Saturday, October 12, 2024

Cephalosporins

Cephalosporins: Overview (quick reference table)

Cephalosporins are β-lactam antibiotics categorized into five generations, each with varying spectrums of activity. Their coverage extends to both Gram-positive and Gram-negative bacteria, with certain generations being more effective against specific pathogens.

1. First-Generation Cephalosporins

  • Examples: Cefazolin (IV), Cephalexin (oral)
  • Spectrum:
    • Gram-positive: Excellent coverage against MSSA and Streptococcus. No enterococcus 
    • Gram-negative: Limited, effective against E. coliProteus, and Klebsiella.
    • Anaerobes: No anaerobic coverage.
  • Key Notes:
    • Commonly used for surgical prophylaxis and skin infections.
    • Great for MSSA, but not effective against MRSA.
    • No CNS penetration!

2. Second-Generation Cephalosporins

  • Examples: Cefuroxime, Cefoxitin, Cefotetan
  • Spectrum:
    • Gram-positive: Similar to 1st generation, covers MSSA and Streptococcus. No enterococcus
    • Gram-negative: Extended to include H. influenzaeMoraxella, and more E. coli strains.
    • AnaerobesCefoxitin and Cefotetan provide some anaerobic coverage.
  • Key Notes:
    • Cefuroxime is commonly used for respiratory infections like pneumonia and sinusitis.
    • Cefoxitin and Cefotetan are used for intra-abdominal surgeries due to their anaerobic activity (less reliable nowadays).

3. Third-Generation Cephalosporins

  • Examples: Ceftriaxone, Ceftazidime
  • Spectrum:
    • Gram-positiveMSSA and Streptococcus (Ceftriaxone); limited Gram-positive coverage (Ceftazidime). No enterococcus 
    • Gram-negative: Broad, including EnterobacteriaceaeH. influenzae, and Neisseria.
    • Ceftazidime covers Pseudomonas, but lacks Gram-positive activity.
    • Anaerobes: No reliable anaerobic coverage.
  • Key Notes:
    • Ceftriaxone is the go-to for community-acquired pneumoniameningitis, gonorrhea, and Lyme. It requires no renal dose adjustment.
    • Ceftazidime is for Pseudomonas infections but lacks Gram-positive coverage.
    • Ceftriaxone does not cover resistant gram negatives and Pseudomonas.

4. Fourth-Generation Cephalosporins

  • Example: Cefepime (improved version of Ceftriaxone and Ceftazidime)
  • Spectrum:
    • Gram-positive: Similar to earlier generations, effective against MSSA and Streptococcus. No enterococcus 
    • Gram-negative: Broad coverage, including Pseudomonas and Enterobacteriaceae.
    • Anaerobes: No anaerobic coverage.
  • Key Notes:
    • Excellent for severe infections, including febrile neutropenia, sepsis, and pneumonia.
    • Good CNS penetration, making it effective for meningitis.
    • Covers Pseudomonas, making it a great broad-spectrum option for empiric therapy.
    • May cause seizures and encephalopathy with higher doses

5. Fifth-Generation Cephalosporins

  • Example: Ceftaroline
  • Spectrum:
    • Gram-positive: Broad, including MRSAMSSA, and Streptococcus. No enterococcus
    • Gram-negative: Extended coverage but no Pseudomonas activity.
    • Anaerobes: No anaerobic coverage.
  • Key Notes:
    • The only cephalosporin effective against MRSA.
    • Used for skin infections and pneumonia, particularly when MRSA is suspected.
    • No Pseudomonas or anaerobic coverage.

6. Cephalosporin/β-lactamase Inhibitor Combinations

  • Examples: Ceftazidime/Avibactam, Ceftolozane/Tazobactam
  • Spectrum:
    • Enhanced activity against ESBL-producing Gram-negative organisms, CRE.
    • Covers multi-drug resistant bacteria, including Pseudomonas.
  • Key Uses:
    • Reserved for serious infections due to multi-drug resistant organisms, especially in hospital settings.

Summary

  • First-Generation Cephalosporins: Great for MSSA and surgical prophylaxis, with limited Gram-negative activity.
  • Second-Generation Cephalosporins: Expanded Gram-negative coverage, particularly for respiratory infections. Some anaerobic coverage with Cefoxitin and Cefotetan.
  • Third-Generation Cephalosporins: Broader Gram-negative activity. Ceftriaxone is ideal for meningitis and pneumonia, while Ceftazidime covers Pseudomonas.
  • Fourth-Generation Cephalosporins: Cefepime, broad-spectrum, including Pseudomonas, but no anaerobic coverage. Used for severe infections. 
  • Fifth-Generation Cephalosporins: Ceftaroline, Effective against MRSA, but lacks Pseudomonas and anaerobic activity.

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