How are antibiotics classified?

Antibiotic Classification Systems

Antibiotics are classified using the WHO AWaRe framework, which categorizes all antibiotics into three groups—Access, Watch, and Reserve—based on resistance potential and appropriate use, serving as the primary global classification system for antimicrobial stewardship. 1, 2

WHO AWaRe Framework (Primary Classification)

The AWaRe system uses a traffic-light approach to guide prescribing behavior and stewardship efforts, with 257 antibiotics globally classified into these groups 1, 2:

Access Group (Green Light)

• Narrow-spectrum agents with favorable risk-benefit ratios and low resistance potential 1, 2
• Should be widely available, affordable, and used as first- or second-choice treatment for common infections 1, 2
• Have good clinical activity against commonly susceptible bacteria 1, 2
• Should be accessible in all healthcare facilities 1, 2

Watch Group (Orange Light)

• Broader-spectrum agents with higher resistance potential and greater toxicity concerns 1, 2
• Include highest priority critically important antimicrobials such as fluoroquinolones and carbapenems 1
• Should be key targets of antimicrobial stewardship and monitoring programs 1, 2
• Often associated with more adverse events, higher toxicity, and higher cost 1
• May be first-choice for some indications but second-choice for others, depending on available alternatives 1

Reserve Group (Red Light)

• Last-resort options for multidrug-resistant organisms when all other alternatives have failed 1, 2
• Only eight antibiotics identified in this group 1
• Show consistent activity against organisms resistant to first- or second-choice options 1
• Should be used exclusively for confirmed or suspected infections due to multidrug-resistant bacteria 1, 2
• Must be protected through intensive stewardship programs that monitor and report usage 1, 2

First-Choice vs. Second-Choice Classification

This independent classification layer operates alongside AWaRe 1, 2:

• First-choice antibiotics: Narrow-spectrum agents with benefits outweighing risks and relatively low resistance levels 1, 2
• Second-choice antibiotics: Broader-spectrum agents with higher reported resistance rates or less favorable risk-benefit ratios 1, 2
• This distinction signals preferred order for specific indications to health professionals, while AWaRe serves policymakers for stewardship targeting 1

Mechanism-Based Classification

Antibiotics can be organized by their mechanism of action 3, 4:

• Cell wall inhibitors: β-lactams (penicillins, cephalosporins, carbapenems, monobactams) that disrupt bacterial cell wall synthesis 5, 4
• Protein synthesis inhibitors: Aminoglycosides (like gentamicin) that bind prokaryotic ribosomes 6, 4
• Nucleic acid inhibitors: Fluoroquinolones (like levofloxacin) that inhibit DNA gyrase and topoisomerase IV 7, 4

Spectrum-Based Classification

Antibiotics are characterized by their range of activity 2:

• Gram-positive coverage: Active against organisms like Staphylococcus and Streptococcus species 7, 6
• Gram-negative coverage: Active against organisms like E. coli, Klebsiella, and Pseudomonas 7, 6
• Broad-spectrum: Active against both Gram-positive and Gram-negative bacteria 7, 6
• Acquired resistance alters spectrum patterns over time and location 2

Susceptibility Classification

Based on laboratory testing, bacteria are categorized as 2:

• Susceptible: Likely inhibited by usual achievable antibiotic concentrations 2
• Intermediate: May respond if antibiotic is concentrated at infection site or dosage increased 2
• Resistant: Unlikely to respond even with maximum doses 2

Cross-Resistance Patterns

• Complete or partial insusceptibility can occur within the same chemical class (β-lactams, aminoglycosides, macrolides) 2
• Associated resistance may affect multiple classes through mechanisms like impermeability or efflux 2
• Fluoroquinolones differ structurally from aminoglycosides, macrolides, and β-lactams, potentially remaining active against bacteria resistant to these other classes 7

Clinical Relevance Note

The traditional bacteriostatic versus bactericidal classification is unlikely to be clinically relevant for abdominal infections, skin and soft tissue infections, and pneumonia, though no conclusions can be drawn for meningitis, endocarditis, or neutropenia 8.