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).