This document discusses several classes of antibiotics including macrolides, clindamycin, vancomycin, linezolid, and polypeptide antibiotics. It provides details on the mechanism of action, pharmacokinetics, resistance, uses, and side effects of erythromycin, clarithromycin, azithromycin, roxithromycin, clindamycin, vancomycin, linezolid, polymyxin B, colistin, and bacitracin.

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