Levofloxacin Dosing for CRRT
For patients on continuous renal replacement therapy (CRRT), administer levofloxacin 500 mg loading dose followed by 250 mg every 48 hours for standard infections, or 750-1000 mg three times weekly for severe infections requiring higher drug exposures. 1
Standard CRRT Dosing Regimen
The Infectious Diseases Society of America recommends 500 mg loading dose, then 250 mg every 48 hours as the primary regimen for patients on CRRT. 1
For severe infections or tuberculosis requiring higher drug exposures, the alternative regimen is 750-1000 mg administered three times weekly. 2
Approximately 80% of levofloxacin undergoes renal clearance, making dose adjustment critical in CRRT to prevent drug accumulation while maintaining therapeutic concentrations. 2, 3
Dosing Strategy Rationale
Extending the dosing interval is preferred over simply reducing the dose, as lowering the dose compromises peak concentrations (Cmax) and treatment efficacy. 2
Levofloxacin exhibits concentration-dependent killing, meaning adequate peak concentrations are essential for bacterial eradication. 2
The elimination half-life extends to 28-39 hours in patients with end-stage renal disease, supporting extended interval dosing. 4
Pathogen-Specific Considerations
For Gram-positive infections (particularly Streptococcus pneumoniae with MIC ≤2 mg/L), levofloxacin 750 mg every 24 hours achieves approximately 90% probability of target attainment. 5
For serious Gram-negative infections, particularly Pseudomonas aeruginosa with MIC of 2 mg/L, conventional FDA-approved levofloxacin doses are insufficient even on CRRT—doses as high as 1750 mg loading then 1500 mg daily would be required, which far exceed maximum approved doses. 5
Levofloxacin cannot be recommended as empiric monotherapy for serious Gram-negative infections in CRRT patients due to suboptimal efficacy. 5
For respiratory pathogens like Haemophilus influenzae, Moraxella catarrhalis, Enterobacter cloacae, and Klebsiella pneumoniae, standard CRRT dosing provides adequate Cmax/MIC ratios of 10 or greater. 4
Critical Clinical Pitfalls
Never assume "normal" serum creatinine indicates adequate renal function in CRRT patients—muscle mass decline can mask severe renal impairment. 6
Avoid administering levofloxacin within 2 hours of antacids or medications containing divalent cations (aluminum, magnesium, iron, calcium), as these significantly reduce bioavailability. 7, 3
If creatinine clearance drops below 30 mL/min or the patient transitions to intermittent hemodialysis, switch to the three-times-weekly dosing regimen (750-1000 mg). 2
Monitoring Recommendations
Consider therapeutic drug monitoring with serum concentrations measured at 2 and 6 hours post-dose to optimize dosing, particularly in patients with borderline renal function or multiple comorbidities. 6
Monitor for drug interactions, as CRRT patients typically receive multiple medications that may alter levofloxacin pharmacokinetics. 2, 6
Reassess renal function periodically during treatment, as CRRT parameters may change. 6
Alternative Fluoroquinolone Option
If a fluoroquinolone is needed for tuberculosis or severe infections in CRRT patients, consider moxifloxacin 400 mg once daily, which requires no dose adjustment for renal impairment and is not significantly removed by dialysis. 7
Unlike levofloxacin (80% renal clearance), moxifloxacin undergoes primarily hepatic metabolism and maintains standard dosing across all levels of renal function. 7