This document discusses macrolide antibiotics, including their mechanism of action, types, and uses. It describes several macrolide antibiotics like erythromycin, clarithromycin, azithromycin, and roxithromycin. It covers their mechanisms of action, spectra of activity, pharmacokinetics, clinical uses, side effects, and interactions. It also briefly discusses newer macrolides like telithromycin and ketolides, as well as the lincosamide antibiotic clindomycin.

1. MACROLIDE ANTIBIOTICS
Dr. Rupendra K Bharti
Asst. Professor
Late BRKM GMC Jagdalpur

2. • Macrolide antibiotics contain a many
membered lactone ring known as macrocyclic
ring to which one or more deoxy-sugars are
attached.
• They are:
• Erythromycin
• Clarithromycin
• Roxithromycin
• Azithromycin

3. • Erythromycin is the first member of this group,
and was isolated from a strain of Streptomyces
erythreus in 1952.
• Clarithromycin, Roxithromycin and
Azithromycin are semi-synthetic derivatives of
erythromycin and these are also called newer
macrolides.
• Some other macrolides are dirithromycin,
oleandomycin and troleandomycin.

5. Mechanism of action
• Macrolide antibiotics are bacteriostatic agents and
inhibit the protein synthesis by binding reversibly to
50s ribosomal subunit of sensitive micro-organism
and interferes with ‘translocation’ step in the protein
synthesis.
• The Gram-positive bacteria accumulate about 100
times more erythromycin than the Gram-negative
bacteria, hence G+ve bacteria are more sensitive
than the G-ve ones.
• Macrolides behave as bactericidal at very high
concentrations.

7. Bacteriostatic effect at low concentration and
bactericidal at high concentrations
• Antimicrobial spectrum
• These antibiotics are more active against G+ve cocci and
inactive against most of the aerobic and enteric G-ve
bacilli.
• Also chlamydia, mycoplasma, spirochetes and
toxoplasma

8. Mechanism of ResistancePost-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.

9. Pharmacokinetics
• Absorption:
• Destroyed by the gastric juice so better given as enteric
coated tablet or in stearate form.
• Distribution:
• Distributed all over the body except in CSF
• Macrolides are concentrated in the phagocytes and
therefore enhance phagocyte killing of bacteria
• Metabolism:
• Occurs in liver by zero order kinetics
→ So the half-life increases with increased dose
→ Contra-indicated in hepatic dysfunction
• Excretion:
• Mainly excreted through the bile
• Renal excretion is only 5%

10. Clinical uses
• Diphtheria
• Pertussis (=whooping cough)
• Tetanus
• Bacterial diarrheas as caused by campylobacter jejuni
• Clarithromycin is also used in peptic ulcer for the eradication of H.
Pylori bacteria, MAC (atypical mycobacteria) infections and
topically in acne
• Genital infections like gonorrhea, syphilis, chancroid and infections
caused by chlamydia
• Mycoplasma pneumonia (DOC in children as tetracyclines, DOC in
adults, are contraindicated) & Legionnaire’s pneumonia (DOC)
• Penicillin alternative in penicillin allergic patients as in Respiratory
& ENT infections
(Can be remembered by names of the vaccines: DPT, BCG, Measles
& Polio)
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11. Drugs

12. Drug properties
Erythromycin
Dose 250-500 mg QID
Route Oral
Duration of treatment 7-14 days
Antibiotics spectrum Narrow
Oral bioavailability Low
t½ 1.5 hr
Special properties  Acid labile, given as enteric coated tablets. Poorly absorbed when given
empty stomach. Has poor tissue penetration.
Indications  As drug of choice in atypical pneumonia, whooping cough, and
chancroid.
 As an alternative to Penicillin in Streptococcal pharyngitis, tonsillitis,
mastoiditis, leptospirosis and prophylaxis of rheumatic fever SABE.
 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.
Side effects  Epigastric distress causing nausea, vomiting and diarrhoea.
 Allergic reaction such as fever and skin eruption
 Cholestatic hepatitis (especially by erythromycin estolate).
 Prolongation of QTc interval.
Interactions  Erythromycin + benzodiazepines= increase sedation.
 Erythromycin + calcium channel blockers = Hypotension, Brady

