What is the recommended dose and duration of Cefepime (Cefepime) for a patient with a positive culture for Proteus mirabilis and a Minimum Inhibitory Concentration (MIC) of 0.12, indicating high sensitivity?

Cefepime Dosing for Proteus mirabilis with MIC 0.12 mg/L in Hemodialysis Patients

For a hemodialysis patient with Proteus mirabilis infection (MIC 0.12 mg/L), administer cefepime 1-2 grams IV every 24 hours after each dialysis session, with treatment duration of 7-14 days for most infections or 4-6 weeks for endocarditis.

Dosing Rationale Based on MIC and Hemodialysis

• Your patient's MIC of 0.12 mg/L indicates high susceptibility to cefepime, as this is well below typical resistance breakpoints 1
• Target pharmacodynamic goal: maintain free cefepime concentration at 4-8 times the MIC (0.48-0.96 mg/L) for 100% of the dosing interval to maximize bacterial eradication and prevent resistance emergence 1
• For hemodialysis patients, cefepime is significantly removed during dialysis sessions, requiring post-dialysis supplementation 1

Specific Dosing Recommendations

Standard Dose for HD Patients:

• Initial loading dose: 2 grams IV immediately 1
• Maintenance: 1-2 grams IV after each hemodialysis session (typically every 24-48 hours depending on dialysis schedule) 1
• On non-dialysis days, administer 1 gram IV once daily 1

Administration Method:

• Consider extended infusion over 3-4 hours rather than standard 30-minute infusion to optimize time above MIC, particularly important in critically ill patients 1
• Extended infusion achieves superior pharmacodynamic targets for beta-lactams in patients with altered pharmacokinetics 1

Duration of Therapy

For Gram-Negative Infections (Non-Endocarditis):

• Uncomplicated infections: 7-10 days 1
• Complicated infections or bacteremia: 10-14 days 1

For Endocarditis (if applicable):

• Proteus mirabilis endocarditis requires 4-6 weeks of IV therapy, typically combined with an aminoglycoside (gentamicin 1 mg/kg after each dialysis session) for the first 2 weeks 1
• The American Heart Association recommends combination therapy with ampicillin or a broad-spectrum cephalosporin plus gentamicin for Enterobacteriaceae endocarditis 1
• Cardiac surgery consultation is essential, as Gram-negative endocarditis often requires valve replacement after 7-10 days of antibiotics 1

Critical Monitoring Parameters

• Monitor cefepime trough levels if available, targeting free drug concentration >0.48 mg/L (4× MIC) but <0.96 mg/L (8× MIC) to avoid neurotoxicity 1
• Hemodialysis patients are at particularly high risk for cefepime neurotoxicity (encephalopathy, seizures, myoclonus) due to drug accumulation 1
• If unexplained neurological symptoms develop, immediately hold cefepime and consider emergency dialysis 1

Important Caveats for Proteus mirabilis

• Proteus mirabilis remains highly susceptible to cefepime (95% susceptibility in European surveillance) with typical MIC90 values around 0.5 mg/L 2
• Your patient's MIC of 0.12 mg/L is well within the susceptible range, making cefepime an excellent choice 3, 2
• Cefepime demonstrates superior activity against Proteus mirabilis compared to third-generation cephalosporins due to enhanced beta-lactamase stability 3, 4

Alternative Considerations

• If endocarditis is confirmed, consider adding gentamicin 1 mg/kg IV after each dialysis session for synergy during the first 2 weeks 1
• Monitor gentamicin levels with target trough <1 μg/mL and peak 10-12 μg/mL (drawn 1 hour post-infusion) 5
• For patients unable to tolerate cefepime, alternatives include piperacillin-tazobactam or meropenem, both with excellent Proteus mirabilis activity 1, 4, 2