Classification of Antibiotics
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Classification of Antibiotics
Antibiotics can be classified along several dimensions: by chemical structure/pharmacophore, by mechanism of action, and by spectrum of activity. The sections below cover all three.
I. Classification by Mechanism of Action
This is the most pharmacologically meaningful classification. Antibiotics target six major biochemical pathways:
1. Cell Wall Synthesis Inhibitors
The most common mechanism of antibiotic activity. Bacteria have a rigid peptidoglycan cell wall that human cells lack, making it an ideal selective target.
A. Beta-Lactams (β-Lactams)
Named for their shared β-lactam ring. They bind penicillin-binding proteins (PBPs) - transpeptidases, transglycosylases, and carboxypeptidases that build and cross-link the peptidoglycan layer. Inhibiting PBPs activates autolysins that degrade the cell wall → bactericidal.
| Subclass | Examples | Notes |
|---|---|---|
| Penicillins | Penicillin G/V, Amoxicillin, Ampicillin, Oxacillin, Piperacillin | Natural, aminopenicillins, antistaphylococcal, antipseudomonal |
| Cephalosporins (1st gen) | Cephalexin, Cefazolin | Gram-positive coverage + limited Gram-negative |
| Cephalosporins (2nd gen) | Cefuroxime, Cefaclor, Cefoxitin, Cefotetan | Expanded Gram-negative (H. influenzae, Enterobacter); cephamycins have anaerobe activity |
| Cephalosporins (3rd gen) | Cefotaxime, Ceftriaxone, Ceftazidime | Broad Gram-negative incl. Pseudomonas |
| Cephalosporins (4th gen) | Cefepime, Cefpirome | Extended spectrum, β-lactamase stable |
| Cephalosporins (5th gen) | Ceftaroline | Active against MRSA |
| Carbapenems | Imipenem, Meropenem, Ertapenem, Doripenem | Broad-spectrum, cover most aerobes + anaerobes; resistant to most β-lactamases |
| Monobactams | Aztreonam | Narrow spectrum - only aerobic Gram-negative bacteria; safe in penicillin allergy |
| β-Lactamase Inhibitors | Clavulanic acid, Sulbactam, Tazobactam | Combined with penicillins to overcome β-lactamase resistance |
B. Glycopeptides
- Vancomycin, Teicoplanin - bind the D-Ala-D-Ala terminus of peptidoglycan precursors, preventing cross-linking. Active against Gram-positive organisms (including MRSA). Bactericidal.
C. Other Cell Wall Agents
- Bacitracin - inhibits lipid carrier recycling in cell wall synthesis; topical use
- Daptomycin - disrupts cell wall synthesis and depolarizes the cell membrane (Gram-positive only)
- Fosfomycin - inhibits MurA, an early step in peptidoglycan synthesis
- Cycloserine - inhibits D-Ala racemase/synthetase; used for tuberculosis
2. Cell Membrane Disruptors
These agents physically disrupt bacterial membrane integrity.
| Drug | Notes |
|---|---|
| Polymyxin B, Colistin (Polymyxin E) | Bind lipopolysaccharide (LPS) on Gram-negative outer membrane → disrupt membrane permeability. Bactericidal. Reserved for MDR Gram-negatives |
| Daptomycin | Calcium-dependent insertion into Gram-positive cell membranes → depolarization and rapid cell death |
3. Protein Synthesis Inhibitors (Ribosomal)
Target bacterial 70S ribosomes (vs. eukaryotic 80S), exploiting structural differences for selectivity.
| Subunit Targeted | Class | Examples | Effect |
|---|---|---|---|
| 30S subunit | Aminoglycosides | Gentamicin, Tobramycin, Amikacin, Streptomycin | Bactericidal; cause misreading of mRNA |
| 30S subunit | Tetracyclines | Doxycycline, Tetracycline, Minocycline, Tigecycline | Bacteriostatic; block tRNA attachment |
| 50S subunit | Macrolides | Erythromycin, Clarithromycin, Azithromycin | Bacteriostatic; block translocation |
| 50S subunit | Lincosamides | Clindamycin, Lincomycin | Bacteriostatic; block peptide elongation |
| 50S subunit | Chloramphenicol | Chloramphenicol | Bacteriostatic; inhibits peptidyl transferase |
| 50S subunit | Oxazolidinones | Linezolid, Tedizolid | Bacteriostatic; prevent 70S initiation complex formation (unique: targets 50S + 30S interaction) |
| 50S subunit | Streptogramins | Quinupristin/Dalfopristin | Bactericidal in combination; each component bacteriostatic alone |
4. Nucleic Acid Synthesis Inhibitors
A. DNA Gyrase/Topoisomerase Inhibitors
- Fluoroquinolones (Ciprofloxacin, Levofloxacin, Moxifloxacin, Norfloxacin): Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV → bactericidal. Broad spectrum.
| Generation | Examples | Coverage |
|---|---|---|
| 1st | Nalidixic acid | Gram-negative only |
| 2nd | Ciprofloxacin, Norfloxacin, Ofloxacin | Extended Gram-negative, some Gram-positive |
| 3rd | Levofloxacin | "Respiratory" fluoroquinolone - adds pneumococcal coverage |
| 4th | Moxifloxacin, Gemifloxacin | Enhanced Gram-positive + anaerobe coverage |
B. RNA Polymerase Inhibitors
- Rifamycins (Rifampicin/Rifampin, Rifabutin, Rifaximin): Inhibit bacterial RNA polymerase β-subunit → bactericidal. Key antitubercular and anti-MRSA agents.
C. DNA-Strand Breakage
- Metronidazole, Tinidazole (Nitroimidazoles): Reduced intracellularly to reactive intermediates that cause DNA strand breaks. Active against strict anaerobes and certain protozoa.
