Ketolides are semisynthetic, 14-membered-ring macrolides, differing from erythromycin by substitution of a 3-keto group for the neutral sugar l-cladinose. Telithromycin is approved for limited clinical use. It is active in vitro against Streptococcus pyogenes, S pneumoniae, S aureus, H influenzae, Moraxella catarrhalis, Mycoplasma sp, L pneumophila, Chlamydia sp, H pylori, Neisseria gonorrhoeae, B fragilis, T gondii, and certain nontuberculous mycobacteria. Many macrolide-resistant strains are susceptible to ketolides because the structural modification of these compounds renders them poor substrates for efflux pump–mediated resistance, and they bind to ribosomes of some bacterial species with higher affinity than macrolides.
Oral bioavailability of telithromycin is 57%, and tissue and intracellular penetration is generally good. Telithromycin is metabolized in the liver and eliminated by a combination of biliary and urinary routes of excretion. It is administered as a once-daily dose of 800 mg, which results in peak serum concentrations of approximately 2 mcg/mL. It is a reversible inhibitor of the CYP3A4 enzyme system and may slightly prolong the QTc interval. In the USA, telithromycin is now indicated only for treatment of community-acquired bacterial pneumonia. Other respiratory tract infections were removed as indications when it was recognized that use of telithromycin can result in hepatitis and liver failure. Telithromycin is also contraindicated in patients with myasthenia gravis because it may exacerbate this condition. Due to its potential for serious toxicity, an FDA-approved patient medication guide detailing these risks must be dispensed to any patient receiving the medication.
Solithromycin is a novel fluoroketolide that is pending FDA approval after two phase 3 clinical trials showed noninferiority when compared with moxifloxacin in the treatment of community-acquired pneumonia. Although not yet marketed, the dose used in clinical trials was a loading dose of 800 mg orally or intravenously, followed by 400 mg daily for a total of 5 days. The intravenous formulation was associated with higher rates of infusion-related reactions compared with moxifloxacin. Similar to telithromycin, solithromycin maintains in vitro activity against macrolide-resistant bacteria, including S pneumoniae, staphylococci, enterococci, Chlamydia trachomatis, and Neisseria gonorrhoeae. Its chemical structure lacks the pyridine-imidazole side chain group, which is thought to contribute to telithromycin’s hepatotoxicity; severe toxicity has not been demonstrated in Phase II or III clinical trials.
Clindamycin is a chlorine-substituted derivative of lincomycin, an antibiotic that is elaborated by Streptomyces lincolnensis.
Mechanism of Action & Antibacterial Activity