13. Drug properties Clarithromycin
Dose 250-500 mg BD
Route Oral
Duration of treatment 7-14 days
Antibiotics spectrum Wide
Oral bioavailability Good
t½ 3-6 hr at low dose
3-9 hr at high dose
Special properties • Acid stable, good absorption occurs when given empty stomach.
• Has good tissue penetration.
Indications • Upper and lower respiratory tract infections, sinusitis, otitis
media, atypical pneumonia, skin and skin structure infections
• As a component of triple drug regimen it eradicates H. pylori in
1–2 weeks.
• It is a first line drug in combination regimens for MAC infection
in AIDS patients.
Side effects • Side effects same as erythromycin but has better gastric
tolerance.
• Reversible hearing loss at high doses.
Interactions • Clarithromycin + zidovudine = Decreased concentration of
zidovudine

14. Drug properties
Azithromycin
Dose 500 mg OD
Route Oral
Duration of treatment 3-5 days
Antibiotics spectrum Wide
Oral bioavailability Good
t½ >50 hr
Special properties  Acid stable, good absorption occurs when given empty
stomach.
 Has good tissue penetration.
Indications  Pharyngitis, tonsillitis, sinusitis, otitis media, pneumonias,
acute exacerbations of chronic bronchitis, skin and soft tissue
infections.
 In the prophylaxis and treatment of MAC in AIDS patients.
 In multidrug resistant typhoid fever (patients allergic to
cephalosporins).
 Toxoplasmosis.
 As drug of choice: Legionnaires, Chlamydia trachomatis,
Donovanosis and Chancroid.
Side effects  Nausea, vomiting, diarrhoea, and abdominal pain.
Interactions • Increases serum concentrations of digoxin, ciclosporin,
hexobarbital and phenytoin

15. Drug properties Roxithromycin
Dose 150 mg BD
Route Oral
Duration of treatment 7-14 days
Antibiotics spectrum Wide
Oral bioavailability Good
t½ 12 hr
Special properties  Acid stable, good absorption occurs
when given empty stomach.
 Has good tissue penetration.
Indications  It is an alternative to erythromycin
for respiratory, ENT, skin and soft
tissue and genital tract infections
with similar efficacy.
Side effects  Nausea, vomiting, diarrhoea, and
abdominal pain.

16. Effect on Motilin receptors
• Erythromycin stimulates motilin receptors in the
GIT which induces gastric contractions.
• This leads to early gastric emptying and increased
intestinal motility without significantly affecting
the colonic motility.
• Due to this property, it is also used in
• diabetic gastroparesis and
• post operatively to promote the peristalsis in the cases
of post-operative paralytic ileus.

17. Spiramycin
• Spiramycin is also a macrolide antibiotic.
• It resembles erythromycin in spectrum of activity
and properties.
• Its specific utility is for toxoplasmosis and
recurrent abortions in pregnant women.
• It limits risk of transplacental transmission of
Toxoplasma gondii infection.

18. Cont…
• It is given in a dose of 3 million units (MU) BD/TDS
for 3 weeks. (Three week course is to be repeated
after 2 weeks gaps till delivery).
• Other indications are similar to erythromycin with a
dose of 6 MU per day for 5 days.
• Common side effects are:
• Gastric irritation,
• Nausea,
• Diarrhoea and
• Rashes.

19. ketolies
Telithromycin, Cethromycin & Solithromycin

20. Telithromycin
• It is a semi-synthetic derivative of erythromycin and
also called as Ketolide, due to a keto group in its
structure.
• It 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.
• Due to this changed structure, it is more active
against the Macrolide resistant G+ve micro-
organisms.

21. Cont..
• It is given orally as once daily dosage
schedule in a dose of 400 mg OD.
• The half-life is 10 hrs.
• Telithromycin is used as treatment of
respiratory tract infections including:
• Acute exacerbation of chronic bronchitis,
• Acute bacterial sinusitis and
• Community acquired pneumonia.

