What is the recommended dosing regimen for tigecycline (Tygacil)?

Tigecycline Dosing Recommendations

The FDA-approved standard dosing for tigecycline is 100 mg IV loading dose followed by 50 mg IV every 12 hours, but for severe infections—particularly pneumonia and bloodstream infections—a high-dose regimen of 200 mg IV loading dose followed by 100 mg IV every 12 hours is recommended to improve clinical outcomes and reduce mortality. 1, 2

Standard Dosing Regimen

For FDA-approved indications (complicated skin/skin structure infections and complicated intra-abdominal infections):

• Initial dose: 100 mg IV loading dose 2
• Maintenance dose: 50 mg IV every 12 hours 2
• Infusion time: 30-60 minutes 2
• Duration: 5-14 days for cSSSI and cIAI; 7-14 days for community-acquired pneumonia 2
• No renal adjustment required: Tigecycline does not require dose modification for renal impairment or continuous renal replacement therapy 1, 2

High-Dose Regimen for Severe Infections

For hospital-acquired pneumonia, ventilator-associated pneumonia, and severe bloodstream infections:

• Initial dose: 200 mg IV loading dose 1
• Maintenance dose: 100 mg IV every 12 hours 1
• Rationale: Standard dosing achieves serum Cmax of only 0.87 mg/L and endothelial lining fluid concentrations of 0.01-0.02 mg/L, which are insufficient for severe infections 1
• Clinical evidence: High-dose regimen achieves 85% cure rate versus 69.6% with standard dosing for pulmonary infections 1, 3

Specific Clinical Scenarios

Carbapenem-Resistant Enterobacterales (CRE)

• Bloodstream infections: 100 mg IV loading dose, then 50 mg IV every 12 hours in combination with colistin OR meropenem (extended infusion) for 7-14 days 4
• Complicated intra-abdominal infections: 100 mg IV loading dose, then 50 mg IV every 12 hours for 5-7 days 4
• Critical caveat: Tigecycline should NOT be used as monotherapy for bacteremia due to poor serum concentrations and documented treatment failures 1, 3

Vancomycin-Resistant Enterococci (VRE)

• Complicated intra-abdominal infections: 100 mg IV loading dose, then 50 mg IV every 12 hours for 5-7 days 4

Carbapenem-Resistant Acinetobacter baumannii (CRAB)

• Pneumonia: 100 mg IV loading dose, then 50 mg IV every 12 hours PLUS colistin PLUS sulbactam as triple combination therapy for at least 7 days 1
• Bloodstream infections: Same dosing for 10-14 days 1
• For non-approved indications or MIC >1 mg/L: Consider high-dose regimen (200 mg loading, then 100 mg every 12 hours) 1
• MIC threshold: Use only if MIC ≤2 mg/L 1

Hepatic Impairment Dosing

• Mild to moderate hepatic impairment (Child-Pugh A and B): No dose adjustment required 2
• Severe hepatic impairment (Child-Pugh C): 100 mg IV loading dose, then 25 mg IV every 12 hours (reduced maintenance dose) 2
• Monitoring: Patients with severe hepatic impairment should be treated with caution and monitored closely for treatment response 2

Pediatric Dosing (Use Only When No Alternatives Available)

Due to increased mortality risk in adults, avoid tigecycline in pediatric patients unless no alternative antibacterial drugs are available: 2

• Ages 8-11 years: 1.2 mg/kg IV every 12 hours (maximum 50 mg per dose) 2
• Ages 12-17 years: 50 mg IV every 12 hours 2

Critical Clinical Caveats

When NOT to Use Standard Dosing

• Bacteremia/bloodstream infections: Standard dosing is inadequate; use high-dose regimen or avoid tigecycline entirely 1, 3
• Hospital-acquired or ventilator-associated pneumonia: Standard dosing has poor efficacy due to low lung tissue concentrations; high-dose regimen is essential 1, 3
• Monotherapy for resistant organisms: Always use combination therapy for CRAB and severe CRE infections 4, 1

Pharmacokinetic Limitations

• Poor serum penetration: Limits efficacy in bloodstream infections 1, 3
• Extremely low endothelial lining fluid concentrations: Explains poor pulmonary efficacy with standard dosing 1, 3
• Large volume of distribution (21.0 L/kg): Extensive tissue penetration but low serum levels 5

Combination Therapy Requirements

• For CRAB: Must combine with colistin and sulbactam 1
• For CRE bloodstream infections: Combine with colistin or meropenem (extended infusion) 4
• For severe infections: Combination with another active agent is recommended over monotherapy 1, 3

Preparation and Administration

• Reconstitution: Add 5.3 mL of 0.9% sodium chloride, 5% dextrose, or lactated Ringer's to achieve 10 mg/mL concentration 2
• Dilution: Withdraw 5 mL and add to 100 mL IV bag (maximum concentration 1 mg/mL) 2
• Storage after reconstitution: Up to 24 hours at room temperature (≤25°C) or 48 hours refrigerated (2-8°C) 2
• Y-site compatibility: Compatible with amikacin, gentamicin, tobramycin, dopamine, morphine, and other common ICU medications 2