Role of Cefepime in the Treatment of Pyelonephritis
Cefepime is an FDA-approved and effective treatment option for both uncomplicated and complicated urinary tract infections, including pyelonephritis, particularly for infections caused by Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis. 1
Indications and Efficacy
Cefepime is specifically indicated for:
- Uncomplicated and complicated urinary tract infections (including pyelonephritis)
- Particularly effective against infections caused by:
- Escherichia coli
- Klebsiella pneumoniae
- Proteus mirabilis
- Including cases with concurrent bacteremia 1
The recommended dosage for pyelonephritis is 1-2 g twice daily, as indicated in clinical guidelines 2. This dosing regimen provides appropriate coverage against the common pathogens responsible for pyelonephritis.
Antimicrobial Coverage and Resistance Considerations
Cefepime offers several advantages in treating pyelonephritis:
- Broad-spectrum activity against common uropathogens
- Effective against ESBL-producing organisms (when combined with β-lactamase inhibitors)
- Lower resistance rates compared to fluoroquinolones and trimethoprim-sulfamethoxazole 3
Research has demonstrated that cephalosporins (including cefepime) have significantly lower treatment failure rates compared to fluoroquinolones and trimethoprim-sulfamethoxazole for pyelonephritis treated in outpatient settings 3.
Special Populations
Pregnancy
- Cefepime can be used during pregnancy as available data from observational studies have not established drug-associated risks of major birth defects, miscarriage, or adverse maternal/fetal outcomes 1
- In pregnant women with pyelonephritis, cefepime is a suitable alternative when fluoroquinolones and aminoglycosides should be avoided due to potential fetal risks 2
Pediatric Patients
- Safety and effectiveness established in children 2 months to 16 years old for UTIs including pyelonephritis 1
- Studies have shown equal efficacy and safety compared to ceftazidime in pediatric pyelonephritis patients 4
Geriatric Patients
- Dose adjustment required based on renal function
- Close monitoring needed as elderly patients are more likely to have decreased renal function 1
- Serious adverse events including encephalopathy, myoclonus, and seizures have occurred in geriatric patients with renal impairment given unadjusted doses 1
Renal Impairment Considerations
- Dose adjustment required for patients with creatinine clearance ≤60 mL/min
- Cefepime is primarily excreted by the kidneys, increasing risk of toxicity in renal impairment 1
- Careful monitoring of renal function is essential, especially in elderly patients 1
Treatment Duration and Follow-up
- Total treatment duration of 10-14 days is recommended for pyelonephritis 2
- Clinical response should be evaluated within 48-72 hours of starting treatment
- Follow-up urine culture should be considered 1-2 weeks after completing therapy 2
Recent Developments
Recent research has shown promising results for cefepime when combined with β-lactamase inhibitors:
- Cefepime/enmetazobactam combination was recently approved (2024) for complicated UTIs including pyelonephritis 5
- This combination demonstrated superiority over piperacillin/tazobactam in clinical cure and microbiological eradication rates (79.1% vs. 58.9%) 6
Practical Considerations
When using cefepime for pyelonephritis:
- Consider local resistance patterns when selecting empiric therapy
- Obtain urine cultures before initiating antibiotics to guide targeted therapy
- Monitor for adverse effects, particularly neurological symptoms in patients with renal impairment
- Consider switching to oral therapy (e.g., oral cephalosporins or amoxicillin-clavulanate) after clinical improvement and when afebrile for 24-48 hours 2