What is the recommended dosing of cefepime for Enterobacter cloacae urinary tract infection (UTI)?

Cefepime Dosing for Enterobacter cloacae UTI

For Enterobacter cloacae urinary tract infection, the recommended cefepime dosing is 1-2 g IV every 12 hours for 7-10 days, with dose adjustment required for renal impairment.

Dosing Recommendations

Standard Dosing

• For mild to moderate uncomplicated or complicated UTI: 0.5-1 g IV every 12 hours for 7-10 days 1
• For severe uncomplicated or complicated UTI: 2 g IV every 12 hours for 10 days 1

Renal Dosage Adjustments

Dosing must be adjusted based on creatinine clearance:

• CrCl >60 mL/min: Standard dosing (no adjustment needed)
• CrCl 30-60 mL/min: Reduce dose by 50% (maintain same interval)
• CrCl <30 mL/min: Reduce dose by 50% and extend interval to every 24 hours 1

Rationale for Dosing

Cefepime is a fourth-generation cephalosporin with excellent activity against Enterobacter cloacae, including many strains that may be resistant to third-generation cephalosporins. The recommended dosing ensures:

1. Adequate drug concentrations in urine (20% of cefepime is excreted unchanged in urine)
2. Sufficient time above MIC (T>MIC ≥50%) for effective bacterial killing 2
3. Appropriate coverage for Enterobacter cloacae with MICs ≤4 mg/L 2

Special Considerations

Monitoring Requirements

• Monitor renal function throughout therapy
• Watch for neurological symptoms (confusion, muscle jerks) which may indicate cefepime toxicity, especially in patients with renal impairment 2
• Assess clinical response within 48-72 hours and adjust therapy based on culture and susceptibility results 3

Potential Resistance Concerns

• For Enterobacter cloacae with MICs ≥8 mg/L, standard dosing may provide inadequate coverage 2
• In such cases, consider:
  1. Higher dosing (2 g every 8 hours) if renal function permits
  2. Alternative agents based on susceptibility testing

Alternative Options for Resistant Strains

If Enterobacter cloacae is resistant to cefepime or the patient fails to respond:

1. For carbapenem-resistant Enterobacterales (CRE):

   • Ceftazidime-avibactam 2.5 g IV q8h 4
   • Meropenem-vaborbactam 4 g IV q8h 4
   • Imipenem-cilastatin-relebactam 1.25 g IV q6h 4

2. For multidrug-resistant strains:

   • Aminoglycosides (gentamicin 5-7 mg/kg/day or amikacin 15 mg/kg/day) may be effective for UTIs 4

Administration

• Administer intravenously over approximately 30 minutes 1
• Do not force thaw frozen container by immersion in water baths or microwave irradiation 1

Treatment Duration

• Uncomplicated UTI: 7-10 days
• Complicated UTI: 10-14 days 1
• Consider longer duration (14 days) if bacteremia is present

Common Pitfalls and Caveats

1. Renal toxicity risk: Closely monitor renal function, particularly when cefepime is co-administered with other nephrotoxic agents or potent diuretics like furosemide 1

2. Neurological toxicity: Patients with renal impairment are at risk for neurotoxicity (confusion, encephalopathy, seizures) due to cefepime accumulation. Prompt monitoring of plasma levels should be considered in patients with CrCl <30 mL/min 2

3. Clostridioides difficile risk: Monitor for diarrhea during and after treatment, which may indicate C. difficile infection 1

4. Cross-reactivity: Be aware of potential cross-hypersensitivity (up to 10%) in patients with penicillin allergy 1

5. Inadequate dosing: Underdosing may lead to treatment failure, especially with pathogens at the upper limits of susceptibility 2

The evidence supports cefepime as an effective treatment for Enterobacter cloacae UTIs when dosed appropriately according to renal function and pathogen susceptibility.