Tigecycline Dosing in ICU Patients
For ICU patients with severe infections, use high-dose tigecycline: 200 mg IV loading dose followed by 100 mg IV every 12 hours, particularly for pneumonia, primary bloodstream infections, and infections caused by multidrug-resistant organisms. 1, 2
Standard vs. High-Dose Regimens
The traditional FDA-approved dosing (100 mg loading, then 50 mg every 12 hours) is inadequate for most ICU infections due to suboptimal serum concentrations (Cmax only 0.87 mg/L). 1, 3 High-dose tigecycline (200 mg loading, then 100 mg every 12 hours) achieves superior outcomes with cure rates of 85% compared to 69.6% with standard dosing. 2
Infection-Specific Dosing:
- Pneumonia (HAP/VAP): 200 mg loading dose, then 100 mg every 12 hours 1, 2
- Intra-abdominal infections: 100-200 mg loading dose, then 50-100 mg every 12 hours 1, 2
- Secondary bacteremia (from approved indications): 100 mg loading, then 50 mg every 12 hours may be adequate 1
- Primary bloodstream infections: 200 mg loading, then 100 mg every 12 hours, preferably in combination therapy 1, 3
Renal Dysfunction Considerations
No dose adjustment is required for renal impairment, including patients on continuous renal replacement therapy (CRRT). 4 Despite high dialysability (saturation coefficients 0.79-0.90), CRRT clearance contributes minimally to total tigecycline elimination (CRRT clearance 1.69-2.71 L/h vs. body clearance 18.3 L/h). 4
- CVVHD/CVVHDF patients: Use standard high-dose regimen without adjustment 4
- Intermittent hemodialysis: No dose adjustment needed 5
Hepatic Impairment
For severe hepatic impairment (Child-Pugh Class C), reduce maintenance dose by 50%: 100 mg loading dose, then 25 mg every 12 hours. 2, 5 Bilirubin levels affect tigecycline clearance, reducing it in patients with elevated bilirubin. 4
- Mild-moderate hepatic impairment (Child-Pugh A-B): No adjustment needed 5
Critical Clinical Caveats
Never use tigecycline as monotherapy for bacteremia or primary bloodstream infections due to poor serum concentrations and documented treatment failures. 1, 2, 3 Always combine with another active agent for these indications.
Avoid tigecycline for carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia as monotherapy. 2 Multiple studies demonstrate sulbactam-based therapy superiority over tigecycline for CRAB infections, with significantly lower ICU mortality (adjusted OR 0.12) and treatment failure rates (adjusted OR 0.14). 1
MIC-Dependent Efficacy:
- MIC ≤ 0.5 mg/L: High-dose tigecycline achieves adequate PK/PD targets for most infection types 6
- MIC > 0.5 mg/L: Consider combination therapy or alternative agents 6
- For CRAB: Tigecycline comparable to polymyxins only when MIC ≤ 2 mg/L; inferior when MIC > 2 mg/L 2
Combination Therapy Recommendations
For multidrug-resistant organisms, use tigecycline in combination with polymyxins or carbapenems rather than monotherapy. 1, 2 This approach is particularly important for:
Safety Profile
Tigecycline demonstrates significantly lower nephrotoxicity compared to colistin-based therapy (15.3% vs. 33%), making it preferable in ICU patients at risk for renal injury. 1, 2 The most common adverse effects are gastrointestinal (nausea 28.5%, vomiting 19.4%, diarrhea 11.6%). 5
Contraindications
Do not use tigecycline for urinary tract infections due to inadequate urinary concentrations. 3 The drug achieves low urinary levels despite renal excretion accounting for 33% of elimination. 5
Pharmacokinetic Considerations in ICU Patients
High-dose tigecycline shows excellent pulmonary penetration with median epithelial lining fluid (ELF)/plasma ratio of 152.9% [73.5-386.8], making it particularly suitable for pneumonia. 6 The large volume of distribution (162 L central compartment, 87.9 L peripheral compartment) may be altered in ICU patients with pathophysiological changes, but interindividual variability in clearance remains < 20%. 7
Population pharmacokinetic modeling demonstrates no need for covariate-based dose adjustments in sepsis/septic shock patients beyond the standard high-dose regimen. 7