5. Folate Synthesis Inhibitors
Target sequential steps in bacterial folate synthesis (bacteria must synthesize folate; humans obtain it from diet).
| Drug | Target |
|---|---|
| Sulfonamides (Sulfamethoxazole, Sulfadiazine) | Inhibit dihydropteroate synthase (competitive inhibition of PABA) |
| Trimethoprim | Inhibits dihydrofolate reductase (DHFR) |
| Trimethoprim-Sulfamethoxazole (Co-trimoxazole) | Sequential/synergistic double block of folate pathway; bactericidal |
6. Mycobacterial-Specific Agents
Targeting unique features of mycobacterial cell walls:
| Drug | Mechanism |
|---|---|
| Isoniazid (INH) | Inhibits mycolic acid synthesis (InhA enzyme) |
| Ethambutol | Inhibits arabinosyltransferase (arabinogalactan synthesis) |
| Pyrazinamide | Disrupts membrane energy (mechanism not fully elucidated) |
| Bedaquiline | Inhibits ATP synthase |
| Delamanid | Inhibits mycolic acid synthesis |
II. Classification by Chemical Structure
| Structural Class | Key Members |
|---|---|
| β-Lactams | Penicillins, Cephalosporins (1st-5th gen), Carbapenems, Monobactams |
| Glycopeptides | Vancomycin, Teicoplanin, Oritavancin, Dalbavancin |
| Aminoglycosides | Gentamicin, Tobramycin, Amikacin, Streptomycin, Neomycin |
| Tetracyclines | Tetracycline, Doxycycline, Minocycline, Tigecycline (glycylcycline) |
| Macrolides | Erythromycin, Clarithromycin, Azithromycin, Roxithromycin |
| Fluoroquinolones | Ciprofloxacin, Levofloxacin, Moxifloxacin, Norfloxacin |
| Sulfonamides | Sulfamethoxazole, Sulfadiazine, Sulfisoxazole |
| Lincosamides | Clindamycin, Lincomycin |
| Oxazolidinones | Linezolid, Tedizolid |
| Rifamycins | Rifampicin, Rifabutin, Rifapentine |
| Nitroimidazoles | Metronidazole, Tinidazole, Ornidazole |
| Polymyxins | Polymyxin B, Colistin |
| Lipopeptides | Daptomycin |
| Streptogramins | Quinupristin + Dalfopristin |
| Nitrofurans | Nitrofurantoin (urinary antiseptic) |
| Chloramphenicol | Chloramphenicol |
III. Classification by Spectrum of Activity
| Spectrum | Definition | Examples |
|---|---|---|
| Narrow-spectrum | Active against a limited range of bacteria | Penicillin G (Gram-positive only), Aztreonam (aerobic Gram-negative only), Isoniazid (mycobacteria) |
| Broad-spectrum | Active against both Gram-positive and Gram-negative | Tetracyclines, Fluoroquinolones, Carbapenems, Chloramphenicol |
| Extended-spectrum | Enhanced activity via modification | Extended-spectrum penicillins (Piperacillin), 4th-gen cephalosporins |
IV. Bactericidal vs. Bacteriostatic
| Bactericidal (kills bacteria) | Bacteriostatic (inhibits growth) |
|---|---|
| β-Lactams, Aminoglycosides, Fluoroquinolones | Tetracyclines, Macrolides, Clindamycin |
| Glycopeptides (Vancomycin), Metronidazole | Chloramphenicol, Sulfonamides, Linezolid |
| Daptomycin, Polymyxins, Rifampicin | Trimethoprim |
Key principle: Bactericidal agents are preferred for immunocompromised patients, infective endocarditis, and meningitis where the host immune system cannot clear static bacteria.
V. Key Definitions (BOX 17.1 - Medical Microbiology 9e)
| Term | Definition |
|---|---|
| Antibacterial spectrum | Range of activity against bacteria; broad vs. narrow |
| Bacteriostatic | Inhibits growth but does not kill |
| Bactericidal | Kills bacteria |
| MIC (Minimum Inhibitory Concentration) | Lowest concentration that inhibits visible bacterial growth |
| MBC (Minimum Bactericidal Concentration) | Lowest concentration that kills ≥99.9% of bacteria |
Summary Diagram
ANTIBIOTICS
├── By MECHANISM
│ ├── Cell wall synthesis inhibitors (β-lactams, glycopeptides, bacitracin, fosfomycin)
│ ├── Cell membrane disruptors (polymyxins, daptomycin)
│ ├── Protein synthesis inhibitors
│ │ ├── 30S: aminoglycosides, tetracyclines
│ │ └── 50S: macrolides, clindamycin, chloramphenicol, linezolid
│ ├── Nucleic acid inhibitors
│ │ ├── DNA gyrase: fluoroquinolones
│ │ ├── RNA polymerase: rifamycins
│ │ └── DNA strand breaks: metronidazole
│ └── Folate synthesis inhibitors (sulfonamides, trimethoprim)
│
├── By STRUCTURE
│ (β-lactams, glycopeptides, aminoglycosides, tetracyclines, macrolides,
│ fluoroquinolones, sulfonamides, lincosamides, oxazolidinones, etc.)
│
└── By SPECTRUM
├── Narrow (penicillin G, aztreonam)
├── Broad (tetracyclines, fluoroquinolones, carbapenems)
└── Bactericidal vs. Bacteriostatic
Sources:
- Medical Microbiology 9e, Chapter 17 - Murray (Cell wall mechanisms, β-lactam classification, terminology box)
- Goodman & Gilman's Pharmacological Basis of Therapeutics - "Antimicrobial Chemotherapy: Classes and Actions"
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