Table of Contents

Antibiotics

Antibiotics are agents that either kill bacteria (bactericidal) or inhibit their growth (bacteriostatic). Their therapeutic success depends on selective toxicity — targeting structures or biochemical pathways unique to bacteria.

Human cells lack:

  • Peptidoglycan cell walls

  • 70S ribosomes

  • Bacterial DNA gyrase

  • Folic acid synthesis pathway

These differences allow targeted drug therapy without harming host cells.

Understanding antibiotics becomes much easier when organized by site of action rather than memorizing drug names.

I. Inhibitors of Cell Wall Synthesis

https://www.researchgate.net/publication/377213335/figure/fig1/AS%3A11431281216244027%401704631242390/Mechanism-of-beta-lactam-antibiotic-resistance-by-mutation-of-penicillin-binding-proteins.png

The bacterial cell wall is composed of peptidoglycan, a rigid structure formed by glycan chains cross-linked by peptides. Disruption of this structure leads to osmotic instability and bacterial lysis.

1. Beta-Lactam Antibiotics

Mechanism

Beta-lactams bind to penicillin-binding proteins (PBPs), inhibiting transpeptidation (cross-linking of peptidoglycan chains). This weakens the cell wall and causes cell rupture.

They are bactericidal and most effective against actively dividing bacteria.

A. Penicillins

Examples:
Penicillin G, Amoxicillin, Ampicillin, Piperacillin

Clinical Notes:

  • Penicillin G → Syphilis

  • Amoxicillin → Otitis media, sinusitis

  • Piperacillin → Pseudomonas coverage

Adverse Effects:
Allergic reactions (rash to anaphylaxis)

B. Cephalosporins

Examples by Generation:

  • 1st Gen: Cefazolin (good gram-positive coverage)

  • 3rd Gen: Ceftriaxone (strong gram-negative coverage)

  • 5th Gen: Ceftaroline (covers MRSA)

Each generation progressively increases gram-negative coverage.

C. Carbapenems

Examples: Imipenem, Meropenem

Broad-spectrum and resistant to many beta-lactamases. Used in severe hospital-acquired infections.

2. Glycopeptides

Vancomycin

Binds directly to D-Ala-D-Ala terminal of peptidoglycan precursors, preventing cell wall synthesis.

Clinical Importance:
Drug of choice for MRSA and serious gram-positive infections.

II. Protein Synthesis Inhibitors

 
https://cwoer.ccbcmd.edu/science/microbiology/lecture/unit2/control/images/aglycomisread_illus.jpg
Bacterial ribosomes are 70S (30S + 50S subunits), distinct from human 80S ribosomes.

1. 30S Subunit Inhibitors

Aminoglycosides

Examples: Gentamicin, Amikacin

Cause misreading of mRNA → defective proteins → bacterial death.

They are bactericidal and particularly effective against aerobic gram-negative organisms.

Major Toxicities:

  • Nephrotoxicity

  • Ototoxicity

Tetracyclines

Examples: Doxycycline, Tetracycline

Block attachment of aminoacyl-tRNA to ribosome.

Broad-spectrum and useful in atypical infections (e.g., Chlamydia, Mycoplasma).

Important Note:
Avoid in children → tooth discoloration.

2. 50S Subunit Inhibitors

Macrolides

Examples: Azithromycin, Clarithromycin

Inhibit translocation of peptide chain.

Used in respiratory infections and atypical pneumonia.

Clindamycin

Effective against anaerobic infections.

Chloramphenicol

Broad-spectrum but rarely used due to risk of aplastic anemia.

III. Inhibitors of Nucleic Acid Synthesis

 

https://journals.asm.org/cms/10.1128/ecosalplus.esp-0017-2019/asset/32e130d8-a789-4e9c-9dea-8fe300302e9e/assets/graphic/esp-0017-2019_fig_002.gifFluoroquinolones

Examples: Ciprofloxacin, Levofloxacin

Inhibit DNA gyrase and topoisomerase IV, preventing DNA replication.

Effective against gram-negative bacteria.

Adverse Effects:

  • Tendon rupture

  • QT prolongation

Rifampin

Inhibits bacterial RNA polymerase.

Essential in tuberculosis therapy.

IV. Antimetabolites (Folic Acid Inhibitors)

 
https://www.researchgate.net/publication/340981780/figure/fig1/AS%3A885343872106498%401588093836360/Design-strategy-and-general-structures-of-newly-synthesized-antimicrobial-DHPS-and-DHFR.png

Bacteria synthesize folate internally, making this pathway an excellent target.

Sulfonamides

Example: Sulfamethoxazole

Inhibit dihydropteroate synthase.

Trimethoprim

Inhibits dihydrofolate reductase.

Together (TMP-SMX), they block sequential steps, producing synergistic bactericidal action.

V. Drugs That Disrupt Cell Membrane

Polymyxins (Colistin)

Disrupt bacterial membrane integrity.

Reserved for multidrug-resistant gram-negative infections.

Mechanisms of Antibiotic Resistance

https://www.researchgate.net/publication/371010308/figure/fig2/AS%3A11431281161508162%401685021921503/Schematic-representation-of-biological-functions-of-bacterial-efflux-pumps-Efflux-pumps.pngResistance may occur through:

  • Beta-lactamase production

  • Altered target site

  • Efflux pumps

  • Reduced permeability

  • Enzymatic drug inactivation

Understanding resistance mechanisms is essential for rational prescribing.

Pharmacokinetic Considerations

  • Some antibiotics are concentration-dependent (e.g., aminoglycosides).

  • Others are time-dependent (e.g., beta-lactams).

  • Renal function must be considered in dosing.

  • Certain drugs penetrate CNS better (e.g., ceftriaxone).

Clinical Integration

In community-acquired pneumonia, empiric therapy often includes a macrolide or doxycycline. In suspected MRSA, vancomycin is added. In septic shock, broad-spectrum carbapenems may be initiated.

Drug choice depends on:

  • Site of infection

  • Likely organism

  • Resistance pattern

  • Patient factors

Conceptual Summary

Antibiotics work by targeting essential bacterial processes:

  1. Cell wall synthesis

  2. Protein synthesis

  3. DNA/RNA synthesis

  4. Metabolic pathways

  5. Cell membrane integrity

A mechanism-based approach transforms antibiotic pharmacology from memorization into understanding.