What are examples of first generation cephalosporins?

First Generation Cephalosporins

First generation cephalosporins include cephalexin, cefazolin, and cefadroxil, which have excellent gram-positive coverage but limited gram-negative activity. 1

Common First Generation Cephalosporins

First generation cephalosporins are characterized by their excellent activity against gram-positive organisms with limited gram-negative coverage. The most commonly used examples include:

• Oral formulations:

  • Cephalexin (Keflex) 2
  • Cefadroxil 3

• Parenteral formulations:

  • Cefazolin 1, 4

Clinical Characteristics

Spectrum of Activity

First generation cephalosporins have:

• Excellent activity against gram-positive organisms including:
  • Streptococci
  • Methicillin-susceptible Staphylococcus aureus (MSSA)
• Limited activity against gram-negative organisms 1
• No activity against enterococci 4

Pharmacokinetic Properties

• Cephalexin: Rapidly absorbed orally, typically requires 4 times daily dosing due to shorter half-life 1
• Cefadroxil: Has an extended half-life allowing for twice daily dosing, which may improve compliance 1, 5
• Cefazolin: IV formulation with longer half-life (1.8 hours) compared to many other IV antibiotics, allowing for q8h dosing 1

Comparative Efficacy

Recent research has shown that cefadroxil and cephalexin have similar in vitro activity against MSSA, with identical MIC50 values of 2 μg/mL and MIC90 values of 4 μg/mL 6. This suggests that cefadroxil could be considered an alternative to cephalexin, with the advantage of less frequent dosing.

Clinical Applications

First generation cephalosporins are commonly used for:

• Skin and soft tissue infections
• Mild diabetic foot infections without complicating factors 1
• Surgical prophylaxis 4
• Treatment of staphylococcal and streptococcal infections in patients allergic to penicillins (except those with history of anaphylaxis, angioedema, or urticaria) 7, 4

Important Limitations

• First-generation cephalosporins such as cephalexin are inactive in vitro against Borrelia burgdorferi and are ineffective clinically for Lyme disease 7
• They have no activity against enterococci, which may lead to superinfection with these organisms during treatment 4
• Cross-reactivity may occur in patients with history of penicillin allergy, particularly those with history of anaphylaxis, angioedema, or urticaria 7

Adverse Effects

Common adverse effects include:

• Gastrointestinal disturbances
• Hypersensitivity reactions
• Increased risk of Clostridioides difficile infection 1

Dosing Considerations

• Dosage adjustments are required in patients with renal impairment 1, 3
• Cephalexin can be administered as 500 mg 2-3 times daily 5
• Cefadroxil can be administered as 500 mg twice daily, potentially improving adherence 5

First generation cephalosporins remain valuable antimicrobials for specific indications, particularly for gram-positive infections, despite the development of newer generations with broader spectrum activity.