What is the recommended cefepime (intravenous) dosing regimen for an adult with bacterial pneumonia, including adjustments for renal function, typical treatment duration, and alternative agents if cefepime is unsuitable?

Cefepime Dosing for Pneumonia

Standard Dosing Regimen

For adults with bacterial pneumonia requiring empiric antipseudomonal coverage, cefepime should be dosed at 2 g IV every 8 hours. 1, 2

• This dosing applies to both community-acquired pneumonia (CAP) with pseudomonal risk factors and hospital-acquired/ventilator-associated pneumonia (HAP/VAP) 1, 2
• The 2 g every 8 hours regimen provides optimal pharmacokinetic/pharmacodynamic parameters for Gram-negative coverage, including Pseudomonas aeruginosa 1, 3

Renal Dose Adjustments

Cefepime requires immediate dose adjustment based on creatinine clearance (CrCl) to prevent neurotoxicity:

• CrCl >60 mL/min: 2 g IV every 8 hours (standard dose) 3
• CrCl 30-60 mL/min: 2 g IV every 12 hours 3
• CrCl 11-29 mL/min: 2 g IV every 24 hours 3
• CrCl <10 mL/min: 1 g IV every 24 hours 3
• Hemodialysis: 1 g after each dialysis session 3

The elimination rate constant correlates directly with CrCl (K₁₀ = 0.0027 × CrCl + 0.071 h⁻¹), making renal function the primary determinant of dosing 3

Treatment Duration

Treat for a minimum of 7 days for HAP/VAP and 5-7 days for severe CAP, with extension to 14-21 days only for documented Pseudomonas aeruginosa, Staphylococcus aureus, or Legionella pneumophila. 2, 4

• For uncomplicated HAP/VAP without resistant organisms, limit therapy to 7-8 days total to minimize resistance development 2
• Continue treatment until the patient is afebrile for 48-72 hours with clinical stability 2
• Do not extend therapy beyond 7-8 days without documented resistant pathogens, as this increases resistance risk without improving outcomes 2

Combination Therapy Requirements

Cefepime should NOT be used as monotherapy when Pseudomonas aeruginosa is suspected or documented:

• Combine cefepime 2 g IV every 8 hours with either levofloxacin 750 mg IV daily OR an aminoglycoside (amikacin 15-20 mg/kg IV daily) for dual pseudomonal coverage 2
• This dual coverage is mandatory for high-risk patients with septic shock, ARDS, or structural lung disease 2
• For severe CAP, combine cefepime with a macrolide (azithromycin 500 mg IV daily) or respiratory fluoroquinolone to cover atypical pathogens 1, 4

MRSA Coverage Considerations

When MRSA risk factors are present (prior MRSA infection, post-influenza pneumonia, cavitary infiltrates, recent hospitalization with IV antibiotics), add vancomycin 15 mg/kg IV every 12 hours or linezolid 600 mg IV every 12 hours to the cefepime regimen. 1, 4

• Cefepime alone does not provide MRSA coverage 1
• Adjust vancomycin dosing based on trough levels (target 15-20 mcg/mL for pneumonia) 4

Alternative Agents When Cefepime is Unsuitable

If cefepime cannot be used (allergy, resistance, unavailability), alternative antipseudomonal beta-lactams include:

• Piperacillin-tazobactam 4.5 g IV every 6 hours (first-line alternative) 1, 2, 5
• Ceftazidime 2 g IV every 8 hours 1, 2
• Meropenem 1 g IV every 8 hours 1, 2
• Imipenem 500 mg IV every 6 hours 1, 2
• Aztreonam 2 g IV every 8 hours (for beta-lactam allergic patients) 1

All alternatives require the same combination therapy approach for pseudomonal coverage 2

Critical Pitfalls to Avoid

• Never use cefepime monotherapy for documented or suspected Pseudomonas aeruginosa—always combine with a fluoroquinolone or aminoglycoside 2
• Adjust doses immediately for renal impairment to prevent drug accumulation and neurotoxicity, particularly in critically ill patients 3, 6
• Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients to allow pathogen-directed de-escalation 4
• Do not extend therapy beyond 7-8 days for HAP/VAP without documented resistant organisms, as prolonged treatment increases resistance without improving outcomes 2
• Ensure free drug minimum concentration to MIC ratio (fCmin/MIC) ≥2.1 for optimal clinical outcomes in Gram-negative pneumonia; ratios below this threshold significantly increase risk of clinical failure (OR=0.11,95% CI 0.02-0.67) 6

Pharmacokinetic Considerations for Critically Ill Patients

In critically ill patients with VAP, consider extended infusions (3-hour infusion of 2 g every 8 hours) to optimize time above MIC:

• Standard 2 g every 8 hours (3-hour infusion) achieves free drug concentrations above MIC for 50% of the dosing interval in 91.8%, 78.1%, and 50.3% of patients for MICs of 8,16, and 32 mcg/mL, respectively 3
• Central distribution volume correlates with total body weight (V₁ = TBW × 0.21 L/kg), requiring dose consideration in obese or cachectic patients 3