What are examples of fourth generation cephalosporins (4th gen cephalosporins)?

Examples of Fourth Generation Cephalosporins

Cefepime is the primary example of a fourth-generation cephalosporin currently available for clinical use. 1

Characteristics of Fourth Generation Cephalosporins

Fourth-generation cephalosporins have several distinguishing features that separate them from earlier generations:

• Broader spectrum of activity that encompasses both gram-positive and gram-negative bacteria, including activity against Pseudomonas aeruginosa 2, 3
• High stability against hydrolysis by most beta-lactamases, including those that inactivate third-generation cephalosporins 3, 4
• Low affinity for chromosomally-encoded beta-lactamases 2
• Rapid penetration into gram-negative bacterial cells 2, 4
• Activity against AmpC-producing organisms, which distinguishes them from third-generation cephalosporins 1

Available Fourth Generation Cephalosporins

• Cefepime - The most widely used and recognized fourth-generation cephalosporin 1, 2
• Cefpirome - Another fourth-generation cephalosporin mentioned in the literature, though less commonly used than cefepime 4, 5

Antimicrobial Spectrum

Fourth-generation cephalosporins are active against:

• Gram-positive bacteria:

  • Staphylococcus aureus (methicillin-susceptible isolates only) 2
  • Streptococcus pneumoniae 2
  • Streptococcus pyogenes (Group A streptococci) 2
  • Viridans group streptococci 2

• Gram-negative bacteria:

  • Enterobacter species 2, 4
  • Escherichia coli 2
  • Klebsiella pneumoniae 2, 4
  • Proteus mirabilis 2
  • Pseudomonas aeruginosa 2, 4
  • Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (controversial) 1

Clinical Applications

Fourth-generation cephalosporins are indicated for:

• Severe community-acquired infections requiring broader spectrum coverage 1
• Empiric treatment of high-severity infections 1
• Treatment of infections caused by ESBL-producing Enterobacteriaceae, though this use is controversial and carbapenems are generally preferred 1
• When combined with metronidazole, can be used for intra-abdominal infections requiring anaerobic coverage 1

Important Limitations

• Not active against most isolates of Enterococcus species 2
• Not active against methicillin-resistant Staphylococcus aureus (MRSA) 2
• Limited activity against Bacteroides fragilis and other anaerobes (requires combination with metronidazole for intra-abdominal infections) 1, 5
• Inactive against many isolates of Stenotrophomonas (formerly Xanthomonas maltophilia and Pseudomonas maltophilia) 2

Clinical Considerations

• Fourth-generation cephalosporins should be reserved for serious infections to minimize development of resistance 1
• For intra-abdominal infections, cefepime should be combined with metronidazole due to lack of anti-anaerobic activity 1
• Dosing adjustments are required in patients with renal impairment 2

Comparison to Other Cephalosporin Generations

• First and second-generation: Fourth-generation cephalosporins have significantly expanded gram-negative coverage while maintaining good gram-positive activity 6
• Third-generation: Fourth-generation cephalosporins have better activity against gram-positive organisms while maintaining excellent gram-negative coverage, including against some resistant strains 3, 6
• Fourth-generation cephalosporins are less likely to induce resistance compared to third-generation agents 4, 5

Fourth-generation cephalosporins represent an important antimicrobial class for treating serious infections, particularly when broad-spectrum coverage is needed or when dealing with resistant gram-negative pathogens.