22. Cont…
• The major side effects are:
• Reversible hepatic dysfunction,
• Prolongation of QTc interval and
• Transient visual disturbances.
• Interactions:
• Additive effect on QT interval prolongation w/ class 1A
(e.g. quinidine, procainamide) or class III (e.g. dofetilide)
antiarrhythmic agents).

23. Cethromycin
• More potent than telithromycin
• Used against macrolide resistant Streptococci and
Enterococci
• Resistance:
• Ribosomal modification via inducible or constitutive
methylation.
• Ribosomal modification via point mutation- H. pylori
• Drug efflux- S. pyogenes
• Adverse reactions
• Diarrhoea, nausea
• Drug interaction
• Prolonged QT interval (cisapride, terfenadine)
• Increased blood levels of theophylline, midazolam

24. • Indicated in:
• Community acquired pneumonia
• Prevention of post exposure inhalational anthrax
• It is discovered as orphan drug.
• Now under Phase III clinical trial.

25. Solithromycin
• MOA:
• Solithromycin inhibits bacterial translation by binding to
the 23S ribosomal RNA, preventing the offending
bacteria from synthesizing proteins.
• Abs spectrum:
• G+ve respiratory tract pathogens, macrolide-resistant
strains.
• Indicated in Community acquired pneumonia.
• M/C ADR: hepatotoxicity.

26. Other indications of Macrolides
• Diffuse pan-bronchiolitis
• Cystic fibrosis
• Acute bacterial sinusitis
• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Bronchiectasis
• Chronic bronchitis

27. LINCOSAMIDE ANTIBIOTICS

28. Clindamycin
• Clindamycin is a Lincosamide antibiotic.
• Its mechanism of action and spectrum of
activity is similar to erythromycin.
• It also inhibits protein synthesis by binding to
50S ribosome.
• Clindamycin inhibits most G+ve cocci and
may anaerobes.

29. Cont..
• It is well absorbed orally.
• It attains good concentration in neutrophils,
macrophages, skeletal and soft tissues.
• It is metabolised in liver with a t½ of 3 hr
and excreted in urine and bile.

30. Mechanism of Resistance
• Alteration of 50s ribosomal subunit by adenine
methylation.
• Chromosomal mutation of 50s ribosomal protein.
• Drug inactivation.

31. Indications
• Anaerobic and mixed infections (abdominal, pelvic
and lung abscess).
• Skin and soft tissue infections.
• Prophylaxis of SABE in penicillin allergic patients,
who undergo dental procedures.
• Alternative to doxycycline for supplementing
quinine/ artesunate in treating multi-drug resistant
malaria.
• Topically for infected acne vulgaris.

32. Indications
• Acute or chronical suppurative osteomyelitis ,
• Arthritis caused by susceptive organisms especially
Staphylococci aureus
• Aerobic G+ cocci infection
• Combination with pyrimethamine for AIDS-related
toxoplasmosis (600, 75)
• Combination with primaquine for AIDS-related
pneumocystis carinii pneumonia
• Dose:
• Adults: oral dose is 150–300 mg QID, 200–600 mg i.v. 8
hourly
• Children: oral dose is 3–6 mg/kg QID.

33. ADRs..
• rashes, urticaria, abdominal pain and
diarrhoea.
• Superinfection due to Clostridium
difficile can occur.
• It causes pseudomembranous
enterocolitis which can be fatal if not
treated timely. (The treatment should be
done by promptly stopping the drug and
giving oral metronidazole (alternatively
vancomycin) to treat it.
• Higher IV dose –neuromuscular
blockade
• Other :Impaired liver function ,
neutropenia, hypersensitivity

34. Lincomycin
• Lincomycin has similar antibiotic and toxic
properties to clindamycin with higher incidence of
diarrhoea and fatal colitis.
• It was used extensively before the introduction of
clindamycin.
• Rarely used nowadays.