Clarithromycin

Indications

Clarithromycin is a versatile antibiotic indicated for several conditions. It serves as an alternative for patients with a history of type I penicillin hypersensitivity to treat acute otitis media caused by Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae. It is also employed in the treatment of pharyngitis and tonsillitis due to susceptible Streptococcus pyogenes, and various respiratory tract infections, including acute maxillary sinusitis, acute bacterial exacerbations of chronic bronchitis, mild to moderate community-acquired pneumonia, Legionnaires' disease, and pertussis. Beyond respiratory infections, clarithromycin is prescribed for uncomplicated skin infections, Helicobacter pylori-associated duodenal ulcers, bartonella infections, early Lyme disease, and encephalitis caused by Toxoplasma gondii in HIV-infected patients when used with pyrimethamine. Additionally, it may help decrease the incidence of cryptosporidiosis, prevent α-hemolytic streptococcal endocarditis, and serve as a primary prevention for Mycobacterium avium complex bacteremia or disseminated infections in individuals with advanced HIV. Lastly, in combination with vonoprazan and amoxicillin, it is used as part of a triple therapy regimen to treat H. pylori infections in adults.

Pharmacodynamics

Clarithromycin belongs to the macrolide class of antibiotics, effective against a broad spectrum of pathogens. It exhibits activity against numerous gram-positive organisms such as Staphylococcus aureus, Streptococcus pneumoniae, and S. pyogenes, as well as gram-negative aerobes including H. influenzae, H. parainfluenzae, and Moraxella catarrhalis. It also targets various anaerobic bacteria, certain mycobacteria, and other organisms like Mycoplasma, Ureaplasma, Chlamydia, Toxoplasma, and Borrelia. Its activity extends to Chlamydophila pneumoniae and Mycoplasma pneumoniae. While primarily bacteriostatic, clarithromycin can be bactericidal depending on the bacterial strain and drug concentration, offering in-vitro activity comparable to or exceeding that of erythromycin against erythromycin-susceptible organisms.

Absorption

Clarithromycin is well-absorbed in the gastrointestinal tract and remains stable in acidic environments, which allows it to be taken with meals. This absorption profile ensures effective drug levels in the bloodstream to combat infections efficiently.

Metabolism

Clarithromycin undergoes substantial hepatic metabolism, primarily through the cytochrome P450 enzyme CYP3A4. This metabolic pathway is responsible for numerous drug interactions, as the enzyme is involved in the metabolism of many medications. Consequently, caution is required when clarithromycin is administered concurrently with other drugs metabolized by CYP3A4 to avoid potential interactions.

Mechanism of Action

Clarithromycin undergoes initial metabolism to form 14-OH clarithromycin, an active metabolite that functions synergistically with its parent compound. As with other macrolides, clarithromycin effectively penetrates the bacterial cell wall and binds reversibly to domain V of the 23S ribosomal RNA within the 50S subunit of the bacterial ribosome. This binding disrupts the translocation of aminoacyl transfer-RNA, thereby inhibiting polypeptide synthesis. Furthermore, clarithromycin also serves as an inhibitor of the hepatic microsomal CYP3A4 isoenzyme and P-glycoprotein, which is an energy-dependent drug efflux transporter.