1. MACROLIDES AND OTHER
ANTIBIOTICS

2. MACROLIDE ANTIBIOTICS
• Group of antibiotics with a
macrocyclic lactone
structure to which one or
more deoxy sugars are
attached
• In 1950 the first drug of this
class was isolated:
Picromycin
• In 1952 Erythromycin and
Carbomycin were introduced
into clinic.
O
CH3
H3C
HO
CH3
HO
N
H3C
H3C
H3C
O
O
O
O
O
CH3
Picromycin
CH3
CH3

3. Macrolides: Erythromycin
• It was isolated from Streptomyces erythreus in 1952
• It was the first of these drugs to find clinical
application, both as a drug of choice and an
alternative to penicillin in individuals who are allergic
to β-lactam antibiotics
• Slightly water soluble
• Macrolides are stable in aqueous solutions at or
below room temperature. They are unstable in acidic
or basic conditions or at high temperatures.

4. Erythromycin: Mechanism of action
• Bacteriostatic at low but cidal at high concentrations
• Cidal action also depends on the organism and its
rate of multiplication
• More active in alkaline medium
• Acts by inhibiting bacterial protein synthesis
• Bind irreversibly to a site on the 50s subunit of the
ribosome and interferes with ‘translocation’

6. Erythromycin: Resistance
• Becoming a serious problem
• Several mechanisms are:
– Inability of organism to take up the antibiotic or presence of efflux
pump
– Decreased affinity
– Presence of plasmid associated erythromycin esterase
• Both clarithromycin and azithromycin show cross
resistance with erythromycin
• But telithromycin can be effective against macrolideresistant organisms

7. Pharmacokinetics
• Erythromycin base is acid labile but all others (newer)
are stable
• Given as enteric coated tablets
• Food delays absorption by retarding gastric emptying
• Its acid esters are better absorbed
• Widely distributed in the body except CSF
• Diffuses into prostatic fluid, accumulates in
macrophages

8. Pharmacokinetics
Cont…
• Concentrates in liver
• Inflammation allows greater tissue penetration
• 70-80% plasma protein bound
• Partly metabolized and excreted primarily in the
active form (some enterohepatic circulation)
• Renal excretion is minor (5%)
• Its plasma t1/2 is 1.5hr, but it persists longer in
tissues

9. Adverse effects
• Epigastric distress
• Cholistatic jaundice
• Ototoxicity (at high doses)
• Hypersensitivity

10. Interactions

11. Uses
• As an alternative to pencillin
– Strep. Inf, Diptheria, Tetanus, Syphylis and Gonorrhoea
• As a first choice drug for:
– Atypical pneumania
– Whooping cough
– Chancroid
• As a second drug choice:
–
–
–
–
Campylobactor enteritis
Legionnaire’s pneumonia
Chlamydia trachomitis
Pencillin resistant Staphylococcal infections

13. Roxithromycin
• Acid stable
• Good enteral absorption and tissue
penetration
• 95% plasma protein bound
• Has longer half life 12hrs

14. Clarithromycin
• Acid stable
• Bioavailability is 50% due to first pass metabolism
• Follows zero order kinetics
• Longer half life (3-6hrs), its metabolite is also active
• Antibacterial spectrum is wider:
– Micobacterium avium complex
– M. leprae
– Toxoplasma gondii

15. Azithromycin
• Extended spectrum
• Better tolerability
• More active against H.influenza but less active
against gram possitive cocci
• Rapidly absorbed from empty stomach
• Longest half life (3days)
• Spectrum is identical to clarithromycin, except that it
is less active against Staphylococci and Streptococci

16. Other antibiotics

17. Clindamycin
• Mechanism of action is same as that of erythromycin
• Resistant mechanisms are same as those of
erythromycin
• It inhibits most of the gram possitive cocci
• Highly active against a vareity of anaerobes, specially
B. fragilis
• Aerobic gram negative bacilli are not effective

18. Clindamycin
Cont…
• Absorption is good
• Distributes well but not to CSF and brain
• Excreted in urine and bile
• Plasma half life is 3hrs

19. Clindamycin
Cont…
Adverse effects:
• Skin rashes
• Diarrhoea and pseudomembranous entero colitis
(C.difficile)

20. Vancomycin
• Glycopeptide antibiotic
• Discovered in 1956 as a pencillin substitute
• Effective against MRSA, Strep.viridans, enterococci
and clost.difficile
• Acts by inhibiting cell wall phospholipid synthesis as
well as peptidoglycon polymerization
(transglycolation step)

21. Vancomycin
Pharmacokinetics:
• No absorption from oral route
• Slow IV infusion is employed for treatment of
systemic infections or for prophylaxis
• Metabolism is minimal
• 90-100% excreted through glomeruar filtration
Cont…

22. Vancomycin
Adverse effects:
• Fever, chills, phlebitis at the infusion site
• Flushing (red man syndrome)
• Dose related hearing loss
Cont…

23. Linezolid
• Was introduced recently to combat resistant
gram possitive organisms such as:
– MRSA and VRSA
– VR enterococcus faecium, E. faecalis
– Pencillin resistant streptococci

24. Linezolid
Cont…
Mech of action:
• Inhibits bacterial protein synthesis by inhibiting the
formation of 70s initiation complex

26. Linezolid
Restance:
• Decreased binding to the target site confers
resistance
Pharmacokinetics:
• Completely absorbed on oral administration
• IV preparations also available
• Widely distributed throughout the body
• Partly metabolized non enzymatically
• Excreted in urine
• Plasma half life is 5hrs
Cont…

27. Linezolid
Cont…
Side effects:
• Well tolerated
• GI upset, nausea, diarrhoea, headache and rash
• Thrombocytopenia (2%)

28. Polypeptide Antibiotics
• Low molecular weight cationic polypeptide antibiotics
• All are powerful bactericidal agents
• Not used systemically due to toxicity
• All are produced by bacteria
• Clinically used ones are:
– Polymyxin B
– Colistin
– Bacitracin