Macrolide antibiotics
Macrolide antibiotics are a broad-spectrum class of antibacterial agents derived from Streptomyces bacteria, characterized by their large, diverse macrocyclic lactone structures attached to sugar moieties. Erythromycin is the most well-known macrolide, with newer semisynthetic derivatives such as azithromycin and clarithromycin expanding their therapeutic applications. These antibiotics primarily function as bacteriostatic agents, inhibiting bacterial growth by disrupting protein synthesis through reversible binding to the 50S ribosomal subunit, although at high concentrations, they can exhibit bactericidal properties.
Macrolides are particularly beneficial for individuals allergic to penicillin and are effective against a variety of infections, including respiratory tract infections like pneumonia and whooping cough, as well as skin infections and certain sexually transmitted diseases. Although generally well-tolerated, common side effects include gastrointestinal disturbances, with more serious effects being possible, such as liver dysfunction and cardiac arrhythmias. Overall, macrolide antibiotics play a crucial role in treating infectious diseases, offering a safe alternative for those with penicillin allergies while remaining a vital option in antibiotic therapy.
Macrolide antibiotics
Definition
Macrolide antibiotics are well-established, broad-spectrum, antibacterial agents derived from Streptomyces bacteria. Macrolides are a large, structurally diverse group of antibiotics composed of different-sized macrocyclic lactones attached to sugar moieties. The best-known macrolide antibiotic is erythromycin. Newer semisynthetic derivatives of erythromycin include azithromycin, clarithromycin, and dirithromycin. Macrolide antibiotics are especially useful as a treatment option for persons who are allergic to penicillin.
Mode of Action
Macrolide antibiotics are generally bacteriostatic agents that disrupt bacterial growth without causing cell death. These agents inhibit bacterial growth by suppressing protein synthesis. This mechanism occurs with the antibiotic reversibly binding to the 50S bacterial ribosomal subunit and inhibiting translocation by dissociating peptidyl-transfer ribonucleic acid (RNA) from the ribosome. This process prevents peptide chain elongation, cell growth, and reproduction. At high concentrations, macrolides have been known to exhibit bactericidal properties and cause cell death by interfering with deoxyribonucleic acid (DNA) replication.
Pharmacology
The pharmacological properties of an antibiotic dictate its effectiveness in inhibiting bacterial infections. Macrolides are typically administered orally but are generally poorly absorbed. Newer erythromycin derivatives exhibit broader activity and effectiveness against intracellular pathogens. Their most important attributes include improved lung and tissue absorption, higher intracellular concentrations and bioavailability, fewer dosing regimens, and less frequent drug-drug interactions.
Indications
Macrolides primarily display antibacterial activity toward most aerobic and anaerobic gram-positive bacteria with the exception of enterococci. Macrolides also inhibit some Mycoplasma species and anaerobic gram-negative pathogens. These antibiotics are effective in treating respiratory tract infections such as Legionnaires’ disease, community acquired pneumonia, pertussis (whooping cough), and diphtheria. Other indications include skin and soft tissue infections and sexually transmitted diseases, including chlamydia, syphilis, and gonorrhea. Macrolides also are potent against Helicobacter pylori infections of the stomach, penicillin-resistant staphylococcal infections, and group A streptococcal and pneumococcal infections in persons allergic to penicillin. Macrolides are not recommended for the treatment of meningitis.
Side Effects
Macrolides are considered one of the safest and best tolerated classes of antibiotics, even in children. The most common side effects include gastrointestinal upsets such as abdominal pain, dyspepsia (indigestion), diarrhea, nausea, and vomiting. More serious side effects can occur depending on the prescribed antibiotic and include allergic and dermatologic reactions, hepatic (liver) dysfunction, drug-drug interactions, cardiac and ventricular arrhythmias, and dose-related complications such as tinnitus and hearing loss.
Impact
Macrolide antibiotics have been essential in the treatment of infectious diseases for many years. Their discovery has provided a safe alternate therapy option for persons with an allergy to penicillin, one of the most frequent causes of severe allergic drug reactions.
Bibliography
Kirst, Herbert A. “Antibiotics: Macrolides.” In Van Nostrand’s Encyclopedia of Chemistry, edited by Glenn D. Considine. 5th ed. Hoboken, N.J.: Wiley-Interscience, 2010.
Sanford, Jay P., et al. The Sanford Guide to Antimicrobial Therapy. 18th ed. Sperryville, Va.: Antimicrobial Therapy, 2010.
Schönfeld, W., and H. A. Kirst, eds. Macrolide Antibiotics. Boston: Birkhäuser, 2002.