What are the alternative cephalosporins (e.g. cefuroxime axetil, cefixime, ceftriaxone) and their dosing regimens for various infections?

Alternative Cephalosporins and Their Dosing Regimens for Various Infections

Cephalosporins are classified by generations, with each offering different antimicrobial coverage profiles, and should be selected based on the suspected pathogen and infection site.

Second-Generation Cephalosporins

Cefuroxime Axetil (Oral)

• Respiratory Tract Infections:

  • Community-acquired pneumonia: 500 mg PO twice daily for 7-10 days 1, 2, 3
  • Acute bronchitis: 250 mg PO twice daily for 10 days 4
  • Pharyngitis/tonsillitis: 250 mg PO twice daily for 5-10 days 2
  • Sinusitis: 250 mg PO twice daily for 5-10 days 2
  • Otitis media: 250 mg PO twice daily for 5-10 days 2

• Urinary Tract Infections:

  • Uncomplicated UTI: 250 mg PO once daily for 10 days 5
  • Complicated UTI: 250 mg PO twice daily 2

• Skin and Soft Tissue Infections:

  • 250-500 mg PO twice daily for 5-10 days 2

• Lyme Disease:

  • Early stage (erythema migrans): 500 mg PO twice daily for 14-21 days 2

Cefuroxime (IV)

• Moderate to Severe Infections:
  • 750 mg to 1.5 g IV every 8 hours for 5-10 days 6
  • Bone and joint infections: 1.5 g IV every 8 hours 6
  • Bacterial meningitis: Up to 3 g IV every 8 hours 6
  • Surgical prophylaxis: 1.5 g IV just before surgery 6

Third-Generation Cephalosporins

Cefixime (Oral)

• Respiratory Tract Infections:

  • Acute bronchitis: 400 mg PO once daily for 10 days 4
  • Community-acquired pneumonia: 400 mg PO once daily 7

• Urinary Tract Infections:

  • Uncomplicated UTI: 400 mg PO once daily 8

• Gonorrhea:

  • Uncomplicated: 400 mg PO as a single dose 8

Ceftriaxone (IV/IM)

• Respiratory Tract Infections:

  • Community-acquired pneumonia: 1-2 g IV/IM once daily or 2 g IV every 12 hours 7
  • Severe pneumonia: 2 g IV once daily 7

• Meningitis:

  • 2 g IV every 12 hours 7

• Skin and Soft Tissue Infections:

  • 1-2 g IV/IM once daily 7

• Gonorrhea:

  • Uncomplicated: 1.5 g IM as a single dose at 2 different sites with 1 g oral probenecid 6

• Infective Endocarditis:

  • 100 mg/kg/day IV divided every 12 hours or 80 mg/kg/day IV every 24 hours (up to 4 g daily) 7

Dosing Adjustments for Special Populations

Renal Impairment (Cefuroxime)

• CrCl >20 mL/min: Standard dose
• CrCl 10-20 mL/min: 750 mg every 12 hours
• CrCl <10 mL/min: 750 mg every 24 hours 6

Pediatric Dosing (Cefuroxime)

• Children >3 months: 50-100 mg/kg/day IV divided every 6-8 hours
• Severe infections: 100 mg/kg/day (not exceeding adult dose)
• Bone/joint infections: 150 mg/kg/day divided every 8 hours
• Bacterial meningitis: 200-240 mg/kg/day IV divided every 6-8 hours 6

Comparative Efficacy and Selection Criteria

When choosing between cephalosporins, consider:

1. Spectrum of Activity:

   • First-generation (cephalexin): Good for gram-positive coverage, poor for H. influenzae 8
   • Second-generation (cefuroxime): Balanced coverage of gram-positive and some gram-negative organisms 8
   • Third-generation (cefixime, ceftriaxone): Enhanced gram-negative coverage, variable gram-positive activity 8

2. Specific Pathogen Considerations:

   • For S. pneumoniae: Cefpodoxime = ceftriaxone > cefuroxime > cephalexin 8
   • For H. influenzae: Third-generation > second-generation > first-generation 8
   • For MRSA: All typical cephalosporins ineffective; consider ceftaroline (fifth-generation) 8

3. Route of Administration:

   • Oral options: Cefuroxime axetil, cefixime (highest generation available orally) 8
   • IV/IM options: Cefuroxime, ceftriaxone (longer half-life allows once-daily dosing) 6

4. Adverse Effects:

   • Cefuroxime axetil has fewer gastrointestinal adverse events (10%) compared to cefixime (18%), particularly diarrhea (5% vs 15%) 4

Common Pitfalls and Caveats

• Resistance Concerns: Resistance rates vary significantly between generations, with first-generation cephalosporins showing up to 96% resistance among viridans group streptococci versus 17% for third-generation 8

• Cross-Reactivity: Patients with severe penicillin allergies may experience cross-reactivity with cephalosporins

• Oral Bioavailability: Cefuroxime axetil has approximately 68% bioavailability when taken with food 1

• Duration of Therapy: For most respiratory infections, 5-7 days is sufficient if the patient becomes afebrile within 48 hours and has no more than one sign of clinical instability 7

• Sequential Therapy: For hospitalized patients with pneumonia, consider IV cefuroxime (750 mg 2-3 times daily for 2-5 days) followed by oral cefuroxime axetil (500 mg twice daily for 3-8 days) 2