3. LEARNING OBJECTIVES
1. General points on macrolides – spectrum, mechanism of
action etc
2. Eryhtromycin, azithro, roxithro & clarithromycin – uses
& side effects
3. Preparations of erythromycin
4. • Antibiotics with Macrocyclic lactone ring with one
or more sugars attached to it.
• Derived from Streptomyces erythreus
• Alternate to penicillin
5. Common Features
used to eradicate carrier state in diphtheria, to treat legionellosis, treat
atypical pneumonia, community acquired pneumonia, H.pylori infection, leprosy,
chancroid, lymphogranuloma venereum
Erythromycin acid labile- enteric coated
tablets
active on gram + rods &
bacilli
6. •H.Influenza
•Legionella
•C.Jejunum
•B.pertusis
•H.Pylori
• Bacteroides fragilis
• M.Avium
• P.Jiroveci - clindamycin
•Staph.aureus
•Strep. Pyogenes
•Strep.pneumoniae
•N.gonorrhea
•Spirochetes –
T.pallidum
•Mycoplasma –
M.pneumonia
•M.Leprae
•Chlamydia –
C.pneumonia,
C.trachomatis
Anaerobes
G + cocci
& G – ve
cocci
G – ve rods
& bacilli
others
ANTI MICROBIAL SPECTRUM
8. RESISTANCE
• Resistance to erythromycin is usually plasmid-encoded.
(1) reduced permeability of the cell membrane or active efflux
(2) production (by Enterobacteriaceae) of esterases that hydrolyze
macrolides
(3) modification of the ribosomal binding site by chromosomal
mutation or by producing methylase. Efflux and methylase
production are the most important resistance mechanisms in
9. ERYTHROMYCIN - PREPARATIONS
• Erythromycin base is destroyed by
stomach acid and must be
administered with enteric coating.
• Food interferes with absorption.
• Stearates, esters & are fairly acid-
resistant and ethyl succinate
better absorbed.
• The lauryl salt of the propionyl
ester of
erythromycin(erythromycin
estolate) is the best-absorbed oral
preparation
• Erythromycin lactobionate &
10. ERYTHROMYCIN - PHARMACOKINETICS
• Wide distribution
• Concentrated in liver, excreted in
bile
• Cross placenta & milk but not
blood brain barrier
• Plasma half life of 1.6 hrs
• No dose adjustment in renal
failure
• Dose – 250-500mg 6th hourly
• 30% GERY OINTMENT to treat
bolis, carbuncles etc
11. MACROLIDES – SIDE EFFECTS
High doses causes reversible
auditory impairment
Stimulates motilin receptors in
gut causing increased gastric
contractions, hasten gastric
emptying & promote intestinal
motility
Hepatitis with
cholestatic
jaundice occur with
estolate & ethyl
succinate after 1-
2wks
Hypersensitivity
reactions to
estolate form
Others – thrombophlebitis on iv use, QT prolongation
13. THERAPEUTIC USES
AS AN ALTERNATE TO PENICILLIN
1. Streptococcal pharyngitis, tonsillitis, mastoiditis,
community acquired respiratory infections caused
by pneumococci and H. Influenzae, alternative
drug for prophylaxis of rheumatic fever and SABE
2. Diphtheria: acute stage as well as for carriers-7
day treatment
3. Tetanus: as an adjuvant to antitoxin, toxoid
therapy
4. Syphilis and gonorrhoea: only if tetracyclines
cannot be used
5. Leptospirosis: 250 mg 6 hourly for 7 days in
patients allergic to penicillins.
AS FIRST CHOICE
1. Atypical mycoplasma pneumonia
2. Diphtheria: eradicate carrier state
3. Chancroid – erythromycin 2gm/day
AS SECOND CHOICE
1. Calymatobacter enteritis – FQ is DOC
2. Legionairre’s pneumonia – azithromycin
is DOC
3. Chlamydia trachomatis - azithromycin is
DOC
4. Penicillinase resistant Staph.aureuseffect on the symptoms depends on the stage of dise
when treatment is started.
(a) Prophylactic: during the 10 day incubation
period-disease is prevented.
