Understanding Macrolides and Lincosamides in Antibiotic Therapy

1. Macrolides • A group of bacteriostatic antibiotics • Consist of a large lactone ring (usually having 14-16 atoms) • Deoxy sugars are attached by means of glycosidic bonds

2. Mostly obtained from Streptomyces • But some of them are semi-synthetically prepared • Erythromycin (isolated from Streptomyces erythreus

3. Tylosin is obtained from Streptomyces fradiae • Clarithromycin (semi-synthetic derivative of Erythromycin) • Tilmicosin • Azithromycin

4. Mechanism of action • Intra-cytoplasmic movement occurs via active transport mechanism • Gram positive bacteria accumulate about 100 times more antibiotics than do the gram negative bacteria • Bind to 50S-ribosomal subunit, generally they do not bind to mammalian ribosomes

5. Mechanism of action • Blockage of the translocation step of bacterial protein synthesis • Unavailability of A-site for the next coming amino-acyl tRNA • Ribosomal complex cannot move to the next codon

7. Bacterial resistance • Mutation in ribosomal structure • Efflux of drugs by an active pump mechanism • Production of drug-inactivating enzymes

8. Pharmacokinetics • Sufficient lipophilicity & rapid absorption from GIT • Enteric coating to avoid inactivation by the gastric HCl • Delayed absorption from rumeno-reticulum • Concentration in acidic fluids (milk, prostatic fluid) & some body cells (like macrophages)

9. Pharmacokinetics • Undergo ionization in acidic environment and remain in un-ionized state at alkaline PH • Can cross the placenta but not the blood brain barrier • Extensively metabolized in the liver through microsomal enzymes

10. Antimicrobial spectrum • They are often used as Penicillin substitutes • Effective against most aerobic and anerobic gram positive bacteria • But ineffective against gram negative bacteria (except Pasteurella & Haemophilus)

11. Antimicrobial spectrum Other susceptible micro-organisms: • Mycobacterium • Mycoplasma • Chlamydia • Rickettsiae Resistantmicro-organisms: • Enterobacteria • Protozoa • Fungi • Viruses

12. Clinical uses Erythromycin: • Most widely used macrolide • Covers mainly gram positive bacteria • Its spectrum is similar to that of Penicillin G • Drug of choice for Compylobacteriosis & • Rhodococcus equi infection in foals • Throat infection in humans • Stimulation of motilin receptors in intestine

13. Clinical uses Tylosin: • Hemorrhagic septicemia • Avian mycoplasmosis (CRD) • Pleuropneumonia Tilmicosin: • Pasteurellosis & Mycoplasmosis • High risk of cardiovascular side effects

14. Clinical uses Helicobacter pylori-induced gastric ulcer in humans: • Clarithromycin + Bismith subsalicylate + Cimitidine/Ranitidine Oleandomycin: • Used as feed additive for growth promotion in food producing animals

15. Adverse effects 1. Gastro-intestinal disturbances: • Characterized by diarrhea, regurgitation and epigastric pain • Less common in animals than in humans • Horses are more susceptible

16. Adverse effects 2. Hypersensitivity reactions: • Occasionally occur • Manifested by rashes, fever & skin eruptions

17. Contraindications & Drug interactions Contraindications: • Horses • Lactating animals Drug interactions: • Macrolides with Amphenicols/Lincosamides • Erythomycin with Warfarin/Carbamazepine

18. Lincosamides • Bacteriostatic antibiotics • Lincomycin is derived from Streptomyces lincolensis • Clindamycin is a semi-synthetic derivative of lincomycin • Pirlimycin

19. Mode of action • Exclusively bind to 50S-ribosomal subunit • Inhibit the bacterial protein synthesis

20. Antimicrobial spectrum • Their antibacterial spectrum resembles that of Macrolides • Generally they are more active against gram positive anaerobes • They are also effective against Toxoplasma and some strains of Mycoplasma but gram negative bacteria are resistant to them

21. Pharmacokinetics • Oral absorption is variable (60-90%) • Absorption after I/M administration is rapid • Cannot penetrate blood brain barrier appreciably even in case of meningitis • Being alkaline in nature they are released in the milk of lactating animals • Prolongation of duration of action by metabolites

22. Clinical uses • Occasionally used in veterinary practice Lincomycin: • Staphylococci • Streptococci • Anaerobes • Mycoplasma • Also used as a growth promoter in poultry

23. Clinical uses Clindamycin: • Peri-odontal disease • Osteomyelitis • Dermatitis (caused by Neospora caninum) • Canine toxoplasmosis

24. Adverse effects 1. Pseudomembranous colitis: • Horses are highly susceptible • Ruminants, rodents & humans are also affected • Characterized by enteritis, severe diarrhea, abdominal pain and mucus or blood discharge in faeces • Suppression of normal gut microflora

25. Adverse effects • Overgrowth of endotoxin-producing Clostridium difficile 2. Lincosamides can also induce ketosis in cattle 3. Inhibition of neuromuscular transmission leading to paralysis of skeletal muscles at high concentrations

26. Contraindications • Animals with fermenting GIT (like ruminants and horses) • Animals suffering from diarrhea • Lactating animals

27. Drug interactions • Skeletal muscle relaxants • General anesthetics • Gastro-intestinal adsorbents such as Kaolin • Amphenicols • Macrolides

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