Mechanism of Action of Erythromycin
Erythromycin exerts its antimicrobial effect by binding to the 50S ribosomal subunit of bacteria, specifically at the 23S rRNA component in the polypeptide exit region, thereby inhibiting RNA-dependent protein synthesis. 1
Primary Mechanism of Protein Synthesis Inhibition
Erythromycin binds to the 50S ribosomal subunit of susceptible bacteria, specifically targeting the polypeptide exit region of the 23S rRNA component. 2
The drug blocks the translocation reaction during protein synthesis, preventing the movement of peptidyl-tRNA from the A-site to the P-site of the ribosome. 3
This binding does not affect nucleic acid synthesis—only protein synthesis is inhibited. 1
Bacteriostatic vs. Bactericidal Activity
Erythromycin is generally considered bacteriostatic, but exhibits bactericidal activity against autolytic species such as pneumococci. 2
The distinction is clinically important: against most organisms, erythromycin stops bacterial growth without killing the bacteria, requiring host immune function for complete clearance. 2
pH-Dependent Activity and Membrane Penetration
Macrolides exhibit better antibacterial activity in neutral to basic pH environments. 2
At low pH, erythromycin becomes positively charged and does not readily cross biological membranes, which significantly reduces its antimicrobial effectiveness. 2
This pH sensitivity is particularly relevant in acidic environments such as abscesses or certain tissue compartments. 2
Resistance Mechanisms
The major route of resistance is modification of the 23S rRNA in the 50S ribosomal subunit, rendering the binding site insensitive to erythromycin. 1
Efflux pumps can also contribute significantly to resistance. 1
Resistance is often plasmid-mediated and closely associated with erythromycin use, particularly through erm gene-mediated methylation of the 23S ribosomal RNA. 3, 4
Clinical Pitfalls and Caveats
Antagonism exists in vitro between erythromycin and clindamycin, lincomycin, and chloramphenicol—these combinations should be avoided. 1
The increasing prevalence of macrolide resistance to S. pneumoniae is associated with significant likelihood of clinical failure. 2
Erythromycin is inactive against Enterobacteriaceae and Pseudomonas aeruginosa except under alkaline conditions, limiting its gram-negative coverage. 3
After oral administration, optimal blood levels are obtained when erythromycin is given in the fasting state (at least 30 minutes and preferably 2 hours before meals). 1