- Macrolides are a class of antibiotics characterized by a macrocyclic lactone ring with attached sugar groups. The first, erythromycin, was discovered in 1952. - Erythromycin is bacteriostatic but can be bactericidal at high concentrations. It inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit. Common uses include atypical pneumonia, whooping cough, and as an alternative to penicillin for various infections. - Adverse effects include gastrointestinal issues and hypersensitivity reactions like rashes. Drug interactions can occur since erythromycin inhibits hepatic oxidation of many other drugs. Newer macrolides have been developed with improved safety profiles.

1. Macrolides
Dr. M N Nadeem,
Associate Professor,
Pharmacology,
MBBS, MD

2. Introduction to Macrolides
• Antibiotics with a macrocyclic lactone ring with
sugars attached.
• Examples: Erythromycin, Roxithromycin,
Clarithromycin,Azithromycin.
• The first among them, Erythromycin, discovered
in 1952 was isolated from Streptomyces
erythreus.
• Was widely used as an alternative to penicillin.

3. Erythromycin
• Bacteriostatic, but Bactericidal at high
concentration
• Susceptible gram positive bacteria accumulate
it intracellularly by active transport.
• Mechanism of action
– Inhibit bacterial protein synthesis
– Binds to the 50S ribosome subunits and interferes
with translocation

4. Erythromycin –
Anti-bacterial spectrum
• Similar to penicillins :
– mostly Gram +ve,
– a few Gram –ve,
– Highly active against: S. pyogenes, S.
pneumoniae, N. gonorrhoea, Clostridia, C.
diphteriae, and Listeria
• Also highly active against: Campylobacter,
Legionella, Branhamella catarhalis, Gardnerella
vaginilis and Mycoplasma
• Moderate sensitive: H. influenza, H.ducreyi, B.
pertussis, N. meningitis, Rickettsiae, Legionella

5. Uses - Erythromycin
• As a first choice drug:
– Atypical Pneumonia (Mycoplasma pneumoniae)
– Whooping cough (Bordatella pertussis)
– Chancroid
• As a second choice drug:
– Legionnaires pneumonia (Legionella)
– Campylobacter enteritis
– Chlamydia trachomatis of urinary tract.
• As an alternative to penicillin:
– URTI – Streptococcus, Staphylococcus, H influenza
– Diphtheria
– Syphilis (2nd line drug after Penicillin)
– Gonorrhoea (penicllin is drug of choice)
– Tetanus & Anthrax
• Topically –boils, acne

6. Adverse effects - Erythromycin
1. Gastrointestinal: Epigastric distress, Nausea,
Vomiting, Diarrhoea
◼ Erythromycin stimulates motilin receptors in GIT -
thus indices gastric contractions, hastens gastric
emptying and promotes intestinal motility.
2. Hypersensitivity: rashes, eosinophilia,
◼ Cholestatic jaundice (reversible): resembles viral
hepatitis, occurs with estolate ester, after 1-3 weeks
of use. It's due to hypersensitivity reaction.
3. High doses of erythromycin may cause
reversible hearing impairment.

7. Drug Interactions - Erythromycin
• It's an enzyme inhibitor (inhibits hepatic
oxidation of many drugs)
– Examples- rise in plasma levels of theophylline,
carbamazepine, valproate, ergotamine, warfarin.
• When given along with drugs like terfinadine/
astemizole/ cisapride, it results in Q-T
prolongation and ventricular arrhythmias, due
to it being a CYP3A4 inhibitor.

8. Newer Macrolides