This document discusses macrolide antibiotics, including their structures, mechanisms of action, antimicrobial spectra, pharmacokinetics, clinical uses, and mechanisms of resistance. Some key macrolides mentioned are erythromycin, clarithromycin, azithromycin, roxithromycin, and telithromycin. Macrolides inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit. They are mainly used for respiratory tract infections caused by atypical bacteria and some community-acquired pneumonia. Resistance can occur via efflux pumps or ribosomal modifications.

1. Dr. RAGHU PRASADA M S
MBBS,MD
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
SSIMS & RC.

2.  Multimembered lactone ring structure
 ERYTHROMYCIN- Streptmyces erythreus
 ROXITHROMYCIN, CLARITHROMYCIN,
AZITHROMYCIN- semisynthetic derivatives
 SPIRAMYCIN –streptomycin ambafaciens

4. 1. Inhibits protein synthesis by reversibly binding to the 50S
ribosomal subunit .
2. Suppression of RNA-dependent protein synthesis
3. Macrolides typically display bacteriostatic activity, but may
be bactericidal when present at high concentrations against
very susceptible organisms
4. Time-dependent activity
5. Selective toxicity

5. Advantage of newer macrolides:
Broader spectrum, higher activity, Orally effective
High blood concentration, Longer t ½,Less toxicity
Mainly used in respiratory tract infection

6. Active efflux (accounts for 80% ) – mef gene encodes for an
efflux pump which pumps the macrolide out of the cell
away from the ribosome; confers low level resistance to
macrolides
Altered target sites – encoded by the erm gene which alters
the macrolide binding site on the ribosome; confers high
level resistance to all macrolides, clindamycin .
Cross-resistance occurs between all macrolides

7. G+ve-S. pneumoniae, C.diptheriae
G-ve- L.pneumophila, B.pertusis
Anaerobes – activity against upper airway anaerobes
Atypical Bacteria – all macrolides have excellent
Activity against atypical bacteria including:
▪ Legionella pneumophila
▪ Chlamydia sp.
▪ Mycoplasma sp.
▪ Ureaplasma urealyticum
Other Bacteria – Mycobacterium avium complex (MAC – only A
and C), Treponema pallidum, Campylobacter, Borrelia,
Brucella, Pasteurella

8. Erythromycin –stearate, ethylsuccinate, lactobionate
As penicillin substitute in penicillin-allergic or resistant patients
with infections caused by
Staphylococci, Streptococci and Pneumococci
Pertussis，diphtheriae
Legionella and mycoplasma pneumonia
Clarithromycin- O methyl derivative
Active metabolite- 14-hydroxyclarithromycin
Has the strongest activity on Gram-positive bacteria,
legionella pneumophila, Chlamydia pneumoniae
H.pylori-clar + Ome +Amox
Has the strongest activity against Mycoplasma pneumoniae
Renal toxicity

9. Azithromycin
More effective on Gram-negative bacteria
Well tolerated, once daily
Mainly used in respiratory tract infection
Roxythromycin
 The highest blood concentration, F -72%~85%
 Respiratory tract infection and soft tissue infection
 Low adverse effects
 long acting, acid stable

10. Erythromycin – variable absorption (F = 15-45%);
food may decrease the absorption
Base: destroyed by gastric acid; enteric coated
Esters and ester salts: more acid stable
Clarithromycin – acid stable and well-absorbed (F =
55%) regardless of presence of food
Azithromycin –acid stable; F = 38%; food decreases
absorption of capsules

11. 1. Extensive tissue and cellular distribution – clarithromycin
and azithromycin with extensive penetration
2. Minimal CSF penetration
3. Clarithromycin is the only macrolide partially eliminated
by the kidney (18% of parent and all metabolites);
requires dose adjustment when CrCl < 30 ml/min
4. Hepatically eliminated: ALL
5. NONE of the macrolides are removed during
hemodialysis!
6. Variable elimination half-lives (1.4 hours for erythro; 3 to
7 hours for clarithro; 68 hours for azithro)

12.  Atypical pneumonia
 Legionnaire’s pneumonia
 Whooping cough
 Eradication of corynebacterium diptheriae
 Camphylobacter gastroenteritis
 Chancroid due to H.ducreyi
 Chlamydial conjunctivitis and urethritis

13. 1. Gastrointestinal – up to 33 %
Nausea, vomiting, diarrhea, dyspepsia
Most common with erythro; less with new agents
2. Cholestatic hepatitis – rare> 1 to 2 weeks of erythromycin
estolate
3. Thrombophlebitis – IV Erythro and Azithro
Dilution of dose; slow administration
4. Ototoxicity (high dose erythro in patients with RI); QTc
prolongation; allergy

14. Erythromycin and Clarithromycin – are inhibitors of
cytochrome p450 system in the liver; may increase
concentrations of:
Theophylline Digoxin, Disopyramide
Carbamazepine Valproic acid
Cyclosporine Terfenadine, Astemizole
Phenytoin Cisapride
Warfarin Ergot alkaloids

15. Anti-inflammatory property & Motilin receptor agonists
 Diffuse panbronchiolitis (DPB)
 Cystic fibrosis (CF)
 Acute bacterial sinusitis (ABS)
 Asthma
 Chronic obstructive pulmonary disease (COPD)
 Bronchiectasis
 Chronic bronchitis

16. Lincomycin Clindamycin
Antibacterial spectrum: lincosamides are active against
staphylococci, gram-positive and gram-negative anaerobes,
including Bacteroides fragilis.
Mechanism
Binding to 50s ribosome subunit and inhibiting protein synthesis
Pharmacokinetics
Absorbed well, Penetrate well into most tissues including
Bone but not CSF.
About 90% protein-bound
Excretion via the liver, bile, and urine

17.  Alteration of 50s ribosomal subunit by adenine
methylation
 Chromosomal mutation of 50s ribosomal protein
 Drug inactivation
Dose -150-300mg every 6th hourly

18. 1. Severe anaerobic infection
2. Acute or chronical suppurative osteomylitis ,
arthritis caused by susceptive organisms especially
Staphylococci aureus
aerobic G+ cocci infection
3. Combination with pyrimethamine for AIDS-related
toxoplasmosis (600, 75)
4. Combination with primaquine for AIDS-related
pneumocystis carinii pneumonia

19. Gastrointestinal effects: severe diarrhea and
pseudomembranous enterocolitis caused by Clostridium
difficile
Higher IV dose –neuromuscular blockade
Other :Impaired liver function , neutropenia, hypersensitivity

20.  TELITHROMYCIN, CETHROMYCIN
 Telithromycin is semisynthetic derivative of erythomycin
 Tighter binding to ribosomes
 Decreased incidence of resistance
 Longer post antibiotic effect
 T1/2- 13hrs
 Has activity against erythromycin resistant G+ve cocci
 Mainly for macrolide resistant CAP, chronic bronchitis
 Dose -800mg OD for 10 days

21.  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
Diarrhea, nausea
Drug interaction
Prolonged QT interval (cisapride, terfenadine)
Increased blood levels of theophylline, midazolam