Can you list the cephalosporins according to each generation?

Cephalosporins by Generation

Cephalosporins are classified into five generations based on their antimicrobial spectrum, with first-generation agents having excellent gram-positive coverage, second and third-generation agents providing expanded gram-negative activity, and fourth and fifth-generation agents offering the broadest spectrum including resistant organisms.

First-Generation Cephalosporins

Parenteral:

• Cefazolin 1, 2, 3

Oral:

• Cephalexin 1, 2, 3
• Cefadroxil 1, 2, 3
• Cephradine 2

These agents maintain excellent activity against streptococci and staphylococci but have poor coverage for H. influenzae 1. Cefazolin notably has a unique side chain with very low cross-reactivity to penicillins despite being first-generation 3.

Second-Generation Cephalosporins

Parenteral:

• Cefuroxime 2
• Cefoxitin 4, 2

Oral:

• Cefuroxime axetil 1
• Cefprozil 1, 2, 1, 3
• Cefaclor 1, 2, 1, 3

These agents have twice-daily administration and significantly enhanced activity against β-lactamase-producing H. influenzae, M. catarrhalis, and S. aureus 1. However, cefaclor has inadequate activity against all β-lactamase-producing M. catarrhalis and carries a high prevalence of serum sickness-like reactions 1.

Third-Generation Cephalosporins

Parenteral:

• Ceftriaxone 4, 2, 3
• Ceftazidime 4, 2, 3
• Cefotaxime 2, 3
• Ceftizoxime 4, 2

Oral:

• Cefixime 1
• Ceftibuten 1, 3
• Cefpodoxime (axetil) 1, 3
• Cefdinir 1

Critical distinction: Cefixime and ceftibuten have poor activity against S. pneumoniae and are especially ineffective against penicillin-resistant strains—neither should be used for acute bacterial sinusitis 1. Cefpodoxime and cefdinir are suitable agents 1.

Ceftazidime and cefoperazone are specifically active against Pseudomonas 5. Ceftibuten has unique side chains making cross-reaction rates with penicillins exceedingly rare 3.

Fourth-Generation Cephalosporins

Parenteral:

• Cefepime 3, 5

Cefepime provides excellent activity against both gram-positive and gram-negative pathogens, including antibiotic-resistant Enterobacteriaceae 5.

Fifth-Generation Cephalosporins

Parenteral:

• Ceftaroline 4, 6
• Ceftobiprole 6

These are the only β-lactams active against MRSA 7. Ceftaroline has bactericidal activity against gram-positive and gram-negative pathogens, including MRSA and drug-resistant S. pneumoniae 6. In severe pneumonia, ceftaroline (600 mg every 12h) was superior to ceftriaxone 6.

Ceftobiprole has extended spectrum activity against MSSA, methicillin-resistant coagulase-negative staphylococci, penicillin and ceftriaxone-resistant S. pneumoniae, P. aeruginosa, and Enterobacteriaceae, but limited efficacy against MRSA 6. It is not approved for pneumonia in the US 6.

Key Clinical Pearls

• First-generation agents (especially cefazolin) are preferred for staphylococcal/streptococcal infections and surgical prophylaxis 2
• Second-generation agents are useful for β-lactamase-producing H. influenzae infections 1
• Third-generation agents represent reasonable alternatives to aminoglycosides for multiply drug-resistant gram-negative bacilli 8
• Cefazolin has unique properties: Despite being first-generation, it has a unique side chain with only 0.7% reaction rate in patients with unverified penicillin allergy 3