What is the overview of first generation cephalosporins (e.g. cefazolin, cephalexin, cefadroxil) in treating infections?

First Generation Cephalosporins: Overview and Clinical Applications

First generation cephalosporins (cefazolin, cephalexin, cefadroxil) are excellent antibiotics for treating gram-positive infections, particularly those caused by Staphylococcus aureus and Streptococcus species, with limited but useful activity against some gram-negative organisms. These antibiotics remain cornerstone treatments for many common infections due to their efficacy, safety profile, and role in antimicrobial stewardship.

Antimicrobial Spectrum

Excellent Coverage:

• Gram-positive organisms:
  • Staphylococcus aureus (methicillin-susceptible)
  • Streptococcus pyogenes (Group A strep)
  • Streptococcus pneumoniae

Limited but Clinically Useful Coverage:

• Gram-negative organisms:
  • Escherichia coli
  • Proteus mirabilis
  • Klebsiella pneumoniae

Important Gaps in Coverage:

• Methicillin-resistant Staphylococcus aureus (MRSA)
• Enterococci
• Pseudomonas aeruginosa
• Anaerobes (including Bacteroides fragilis)
• Extended-spectrum beta-lactamase (ESBL) producing organisms

Key First Generation Agents

Cefazolin (IV)

• FDA-approved indications 1:
  • Respiratory tract infections
  • Urinary tract infections
  • Skin and skin structure infections
  • Bone and joint infections
  • Biliary tract infections
  • Septicemia
  • Endocarditis due to susceptible S. aureus
  • Surgical prophylaxis

Cephalexin (PO)

• FDA-approved indications 2:
  • Respiratory tract infections
  • Otitis media
  • Skin and skin structure infections
  • Bone infections
  • Genitourinary tract infections

Cefadroxil (PO)

• FDA-approved indications 3:
  • Urinary tract infections
  • Skin and skin structure infections
  • Pharyngitis/tonsillitis

Clinical Applications

First-line Uses:

• Skin and soft tissue infections (uncomplicated) 4, 5
• Surgical prophylaxis 5
• Mild diabetic foot infections without complicating factors 4, 5
• Uncomplicated urinary tract infections (particularly cephalexin and cefadroxil) 6

Second-line Uses:

• Respiratory infections in penicillin-allergic patients (non-anaphylactic) 2, 1
• Streptococcal pharyngitis in penicillin-allergic patients 3
  • Note: Unlike penicillin, cephalosporins have not been proven effective for rheumatic fever prophylaxis 2, 1, 3

Pharmacokinetic Considerations

• Cefazolin (IV): Longer half-life (1.8 hours) compared to many other IV antibiotics, allowing for q8h dosing 7
• Cephalexin (PO): Rapid absorption, 4 times daily dosing typical 2
• Cefadroxil (PO): Extended half-life allows for twice daily dosing, improving compliance 3, 6

Antimicrobial Stewardship Considerations

• First generation cephalosporins should be preferred over broader-spectrum agents when the infection is likely caused by susceptible organisms 5
• Using first-generation cephalosporins for appropriate indications helps preserve broader-spectrum antibiotics for more resistant infections 5, 7
• First-generation cephalosporins are classified in the WHO "Access" category, indicating they should be widely available as first-line options 5

Important Clinical Pearls

• Cross-reactivity with penicillin allergy occurs in approximately 10% of patients 5

• First-generation cephalosporins generally should not be used for:

  • Infections requiring gram-negative coverage beyond E. coli, Proteus, and Klebsiella 5
  • Anaerobic infections (require combination with metronidazole) 5
  • MRSA infections (require fifth-generation cephalosporins like ceftaroline) 5

• For empiric therapy of diabetic foot infections, first-generation cephalosporins may be appropriate for mild infections without complicating factors 4

Adverse Effects and Safety

• Generally well-tolerated with low toxicity 7, 8
• Most common adverse effects: gastrointestinal disturbances, hypersensitivity reactions
• Risk of Clostridioides difficile infection 5
• Dosage adjustments required in renal impairment 5

First-generation cephalosporins remain valuable antibiotics in the modern era of increasing resistance. Their targeted spectrum against gram-positive organisms with limited but useful gram-negative activity makes them excellent choices for many common infections, supporting antimicrobial stewardship efforts by avoiding unnecessary use of broader-spectrum agents.