Antibiotic Classification
Antibiotics are classified using multiple complementary systems: the WHO AWaRe framework (Access, Watch, Reserve groups based on resistance potential), mechanism of action (cell wall inhibitors, protein synthesis inhibitors, nucleic acid inhibitors), chemical structure (β-lactams, aminoglycosides, macrolides, etc.), and antimicrobial spectrum (Gram-positive, Gram-negative, anaerobic coverage). 1
WHO AWaRe Framework (Primary Clinical Classification)
The WHO categorizes 257 antibiotics into three stewardship-based groups that should guide prescribing decisions: 1
Access group: Narrow-spectrum agents with favorable risk-benefit ratios and low resistance levels that should be widely available and used as first- or second-choice treatment for common infections 1
Watch group: Broader-spectrum agents with higher resistance potential and greater toxicity concerns that should be key targets of antimicrobial stewardship and monitoring programs 1
Reserve group: Last-resort options for multidrug-resistant organisms that should be used exclusively for confirmed or suspected infections when other alternatives have failed 1
This framework prioritizes appropriate use over purely pharmacological properties, making it the most clinically relevant classification system for reducing antimicrobial resistance. 1
Mechanism of Action Classification
Antibiotics are organized by their bacterial target site: 2
Cell wall inhibitors: β-lactams (penicillins, cephalosporins, carbapenems, monobactams) that disrupt peptidoglycan synthesis by inhibiting transpeptidase and DD-carboxypeptidase enzymes 3, 4
Protein synthesis inhibitors: Aminoglycosides (bind 30S ribosomal subunit causing misreading of mRNA), macrolides, tetracyclines, and oxazolidinones 2, 3, 5
Nucleic acid inhibitors: Quinolones and rifamycins (rifampicin binds RNA polymerase β-subunit, preventing RNA messenger synthesis) 2, 3
This classification helps predict cross-resistance patterns and adverse effects, as drugs within the same mechanistic class often share resistance mechanisms. 2
Chemical Structure Classification
Antibiotics are grouped by their core chemical scaffold, with subclassification by generation reflecting chronological development and expanded spectrum: 2, 6, 5
β-lactams: Penicillins, cephalosporins (organized by generations 1-5), carbapenems, monobactams, and penems—all containing the β-lactam ring structure 4, 5
Aminoglycosides: Streptomycin, gentamicin, tobramycin, amikacin 5
Macrolides: Erythromycin, azithromycin, clarithromycin 5
Quinolones: Fluoroquinolones organized by generations 5
Other major classes: Tetracyclines, oxazolidinones, pleuromutilins, lipoglycopeptides, polymyxins, cyclic lipopeptides 5
Studying penicillins chronologically and cephalosporins by generation provides perspective on each agent's role, as later generations typically offer broader spectrum but higher resistance potential. 6
Antimicrobial Spectrum Classification
Antibiotics are characterized by their range of activity against specific bacterial types: 1
Gram-positive coverage: Activity against organisms like Streptococcus pneumoniae and Staphylococcus aureus 1
Gram-negative coverage: Activity against organisms like Escherichia coli and Pseudomonas aeruginae 1
Anaerobic coverage: Activity against obligate anaerobes 1
Atypical coverage: Activity against Mycoplasma, Chlamydophila, and Legionella 7
Critical caveat: Acquired resistance alters spectrum patterns over time and location, so local antibiograms must guide empiric therapy rather than relying solely on traditional spectrum classifications. 1
Susceptibility-Based Classification
Laboratory testing categorizes bacterial isolates relative to antibiotic concentrations: 1
Susceptible: Bacteria likely inhibited by usual achievable antibiotic concentrations at the infection site 1
Intermediate: Bacteria may respond if the antibiotic is concentrated at the infection site or dosage is increased 1
Resistant: Bacteria unlikely to respond even with maximum antibiotic doses 1
This classification directly impacts clinical decision-making, as intermediate results require either dose optimization or alternative agent selection. 1
Cross-Resistance Patterns
Understanding resistance mechanisms prevents predictable treatment failures: 1
Class-specific resistance: Complete or partial insusceptibility within the same chemical class (e.g., all β-lactams, all aminoglycosides, all macrolides) 1
Associated resistance: Resistance mechanisms like impermeability or efflux pumps may affect multiple unrelated classes simultaneously 1
Common pitfall: Prescribers often assume that switching within a chemical class overcomes resistance, but cross-resistance within classes is common and requires switching to a different mechanistic class. 1