What is the recommended cefepime (Cefepime) dosing for a patient with Enterobacter cloacae in their urine, impaired renal function, and scheduled for kidney stone removal and stent placement?

Cefepime Dosing for Enterobacter cloacae UTI with Renal Impairment and Scheduled Stone Removal

For a patient with Enterobacter cloacae in urine, impaired renal function, and scheduled kidney stone removal with stent placement, administer cefepime 2 g IV every 24 hours (adjusted for renal function) starting immediately before the procedure, with dosing based on creatinine clearance and continued for 7-10 days post-operatively. 1

Pre-Procedural Antimicrobial Prophylaxis

Antimicrobial prophylaxis must be administered within 60 minutes prior to stone manipulation and stent placement procedures. 2

• Stone manipulation procedures (including stent placement) carry increased risk of bacteremia and require prophylactic antibiotics 2
• If purulent urine is encountered during the procedure, immediately abort stone removal, establish drainage (nephrostomy or ureteral stent), culture the purulent urine, and continue broad-spectrum antibiotics pending culture results 2, 3
• The presence of known Enterobacter cloacae in urine necessitates treatment rather than simple prophylaxis 2, 3

Cefepime Dosing Based on Renal Function

Cefepime dosing must be adjusted based on creatinine clearance to prevent neurotoxicity, which can occur even with appropriate dose adjustment. 1, 4, 5

Standard Dosing for Complicated UTI (CrCL >60 mL/min):

• 2 g IV every 12 hours for severe complicated UTI 1
• Duration: 7-10 days 1

Renal Dose Adjustments (Critical):

• CrCL 30-60 mL/min: 2 g IV every 24 hours 1
• CrCL 11-29 mL/min: 1 g IV every 24 hours 1
• CrCL <11 mL/min: 500 mg IV every 24 hours 1
• Hemodialysis: 1 g on day 1, then 500 mg every 24 hours after dialysis 1
• CAPD: 2 g every 48 hours 1

Rationale for Cefepime in Enterobacter cloacae

Cefepime is specifically advantageous for Enterobacter species due to its stability against AmpC beta-lactamases and low propensity for resistance induction. 2, 6

• Enterobacter cloacae commonly produces inducible AmpC beta-lactamases that confer resistance to third-generation cephalosporins 6
• Cefepime retains activity against E. cloacae strains resistant to other cephalosporins 6
• For AmpC-producing organisms like Enterobacter, cefepime shows no significant mortality difference compared to carbapenems when MIC is low 2
• However, if cefepime MIC is in the susceptible dose-dependent category (higher end of susceptible range), consider carbapenem instead 2

Critical Monitoring for Neurotoxicity

Monitor closely for cefepime-induced neurotoxicity, particularly in patients with any degree of renal impairment, as this can occur despite appropriate dose adjustment. 4, 5, 7

Warning Signs of Cefepime Neurotoxicity:

• Altered mental status, confusion, or encephalopathy 4, 7
• Myoclonus, twitching, or seizures (including non-convulsive status epilepticus) 5
• Onset typically 96 hours after therapy initiation 5
• If neurotoxicity occurs: immediately discontinue cefepime, administer benzodiazepines if seizures present, and consider hemodialysis for drug clearance 5

Alternative Considerations

If cefepime is contraindicated or neurotoxicity develops, alternative agents for Enterobacter cloacae include: 2

• Carbapenems (meropenem 1 g IV q8h or imipenem 500 mg IV q6h) - preferred if cefepime MIC is elevated or patient develops neurotoxicity 2
• Ceftazidime-avibactam 2.5 g IV q8h - for carbapenem-resistant Enterobacteriaceae 2
• Aminoglycosides (gentamicin 5 mg/kg IV daily) - may be considered for UTI of urinary tract source, though data are limited 2

Post-Procedural Management

Continue antibiotics for 7-10 days post-operatively, with adjustment based on culture results and clinical response. 1, 3

• Obtain urine culture from nephrostomy or stent if placed to guide targeted therapy 3, 8
• Re-evaluate antibiotic regimen within 48-72 hours based on culture results and antibiogram 8
• For patients with infected stones or pyonephrosis, drainage is lifesaving and must accompany antibiotic therapy 8

Common Pitfalls to Avoid

• Failure to adjust cefepime dose for renal function is the most common cause of neurotoxicity 1, 4, 7
• Do not use fluoroquinolones empirically if third-generation cephalosporins or cefepime are available, as cephalosporins show superior outcomes 8
• Do not proceed with stone removal if purulent urine is encountered - establish drainage first 2, 3
• Calculate creatinine clearance using Cockcroft-Gault equation, not just serum creatinine alone 1