Can Tigecycline Be Used at High Dose in AKI Patients?
Yes, tigecycline can be used at high doses in patients with acute kidney injury (AKI) without dose adjustment, as tigecycline is primarily eliminated hepatically and renal clearance contributes minimally to total drug elimination. 1, 2, 3
Pharmacokinetic Rationale in AKI
- Tigecycline renal clearance represents only approximately 20% of total systemic clearance in patients with normal renal function 3
- In patients with severe renal impairment (creatinine clearance <30 mL/min), tigecycline clearance is reduced by only approximately 20%, with AUC increased by approximately 30% 3
- No dose adjustment is required for patients with renal impairment, including those on hemodialysis 2, 3
- Tigecycline is not efficiently removed by dialysis and can be administered without regard to timing of hemodialysis 3
Evidence from CRRT Patients
- In critically ill patients receiving continuous renal replacement therapy (CRRT), despite high dialysability (saturation coefficients of 0.79 for CVVHD and 0.90 for CVVHDF), CRRT clearance contributes only moderately to total tigecycline elimination 4
- CRRT clearance was 1.69 L/h for CVVHD and 2.71 L/h for CVVHDF, compared to physiological clearance of 18.3 L/h 4
- The probability of target attainment under CRRT was ≥88% for MIC values ≤0.5 mg/L, similar to patients without AKI 4
High-Dose Regimen Recommendations
For severe infections in AKI patients, particularly hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), high-dose tigecycline should be used: 1, 5
- Loading dose: 200 mg IV
- Maintenance dose: 100 mg IV every 12 hours 1, 5
- This high-dose regimen achieved cure rates of 85% compared to 69.6% with standard dosing 1
- High-dose tigecycline is the only independent predictor of clinical cure in critically ill patients with VAP 1, 5
Standard Dosing for Other Infections
For complicated intra-abdominal infections (cIAI) and complicated skin and skin structure infections (cSSSI) in AKI patients: 2
- Loading dose: 100 mg IV
- Maintenance dose: 50 mg IV every 12 hours 2
Critical Caveats and Contraindications
- Tigecycline should NOT be used as monotherapy for bacteremia due to poor serum concentrations (Cmax does not exceed 0.87 mg/L with standard dosing) 5
- Tigecycline should NOT be used for urinary tract infections as it achieves low urinary concentrations 5
- Tigecycline is inferior to aminoglycosides for complicated UTI caused by carbapenem-resistant Enterobacterales 6
- The FDA issued a boxed warning noting increased all-cause mortality (0.6% absolute risk difference) in tigecycline-treated patients versus comparators 1
Hepatic Impairment Considerations
While AKI does not require dose adjustment, hepatic impairment does require dose reduction: 1
- For severe hepatic impairment (Child-Pugh C): reduce maintenance dose by 50% (50 mg loading dose followed by 25 mg every 12 hours) 1
- Bilirubin levels affect tigecycline clearance and should be monitored 4, 7
Advantages in AKI Patients
- Tigecycline has significantly lower nephrotoxicity compared to polymyxins (RR 0.23,95% CI 0.11-0.46) 1, 5
- This makes tigecycline a safer alternative to colistin/polymyxins in patients with existing renal impairment 1
Monitoring Recommendations
- Regular monitoring of hepatic function is essential, as tigecycline is primarily hepatically eliminated 7
- Monitor for common adverse effects including nausea, vomiting, diarrhea, and elevated liver enzymes 2
- Consider therapeutic drug monitoring in critically ill patients, though specific target levels are not well-established 8