1. Introduction to Antibiotics

Antibiotics are chemical substances produced by microorganisms (bacteria, fungi) or synthesized chemically that inhibit the growth of or destroy other microorganisms at low concentrations.

They are mainly used to treat bacterial infections.

2. History of Antibiotics

1928 – Alexander Fleming discovered Penicillin from Penicillium notatum.
1940s – Mass production of penicillin began.
After that, many classes of antibiotics were discovered.

3. Classification of Antibiotics

Antibiotics are classified based on:

A) Based on Mechanism of Action

1. Cell Wall Synthesis Inhibitors

They inhibit peptidoglycan formation in bacterial cell wall.

Examples:

Penicillins
Cephalosporins
Carbapenems
Monobactams
Vancomycin

👉 These are bactericidal drugs.

2. Protein Synthesis Inhibitors

They act on bacterial ribosomes (30S or 50S).

a) 30S Ribosomal Inhibitors

Aminoglycosides
Tetracyclines

b) 50S Ribosomal Inhibitors

Macrolides
Chloramphenicol
Clindamycin
Linezolid

👉 Mostly bacteriostatic (except aminoglycosides – bactericidal).

3. Nucleic Acid Synthesis Inhibitors

Fluoroquinolones → inhibit DNA gyrase
Rifampicin → inhibits RNA polymerase
Metronidazole → damages DNA

4. Antimetabolites (Folic Acid Inhibitors)

Sulfonamides
Trimethoprim

They inhibit folic acid synthesis required for bacterial growth.

B) Based on Spectrum of Activity

1. Broad Spectrum Antibiotics

Act against both Gram-positive and Gram-negative bacteria.
Examples:

Tetracycline
Chloramphenicol
Amoxicillin

2. Narrow Spectrum Antibiotics

Act against specific bacteria only.
Examples:

Penicillin G
Vancomycin

C) Based on Effect on Bacteria

1. Bactericidal

Kill bacteria.
Examples:

Penicillins
Cephalosporins
Aminoglycosides
Fluoroquinolones

2. Bacteriostatic

Inhibit growth.
Examples:

Tetracycline
Macrolides
Chloramphenicol

4. Mechanism of Action (Detailed)

1. Inhibition of Cell Wall Synthesis

Bacteria have peptidoglycan in cell wall.
Beta-lactam antibiotics bind to Penicillin Binding Proteins (PBPs).
Prevent cross-linking → weak cell wall → cell lysis.

Selective toxicity:
Human cells do not have cell walls → safe target.

2. Inhibition of Protein Synthesis

Bacterial ribosome = 70S (30S + 50S)
Human ribosome = 80S

So antibiotics selectively act on bacteria.

Aminoglycosides → misreading of mRNA
Tetracyclines → block tRNA attachment
Macrolides → inhibit translocation

3. Inhibition of DNA/RNA Synthesis

Fluoroquinolones inhibit DNA gyrase → prevent replication.
Rifampicin inhibits RNA polymerase → no transcription.

4. Antimetabolite Action

Sulfonamides resemble PABA.
Block folic acid synthesis.
Humans obtain folic acid from diet → selective toxicity.

5. Resistance to Antibiotics

Antibiotic resistance is a major global problem.

Mechanisms of Resistance:

Enzyme production
- Beta-lactamase destroys beta-lactam ring.
Alteration of target site
- Mutation in PBPs.
Efflux pump
- Drug pumped out of bacteria.
Reduced permeability
- Drug cannot enter cell.

6. Factors Affecting Antibiotic Action

Dose
Route of administration
Patient immunity
Site of infection
pH of environment
Drug interactions

7. Adverse Effects of Antibiotics

Hypersensitivity reactions (Penicillins)
Nephrotoxicity (Aminoglycosides)
Ototoxicity (Aminoglycosides)
Hepatotoxicity (Rifampicin)
Bone marrow suppression (Chloramphenicol)
Photosensitivity (Tetracycline)
Superinfection (due to destruction of normal flora)

8. Superinfection

When broad-spectrum antibiotics destroy normal flora → opportunistic organisms grow.

Example:

Fungal infections (Candida)

9. Combination Therapy

Used to:

Prevent resistance (e.g., Tuberculosis treatment)
Broaden spectrum
Synergistic action
Reduce toxicity