What is the recommended dosing regimen for Cefepime (Cefepime) for the treatment of Pseudomonas aeruginosa infections?

Cefepime Dosing for Pseudomonas aeruginosa Infections

For Pseudomonas aeruginosa infections, administer cefepime 2 g IV every 8 hours as the standard regimen, infused over 30 minutes, with treatment duration of 7-14 days depending on infection site and severity. 1

Standard Dosing Regimen

The FDA-approved dosing for moderate to severe pneumonia caused by Pseudomonas aeruginosa is 1-2 g IV every 8-12 hours for 10 days. 1 However, the most recent guideline evidence strongly supports using the higher end of this range:

• For carbapenem-resistant Pseudomonas aeruginosa (CRPA) susceptible to cefepime, use 2 g IV every 8-12 hours 2
• The 2 g every 8-hour regimen is specifically recommended when targeting Pseudomonas aeruginosa to optimize pharmacodynamic exposure 2, 3
• Infuse each dose over approximately 30 minutes 1

Pharmacodynamic Rationale

The critical pharmacodynamic target for cefepime against Pseudomonas aeruginosa is achieving free drug concentrations above the MIC for >60% of the dosing interval (fT>MIC >60%). 4 Patients who fail to achieve this target are 8.1 times more likely to experience microbiological failure. 4

• Cefepime doses of at least 2 g every 8 hours are required to achieve the >60% fT>MIC target against CLSI-susceptible Pseudomonas aeruginosa in patients with normal renal function 4
• The every 8-hour interval is superior to every 12-hour dosing for maintaining adequate drug concentrations above the MIC throughout the dosing interval 5, 4
• Against mucoid Pseudomonas strains, monotherapy may be insufficient even with optimal dosing 5

Site-Specific Dosing

Pneumonia (Moderate to Severe)

• 2 g IV every 8 hours for 10-14 days 2, 1
• For ventilator-associated or nosocomial pneumonia, maintain the 10-14 day duration 2

Complicated Intra-Abdominal Infections

• 2 g IV every 8-12 hours for 7-10 days (in combination with metronidazole) 1

Urinary Tract Infections

• Severe UTI: 2 g IV every 12 hours for 10 days 1
• The every 12-hour interval is acceptable for UTIs due to high urinary drug concentrations 1

Bloodstream Infections

• 2 g IV every 8 hours for 10-14 days 2

Combination Therapy Considerations

Add a second antipseudomonal agent (aminoglycoside or ciprofloxacin) for severe infections, nosocomial pneumonia, or high-risk patients. 2, 3

Indications for combination therapy include:

• Critically ill or septic shock patients 3
• Ventilator-associated or nosocomial pneumonia 3
• Structural lung disease (bronchiectasis, cystic fibrosis) 3
• Mucoid Pseudomonas strains 5
• Prior IV antibiotic use within 90 days 3

When combining with tobramycin, the enhanced killing activity is particularly beneficial against both mucoid and nonmucoid strains. 5, 6

Renal Dose Adjustments

For patients with creatinine clearance ≤60 mL/min, adjust dosing as follows per FDA labeling: 1

• CrCl 30-60 mL/min: 2 g every 12-24 hours (depending on infection severity)
• CrCl 11-29 mL/min: 2 g every 24 hours
• CrCl <11 mL/min: 1 g every 24 hours
• Hemodialysis: 1 g on day 1, then 500 mg-1 g every 24 hours

The initial dose should match that for normal renal function patients. 1

Pediatric Dosing (2 months to 16 years)

• For moderate to severe pneumonia due to Pseudomonas aeruginosa: 50 mg/kg every 8 hours (maximum 2 g per dose) 1
• For other infections: 50 mg/kg every 12 hours 1
• Do not exceed the recommended adult dose 1

Extended or Continuous Infusion

While the FDA label recommends 30-minute infusions 1, emerging pharmacodynamic data suggests potential benefits of extended infusion strategies:

• Continuous infusion maintains concentrations above the MIC throughout the dosing interval, optimizing time-dependent killing 6
• Extended infusions (3-4 hours) may be considered for severe infections or organisms with higher MICs 7
• However, standard intermittent dosing at 2 g every 8 hours remains the guideline-supported approach 2, 1

Critical Pitfalls to Avoid

• Never use the every 12-hour interval for severe Pseudomonas infections with normal renal function - this fails to maintain adequate fT>MIC, particularly against organisms with MICs ≥4 mcg/mL 5, 4
• Do not assume monotherapy is adequate for mucoid strains - these require combination therapy even when susceptibility testing shows sensitivity 5
• Avoid underdosing - using 1 g instead of 2 g significantly reduces the probability of achieving pharmacodynamic targets 4, 8
• Do not stop therapy prematurely - complete the full 10-14 day course for pneumonia and bloodstream infections to prevent relapse and resistance 2, 1