What are the indications and usage of Tigecycline (generic name) in treating infections?

Tigecycline: Indications and Usage

FDA-Approved Indications

Tigecycline is FDA-approved for three specific indications in adults ≥18 years: complicated skin and skin structure infections (cSSSI), complicated intra-abdominal infections (cIAI), and community-acquired bacterial pneumonia (CAP). 1

Approved Uses:

• Complicated skin and skin structure infections (cSSSI) - Standard dosing: 100 mg IV loading dose, then 50 mg IV every 12 hours for 5-14 days 2, 1
• Complicated intra-abdominal infections (cIAI) - Same dosing regimen as cSSSI 2, 1
• Community-acquired bacterial pneumonia (CAP) - 100 mg IV loading dose, then 50 mg IV every 12 hours for 7-14 days 2, 1

Critical FDA Limitations:

• Tigecycline is explicitly NOT indicated for diabetic foot infections or hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP) 1
• The FDA issued a boxed warning for increased all-cause mortality (0.6% absolute risk difference, 95% CI 0.1-1.2) compared to comparators, with the greatest mortality difference seen in VAP patients 3, 1
• Tigecycline should be reserved only for situations when alternative treatments are not suitable 1

Off-Label Uses for Multidrug-Resistant Organisms

Carbapenem-Resistant Enterobacterales (CRE):

• Tigecycline is recommended for pulmonary and intra-abdominal infections caused by CRE when newer agents are unavailable or inactive 3
• Dosing: 100 mg IV loading dose, then 50 mg IV every 12 hours 2, 3
• Do NOT use tigecycline for CRE complicated urinary tract infections - aminoglycosides are superior 3
• Do NOT use as monotherapy for bacteremia due to poor plasma concentrations and outcomes 2, 4

Carbapenem-Resistant Acinetobacter baumannii (CRAB):

• Tigecycline should NOT be used as monotherapy for CRAB pneumonia - guidelines strongly recommend against this due to higher mortality and treatment failure rates 5, 4
• Tigecycline efficacy is MIC-dependent: comparable to polymyxin when MIC ≤2 mg/L, but inferior when MIC >2 mg/L 5, 3, 4
• For CRAB pulmonary infections, tigecycline-based combination therapy can be used as an alternative to polymyxin-based therapy, particularly when nephrotoxicity is a concern 5
• Tigecycline-based therapy has significantly lower nephrotoxicity (RR 0.23,95% CI 0.11-0.46) compared to colistin-based therapy 5, 3
• Combination with sulbactam or polymyxins is recommended rather than monotherapy 5, 4

Vancomycin-Resistant Enterococci (VRE):

• For VRE complicated intra-abdominal infections: 100 mg IV loading dose, then 50 mg IV every 12 hours 2, 3

Special Dosing Considerations

High-Dose Regimen:

• For severe infections, particularly HAP/VAP (when no alternatives exist), consider high-dose tigecycline: 200 mg IV loading dose, then 100 mg IV every 12 hours - this achieves cure rates of 85% versus 69.6% with standard dosing 3

Hepatic Impairment:

• Severe hepatic impairment (Child-Pugh C): reduce maintenance dose by 50% - give 100 mg loading dose, then 25 mg every 12 hours 3, 1

Renal Impairment:

• No dose adjustment required for renal impairment 2

Critical Safety Warnings and Contraindications

Absolute Contraindications:

• Known hypersensitivity to tigecycline or tetracyclines 2, 1
• Pregnancy - evidence of fetal harm in animal studies 2, 1
• Breastfeeding 2
• Children under 8 years - risk of permanent tooth discoloration 2, 1

Major Clinical Pitfalls to Avoid:

• Never use tigecycline as monotherapy for bacteremia - poor plasma concentrations lead to treatment failure 2, 4
• Never use for HAP/VAP as first-line therapy - associated with increased mortality 2, 4, 1
• Never use for Pseudomonas aeruginosa infections - inadequate activity 4
• Check MIC before using for CRAB - if MIC >2 mg/L, choose polymyxin-based therapy instead 5, 3, 4
• Monitor for superinfection - Pseudomonas aeruginosa is the most common superinfecting organism (46.9% of superinfections) 6

Common Adverse Effects:

• Nausea, vomiting, and diarrhea are most common (>5% incidence) 2, 1, 7
• Tigecycline has lower incidence of nausea/vomiting (6.3%) compared to polymyxins (35.9%) 5, 3
• Higher incidence of abdominal pain (18.8%) compared to polymyxins (2.6%) 5, 3
• Monitor liver function tests - hepatic adverse effects have been reported 1
• Pancreatitis, including fatalities, has been reported - discontinue if suspected 1

Drug Interactions:

• Monitor anticoagulation tests if administered with warfarin 1

Administration Details:

• Available as 50 mg powder for reconstitution 2
• Administer intravenously over 30-60 minutes 2, 1
• Tigecycline achieves lung tissue concentrations 2 times higher than simultaneous serum concentrations 5