Dr Sunil Kumar

1. Antibiotics and Antimicrobial
Agents
Dr Sunil Kumar
Assistant Professor
MMDU-Mullana

2. Layout
• Introduction
• Sources of A/b
• Types of A/b
• Target of A/b
• Mode of Action
• Antimicrobial Resistance

3. Intro..
• A/b - Drug used in the treatment & prevention
• of bacterial infections
• Bactericidal/ bacteriostatic
• Few show activity against parasites
– e.g. anti-malarial
• not effective against viruses
• antiviral drugs for viral infection

4. Synthesis
• A/b – Produced naturally
• A/m – synthetic
• Purpose - same
– Kill or prevent growth of m/o

5. Synthesis
• Beta-lactam antibiotics – e.g. penicillins
– Produced by fungus Penicillium
• Cephalosporins – (fungus Acremonium)
– Previously k/s Caphalosporium
• Carbapenems – thienamycin
• naturally derived from Streptomyces (GPB)

6. Synthesis
α-ketoglutarate + AcCoA
homocitrate
L-α-aminoadipic acid
L-lysine + β-lactam

7. Synthesis
• The Penicillium cells grown –
– fed-batch culture
• Cells are constantly subject to stress
• Required for penicillin production

8. Biosynthesis

9. Basic Structure of Penicillins

11. Penicillins
• Penicillins
– First medications effective against many bacterial
infections
– discovered in 1928 by Alexander Fleming
• Penicillin G or benzylpenicillin – IV
• Penicillin V or phenoxymethylpenicillin – Oral
• Procaine penicillin & Benzathine penicillin
– Intramuscular use

12. Members of Penicillin
• Natural penicillins (G,K,N,O,V)
• β-lactamase-resistant
• Aminopenicillins
• Carboxypenicillins
• Ureidopenicillins
• β-lactamase inhibitors

13. β-lactamase-resistant
• Methicillin
• Nafcillin
• Oxacillin
• Cloxacillin
• Dicloxacillin
• Flucloxacillin

14. Aminopenicillins
• Ampicillin
• Amoxicillin
• Pivampicillin
• Hetacillin
• Bacampicillin
• Metampicillin
• Talampicillin
• Epicillin

15. Carboxypenicillins
• Carbenicillin
• Ticarcillin
• Temocillin

16. Ureidopenicillins
• Mezlocillin
• Piperacillin

17. β-lactamase inhibitors
• Clavulanic acid
• Sulbactam
• Tazobactam

18. Mode of Action
• Bacteria constantly remodel their
peptidoglycan layer
• Beta lactam ring binds with DD-transpeptidase
• Inhibition the formation of crosslinks b/w
peptidoglycan layer
• Cell wall not synthesized
• Bacterial cell die

19. Classes of A/b
• Classified based on
– Mechanism of action
– Chemical structure
– Spectrum of activity

20. Classes of A/b
• Penicillins
• Cephalosporins
• Polymyxins

22. Target of A/b
• Bacterial functions or Growth processes
• Cell wall
– Penicillins & Cephalosporins
• Cell membrane (lipopolysaccharide)
– Polymyxin also k/s colistin
• Bacterial enzymes
– Rifamycins, quinolones & sulfonamides
– All bactericidal

23. Target of A/b
• Protein synthesis inhibitors
– Macrolides, lincosamides & tetracyclines
– usually bacteriostatic
– Aminoglycosides (exception)
• Transcription
– Rifampin
• Structure & function of DNA
– Quinolones, Nitrofurantoin, Nitrimidzole

24. Target of A/b
Target specific:
• Narrow-spectrum" antibiotics
– Target specific types of bacteria
• Broad-spectrum antibiotics
– Affect wide range of bacteria

26. Antimicrobial Resistance Development
• Enzymatic – beta-lactamases
• Non-enzymatic – efflux pumps & Porins
• PBPs