(b) Catarrhal stage: which lasts for about a week-
erythromycin may abort the next stage or reduce its
duration and severity.
(c) Paroxysmal stage: lasting 2-4 weeks-no effect on
duration and severity of 'croup' despite eradication of
the causative organism.
(d) Convalescent stage: during which 'croup‘ gradual
resolves (4-12 weeks)-is not modified
16. ROXITHROMYCIN
• Semisynthetic
• Long-acting
• Acid-stable Macrolide;
• More Potent Against Branh. Catarrhalis,
Card. Vaginalis And Legionella But Less
Potent Against B. Pertussis.
• Good Enteral Absorption And Tissue
Penetration,
• Plasma t1/2 Of 12 Hr, Twice Daily Dosing
• Alternative To Erythromycin For Respiratory,
ENT, Skin And Soft Tissue And Genital Tract
Infections
17. CLARITHROMYCIN
More active
on MAC,
My.leprae,
My.pneumoni
ae, H.pylori
Acid stable
bioavailability of 50%
metabolized by saturation kinetics-
t1/2 is prolonged from 3-6 hours at lower doses to 6-9
hours at higher doses.
SIDE EFECTS - High doses can cause reversible hearing loss,
pseudomembranous enterocolitis, hepatic dysfunction or
USES – URI, LRI, sinusitis, otitis media, whooping cough, atypical
pneumonia, skin infections due to Strep. pyogenes and Staph. Aureus, MAC
complex in AIDS, component of triple drug therapy in eradicating H.pylori,
second choice in leprosy
18. AZITHROMYCIN
1. Expanded Spectrum
2. Improved
Pharmacokinetics
3. Better Tolerability
4. Less Drug Interactions
5. Good acid-stability
6. Rapid oral absorption
7. Marked tissue
distribution and
intracellular
penetration –
macrophages
&fibroblasts
8. higher efficacy
9. better gastric tolerance
USES:
1. DOC in Legionairre’s pneumonia – 500mg
OD 1-2 wks
2. to treat chancroid – 1gm single dose
3. to treat LGV by C.trachomatis 1gm/day x 3
wks
4. DOC for Ch. Pneumonia
5. to treat donovanosis by Calymatobacter
granulomatis
6. URI, LRI, sinusitis, otitis media, whooping
cough, atypical pneumonia, skin infections due
to Strep. pyogenes and Staph. Aureus, MAC
complex in AIDS
7. to treat toxoplasmosis, typhoid,
malaria
20. CLINDAMYCIN
1. MOA, Spectrum &
resistance similar to
erythrocin
2. More active on
anaerobes namely
Bacterioides fragilis
3. Pesudomembranous
enterocolitis is
important side effect
treated by vancomycin,
metronidazole
USES:
1. Cl.perfringens infections of bones & joints
2. anaerobic B.fragilis infection causing
abdominal, pelvic or lung abscess
3. prophylaxis of endocarditis in penicillin
allergic patients undergoing dental surgery.
4. combined with pyrimethamine for
toxoplasmosis and with
21. SUMMARY
Bacteriostatic & bactericidal at high
concentrations
Inhibits bacterial protein
synthesis
inactive on aerobic gram –ve
bacilli
alternate to
penicillin
used to eradicate carrier state in diphtheria,legionellosis,atypical pneumonia,com
acqpneum, H.pylori infection, leprosy, chancroid, LGV, toxoplasmosis, malaria, typhoid
Narrow
spectrum
derived from Streptomyces
erythreus
stimulates motilin receptors in
gut
Erythromycin acid
labile-
enteric coated tablets
active on gram + rods &
bacilli
S/E – diahorrea, hepatitis with cholestatic jaundice,
ototoxicity, hypersensitivity, QT prolongation,
thrombophlebitis
AZITHROMYCIN – expanded spectrum, acid stable, OD dosing, less drug
interaction
CLARITHROMYCIN – MAC, My.pneum, My.leprae, H.pylori (triple drug regimen)
ROXITHROMYCIN – Long acting, acid stable, active on Branhella caterhalis
CLINDAMYCIN – More action on B.fragilis, Cause pseudomembranous
enterocolitis
