How are antibiotics classified?

Antibiotic Classification

Antibiotics are classified using multiple complementary systems: the WHO AWaRe framework (Access, Watch, Reserve), chemical structure classes (β-lactams, aminoglycosides, macrolides, etc.), mechanism of action (cell wall synthesis inhibitors, protein synthesis inhibitors, etc.), spectrum of activity (narrow vs. broad), and clinical susceptibility categories (susceptible, intermediate, resistant).

WHO AWaRe Framework (Primary Clinical Classification)

The WHO AWaRe system represents the most clinically relevant modern classification for guiding antibiotic selection and stewardship 1:

Access Group (Green Light)

• Narrow-spectrum agents with favorable risk-benefit ratios and low resistance potential 1
• Should be widely available, affordable, and first-line choices for common infections 2
• Examples include amoxicillin, ampicillin, benzylpenicillin, gentamicin, and cloxacillin 2
• These antibiotics have good clinical activity against commonly susceptible bacteria 2

Watch Group (Orange Light)

• Broader-spectrum agents with higher resistance potential, more adverse events, and greater costs 1
• Often serve as first- or second-choice options for specific common infectious syndromes 1
• Major targets for antimicrobial stewardship programs 1
• Examples include fluoroquinolones, carbapenems, and third-generation cephalosporins (cefotaxime, ceftriaxone) 2

Reserve Group (Red Light)

• Last-resort options for confirmed or suspected multidrug-resistant organisms (MDROs) 1
• Should only be used when other alternatives have failed or are inadequate 2
• Highest priority for antimicrobial stewardship monitoring 1

The WHO has classified 257 antibiotics globally into AWaRe groups, with 41 listed as essential medicines 1

First-Choice vs. Second-Choice Classification

This independent classification layer helps clinicians prioritize agents for specific infections 1:

• First-choice antibiotics: Usually narrow-spectrum with favorable risk-benefit ratios and relatively low resistance levels 1
• Second-choice antibiotics: Generally broader-spectrum with higher reported resistance rates or less favorable risk-benefit ratios 1

These categories are independent of AWaRe grouping and apply primarily to specific clinical indications 1

Chemical Structure Classification

Antibiotics are grouped by their core molecular structure 3, 4:

β-Lactam Antibiotics

• Share a common β-lactam ring structure and mechanism of action 3, 4
• Subclasses include:
  • Penicillins 3, 4
  • Penicillinase-resistant penicillins 3
  • Extended-spectrum penicillins 3
  • Cephalosporins (multiple generations) 3, 4
  • Carbapenems 3, 4
  • Monobactams 3, 4

Other Major Chemical Classes

• Aminoglycosides 1
• Macrolides 1
• Fluoroquinolones 2
• Glycopeptides 1

Cross-resistance typically occurs within the same chemical class (e.g., among β-lactams or macrolides), though resistance mechanisms like impermeability or efflux can affect multiple classes 1

Mechanism of Action Classification

Antibiotics are categorized by their primary cellular target 5:

1. Inhibitors of bacterial cell wall biosynthesis (e.g., β-lactams inhibit cell wall synthesis by binding penicillin-binding proteins) 6, 5, 4
2. Inhibitors of bacterial protein synthesis 5
3. Inhibitors of nucleic acid metabolism 5
4. Membrane-active antibiotics 5

Spectrum of Activity Classification

Spectrum characterizes the range of activity against various bacterial species or groups 1:

• Gram-positive coverage 1
• Gram-negative coverage 1
• Aerobic vs. anaerobic activity 1
• Narrow-spectrum vs. broad-spectrum 1

Acquired resistance can alter the spectrum pattern over time and varies by geographic location 1

Clinical Susceptibility Classification

Bacteria are classified based on their response to antibiotics using standardized breakpoints 1:

Susceptible (Sensitive)

• Infection highly likely to respond to standard dosing regimens 1
• Benefits outweigh risks at achievable concentrations 1

Intermediate

• Variable or indeterminate response to therapy 1
• May respond if antibiotic concentrates at infection site or dosage is increased 1
• Provides technical buffer for organisms with MICs near breakpoints 1

Resistant

• Two definitions exist 1:
  • Microbiological resistance: Organisms possess resistance mechanisms (phenotypic or genotypic), qualified as low-level, moderate, or high-level 1
  • Clinical resistance: Infection highly unlikely to respond even to maximum doses 1

Breakpoints are specific MIC or zone diameter values used to assign these clinical categories 1

Bactericidal vs. Bacteriostatic Classification

• Bactericidal agents: Kill bacteria (e.g., β-lactams, aminoglycosides) 6, 4
• Bacteriostatic agents: Inhibit bacterial growth without killing 7

This distinction has limited clinical relevance for most serious infections (pneumonia, skin/soft tissue, intra-abdominal), as clinical cure and mortality rates show no significant difference between bactericidal and bacteriostatic agents 7

Common Pitfalls

• Do not assume AWaRe classification determines first- vs. second-choice status—these are independent systems 1
• Avoid using Watch or Reserve antibiotics empirically when Access group agents are appropriate, as this drives resistance 1, 2
• Recognize that low-level microbiological resistance may still be clinically susceptible 1
• Do not rely solely on bactericidal vs. bacteriostatic classification for treatment decisions in most infections 7