Is there an oral 4th generation (fourth-generation) cephalosporin available?

Oral Fourth-Generation Cephalosporins: Availability and Options

There are currently no oral fourth-generation cephalosporins available for clinical use. Fourth-generation cephalosporins such as cefepime are only available in parenteral (intravenous or intramuscular) formulations 1.

Fourth-Generation Cephalosporins: Overview

Fourth-generation cephalosporins are characterized by:

• Broad spectrum of activity against both gram-positive and gram-negative bacteria
• Enhanced stability against bacterial beta-lactamases
• Activity against Pseudomonas aeruginosa
• Improved penetration through the outer membrane of gram-negative bacteria

Currently available fourth-generation cephalosporins include:

• Cefepime - IV/IM only
• Cefpirome - IV/IM only (not available in all countries)

Available Oral Cephalosporin Options

While no oral fourth-generation cephalosporins exist, the following oral cephalosporins are available:

First-Generation Oral Cephalosporins:

• Cephalexin
• Cefadroxil

Second-Generation Oral Cephalosporins:

• Cefuroxime axetil
• Cefaclor
• Cefprozil

Third-Generation Oral Cephalosporins:

• Cefixime
• Cefpodoxime proxetil
• Ceftibuten
• Cefdinir 2

Clinical Implications

When oral therapy with advanced-generation cephalosporin coverage is needed:

1. Step-down therapy options:

   • Begin with IV fourth-generation cephalosporin (cefepime)
   • Step down to an oral third-generation cephalosporin when clinically appropriate

2. Alternative oral options:

   • Third-generation oral cephalosporins provide the broadest spectrum among oral cephalosporins
   • Fluoroquinolones (e.g., ciprofloxacin, levofloxacin, moxifloxacin) may be considered as alternatives when broader gram-negative coverage is needed 1

Important Considerations

• Third-generation oral cephalosporins have improved gram-negative coverage compared to first/second-generation agents but generally have weaker activity against Staphylococcus aureus 2
• None of the oral cephalosporins provide adequate anaerobic coverage; metronidazole should be added when anaerobic coverage is needed 3
• For infections requiring Pseudomonas coverage, oral options are limited to certain fluoroquinolones rather than cephalosporins 1
• Newer agents like ceftaroline (fifth-generation cephalosporin) are also only available in parenteral form 1

Conclusion

For patients requiring the spectrum of a fourth-generation cephalosporin but needing oral therapy, clinicians must either:

1. Use parenteral fourth-generation therapy until oral step-down is appropriate
2. Select an alternative oral agent based on the specific pathogens being targeted
3. Consider oral third-generation cephalosporins as the closest available option, recognizing their more limited spectrum compared to fourth-generation agents