What is the recommended dosage of cefepime for treating sepsis from pneumonia in adults with normal renal function?

Cefepime Dosing for Sepsis from Pneumonia

For adults with sepsis from pneumonia and normal renal function, administer cefepime 2 g IV every 8 hours as a 30-minute infusion, with strong consideration for extended 3-4 hour infusions in critically ill patients to optimize pharmacodynamic target attainment. 1, 2

Standard Dosing for Septic Patients

• The FDA-approved dose for moderate to severe pneumonia is 1-2 g IV every 8-12 hours, but critically ill septic patients require the higher end of this range 2
• For sepsis specifically, 2 g every 8 hours is the recommended dose based on the increased clearance and expanded volume of distribution that occurs in critically ill patients 1
• Studies demonstrate that 37-44% of ICU patients fail to achieve therapeutic targets with standard dosing, necessitating higher initial doses 1

Pharmacodynamic Optimization

β-lactam antibiotics like cefepime achieve optimal efficacy when free drug concentrations remain above the pathogen MIC for the entire dosing interval (100% T>MIC) in severe infections like sepsis 3:

• Extended infusions over 3-4 hours (rather than standard 30-minute infusions) significantly improve target attainment, particularly for organisms with MIC ≥4 mg/L 1, 4
• Continuous infusion strategies may provide additional benefit in critically ill patients with sepsis, as demonstrated by meta-analyses showing independent protective effects 3
• A loading dose can be given as a rapid bolus initially, followed by extended infusions for subsequent doses 3

Special Considerations for Pseudomonas Coverage

If Pseudomonas aeruginosa is suspected or confirmed, use 2 g IV every 8 hours 1, 2:

• Doses exceeding 4 g daily may be required for Pseudomonas infections with elevated MICs 1
• For severe pneumonia specifically caused by P. aeruginosa, the 2 g every 8-hour regimen is explicitly recommended 1, 2
• Only 50-65% of patients achieve adequate coverage for pathogens with MIC ≥8 mg/L using standard dosing 5

Critical Monitoring Parameters

Therapeutic drug monitoring should be strongly considered in septic patients, especially those with fluctuating renal function 1:

• Target trough concentrations should not exceed 8× the pathogen MIC due to neurotoxicity risk 1
• Monitor for signs of neurotoxicity including confusion, encephalopathy, myoclonus, and seizures, particularly in patients with any degree of renal impairment 1, 5
• Two case reports documented non-convulsive seizure activity (confusion and muscle jerks) in patients with creatinine clearance <30 mL/min despite dose adjustment, with trough levels of 20-30 mg/L 5

Renal Dose Adjustments

The 2 g every 8-hour regimen applies ONLY to patients with creatinine clearance >60 mL/min 2:

• For CrCl 30-60 mL/min: reduce to 2 g every 12 hours 2
• For CrCl 11-29 mL/min: reduce to 2 g every 24 hours 2
• For CrCl <11 mL/min: reduce to 1 g every 24 hours 2
• For hemodialysis patients: 1 g on day 1, then 1 g every 24 hours (for febrile neutropenia/sepsis), administered after dialysis 2

Duration of Therapy

Treat for 10 days for pneumonia-related sepsis 2:

• This duration applies to moderate to severe pneumonia caused by S. pneumoniae, P. aeruginosa, K. pneumoniae, or Enterobacter species 2
• Clinical response should guide continuation, with frequent reassessment in patients not improving by day 3-5 1

Common Pitfalls to Avoid

• Do not use standard 30-minute infusions for critically ill septic patients with high-MIC organisms—extended infusions are superior 1, 4
• Do not assume standard dosing is adequate in ICU patients—nearly half fail to achieve therapeutic targets 1
• Do not overlook subtle neurotoxicity in renally impaired patients—symptoms may be attributed to septic encephalopathy rather than drug toxicity 5
• Do not use the lower 1 g dose for sepsis—this is inadequate for critically ill patients 1, 2