Macrolides

Introduction
They are antibiotics having a macrocyclic
lactone ring with attached sugars.

THE COMMONLY USED MACROLIDES ARE:

 Erythromycin (Streptomyces erythreus)-1952
 Clarithromycin
 Roxithromycin
 Azithromycin
 Antimicrobial spectrum
Erythromycin is effective against gram-positive organisms,
especially pneumococci, streptococci, staphylococci, and
corynebacteria.

Mycoplasma, legionella, Chlamydia trachomatis, C psittaci, C

pneumoniae, helicobacter, listeria, and certain mycobacteria are
also susceptible.

Gram-negative organisms eg. Neisseria sp, Bordetella pertussis,

Bartonella henselae, and B quintana some rickettsia sp,
Treponema pallidum, and campylobacter sp are susceptible.
Mechanism of action
 Mechanism of Action
It is bacteriostatic at low conc. & bactericidal at
high conc.

Bactericidal property depends on the conc.;

organism concerned and its rate of multiplication.

Erythromycin acts by inhibiting bacterial protein

synthesis. It combines with 50s ribosome subunits
and prevent translocation.
 Resistance
All cocci develop resistance, mostly by acquiring
capacity to pump it out or reduced permeability.
Most of the resistance are plasmid mediated.

Production (by Enterobacteriaceae) of esterases

that hydrolyze macrolides

Modification of the ribosomal binding site

(ribosomal protection) by chromosomal mutation.
 Resistance

Bacteria that develop resistance to

erythromycin shows cross resistance with
other macrolides.

Cross resistance with clindamycin and

chloramphenicol can also occur.
 Pharmacokinetics
Erythromycin base is destroyed by stomach acid
and must be administered with enteric coating.

Food interferes with absorption

The serum half-life is approximately 1.5 hours

normally and 5 hours in patients with anuria

Adjustment for renal failure is not necessary.

 Pharmacokintics
Erythromycin is not removed by dialysis. Large
amounts of an administered dose are excreted in
the bile and lost in feces, and only 5% is excreted
in the urine.

Absorbed drug is distributed widely except to the

brain and CSF.

It traverses the placenta and reaches the fetus.

 Clinical Uses
Erythromycin is a drug of choice in corynebacterial
infections (diphtheria, corynebacterial sepsis,
erythrasma); in respiratory, neonatal, ocular, or
genital chlamydial infections; and in treatment of
community-acquired pneumonia.

Erythromycin is also useful as a penicillin substitute

in penicillin-allergic individuals with infections
caused by staphylococci.
 Clinical Uses
Erythromycin has been recommended as prophylaxis
against endocarditis during dental procedures in
individuals with valvular heart disease. clindamycin,
better tolerated, has largely replaced it.

The oral dosage of erythromycin base, stearate, or

estolate is 0.25–0.5 g every 6 hours (for children, 40
mg/kg/d).

Whooping cough
 Clinical Uses
 Streptococcal pharyngitis, tonsillitis, mastoiditis

 Alternative prophylaxis for RF and SABE

 Diphtheria

 Tetanus as an adjuvant to TT

 Syphilis and gonorrhoea

 Leptospirosis
 Adverse Drug Reaction
Anorexia, NVD.

Acute cholestatic hepatitis

(fever, jaundice,
impaired liver function).

fever, eosinophilia, and rashes.

 Drug Interactions
Erythromycin metabolites can inhibit
cytochrome P450 enzymes and increase the
serum concentrations of numerous drugs,
including theophylline, oral anticoagulants,
cyclosporine, and methylprednisolone.

Erythromycin increases serum concentrations

of oral digoxin by increasing its bioavailability
 Clarithromysin
Improved acid stability and oral absorption.

Longer half-life than Erythromysin.

Lesser GIT intolerance than Erythromysin.

Less Frequent dosing

 Azithromysin

Slow elimination from tissues (2-4 days).

Raised half-life; permits OD dose.

Do not inhibits Liver enzyme P-450.

Diptheria Erythresema
Mastoiditis
 CHLORAMPHENICOL

Chloramphenicol is a bacteriostatic broad-

spectrum antibiotic

Active against both aerobic and anaerobic

gram-positive and gram-negative organisms.
 CHLORAMPHENICOL
Mechanism of action
Binds with 50s subunit of ribosomes and
inhibits the peptidyl transferase step of protein
synthesis.

Antibacterial activity
H. Influenzae S. typhi
N. Meningitidis E. coli
S. Pneumoniae V.cholera
Ricketsiae Anaerobes- clostridium &
B. fragilis
 Mechanism of Resistance

Mutation in the bacterial species, which cause

less penetration of the drug.

Chloramphenicol acetyltransferase, a plasmid-

encoded enzyme that inactivates the drug.
 Chloramphenicol
Pharmacokinetics:

 Rapidly & completely absorbed from GIT

 30 % protein bound

 Metabolized by liver – glucuronidation

 Well distributed in all body tissues including CNS and CSF

 Excreted in urine
 Chloramphenicol
Pharmacokinetics:

Most of the drug is inactivated either by conjugation

with glucuronic acid or reduction to inactive aryl amines

A small amount of active drug is excreted into bile and

feces

Dose must be adjusted in renal and hepatic patients

 Clinical Uses
Potential toxicity, bacterial resistance, and the availability of
many other effective alternatives, chloramphenicol is rarely
used.

Can be used in “Rocky Mountain spotted fever”

Treatment of “Meningococcal meningitis” in Penecillin allergic

patients.

Chloramphenicol is used topically in the treatment of “eye

infections”
 Side effects
1.Hypersensitivity- low incidence

2. Aplastic anaemia ( fatal )

3.Grey baby syndrome

4.Suprainfections

5. Interaction with other drugs :

Inhibits liver microsomal enzymes
Phenytoin
Tolbutamide
Chlorpropamide
Anticoagulants
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