrobial properties of macrolides seem to be responsible for
the beneficial effects.
More information about use of azithromycin in the treatment of cystic fibrosis:
Azithromycin "pros" and "cons"
- Excellent efficacy. Many scientific studies have shown that
azithromycin is better or equally effective compared to other antibiotics.
- Low potential for drug interactions. Azithromycin, unlike
the majority of macrolides, does not bind to cytochrome P-450 in the
liver, resulting in low potential for drug to drug interaction.
- Low rate of side effects. Side effects with azithromycin
are mild to moderate, mostly gastrointestinal.
- Sustained antimicrobial activity. Azithromycin reaches high
and sustained tissue concentrations that results in sustained antimicrobial activity.
- Active against intracellular bacteria (Chlamydia pneumoniae,
Chlamydia trachomatis, Mycoplasma pneumoniae, Legionella spp.). Since
azithromycin is a weak base, it easily penetrates the cell membrane and stays within the cell.
- Targeted activity at the site of infection. Because of the
transport with white blood cells, azithromycin possesses a unique
property - targeted activity at the site of infection. In infected
tissues, azithromycin achieves high and sustained therapeutic concentrations
that last five to seven days after the last dose.
- Suitable choice for empirical therapy. Since azithromycin
has a good activity against the most common pathogens it is used as a choice for empirical therapy.
- Good compliance: short once daily dosing regimen. Azithromycin's
short dosing regimen is convenient and improves patient compliance.
For the majority of infections, azithromycin is administered once
daily for three days. In the treatment of sexually transmitted diseases,
azithromycin is administered as a single dose.
- Active against most respiratory tract infections. Betalactams
lack activity against atypical pathogens. Among macrolides, azithromycin
shows the best activity against H. influenzae.
- Food reduces absorption rate of azithromycin capsules. Capsules
should not be mixed with or taken with food, however tablets may be taken without regard to food.
- In 2013, the U.S. FDA sent out a communication18 stating that azithromycin may cause irregular heartbeats. However, in the study19 (published in the New England Journal of Medicine on May 2013) azithromycin use was not linked with an increased risk of death from cardiovascular (heart) causes in a general population of young and middle-aged adults.
Mode of action
Azithromycin acts by interfering with bacterial protein synthesis.
Although this mechanism is considered bacteriostatic, concentrations
several times higher than minimum inhibitory concentrations (MIC) contribute
to the bactericidal activity of azithromycin.
Rapid distribution of azithromycin into tissues and high concentration within cells result in very high tissues concentrations, that are greater than plasma concentration.
Azithromycin accumulates in macrophages, neutrophils, and fibroblasts.
Non-antibiotic properties: immunomodulating effect
Data indicate that macrolides may have immunomodulatory activities:
in vitro and ex vivo studies clearly show that macrolides can influence
cytokine production by several cell types; furthermore, macrolides can
alter polymorphonuclear cell functions in vitro and ex vivo. Although
immunomodulation may serve as one explanation for the beneficial effects
of macrolides in patients with chronic pulmonary inflammation, the effect
of low-dose macrolide therapy on biofilm-formation may form a second
explanation for the positive effects of long-term low-dose macrolide therapy.
Time for Azithromycin to leave the system
The half-life of Azithromycin is about 68 hours. So it takes about 16-17 days to clear out of the system.
Azithromycin and Alcohol
There are no known interactions between Azithromycin and alcohol. Alcohol does not affect how azithromycin works and does not lessen its effectiveness.
Animal study demonstrated that alcohol doesn’t alter the pharmacokinetics of azithromycin and doesn’t reduce its antibacterial effects 20.
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azithromycin on disease parameters in cystic fibrosis: a randomised trial.
Thorax. 2002 Mar;57(3):212-6.
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and safety of azithromycin compared with two standard multidrug regimens for the treatment of
acute pelvic inflammatory disease. J Int Med Res. 2003 Jan-Feb;31(1):45-54.
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treatment of pertussis. Pediatrics.
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azithromycin. J Chemother. 2000 Jun;12(3):240-3.
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Published: March 31, 2008
Last updated: May 14, 2015