What are the different types of cephalosporins (a class of beta-lactam antibiotics) and their typical dosages?

Cephalosporin Classification and Typical Dosages

Cephalosporins are categorized into four generations based on their spectrum of antimicrobial activity, with each generation offering distinct advantages for treating specific bacterial infections. 1, 2

First-Generation Cephalosporins

First-generation agents provide the strongest activity against gram-positive organisms, particularly staphylococci and streptococci, but have limited gram-negative coverage. 3, 4

• Cephalexin (oral): 250-500 mg every 6 hours; for streptococcal pharyngitis and uncomplicated skin infections, 500 mg every 12 hours is acceptable 5

  • Pediatric dosing: 25-50 mg/kg/day in divided doses; for otitis media, 75-100 mg/kg/day in 4 divided doses 5
  • Maximum adult dose: 4 g daily 5

• Cefazolin (IV): Most commonly used first-generation parenteral agent, particularly effective against sensitive staphylococci and streptococci 3

  • Used in combination with metronidazole for mild-to-moderate intra-abdominal infections 6

Second-Generation Cephalosporins

Second-generation cephalosporins have enhanced activity against β-lactamase-producing organisms, particularly H. influenzae and M. catarrhalis, making them superior for respiratory tract infections. 7, 3

• Cefuroxime: 500 mg PO twice daily for outpatient infections; 1.5 g IV every 8 hours for pneumonia 7

  • Recommended for moderate-to-severe diabetic foot infections and intra-abdominal infections when combined with metronidazole 6

• Cefaclor: 500 mg PO three times daily 7

  • Important caveat: Higher risk of serum sickness-like reactions compared to other second-generation agents 7

• Cefprozil: 500 mg PO every 12 hours, with good activity against β-lactamase-producing organisms 7

• Cefoxitin: 1-2 g IV every 8 hours 7

  • Key advantage: Anaerobic coverage, making it useful for mixed infections including intra-abdominal and diabetic foot infections 6, 7

Third-Generation Cephalosporins

Third-generation agents provide excellent gram-negative coverage, including Enterobacteriaceae, and are the preferred cephalosporins for serious infections and those requiring CNS penetration. 1, 2

• Ceftriaxone: 1-2 g IV daily (once-daily dosing advantage) 3

  • Recommended for moderate-to-severe intra-abdominal infections with metronidazole 6
  • Used in diabetic foot infections for moderate-to-severe cases 6

• Cefotaxime: 1-2 g IV every 8 hours 6

  • Similar indications to ceftriaxone; recommended with metronidazole for intra-abdominal infections 6

• Ceftazidime: 2 g IV every 8 hours 6

  • Critical distinction: Anti-pseudomonal activity, making it essential for Pseudomonas coverage 1, 3
  • Used in diabetic foot infections with macerated ulcers or warm climate exposure where Pseudomonas is suspected 6

• Ceftizoxime: Described as the "workhorse" third-generation cephalosporin 1

Fourth-Generation Cephalosporins

Fourth-generation agents provide excellent activity against both gram-positive and gram-negative pathogens, including antibiotic-resistant Enterobacteriaceae. 1, 8

• Cefepime: 2 g IV every 8-12 hours 6
  • Offers broader spectrum than third-generation agents, particularly against resistant organisms 1, 8
  • Recommended for severe intra-abdominal infections 6

Advanced Cephalosporin Combinations

Newer β-lactam/β-lactamase inhibitor combinations provide enhanced coverage against multidrug-resistant organisms. 6

• Ceftazidime/avibactam: 2.5 g IV every 8 hours 6

  • Effective against carbapenem-resistant Enterobacteriaceae and difficult-to-treat Pseudomonas 6

• Ceftolozane/tazobactam: 1.5 g IV every 8 hours (3 g every 8 hours for hospital-acquired pneumonia) 6

  • Specifically indicated for multidrug-resistant Pseudomonas infections 6

Clinical Selection Algorithm

When selecting a cephalosporin, prioritize based on infection severity, anatomic site, and anticipated pathogens: 6

• Mild infections with gram-positive organisms: First-generation agents (cephalexin, cefazolin) 6

• Respiratory infections or β-lactamase producers: Second-generation agents (cefuroxime, cefprozil) 7, 3

  • Critical pitfall: First-generation cephalosporins have poor H. influenzae coverage and are inappropriate for respiratory infections 7

• Serious gram-negative infections or CNS involvement: Third-generation agents (ceftriaxone, cefotaxime) 6

  • For suspected meningitis: Third-generation cephalosporins are mandatory over second-generation agents 7

• Pseudomonas coverage required: Ceftazidime or cefepime 6, 1

• Anaerobic coverage needed: Cefoxitin (second-generation) or add metronidazole to other cephalosporins 6, 7

• Multidrug-resistant organisms: Fourth-generation agents or advanced combinations (ceftazidime/avibactam, ceftolozane/tazobactam) 6

Important Resistance Considerations

Bacterial resistance patterns must guide empiric therapy, particularly for B. fragilis and Enterobacteriaceae. 6

• B. fragilis demonstrates substantial resistance to cefoxitin and cefotetan; these should not be used alone when B. fragilis is likely 6

• Local susceptibility profiles should be reviewed before using ampicillin-based regimens due to increasing E. coli resistance 6

• Consider local resistance patterns for S. pneumoniae and H. influenzae when selecting empiric therapy 7