- Macrolides are a class of antibiotics that are produced by Streptomyces bacteria and contain a macrocyclic lactone ring. Erythromycin was the first macrolide discovered in 1952. - Macrolides work by attaching to the 50S subunit of bacterial ribosomes and inhibiting protein synthesis. They are bacteriostatic and have selectivity for bacterial over mammalian cells. - Common macrolides include erythromycin, clarithromycin, roxithromycin, and azithromycin. They are effective against many gram-positive bacteria and some gram-negatives. Azithromycin has the broadest spectrum of activity.

1. By Dr. Mohammed Yaqub Pasha

2. Introduction
The term Macrolide was originally given to
antibiotics produced by species of Streptomyces.
Erythromycin was discovered in 1952 by McGuire
and coworkers from a strain of Streptomyces
erythreus.

3. General Structure
O
O
O
CH3
R1
H3C
CH3
CH3
O
H3C
OH
H3C
CH3
OH
O
O
HO
CH3
N
CH3
CH3
O OH
CH3
CH3
OR2
1 3
5
9
12
1`
1``
Erythromycin
Glycon
Aglycone
They all contain three characteristics parts in the molecule:
 A highly substituted macrocyclic lactone: aglycone.
 A ketone group.
 An amino desoxysugar: glycon, and in some of the macrolides, a
neutral desoxysugar which are glycosisically attached to the
aglycone ring.

4. Mechanism of Action
 Macrolides - bacteriostatic agents
 Attach to the P site of 50s portion of bacterial
ribosomes and inhibit the protein synthesis
 Prevent translocation during elongation of protein
synthesis
 Do not inhibit the 60s/40s subunits of mammalian
cells – selective toxicity

5. Mechanism of action

6. Resistance
From one of four mechanisms
 Drug efflux by an active pump mechanism
 Modification of receptor sites on 50s ribosome –
decreased binding of the drug
 Macrolide hydrolysis by esterases produced by
Enterobacteriaceae
 Failure to permeate through bacterial cell
membrane

7. Spectrum of Antibacterial Activity
Macrolides are similar to penicillins
regarding their spectrum of activity
They are effective against penicillin-resistant
strains
Macrolides are effective against most of the
G(+) bacteria, cocci or bacillus, they have
antibiotic activity against G(-) cocci
,especially Neisseria Species

8. Typical therapeutic applications of macrolides.

9. ERYTHROMYCIN
Antimicrobial spectrum: Mostly gram-positive
 Highly sensitive: Str. pyogenus, Str. pneumoniae,
N. gonorrhoeae, C. diphtheriae, Listeria,
Campylobacter, Legionella, Branhamella catarrhalis,
Gardnerella vaginalis, Mycoplasma
 Moderately sensitive: H. ducreyi, H. influenzae, B.
pertussis, Chlamydia trachomatis, Str. Viridans,
N.meningitidis, Rickettsiae
 Not sensitive: Enterobacteriaceae, B. fragilis

10. Pharmacokinetics:
 Acid labile
 Incomplete absorption
 Food delays absorption
 Inactivated by gastric acid – Enteric coated tablets/ester
salts
 Widely distributed, 70-80% plasma protein bound
 Does not cross blood brain barrier
 t-1.5 hr, persists longer in tissues
 No need of dose alteration in renal failure

11. USES
As an alternative to penicillin:
 Streptococcal pharyngitis, tonsillitis, mastoiditis,
community acquired pneumonia
 Prophylaxis of rheumatic fever and SABE
 Diphtheria
 Tetanus
 Syphilis and gonorrhoea
 Leptospirosis

12. 1st choice in
 Atypical pneumonia (mycoplasma
pneumonia)
 Whooping cough
 Chancroid
2nd choice in
 Campylobacter gastroenteritis
 Legionnaires pneumonia
 Chlamydia trachomatis

13. ROXITHROMYCIN
 Semisynthetic longer-acting acid stable macrolide
 More potent against Branhamella catarrhalis,
Gardnerella vaginalis, Legionella
 Less potent against B. pertussis
 Similar efficacy, better gastric tolerability

14.  Spectrum includes MAC, Mycobacterium
leprae
 More active against H. pylori, Moraxella,
Legionella, Mycoplasma pneumonia
 More acid stable, rapidly absorbed

15. CLARITHROMYCIN
 Absorbed rapidly from the GI tract
 Can be given with or without food
 saturation kinetics
 active metabolite
 Bioavailability - 50-55%
 T1/2 6-7 hrs, excreted through kidney

16.  Spectrum includes MAC, Mycobacterium
leprae
 More active against H. pylori, Moraxella,
Legionella, Mycoplasma pneumonia

17. USES
 200-500 mg BD
 Clarithromycin or azithromycin - first-line
therapy for prophylaxis and treatment of
disseminated infection caused by M. avium-
intracellulare in AIDS patients
 Clarithromycin + minocycline used in
lepromatous leprosy
 Clarithromycin 500mg + omeprazole 20mg
+ amoxycillin 1gm BD (14 days) – PUD

18. AZITHROMYCIN
 Expanded spectrum – H. influenza,
Mycoplasma, Chlamydia pneumoniae,
Legionella, Moraxella, MAC, Campylobacter,
Ch. Trachomatis, H. ducreyi, N.gonorrhoeae,
penicillinase producing Staph. Aureus
 Higher efficacy

19.  Improved pharmacokinetics – acid-stability,
rapid oral absorption, intracellular
penetration, high concentrations inside
macrophages and fibroblasts
 Better gastric tolerability
 Fewer drug interactions
 Convenient once daily dosing

20. Administration and fate of the macrolide antibiotics

21. 1st choice in
 Legionnaire pneumonia
 Clamydia trachomatis
 Donovanosis
 Chancroid
 PPNG
 Single 1gm dose – chlamydia cervicitis &
urethritis
 500mg OD – disseminated infection by
MAC in AIDS
 Excellent action against Toxoplasma gondii

22.  Other uses –
Pharyngitis, otitis media, skin and soft
tissue infections, prophylaxis and treatment
of MAC in AIDS patients

23. Adverse effects
1. Hepatotoxicity
 Cholestatic hepatitis - erythromycin estolate
 Nausea, vomiting, intestinal cramps
 Hypersensitivity reaction
2. GI toxicity
 Erythromycin- epigastric distress
 Dose related
 Reduced by prolonging the infusion time to 1 hr/
pretreatment with glycopyrrolate

24. 3. Cardiac toxicity
 Cardiac arrythmias, QT prolongation, ventricular
tachycardia
4. Toxic and irritative effects
 Fever, eosinophilia, skin eruptions
 Transient auditory impairment- erythromycin
 i.v erythromycin – thrombophlebitis

25. DRUG INTERACTIONS
 Erythromycin, clarithromycin- inhibit CYP3A4. may
increase concentrations of:
Theophylline Digoxin, Disopyramide
Carbamazepine Valproic acid
Cyclosporine Terfenadine, Astemizole
Phenytoin Cisapride
Warfarin Ergot alkaloids
 Azithromycin - no drug interactions

26. THANK YOU