title: [Macrolides and ketolides].
abstract: Macrolides and ketolides are two families of antibiotics that share the same mechanism of action. They bind to different bases of the peptidyl transferase center of 23S RNA. The antibacterial spectrum of these drugs virtually overlaps, but dissimilarities in the affinity and number of binding sites results in differences in the intensity of their antibacterial effects (bacteriostatic or bactericidal) and their activity against strains with acquired resistance mechanisms. These agents are active against most gram-positive microorganisms and many intracellular microorganisms. Over the last ten years in Spain, the percentage of macrolide-resistant pneumococci and Streptococcus pyogenes strains has increased substantially. Telithromycin, a ketolide, has maintained the activity against these strains. Macrolides and ketolides are metabolized in the liver through CYP3A4 and they can partially block the activity of the enzyme, interfering with the metabolism of other drugs that use the same metabolic pathway. There is little elimination through the urine, with the exception of clarithromycin. High concentrations are reached in the cellular cytoplasm, but they do not diffuse to cerebrospinal fluid. These agents are included among class B drugs for use during pregnancy. Tolerance to macrolides is good and they have few associated adverse effects. The main clinical indication for these drugs is in empirical treatment of mild to moderate, community-acquired, upper and lower respiratory tract infections. Some patients treated with telithromycin developed severe hepatitis; therefore, its use is limited to community-acquired pneumonia in cases with no other available alternative.
authors.affiliation: Hospital Clínic, IDIBAPS, Universidad de Barcelona, España.
authors.forename: Nazaret
authors.initials: N
authors.lastname: Cobos-Trigueros
authors.forename: Oier
authors.initials: O
authors.lastname: Ateka
authors.forename: Cristina
authors.initials: C
authors.lastname: Pitart
authors.forename: Jordi
authors.initials: J
authors.lastname: Vila
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000981:Antiprotozoal Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004347:Drug Interactions; D004352:Drug Resistance, Microbial; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced; D006801:Humans; D018942:Macrolides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D010458:Peptidyl Transferases / Q000037:antagonists & inhibitors; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D011528:Protozoan Infections / Q000188:drug therapy*; D012338:RNA, Ribosomal, 23S / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000981:Antiprotozoal Agents; D018942:Macrolides; D012338:RNA, Ribosomal, 23S; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D010458:Peptidyl Transferases