How should tigecycline be dosed intravenously in an adult with a serious multidrug‑resistant infection, including loading dose, maintenance dose, treatment duration, adjustments for moderate to severe hepatic impairment, contraindications, and common adverse effects?

Tigecycline Dosing for Serious Multidrug-Resistant Infections in Adults

For serious multidrug-resistant infections in adults, administer tigecycline as a 100 mg IV loading dose followed by 50 mg IV every 12 hours over 30-60 minutes, with treatment duration of 5-14 days depending on infection site; however, for hospital-acquired pneumonia or ventilator-associated pneumonia caused by MDR organisms, use high-dose tigecycline (200 mg loading dose followed by 100 mg every 12 hours) in combination with another active agent, and reduce the maintenance dose to 25 mg every 12 hours in patients with severe hepatic impairment (Child-Pugh C). 1, 2

Standard Dosing Regimen

Loading and Maintenance Doses

• Loading dose: 100 mg IV administered over 30-60 minutes 1
• Maintenance dose: 50 mg IV every 12 hours, infused over 30-60 minutes 1, 3
• Reconstitution: Add 5.3 mL of 0.9% sodium chloride, 5% dextrose, or lactated Ringer's to each 50 mg vial to achieve 10 mg/mL concentration, then dilute to final concentration of 1 mg/mL in 100 mL IV bag 3, 1

Treatment Duration by Indication

• Complicated skin and skin structure infections (cSSSI): 5-14 days 1
• Complicated intra-abdominal infections (cIAI): 5-14 days 1
• Community-acquired bacterial pneumonia (CABP): 7-14 days 1
• Duration should be guided by infection severity, site, and clinical/bacteriological response 1

High-Dose Regimen for Severe Infections

When to Use High-Dose Tigecycline

For hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) caused by multidrug-resistant organisms, particularly Acinetobacter baumannii, use the high-dose regimen: 200 mg loading dose followed by 100 mg every 12 hours. 2

• Standard-dose tigecycline achieves very low concentrations in endothelial lining fluid (0.01-0.02 mg/L) and has demonstrated inferior cure rates compared to imipenem for VAP (47.9% vs 70.1%) 2
• High-dose tigecycline (100 mg twice daily maintenance) showed numerically higher efficacy (85%) compared to standard dosing (69.6%) in HAP/VAP trials 2
• Among critically ill patients with MDR infections, high-dose tigecycline was the only independent predictor of clinical cure in VAP patients 2

Critical Caveat for Pulmonary Infections

Tigecycline should always be used in combination with another active antimicrobial agent for non-approved indications like HAP/VAP, due to uncertainties about efficacy and poor lung penetration. 2

Hepatic Impairment Adjustments

Dosing by Child-Pugh Classification

• Mild hepatic impairment (Child-Pugh A): No dose adjustment required 1, 4
• Moderate hepatic impairment (Child-Pugh B): No dose adjustment required 1, 4
• Severe hepatic impairment (Child-Pugh C): 100 mg loading dose, then reduce maintenance dose to 25 mg every 12 hours 1, 4

Pharmacokinetic Rationale

• Tigecycline clearance decreases progressively with worsening hepatic function: 31.2 L/h (Child-Pugh A), 22.1 L/h (Child-Pugh B), and 13.5 L/h (Child-Pugh C) 4
• Patients with severe hepatic impairment should be treated with caution and monitored closely for treatment response 1

Renal Impairment

No dose adjustment is necessary for any degree of renal impairment, as tigecycline undergoes primarily biliary/fecal excretion (59%) with only 33% renal elimination. 1, 5, 6

Contraindications and Warnings

Absolute Contraindications

• Hypersensitivity to tigecycline or any tetracycline-class antibiotics 3, 1
• Pregnancy and breastfeeding: Evidence of fetal harm in animal studies 3

Black Box Warning: Increased Mortality Risk

The FDA issued a boxed warning for tigecycline due to increased all-cause mortality compared to comparator antibiotics across multiple Phase III and IV clinical trials. 2, 7, 3

• Tigecycline should be reserved for situations when alternative treatments are not suitable 1
• Infectious disease consultation is recommended when considering tigecycline use 2

Specific Clinical Situations to Avoid

• Hospital-acquired or ventilator-associated pneumonia as monotherapy: Greater mortality and decreased efficacy reported in comparative trials 1
• Diabetic foot infections: Clinical trial failed to demonstrate non-inferiority 1
• Bacteremia/bloodstream infections: Standard-dose tigecycline achieves maximum serum concentration of only 0.87 mg/L, insufficient for intravascular infections 2, 8
• Urinary tract infections: Tigecycline achieves inadequate urinary concentrations due to large volume of distribution 7, 8
• Carbapenem-resistant Enterobacterales (CRE) urinary tract infections: Tigecycline is inferior to aminoglycosides (moderate certainty evidence) 2, 8

Common Adverse Effects

Gastrointestinal Effects (Most Common)

• Nausea: 28.5% of patients 6
• Vomiting: 19.4% of patients 6
• Diarrhea: 11.6% of patients 6
• These effects are dose-related and typically mild to moderate in severity 5, 9

Other Frequent Adverse Events (≥5%)

• Local IV-site reactions: 8.2% 6
• Infection: 6.7% 6
• Fever: 6.3% 6
• Abdominal pain: 6.0% 6
• Headache: 5.6% 6

Serious Adverse Effects Requiring Monitoring

• Coagulopathy: Tigecycline prolongs both prothrombin time (PT) and activated partial thromboplastin time (aPTT) 7, 3
  • Monitor PT/aPTT regularly during therapy 7
• Hepatotoxicity: Monitor liver function tests 7
• Hypoglycemia and hypoproteinemia: Assess periodically 7

Critical Pitfalls to Avoid

Inappropriate Use Scenarios

1. Never use tigecycline as first-line therapy for urinary tract infections - it achieves inadequate urinary levels regardless of susceptibility 7, 8
2. Avoid tigecycline monotherapy for bacteremic infections - serum concentrations are insufficient for bloodstream clearance 2, 8
3. Do not use standard dosing for HAP/VAP - high-dose regimen (200 mg loading, 100 mg q12h) is required for adequate lung penetration 2
4. Never use tigecycline alone for non-approved indications - always combine with another active agent when treating HAP/VAP or other off-label infections 2

MIC Considerations

• For Acinetobacter baumannii infections, tigecycline should only be used when MIC is ≤1 mg/L 2
• For approved indications (cSSSI, cIAI), standard dosing may be appropriate even for severe infections when MIC ≤1 mg/L 2

Pediatric Considerations

Avoid tigecycline in all pediatric patients unless no alternative antibacterial drugs are available, due to increased mortality risk in adults and potential for permanent tooth discoloration in children under 8 years. 7, 1

• If absolutely necessary in children 8-11 years: 1.2 mg/kg IV every 12 hours (maximum 50 mg per dose) 7, 1
• If absolutely necessary in children 12-17 years: 50 mg IV every 12 hours 7, 1