This document discusses macrolide antibiotics, including their classification, mechanism of action, mechanisms of resistance, and examples like erythromycin, clarithromycin, azithromycin, and telithromycin. Macrolides are a class of natural products consisting of a large macrocyclic lactone ring with attached deoxy sugars. They inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit and blocking polypeptide chain elongation. Resistance can develop via ribosomal methylation, drug-inactivating enzymes, or efflux pumps. The macrolides discussed have similar spectra but differ in absorption, distribution, metabolism, excretion, and indications.

1. Jagir R. Patel
Asst Professor
Dept of Pharmacology
Macrolides

2. Classification
 The macrolides are a class of natural
products that consist of a
large macrocyclic lactone ring to
which one or more deoxy sugars,
usually cladinose and desosamine,
may be attached.
 They are class of Protein synthesis
inhibitors
Macrolides
Erythromycin
clarithromycin
Azithromycin
Telithromycin
Roxithromycin
Spiramycin
Rokitamycin

3. Mechanism of Action Protein synthesis
inhibitors
Bind to 50S ribosomal
subunit
Inhibit polypeptide chain elongation
and protein synthesis
Result in inhibition of growth and
multiplication
• Preventing the Transfer of the Peptidyl tRNA from the A-site to the P-site.
• Promotion of Peptidyl tRNA Dissociation
• Blocking Peptidyl Transferase.
• Preventing Ribosomal Assembly

5. Mechanism of Resistance
Acquired resistance
Post-transcriptional methylation of the 23S bacterial ribosomal RNA.
This acquired resistance can be either plasmid-mediated or chromosomal,
cross-resistance to macrolides
Due to production of drug-inactivating enzymes (esterase's or kinases),
production of active ATP-dependent efflux proteins that transport the drug
outside of the cell.

6. Erythromycin
Erythromycin – Mainly effective on
G+ bacteria
A. Gram- positive bacteria
Staph. Aureus
S. pneumoniae
URTIs (eg. Otitis media,
pharyngitis )
LRTIs (eg.Pneumoniae )
S. Pyrogens
C. diphtheria
B. Gram- negative bacteria
T. pallidum
C. Intracellular organisms
L. pneumophila
M. pneumoniae
C. trachomatis
 Absorption: Variable and unreliable
due to instability in gastric acid. Food
may reduce absorption of the base or
the stearate. Time to peak plasma
concentration: 1-4 hr.

Distribution: Widely distributed into
body tissues and fluids. Crosses the
placenta and enters breast milk.

Metabolism: Partly metabolised in the
liver via N-demethylation to inactive,
unidentified metabolites.

Excretion: Via faeces and urine (as
unchanged drug). Plasma half-life:
1.5-2.5 hr.

7.  Interactions: erythromycin+ benzodiazepines= increase sedation
 erythromycin+ calcium channel blockers = Hypotension, Brady arrhythmia
 Indications: Respiratory tract infections
 Skin and soft tissue infections
 Susceptible infections
 Acne
 Prophylaxis of streptococcal infections in patients with evidence of rheumatic
fever or heart disease
 Treatment and prophylaxis of ophthalmic infections and neonatal
conjunctivitis

8. Clarithromycin
Antibacterial spectrum
A. Gram- positive bacteria
Staph. Aureus
S. Pneumoniae
S. Pyrogens
B. Gram- negative bacteria
H. influenzae
H. Pylori
M. catarrhalis
C. Intracellular organisms
M. pneumoniae
L. Pneumophila
 Absorption: Rapidly absorbed from the GI
tract. Food delays rate of absorption.
 Bioavailability: Approx 50%.
 Distribution: Widely distributed into most
body tissues. Enters breast milk and
distributed into CSF.
 Plasma protein binding: Approx 42-70%.
Metabolism: Partially hepatic converted to
14-hydroxyclarithromycin (active
metabolite).
Excretion: Via urine and faeces Plasma
half-life: 3-7 hr (clarithromycin), 5-9 hr
(14-hydroxyclarithromycin).
 Interaction : Clarithromycin + zidovudine = Decreased concentration of
zidovudine
 Indications: Respiratory tract infections; Skin and soft tissue infections ;
Susceptible infections, Eradication of H. pylori associated with peptic ulcer
disease, Respiratory tract infections; Skin and soft tissue infections

9. Azithromycin
 Azithromycin is a semisynthetic
azalide antibiotic.
Antibacterial spectrum
A. Gram- positive bacteria
Staph. Aureus
S. Pneumoniae
S. Pyrogens
B. Gram- negative bacteria (>
erythromycin)
M. catarrhalis
H. influenzae
C. Intracellular organisms (>
erythromycin)
L. Pneumophila
M. pneumoniae
Chlamydia species
 Absorption:
 Rapidly absorbed from the GI tract. Reduced by
food .
 bioavailability: Approx 34-52%. Time to peak
plasma concentration: Oral tab: 2-3 hr; IV: 1-2 hr.

Distribution: Extensive into the tissues (higher
than those in blood), CSF (small
amounts).Plasma protein binding: 7-51% (oral
and IV).
 Metabolism: Hepatic metabolism via
demethylation.

Excretion: Via bile urine. Terminal elimination
half-life: About 68 hr.
 Interaction : Increases serum concentrations of
digoxin, ciclosporin, hexobarbital and
phenytoin.

11.  Indications:
 Skin and soft tissue infections
 Respiratory tract infections
 Uncomplicated genital infections due to Chlamydia trachomatis
 Non-gonococcal cervicitis/urethritis due to Chlamydia trachomatis
 Chancroid, Uncomplicated Gonorrhoea,
 Active immunization against typhoid fever caused by Salmonella typhi,
 Community-acquired pneumonia
 Bacterial conjunctivitis

12. Telithromycin
 Telithromycin is a semisynthetic ketolide antibiotic that blocks protein synthesis
by binding to domains II and V of 23S ribosomal RNA of the 50S ribosome
subunit. It may also inhibit the assembly of nascent ribosomal units.
 Absorption: Rapidly absorbed from the GI tract. Bioavailability: 57%. Time to
peak plasma concentration: Approx 1-3 hr.
 Distribution: Widely distributed in body fluids and tissues, including the resp
tract.. Plasma protein binding: 60-70%.
 Metabolism: Undergoes hepatic metabolism to 4 major metabolites
 Excretion: Via urine (13% as unchanged drug; remainder as metabolites) and
faeces (7%). Elimination half-life: 2-3 hr. Terminal half-life: Approx 10 hr.
 Interactions: Additive effect on QT interval prolongation w/ class 1A (e.g.
quinidine, procainamide) or class III (e.g. dofetilide) antiarrhythmic agents
 Indications: Community-acquired pneumonia

13. Roxithromycin
 Absorption: oral reduced if taken after
food. Bioavailability: about 50%.

Distribution: Widely distributed into
body tissues and fluids.

Metabolism: Small amounts are
metabolised in the liver.

Excretion: Mainly via the faeces as
unchanged drug and metabolites, via the
urine & the lungs
 Elimination half-life: 8-13 hr.
 Interactions: May raise serum levels of
ciclosporin and digoxin
 Susceptible infections
Irreversibly binding
to the 50s ribosomal
subunits
Blocking the
transpeptidation or
translocation reactions
Resulting in stunted cell growth.

14. Common Adverse Effects