General Mechanism of Action of Macrolides:
The macrolide family of antibiotics is widely used for bacterial
infections and especially those produced by Mycoplasmas and Atypical
bacteria. They include several drugs such as erythromycin, azithromycin,
clarithromycin, and telithromycin between others (31) (32). Side effects
of these drugs are rare but may include stomach upset, diarrhea, nausea,
vomiting, or abdominal pain. Much more less common but serious side
effects include hearing damage or deafness, drooping eyelids and blurred
vision, difficulty swallowing or speaking, muscle weakness, and liver
damage. It is contraindicated for people allergic to erythromycin,
clarithromycin, azithromycin and/or telithromycin. It is also
contraindicated in people with severe liver and kidney disease (33).
Clarithromycin is several-fold more active in vitro than Erythromycin
against gram-positive organisms, while Azithromycin is 2- to 4-fold less
potent. Clarithromycin has a longer serum half- life and better tissue
penetration than erythromycin, allowing twice-a-day or once-a-day long
acting formulation dosing for most common infections (32)(33). In
addition to common bacteria, Azithromycin and Clarithromycin have
demonstrated to be also active as single agents against some unexpected
pathogens (e.g., Borrelia burgdorferi, Toxoplasma gondii, Mycobacterium
avium complex, and M. leprae), Zica Virus and maybe also, against
SARS-CoV-2 as we are postulating (34) (35) (36) (37). Efficacy of
Clarithromycin has been examined against H5N1 highly pathogenic and H7N9
low pathogenic avian influenza virus infections in cynomolgus monkeys,
showing viral suppression and clinical improvement (38) (39). A study
assessed the efficacy and safety of a
Clarithromycin-Naproxen-Oseltamivir combination for the treatment of
serious influenza, also showing good results reducing both 30- and
90-day mortality and length of hospital stay (40).
Clarithromycin is also used in conjunction with other medications to
treat stomach ulcers caused by Helicobacter pylori (41); and it has been
used as an anti-cancer agent especially for Lymphomas (42).
It is usually administered as 500 mg oral dose every 12 hours or as a
500 mg long acting formulation once a day, both for 8 days (32).
It is several folds more active and has a better bioavailability than
Azithromycin (55% vs 37%), it is resistant to gastric acid and its
absorption and bioavailability are enhanced by food (70% vs 55%) while
a decrease of 52% is recorded for Azithromycin, its metabolite in
human, the 14-Hydroxy-Clarithromycin, is also microbiologically active
thus enhancing the activity of the parent molecule, it reaches peak
serum concentration faster than Azithromycin (1.8 hr. vs 2.5 hr.), it
attains higher peak concentration than Azithromycin (3 mg/L vs 0,4 mg/L)
and it has a better concentration in the nasal mucosa, tonsils and lung
tissue (33) (43).