What are the main antibiotic classes, their modes of action, and examples?

Antibiotic Classes, Mechanisms of Action, and Examples

β-Lactam Antibiotics

β-lactams are the most widely used antibiotic class, characterized by a β-lactam ring structure that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), ultimately causing bacterial autolysis. 1

Penicillins

• Mechanism: Inhibit cell wall synthesis by binding to PBPs in the bacterial cell wall, blocking peptidoglycan cross-linking and triggering autolysis 1
• Examples:
  • Amoxicillin: Most active oral β-lactam against streptococci including pneumococci; high-dose formulations (4 g/day adults, 90 mg/kg/day children) overcome penicillin resistance in S. pneumoniae 1
  • Amoxicillin/clavulanate: Addition of clavulanate (β-lactamase inhibitor) preserves amoxicillin activity against β-lactamase-producing organisms 1
  • Ampicillin/sulbactam: Parenteral β-lactam/β-lactamase inhibitor combination for moderate-severe infections 1
  • Piperacillin/tazobactam: Broad-spectrum coverage including Pseudomonas species 1

Cephalosporins

• Mechanism: Inhibit cell wall synthesis through PBP binding; modified to increase β-lactamase stability and broaden antimicrobial spectrum 1
• Classification by generation with varying activity:
  • First-generation (cefazolin, cephalexin): Good activity against staphylococci and streptococci 1
  • Second-generation (cefuroxime, cefoxitin): Expanded gram-negative coverage 1
  • Third-generation (ceftriaxone, cefotaxime, ceftazidime): Broad gram-negative activity; ceftazidime covers Pseudomonas 1
  • Fourth-generation (cefepime): Enhanced gram-positive and gram-negative coverage 2
• Note: Cephalosporins are inherently less active than amoxicillin against S. pneumoniae with baseline MICs fourfold higher 1

Carbapenems

• Mechanism: Inhibit cell wall synthesis with broadest spectrum β-lactam activity and high β-lactamase stability 1
• Examples:
  • Ertapenem (Group 1): For moderate-severe infections without Pseudomonas coverage 1
  • Meropenem, imipenem (Group 2): Broadest spectrum including Pseudomonas and multidrug-resistant organisms 1

Monobactams

• Mechanism: Inhibit cell wall synthesis; resistant to most β-lactamases 3
• Example: Aztreonam for gram-negative infections 3

Fluoroquinolones

• Mechanism: Inhibit bacterial DNA replication by targeting topoisomerase II (DNA gyrase) and topoisomerase IV, preventing DNA replication, transcription, repair, and recombination 4
• Examples:
  • Ciprofloxacin: Broad gram-negative activity including Pseudomonas; 500 mg orally for prophylaxis 1, 4
  • Levofloxacin: Respiratory fluoroquinolone with 99% activity against S. pneumoniae; 500 mg dose 1
  • Moxifloxacin: Enhanced gram-positive and atypical pathogen coverage 1, 2
• Clinical note: Respiratory fluoroquinolones (levofloxacin, moxifloxacin) have greatest in vitro activity against respiratory pathogens but should be reserved for specific indications per stewardship principles 1, 5

Macrolides/Azalides

• Mechanism: Inhibit bacterial protein synthesis by binding to 23S rRNA of the 50S ribosomal subunit, blocking transpeptidation and ribosomal assembly 6
• Examples:
  • Azithromycin: Concentrates in phagocytes (intracellular:extracellular ratio >30); effective against respiratory pathogens and atypical organisms 2, 6
  • Clarithromycin: For community-acquired pneumonia and respiratory infections 7, 2
  • Erythromycin: Original macrolide with variable activity (25-100% against common pathogens) 1, 2
• Resistance concern: Up to 44% of S. pyogenes and 74% of S. faecalis strains are tetracycline-resistant; culture and susceptibility testing recommended 8

Tetracyclines

• Mechanism: Bacteriostatic agents that inhibit protein synthesis by blocking the binding of aminoacyl-tRNA to the ribosomal acceptor site 8
• Examples:
  • Doxycycline: Virtually completely absorbed orally; serum half-life 18-22 hours; effective against atypical pathogens, rickettsial diseases, and some skin infections 2, 8
  • Minocycline: Similar spectrum to doxycycline 2
• Clinical note: Active against wide range of gram-positive and gram-negative organisms, but cross-resistance is common 8

Aminoglycosides

• Mechanism: Inhibit protein synthesis by binding to bacterial ribosomes 1
• Examples:
  • Gentamicin: 5 mg/kg IV single dose; often combined with β-lactams for serious gram-negative infections including Pseudomonas 1, 2
  • Tobramycin: 5 mg/kg IV single dose 1
  • Amikacin: 15 mg/kg IV single dose; reserved for resistant organisms 1

Glycopeptides

• Mechanism: Inhibit cell wall synthesis by binding to D-alanyl-D-alanine terminus of peptidoglycan precursors 2
• Examples:
  • Vancomycin: 1 g IV every 12 hours; for serious MRSA and resistant gram-positive infections 1, 2
  • Teicoplanin: Alternative glycopeptide for MRSA 1, 2
  • Dalbavancin, oritavancin: New lipoglycopeptides with insufficient evidence for routine DFI use 1

Oxazolidinones

• Mechanism: Unique mechanism inhibiting protein synthesis at an early stage by preventing 70S ribosomal initiation complex formation 2
• Examples:
  • Linezolid: Oral and parenteral formulations; effective against MRSA and VRE with unique mechanism avoiding cross-resistance 1, 2

Lincosamides

• Mechanism: Inhibit protein synthesis by binding to 50S ribosomal subunit 1
• Examples:
  • Clindamycin: 600 mg IV every 8 hours; effective against gram-positive cocci and anaerobes; 90-92% activity against S. pneumoniae 1

Sulfonamides/Trimethoprim

• Mechanism: Sequential blockade of folate synthesis pathway 1
• Examples:
  • Trimethoprim-sulfamethoxazole (TMP-SMX): One double-strength tablet orally every 12 hours; variable activity (20-75%) against respiratory pathogens 1

Other Agents

Metronidazole

• Mechanism: Disrupts DNA and inhibits nucleic acid synthesis in anaerobic bacteria 1
• Use: Anaerobic coverage, often combined with other agents for polymicrobial infections 1

Daptomycin

• Mechanism: Targets both membrane function and peptidoglycan synthesis through calcium-dependent membrane insertion 1, 9
• Use: Especially effective for staphylococcal infections including MRSA 1

Fosfomycin

• Mechanism: Inhibits early cell wall synthesis by blocking peptidoglycan precursor formation 9
• Use: Recently employed for multidrug-resistant gram-negative bacteria 9

Polymyxins (Colistin)

• Mechanism: Disrupt bacterial cell membranes 1, 9
• Use: Reserved for multidrug-resistant gram-negative infections including ESBL-producing organisms 1, 9

Key Clinical Considerations

Antibiotic selection should prioritize Access group agents (amoxicillin, doxycycline) as first-line options, reserving Watch group agents (fluoroquinolones, carbapenems) for specific indications where Access agents are inadequate, and Reserve group agents (colistin, tigecycline) only for multidrug-resistant organisms when all alternatives have failed. 5

• Shorter antibiotic courses (5 days) are recommended for common infections like pneumonia and COPD exacerbations, with extension based on clinical response rather than default longer durations 7, 5
• Local resistance patterns must guide empiric therapy selection 7
• β-lactam antibiotics remain clinically relevant due to high bacterial target specificity and low human toxicity despite increasing resistance 10