Erythromycin

Erythromycin is isolated from Streptomyces erythreus. The water solubility of erythromycin is limited, and the solution remains stable only when kept in the cold.

Mechanism of action

• Bonds to 50 s subunit of bacterial ribosomes and inhibits bacterial protein synthesis by preventing attachment of aminoacyl transfer RNA to its acceptor site on ribosomes.
• This prevents peptide bond formation by a peptidyl transferase.

Indication.

The antimicrobial spectrum is narrow,

• Str. pyogenes and Str. pneumoniae, N.gonorrhoeae, Clostridia,
• C. diphtheriae and Listeria,
• Penicillin-resistant Staphylococci and Streptococci are now resistant to erythromycin also.
• Gardnerella vaginalis and Mycoplasma are not affected by penicillin but are highly sensitive to erythromycin.

Resistance

• Acquire the capacity to pump out the drug.
• Resistant Enterobacteriaceae have been found to produce an erythromycin esterase hence resistance.
• Alteration in the ribosomal binding site for erythromycin by a plasmid-encoded methylase enzyme by gram-positive bacteria.
• All the above types of resistance are plasmid-mediated.
• Change in the 50S ribosome by chromosomal mutation reduces the macrolide binding affinity in some gram-positive bacteria.
• Bacteria that develop resistance to erythromycin are cross-resistant to other macrolides such as clindamycin.

Adverse effects

• Gastrointestinal epigastric pain is experienced especially by children on oral ingestion.
• Diarrhoea is occasional.
• Reversible hearing impairment.
• Hypersensitivity; rashes and fever.
• Hepatitis with cholestatic jaundice resembling viral hepatitis and extrahepatic biliary obstruction occurs.
• Ventricular arrhythmias with prolonged QT interval.
• Stevens-Johnson and toxic epidermal necrolysis.

Drug interaction.

• Interactions of Erythromycin inhibit the hepatic oxidation of many drugs. Ie.—rise in plasma levels of theophylline, carbamazepine, valproate, ergotamine and warfarin.
• The clearance of zopiclone is reduced.

Clinical Uses

• Alternative to penicillin in; Streptococcal pharyngitis, tonsillitis, mastoiditis and community-acquired respiratory infections caused by pneumococci and H. influenzae.
• As a second choice drug in;

√Campylobacter enteritis reduces the duration of diarrhoea and the presence of organisms in stools.

√Legionnaires’ pneumonia: 3-week erythromycin treatment is effective.

√ Chlamydia trachomatis infection of urogenital tract.

√ Penicillin-resistant Staphylococcal infections.

Dosage.

• 250–500 mg 6 hourly (max. 4 g/day), children 30–60 mg/kg/day.
• Erythromycin (base): ERYSAFE 250, mg tablets, EROMED 333 mg tablets 125 mg/5 ml suspension.
• Erythromycin stearate: ERYTHROCIN 250, 500 mg tab, 100 mg/5 ml suspension., 100 mg/ml pediatric. drops. ETROCIN, ERYSTER 250 mg tablets, 100 mg/5 ml dry syrup.
• Erythromycin estolate (lauryl sulphate) is relatively acid-stable and better absorbed after oral administration.