What is the renal‑adjusted dose of Fortum (cefepime) for an adult with melioidosis?

Renal-Adjusted Dosing of Ceftazidime (Fortum) for Melioidosis in Adults

For adults with melioidosis and renal impairment, ceftazidime dosing must be adjusted based on creatinine clearance, with the critical principle being to reduce dosing frequency rather than individual dose size to maintain adequate peak concentrations for this difficult-to-treat infection.

Standard Dosing in Normal Renal Function

• For severe melioidosis with normal renal function (CrCl ≥50 mL/min), the standard dose is ceftazidime 2 g IV every 8 hours or 40 mg/kg every 8 hours 1
• Alternatively, continuous infusion at 4 mg/kg/hour following a 12 mg/kg loading dose has been studied and may offer pharmacokinetic advantages 1
• The target plasma concentration should remain above 8 mg/L (4× the typical MIC of 2 mg/L for Burkholderia pseudomallei) 1

Renal Dose Adjustments

For CrCl 30-50 mL/min:

• Reduce frequency to 2 g every 12 hours while maintaining the full 2 g dose 1
• This approach preserves peak concentrations needed for concentration-dependent killing while accounting for reduced clearance 1

For CrCl 11-29 mL/min:

• Further reduce to 2 g every 24 hours 2
• Monitor clinical response closely as trough levels may be suboptimal for pathogens at the upper MIC range 3

For CrCl <10 mL/min (not on dialysis):

• Dose at 1 g every 24 hours 2
• Consider therapeutic drug monitoring if available, as accumulation risk increases 3

For patients on hemodialysis:

• Administer 2 g after each dialysis session (typically 3 times weekly) 2, 1
• Ceftazidime is significantly cleared by hemodialysis, so post-dialysis dosing is essential to avoid premature drug removal 2
• On non-dialysis days, no supplemental dose is typically needed 2

For continuous ambulatory peritoneal dialysis (CAPD):

• Dose at 2 g every 48 hours 4

Critical Pharmacokinetic Considerations

• Ceftazidime clearance correlates closely with creatinine clearance (r = 0.71, P <0.001), with minimal non-renal elimination 1
• The elimination half-life increases dramatically in renal impairment, from approximately 2 hours in normal function to a median of 7.74 hours (range 1.95-44.71 hours) in septicemic melioidosis patients with varying degrees of renal dysfunction 1
• The Cockcroft-Gault equation should be used to estimate creatinine clearance when direct measurement is unavailable, adjusting for age, weight, and sex 4

Alternative Dosing Strategy: Continuous Infusion

• For patients with CrCl ≥50 mL/min, continuous infusion at 120 mg/kg/day (approximately 4 mg/kg/hour) after a loading dose of 12 mg/kg maintains more consistent plasma levels above the target concentration 1
• This approach may allow dose reduction while maintaining efficacy and is particularly useful for organisms with MICs at the upper limit of susceptibility 1
• Continuous infusion via elastomeric infusors through peripherally inserted central catheters (PICC lines) has been successfully used for outpatient management in Darwin, Australia 5

Monitoring and Safety

• Measure baseline creatinine clearance and reassess every 2-3 days during intensive therapy, as renal function commonly fluctuates in severe melioidosis 1
• In patients with CrCl <30 mL/min, consider therapeutic drug monitoring if available to ensure trough concentrations remain between 8-20 mg/L 3
• Trough concentrations >30 mg/L may indicate accumulation and increased risk of neurotoxicity, though this is less common with ceftazidime than cefepime 3

Common Pitfalls to Avoid

• Do not reduce the individual dose below 2 g in severe infections—instead, extend the dosing interval to maintain adequate peak concentrations for bacterial killing 1
• Do not administer ceftazidime before hemodialysis sessions, as this results in premature drug removal and subtherapeutic levels 2
• Do not rely on serum creatinine alone in elderly patients or those with reduced muscle mass, as this may overestimate renal function; calculate CrCl using the Cockcroft-Gault equation 4
• For organisms with ceftazidime MIC ≥8 mg/L, standard dosing may provide inadequate coverage even with dose adjustment—consider alternative agents or combination therapy 3

Duration of Therapy

• The intensive phase of melioidosis treatment typically requires 10-14 days of IV ceftazidime, followed by oral eradication therapy with trimethoprim-sulfamethoxazole for 3-6 months 5
• Clinical improvement often occurs within the first week, allowing transition to outpatient parenteral therapy in stable patients 5