In an adult receiving thrice‑weekly intermittent hemodialysis with a session on Monday, what is the appropriate timing and dose of intravenous cefepime?

Cefepime Dosing for Thrice-Weekly Hemodialysis

For an adult receiving thrice-weekly intermittent hemodialysis with a Monday session, administer cefepime 1–2 g intravenously immediately after each dialysis session (Monday, Wednesday, Friday), with the specific dose determined by infection severity and pathogen susceptibility. 1, 2, 3

Recommended Dosing Strategy

Standard Post-Dialysis Regimen

• Administer cefepime immediately following completion of hemodialysis on each dialysis day to prevent premature drug removal and ensure adequate therapeutic levels 1, 2
• For infections caused by highly susceptible pathogens (MIC ≤1 mg/L):
  • 1 g after the dialysis session before a 48-hour interval (e.g., Monday → Wednesday) 3
  • 1.5 g after the dialysis session before a 72-hour interval (e.g., Friday → Monday) 3

Higher-Dose Regimen for Resistant Pathogens

• For infections with less susceptible organisms such as Pseudomonas aeruginosa (MIC >8 mg/L), or in patients with residual renal function:
  • 1.5 g before a 48-hour interval 3
  • 2 g before a 72-hour interval 3
• The FDA label supports up to 2 g every 8–12 hours in patients with normal renal function, but for hemodialysis patients the total dose is maintained while extending the interval 1

Critical Dosing Principles

Timing Relative to Dialysis

• Always administer cefepime after dialysis is complete, never before or during the early phases of dialysis 1, 2
• Approximately 72–81% of cefepime is removed during a 3–3.5 hour high-flux hemodialysis session, making pre-dialysis administration ineffective 1, 3, 4
• The intradialytic half-life is only 1.6 hours, while the interdialytic half-life extends to 22 hours, supporting thrice-weekly dosing 4

Dose Adjustment Rationale

• Maintain full individual doses while extending the dosing interval—do not reduce the individual dose size, as this produces subtherapeutic peak concentrations and increases treatment failure risk 5, 2
• Cefepime has linear pharmacokinetics and an elimination half-life of approximately 2 hours in patients with normal renal function, but this extends dramatically in hemodialysis patients between sessions 6, 4

Pharmacokinetic Considerations

Expected Drug Levels

• With the recommended dosing, trough pre-dialysis concentrations range from 10.7–11.3 mg/L at 48–72 hours, which consistently exceed the EUCAST susceptibility breakpoint of 1 mg/L for most pathogens 3
• Peak serum concentrations after a 2 g dose average 165.6 mg/L, providing robust concentration-dependent bacterial killing 4

Impact of Residual Renal Function

• Anuric patients achieve higher trough levels (15.6 mg/L) compared to those with preserved diuresis (9.25 mg/L), necessitating higher initial doses in patients with residual urine output 3
• When residual renal function exists, consider starting with higher doses and adjusting based on therapeutic drug monitoring 3

Practical Administration

Route and Infusion Time

• Administer cefepime intravenously over approximately 30 minutes 1
• Cefepime can be administered through the dialysis circuit during the last 30 minutes of dialysis if needed, avoiding additional venipuncture 7, 2

Monitoring

• Measure trough serum cefepime concentrations before the subsequent dialysis session to verify adequate exposure and guide dose adjustments 3
• Target trough levels should exceed the MIC90 for the identified pathogen (≥1 mg/L for most organisms, ≥8 mg/L for P. aeruginosa) 3

Common Pitfalls to Avoid

• Never administer cefepime on a daily schedule in hemodialysis patients—this leads to dangerous drug accumulation 1, 8
• Do not reduce individual dose sizes (e.g., giving 500 mg instead of 1–2 g)—this creates subtherapeutic levels despite appropriate interval extension 5, 2
• Avoid administering cefepime before or during early dialysis—approximately 68–81% will be removed before achieving therapeutic effect 1, 3, 4
• Do not assume a fixed dose works for all patients—those with residual renal function or Pseudomonas infections require individualized dosing with therapeutic monitoring 3

Duration of Therapy

• Continue treatment for 7–10 days for most infections (pneumonia, complicated UTI, skin/soft tissue infections) 1
• Extend to 10–14 days for severe infections or those with delayed clinical response 1
• For febrile neutropenia, reassess the need for continued therapy after 7 days if fever resolves but neutropenia persists 1