What are the recommended dosages of vancomycin, cefepime, and metronidazole for broad-spectrum antibiotic coverage?

Recommended Dosages for Broad-Spectrum Antibiotic Coverage with Vancomycin, Cefepime, and Metronidazole

For broad-spectrum antibiotic coverage in adults, vancomycin should be dosed at 15-20 mg/kg IV every 8-12 hours (not to exceed 2g per dose), cefepime at 1-2g IV every 8-12 hours, and metronidazole at 500mg IV every 8 hours. 1, 2

Vancomycin Dosing

Adult Dosing:

• Standard dosing: 15-20 mg/kg IV every 8-12 hours based on actual body weight
• Maximum dose: 2g per dose
• Target trough levels: 15-20 mg/L for serious infections
• Alternative regimen for empiric therapy: 60 mg/kg/day divided every 6 hours (for severe infections) 1

Pediatric Dosing:

• 40-60 mg/kg/day IV divided every 6-8 hours, not to exceed 2g daily 1

Key Considerations:

• Higher doses (15-20 mg/kg every 8 hours) are needed to achieve target trough concentrations of 15-20 mg/L for serious infections like pneumonia 3
• Standard 1g every 12 hours regimens often fail to achieve therapeutic troughs in critically ill patients 3
• Therapeutic drug monitoring is essential to minimize nephrotoxicity risk 4

Cefepime Dosing

Adult Dosing:

• Standard dosing: 1-2g IV every 8-12 hours
• Severe infections: 2g IV every 8 hours (up to 6g daily) 1

Pediatric Dosing:

• 100-150 mg/kg/day IV divided every 8-12 hours, not to exceed 6g daily 1

Key Considerations:

• Cefepime has broad-spectrum activity against gram-negative and some gram-positive organisms
• Dosing interval should be adjusted for renal impairment
• Higher doses are recommended for Pseudomonas infections

Metronidazole Dosing

Adult Dosing:

• Standard dosing: 500mg IV every 8 hours 2, 5
• Alternative: 1g IV every 12 hours for severe infections 1

Pediatric Dosing:

• 30 mg/kg/day divided into three doses (maximum 500 mg/dose) 2

Key Considerations:

• Excellent anaerobic coverage
• No dosage adjustment needed for renal impairment
• Can cause metallic taste and disulfiram-like reaction with alcohol

Clinical Applications for Broad-Spectrum Coverage

Empiric Therapy for Nosocomial Infections:

• Vancomycin + cefepime + metronidazole is appropriate for:
  • Healthcare-associated pneumonia with MRSA risk
  • Complicated intra-abdominal infections
  • Severe skin/soft tissue infections
  • Empiric coverage for neutropenic fever 1

Specific Indications:

1. Nosocomial endocarditis/bacteremia:

   • Vancomycin (15-20 mg/kg IV every 8-12h)
   • Plus cefepime (2g IV every 8h)
   • Consider adding gentamicin for synergy in prosthetic valve endocarditis 1

2. Complicated intra-abdominal infections:

   • Cefepime (2g IV every 12h) plus
   • Metronidazole (500mg IV every 8h) 5

3. Necrotizing soft tissue infections:

   • Vancomycin (15-20 mg/kg IV every 8-12h)
   • Plus broad-spectrum gram-negative coverage (cefepime)
   • Plus anaerobic coverage (metronidazole) 1

Common Pitfalls to Avoid

1. Underdosing vancomycin:

   • 1g every 12h regimens rarely achieve therapeutic troughs of 15-20 mg/L
   • Use weight-based dosing (15-20 mg/kg) rather than fixed doses 4, 3

2. Inadequate monitoring:

   • Obtain vancomycin trough levels before the 4th dose
   • Monitor renal function regularly during therapy

3. Inappropriate duration:

   • Reassess need for broad-spectrum coverage after 48-72 hours
   • De-escalate based on culture results when possible

4. Drug interactions:

   • Avoid concurrent nephrotoxic agents when possible
   • Monitor for C. difficile infection, especially with prolonged therapy 2

Remember that dosing may need adjustment based on specific patient factors including renal function, severity of infection, and patient-specific pharmacokinetics.