What is a straightforward approach to classifying antibiotics?

Antibiotics Classification: The WHO AWaRe Framework

The most straightforward approach to classifying antibiotics is the WHO AWaRe framework, which categorizes antibiotics into Access, Watch, and Reserve groups based on their resistance potential and clinical importance for antimicrobial stewardship. 1

The AWaRe Classification System

The WHO AWaRe framework uses a traffic-light approach to antibiotics classification:

1. Access (Green) - First-line antibiotics that:

   • Have good clinical activity against commonly susceptible bacteria
   • Show lower resistance potential than other groups
   • Should be widely available in all healthcare facilities
   • Examples: amoxicillin, trimethoprim-sulfamethoxazole, doxycycline

2. Watch (Orange) - Second-line antibiotics that:

   • Have higher risk of selecting for antibiotic resistance
   • Should be targets of antimicrobial stewardship programs
   • Are associated with more adverse events and toxicities
   • Often come at a higher price
   • Examples: fluoroquinolones, macrolides, carbapenems

3. Reserve (Red) - Last-resort antibiotics that:

   • Should only be used for confirmed or suspected multidrug-resistant infections
   • Are preserved for when other alternatives are inadequate or have failed
   • Should be protected and prioritized in stewardship programs
   • Examples: colistin, linezolid, some newer cephalosporins

Alternative Classification Methods

1. By Mechanism of Action

This classification organizes antibiotics based on how they kill or inhibit bacteria 2, 3, 4:

• Cell Wall Synthesis Inhibitors:

  • β-lactams (penicillins, cephalosporins, carbapenems, monobactams)
  • Glycopeptides (vancomycin, teicoplanin)
  • Others (fosfomycin, bacitracin)

• Protein Synthesis Inhibitors:

  • 30S ribosomal subunit inhibitors (aminoglycosides, tetracyclines)
  • 50S ribosomal subunit inhibitors (macrolides, lincosamides, chloramphenicol)

• Nucleic Acid Synthesis Inhibitors:

  • DNA synthesis inhibitors (fluoroquinolones)
  • RNA synthesis inhibitors (rifampin)

• Metabolic Pathway Inhibitors:

  • Folic acid synthesis inhibitors (trimethoprim, sulfonamides)

• Cell Membrane Disruptors:

  • Polymyxins (colistin)
  • Daptomycin

2. By Chemical Structure

Antibiotics can be grouped by their structural similarities:

• β-lactams: Share a β-lactam ring structure

  • Penicillins (ampicillin, amoxicillin)
  • Cephalosporins (1st to 5th generation)
  • Carbapenems (meropenem, imipenem)
  • Monobactams (aztreonam)

• Macrolides: Large lactone rings (azithromycin, clarithromycin)

• Tetracyclines: Four fused rings (doxycycline, minocycline)

• Aminoglycosides: Amino-modified sugars (gentamicin, amikacin)

• Fluoroquinolones: Fluorinated quinolone structure (ciprofloxacin, levofloxacin)

3. By Spectrum of Activity

• Narrow-spectrum: Target specific types of bacteria

  • Gram-positive focused (vancomycin, clindamycin)
  • Gram-negative focused (aztreonam)
  • Anaerobe focused (metronidazole)

• Broad-spectrum: Effective against many bacterial types

  • Extended-spectrum penicillins
  • Later-generation cephalosporins
  • Carbapenems
  • Some fluoroquinolones

Clinical Application of Antibiotic Classification

Practical Examples

1. Skin and Soft Tissue Infections:

   • First choice (Access): Dicloxacillin, cefalexin
   • Second choice (Watch): Clindamycin
   • MRSA coverage: Vancomycin, linezolid (Reserve) 1

2. Bacterial Diarrhea:

   • First choice (Access): Trimethoprim-sulfamethoxazole
   • Second choice (Watch): Azithromycin, ciprofloxacin 1

Antibiotic Mechanisms Simplified

• β-lactams (penicillins, cephalosporins): Block cell wall synthesis by binding to penicillin-binding proteins (PBPs) 2
• Macrolides (azithromycin): Bind to the 23S rRNA of the bacterial 50S ribosomal subunit, blocking protein synthesis 5
• Cephalosporins: Inhibit cell wall synthesis, with different generations having expanded gram-negative coverage 6

Common Pitfalls in Antibiotic Classification

• Confusing generations of cephalosporins: Remember that higher generations generally have broader gram-negative coverage but may have reduced gram-positive activity
• Assuming all antibiotics in a class have identical spectra: Individual drugs within classes may have important differences in coverage
• Overlooking resistance mechanisms: MRSA is resistant to all β-lactams except newer anti-MRSA cephalosporins (ceftaroline)
• Forgetting pharmacokinetic differences: Some antibiotics concentrate in specific tissues (e.g., azithromycin concentrates in phagocytes and fibroblasts) 5

Conclusion

The WHO AWaRe framework provides the most clinically relevant classification system for antibiotics today, focusing on antimicrobial stewardship and resistance potential. Understanding additional classification methods based on mechanism, structure, and spectrum enhances clinical decision-making and helps combat antimicrobial resistance.