What is the recommended dose of Cefepime (Cefepime) for treating Pseudomonas infections?

Cefepime Dosing for Pseudomonas aeruginosa Infections

For Pseudomonas aeruginosa infections, administer cefepime 2 g IV every 8 hours in adults with normal renal function, as this dosing regimen is necessary to achieve adequate pharmacodynamic targets against this pathogen. 1, 2

Adult Dosing Recommendations

Standard Dosing for Pseudomonas Infections

• Administer 2 g IV every 8 hours for moderate to severe pneumonia caused by Pseudomonas aeruginosa 1, 2
• The every 8-hour interval is critical—do not use the every 12-hour regimen for Pseudomonas infections, as this fails to maintain adequate drug concentrations above the MIC for sufficient time 3
• Infuse each dose over approximately 30 minutes 2

Alternative Dosing (Less Optimal)

• 2 g IV every 8-12 hours may be listed for carbapenem-resistant Pseudomonas aeruginosa (CRPA) susceptible to cefepime, but the every 8-hour interval is preferred 1
• The every 12-hour regimen should only be considered if the MIC is ≤4 mg/L and renal function is normal 4, 3

Pharmacodynamic Rationale

The critical pharmacodynamic target is maintaining free drug concentrations above the MIC for >60% of the dosing interval (fT>MIC >60%). 3

• Patients achieving fT>MIC ≤60% had a 77.8% microbiological failure rate, compared to 36.2% failure when fT>MIC was >60% 3
• Against Pseudomonas with MIC ≥8 mg/L (upper limit of susceptibility), only 45-65% of patients achieve adequate coverage with standard dosing 4
• For organisms with MIC >4 mg/L, consider therapeutic drug monitoring or alternative agents 4, 3

Pediatric Dosing

• 50 mg/kg/dose IV every 8 hours for moderate to severe pneumonia due to Pseudomonas aeruginosa (maximum 2 g per dose) 1, 2
• For other Pseudomonas infections in children: 50 mg/kg/dose every 12 hours may be adequate if infection is less severe 1, 2
• Do not exceed the recommended adult dose regardless of weight 2

Renal Dose Adjustments

Adjust dosing based on creatinine clearance to prevent both underdosing and neurotoxicity: 2, 4

• CrCL >60 mL/min: 2 g IV every 8 hours (no adjustment needed) 2
• CrCL 30-60 mL/min: 2 g IV every 12-24 hours 2
• CrCL <30 mL/min: Requires significant dose reduction; consider therapeutic drug monitoring 2, 4

Critical Pitfall: Neurotoxicity in Renal Impairment

• 10% of patients with renal impairment (CrCL <30 mL/min) developed cefepime accumulation causing non-convulsive neurological symptoms (confusion, muscle jerks) despite dose adjustment 4
• Trough concentrations of 20-30 mg/L were associated with neurotoxicity 4
• Monitor for neurological symptoms in any patient with reduced renal function and consider measuring cefepime levels if available 4

Treatment Duration

• Complicated urinary tract infections: 7-10 days 1, 2
• Hospital-acquired or ventilator-associated pneumonia: 10-14 days 1, 2
• Bloodstream infections: 10-14 days 1, 2
• Febrile neutropenia: 7 days or until resolution of neutropenia 2

Combination Therapy Considerations

For difficult-to-treat Pseudomonas aeruginosa (DTR-PA) or severe infections, monotherapy may be insufficient: 1

• Consider adding an aminoglycoside (amikacin 15 mg/kg IV daily) when susceptibility results support combination therapy 1
• Combination therapy enhanced killing of both mucoid and non-mucoid Pseudomonas strains in pharmacodynamic models 5
• For DTR-PA, newer agents like ceftolozane/tazobactam (3 g IV every 8 hours) or ceftazidime/avibactam (2.5 g IV every 8 hours) are preferred over cefepime 1

Key Clinical Caveats

• Plasma concentrations vary 2-3 fold at peak and up to 40-fold at trough between individuals, making some patients vulnerable to treatment failure despite standard dosing 4
• The every 12-hour regimen provides adequate coverage only when MIC ≤4 mg/L and CrCL is normal 4, 3
• Against mucoid Pseudomonas strains, monotherapy often fails regardless of adequate drug concentrations 5
• Extended or continuous infusion strategies may improve outcomes but require further clinical validation 6