Third-Generation Cephalosporins

Third-Generation Cephalosporins

Overview

  • Parenteral Agents:

    • Cefotaxime & Ceftriaxone: effective for community-acquired pneumonia

Spectrum of Activity

  • Expanded Gram-Negative Coverage:

    • Some agents can cross the blood-brain barrier which penetrate body fluids and tissues well.

    • These cephalosporins exhibit activity against various gram-negative bacteria, including:

      • Citrobacter

      • Serratia marcescens

      • Providencia

      • Beta-lactamase producing strains of Haemophilus and Neisseria.

    • HENMPEcKSSS Coverage:

      • Includes H. influenzae, Enterobacter, Neisseria, Moraxella catarrhalis, Proteus mirabilis, E. coli, K. pneumoniae, Serratia, Salmonella, and Shigella.

Resistance and Excretion

  • AmpC Beta-Lactamase Hydrolysis:

    • Susceptibility is compromised for Enterobacter as they can hydrolyze these agents.

  • Renal Excretion:

    • All are excreted through the kidney except ceftriaxone (which is mainly via the bile as mixed)

Antipseudomonal Cephalosporins

  • Cefoperazone, Cefotaxime, Ceftazidime, Ceftriaxone, Moxalactam

Specific Dosages and Use Cases

  • Ceftriaxone:

    • 2g every 12 hours for meningitis treatment, 2g once daily for endocarditis.

    • Excellent CNS penetration allows effective treatment of central nervous system infections.

    • Broad activity including treatment for pneumonia, meningitis, pyelonephritis, and gonorrhea

    • Has primarily mixed clearance (renal and biliary) with a half-life of approximately 6 hours.

    • Recommended regimen along with Azithromycin for gonococcal infections via the intramuscular (IM) route.

    • The drug is considered the new drug of choice (DOC) for typhoid fever.

  • Cefotaxime:

    • Similar in efficacy to Ceftriaxone but primarily renally cleared with a half-life of 1 hour.

  • Cefixime (PO):

    • 200 mg twice a day or 400 mg once a day for urinary tract infections

    • However, no longer recommended for uncomplicated gonococcal urethritis and cervicitis.

    • Noted to have lesser activity against pneumococci and poor activity against Staphylococcus aureus.

  • Ceftazidime:

    • Poor Gram-Positive Activity:

      • Limited efficacy against gram-positive organisms with absence of activity against Staphylococcus aureus.

    • It is the only third-generation cephalosporin with activity against Pseudomonas aeruginosa.

  • Ceftibuten:

    • 400 mg once a day; noted to have lesser activity against pneumococci and poor activity against Staphylococcus aureus.

  • Cefpodoxime proxetil or Cefditoren pivoxil:

    • 200-400 mg twice a day, with limited usage against certain organisms.