Clarithromycin

Clarithromycin is a macrolide antibiotic and a CYP3A4 inhibitor. Target: Antibacterial; CYP3A4 Clarithromycin is a macrolide antibiotic used to treat pharyngitis, tonsillitis, acute maxillary sinusitis, acute bacterial exacerbation of chronic bronchitis, pneumonia (especially atypical pneumonias associated with Chlamydophila pneumoniae), skin and skin structure infections. Clarithromycin prevents bacteria from growing by interfering with their protein synthesis. It binds to the subunit 50S of the bacterial ribosome and thus inhibits the translation of peptides. Clarithromycin has similar antimicrobial spectrum as erythromycin, but is more effective against certain Gram-negative bacteria, particularly Legionella pneumophila. Besides this bacteriostatic effect, clarithromycin also has bactericidal effect on certain strains, such as Haemophilus influenzae, Streptococcus pneumoniae and Neisseria gonorrhoeae. Clarithromycin is a CYP3A4 inhibitor. Even low doses of the cytochrome P4503A4 (CYP3A4) inhibitor clarithromycin increase the plasma concentrations and effects of repaglinide. Concomitant use of clarithromycin or other potent inhibitors of CYP3A4 with repaglinide may enhance its blood glucose-lowering effect and increase the risk of hypoglycemia [1, 2].

References:
[1]. http://en.wikipedia.org/wiki/Clarithromycin [2]. Niemi, M., P.J. Neuvonen, and K.T. Kivisto, The cytochrome P4503A4 inhibitor clarithromycin increases the plasma concentrations and effects of repaglinide. Clin Pharmacol Ther, 2001. 70(1): p. 58-65.

Comparison of in vitro synergistic effect between clarithromycin and azithromycin in combination with amikacin against Mycobacterium intracellulare.[Pubmed:30953831]

J Glob Antimicrob Resist. 2019 Apr 3. pii: S2213-7165(19)30086-4.

OBJECTIVE: The purpose of this study was to compare the in vitro synergistic effect between Clarithromycin and azithromycin in combination with amikacin against Mycobacterium intracellulare. METHODS: The broth microdilution in cation-adjusted Mueller-Hilton (MH) broth was used to determine in vitro susceptibility of M. intracellulare isolates to antimicrobial agents tested. In addition, the fractional inhibitory concentration index (FICI) was calculated to assess synergy. RESULTS: A total of 32 respiratory isolates of M. intracellulare were enrolled in this study. Clarithromycin was the most potent agent against M. intracellulare isolates, the MIC50 and MIC90 of which were 0.5 and 8mug/ml, respectively. Azithromycin and amikacin also showed moderate activity against M. intracellulare, with MIC90s of 16mug/ml and 4mug/ml, respectively. The percentages of resistant strains among the 32M. intracellulare isolates was 3.1% for Clarithromycin, 9.3% for amikacin and 12.5% for azithromycin. The presence of amikacin had no effect on the MIC50 of Clarithromycin, while the presence of amikacin resulted in a two-fold increase in the MIC50 of azithromycin. In addition, antagonism for Clarithromycin-amikacin combination was noted in 5M. intracellulare isolates (5/32, 15.6%), which was significantly lower than that (14/32, 43.8%) for azithromycin-amikacin combination (P=0.042). CONCLUSIONS: To conclude, our data have demonstrated that Clarithromycin displayed more potent in vitro activity against M. intracellulare isolates than azithromycin. In addition, the antagonistic effect between azithromycin and amikacin was more frequent in M. inracellulare isolates than that between Clarithromycin and amikacin.

JVA, an isoniazid analogue, is a bioactive compound against a clinical isolate of the Mycobacterium avium complex.[Pubmed:30948164]

Tuberculosis (Edinb). 2019 Mar;115:108-112.

Bacteria belonging to Mycobacterium avium complex are organisms of low pathogenicity that infect immunosuppressed individuals. Infection is treated with an antimicrobial macrolide, Clarithromycin (CAM) or Azitromycin, associated with Ethambutol and Rifabutin during 12 months. Regimen long duration and side effects hinder patient's commitment to treatment favoring emergence of antibiotic resistance. In this present study, we evaluated the activity of JVA, an Isoniazid (INH) derivative, against M. avium 2447, a clinical isolate. We demonstrated that JVA reduces M. avium 2447 growth in macrophages, more efficiently than CAM and INH. In order to explore JVA mechanism of action, we investigated compound properties and performed pH-dependent stability studies. Our results suggest an enhanced ability of JVA to cross biological membranes. Furthermore, we suggest that in acidic conditions of macrophages' phagosomes, where mycobacteria replicate, JVA would be promptly hydrolyzed to INH, delivering the adduct INH-nicotinamide adenine dinucleotide and thus inhibiting M. avium 2447 growth.

Acute Colchicine-induced Neuromyopathy in a Patient Treated with Atorvastatin and Clarithromycin.[Pubmed:30931282]

Eur J Case Rep Intern Med. 2019 Mar 18;6(3):001066.

Neuromyopathy is a rare side effect of chronic colchicine therapy, especially without renal impairment. Drugs interacting with colchicine metabolism through CYP3A4 can accelerate accumulation and toxicity. We describe a case of an interaction between atorvastatin, Clarithromycin and colchicine resulting in acute neuromyopathy. LEARNING POINTS: Colchicine has a narrow therapeutic window, and therefore, often produces side effects.Special caution should be adopted if patients with renal disease and concomitant medications are given colchicine.Before prescribing colchicine, the clinical history, including previous medications and conditions, should be carefully considered.