Recommended Dosing for Cefepime-Tazobactam
The recommended dose of cefepime-tazobactam is 2 grams of cefepime with 2 grams of tazobactam administered intravenously every 8 hours with a 90-minute infusion time for patients with normal renal function. 1
Dosing Based on Renal Function
Cefepime-tazobactam dosing should be adjusted according to renal function:
- Normal renal function to augmented clearance (CrCl ≥60 mL/min): 2g/2g IV q8h with 90-minute infusion
- Moderate renal impairment (CrCl 30-59 mL/min): 1g/1g IV q8h
- Severe renal impairment (CrCl 15-29 mL/min): 500mg/500mg IV q8h
- End-stage renal disease (CrCl 8-14 mL/min): 500mg/500mg IV q12h
- Hemodialysis patients: 500mg/500mg IV q12h with an additional dose after each dialysis session 1
For patients with high to augmented renal clearance (CrCl 120-180 mL/min), a prolonged 4-hour infusion of the standard dose is recommended to maintain adequate drug concentrations. 1
Clinical Applications
Cefepime-tazobactam has demonstrated efficacy against various infections, including:
- Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP)
- Complicated urinary tract infections
- Intra-abdominal infections
- Bloodstream infections
This combination is particularly valuable for treating infections caused by ESBL-producing organisms that may be resistant to piperacillin-tazobactam. 2
Pediatric Dosing
While specific pediatric dosing for cefepime-tazobactam is not well established in the guidelines, cefepime alone is dosed as follows:
- Neonates with gestational age <36 weeks: 30 mg/kg IV q12h
- Neonates with gestational age ≥36 weeks: 50 mg/kg IV q12h
- Children: 50 mg/kg IV q8h for Pseudomonas infections (maximum 2g per dose) 3
Comparative Efficacy
Recent research shows that cefepime-tazobactam has activity comparable to carbapenems against Enterobacterales (97.6% vs. 97.0% susceptibility) and greater than piperacillin-tazobactam (88.0% susceptibility). Against Pseudomonas aeruginosa, cefepime-tazobactam inhibited 82.7% of isolates at ≤8 mg/L, which was higher than meropenem (76.0%) or piperacillin-tazobactam (76.4%). 2
Duration of Therapy
The duration of therapy with cefepime-tazobactam depends on the infection type:
- Complicated urinary tract infections: 5-10 days
- Intra-abdominal infections: 5-10 days
- Hospital-acquired or ventilator-associated pneumonia: 10-14 days
- Bloodstream infections: 10-14 days 3
Important Considerations
- Cefepime-tazobactam is a novel combination being developed specifically to address infections caused by ESBL-producing organisms that are resistant to both cefepime alone and piperacillin-tazobactam. 1
- The addition of tazobactam significantly enhances the spectrum of activity of cefepime against beta-lactamase-producing organisms. 2
- For critically ill patients or those with severe infections, using the higher end of the dosing range is recommended to ensure adequate drug concentrations at the infection site.
- Regular monitoring of renal function is important, especially in critically ill patients, as cefepime is primarily excreted unchanged through the kidneys. 4
Potential Pitfalls
- Underdosing in patients with augmented renal clearance (common in critically ill patients) may lead to treatment failure. Consider extended infusion times (4 hours) in these patients. 1
- Failure to adjust dosing based on renal function may lead to drug accumulation and increased risk of neurotoxicity in patients with renal impairment.
- When treating suspected or confirmed Pseudomonas aeruginosa infections, ensure that the higher dosing regimen is used to achieve adequate coverage.
By following these dosing recommendations, clinicians can optimize the efficacy of cefepime-tazobactam while minimizing the risk of adverse effects and antimicrobial resistance.