Antibiotics

2. • 1952 Erythromycin
• 1970s Acetylspiramycin
Medecamycin, Josamycin
• 1980s Clarithromycin
Roxithromycin
Azithromycin
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3. • Belong to the Polyketide class of natural
products.
• A group of antibiotics consisting of a
macrolide ring
• A large lactone ring to which one or more deoxy
sugars, are attached.
• The lactone ring can be either 14, 15 or 16
membered.
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4. • Naturally-occurring macrolide derived from
Streptomyces erythreus
• Problems with erythromycin
• Acid labile
• Narrow spectrum
• Poor GI tolerance
• Short elimination half-life
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5. Clarithromycin and Azithromycin
• Broader spectrum of activity
• Improved PK properties –
• Better bioavailability
• Better tissue penetration
• Prolonged half-lives
• Improved tolerability
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6. • Inhibits protein synthesis by reversibly
binding to the 50S ribosomal subunit
• Suppression of RNA-dependent protein
synthesis by inhibition of translocation of
mRNA
• Typically bacteriostatic activity
• Bactericidal at high concentrations against
very susceptible organisms
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7. 8/20/2016
RAHUL

8. 8/20/2016

9. Gram-Positive Aerobes :
Erythromycin & clarithromycin display the best activity
(Clarithro>Erythro>Azithro)
• Methicillin-susceptible Staphylococcus aureus
• Streptococcus pneumoniae (only PSSP) –
resistance is developing
• Group and viridans streptococci
• Bacillus sp.
• Corynebacterium sp.
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10. Gram-Negative Aerobes – Newer macrolides
with enhanced activity
(Azithro>Clarithro>Erythro)
• H. influenzae (not erythro),
• M. catarrhalis,
• Neisseria sp.
• Do NOT have activity against any Enterobacteriaceae
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11. Anaerobes – Upper airway anaerobes
Atypical Bacteria – All have excellent activity
• Legionella pneumophila - DOC
• Chlamydia sp.
• Mycoplasma sp.
• Ureaplasma
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12. Other Bacteria –
• Mycobacterium avium complex
(MAC – only A and C),
• Treponema pallidum,
• Campylobacter
• Borrelia, Bordetella
• Brucella
• Pasteurella
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13. Activity Erythro Azithro Clarithro
H. infuenzae ++ +++ ++
Moraxella
catarahalis
++ +++ ++
Mycoplasma ++ +++ ++
Legionella ++ +++ ++
Strepto/staph +++ ++ +++
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14. Absorption
Erythromycin – variable absorption, 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
regardless of presence of food
Azithromycin –acid stable; food decreases
absorption of capsules
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15. Distribution
 Extensive tissue and cellular
distribution
 clarithromycin and azithromycin with
extensive penetration
 Minimal CSF penetration
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16. Elimination
 Clarithromycin is the only macrolide partially
eliminated by the kidney (18% of parent and all
metabolites)
 Hepatically eliminated: ALL
 NONE of the macrolides are removed during
hemodialysis !....
 Variable elimination half-lives
 1.4 hours for erythr
3 to 7 hours for clarithro;
 68 hours for azithro
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17. • Gastrointestinal – up to 33 %
Nausea, vomiting, diarrhea, dyspepsia
Gastic pain, cramps
Most common with erythro; less with new agents
• Cholestatic hepatitis - rare
 > 1 to 2 weeks of erythromycin estolate
• Thrombophlebitis – IV Erythro and Azithro
Dilution of dose; slow administration
• Other: Ototoxicity (high dose erythro );
QTc prolongation;
Allergy
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18. Erythromycin and Clarithromycin ONLY–
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
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19. • ENT infections , Tonsillitis, URTI
• Mycoplasma pneumonie infections
• Legionnaires Disease
• Chlamydial infections (any macrolides)
• Diphtheria (erythromycin)
• Pertussis (erythromycin)
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20. • Strep/Staph Infections; alternatives in
patients allergic to Penicillin
• Prophylaxis against endocarditis in dental
procedures
• Campylobacter/ Helicobacter Infections
:clarithro
• Tetanus: in patients allergic to Penicillin
• Mycobacterial Infections: Clathri / Azithro Ist
choice
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21. “Drug of Choice” for
 Mycoplasma pneumoniae
Legionella pneumophila
 Chlamydia pneumoniae, C. trachomatis
Bordetella pertussis (whooping cough)
C. diphtheriae
Esters of erythromycin -sterate/estolate/ethylsuccinate
are resistant to inactivation.
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22. • Advantages :
• Broader spectrum, higher activity
• Orally effective
• High blood concentration
• Longer t 1/2
• Less toxicity
• Mainly used in respiratory tract infection
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23. • Strongest activity against mycoplasma pneumoniae.
• Less effective against gram (+) bacteria than erythro
/clarithro.
• More effective on Gram-negative bacteria,
H.influenzae, Legionella.
• Excellent action against Toxoplasma gondii
• Well tolerated
• T1/2 :35~48h once daily
• Mainly used in respitory tract infection
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24. • Excellent tissue concentration : 10- to 100-
fold higher conc. than serum
• prolonged persistence of good conc. in
cells
• 3- or 5-days therapy is possible (except for
severe Legionella pneumonia)
• Pregnant women infected with Scrub typhus :
Azithromycin can substitute for doxycycline
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25. • 1987 France
• Reaches highest blood concentration
• Bioavailability upto 72%~85%
• Respiratory tract infection and soft
tissue infection
• Low adverse effects
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26. • Has the strongest activity on Gram-positive bacteria,
Legionella pneumophila, Chlamydia pneumoniae and
H.pylori
• Good pharmacokinetic property
• Low toxicity
USES :
• Atypical mycobacterial infections (MAC)
• Resistant leprosy
• Toxoplasmosis
• H.Pylori induced peptic ulcers.
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27. • Erythromycin: 1-2 g/ day divided into 4
doses
• Clarithromycin: 250-500 mg twice a day.
• Azithromycin: 250 mg/ day
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