What are 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.