When should tigecycline be used?

When to Use Tigecycline

Tigecycline should be reserved as a last-resort agent for complicated intra-abdominal infections, complicated skin and skin structure infections, and community-acquired pneumonia caused by multidrug-resistant organisms when alternative treatments are not suitable, and it should NOT be used for hospital-acquired/ventilator-associated pneumonia, diabetic foot infections, or as monotherapy for bloodstream infections. 1

FDA-Approved Indications (Adults ≥18 years only)

Tigecycline is FDA-approved for three specific conditions 1:

• Complicated skin and skin structure infections caused by susceptible organisms including MRSA, VRE, and ESBL-producing Enterobacteriaceae 1
• Complicated intra-abdominal infections caused by susceptible polymicrobial pathogens 1
• Community-acquired bacterial pneumonia (NOT hospital-acquired or ventilator-associated pneumonia) 1

Critical Contraindications and Limitations

Absolute Contraindications

Do NOT use tigecycline for: 1

• Hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) - A comparative trial showed greater mortality and decreased efficacy in tigecycline-treated patients 1
• Diabetic foot infections - Clinical trial failed to demonstrate non-inferiority 1
• Bloodstream infections as monotherapy - Poor outcomes with standard dosing due to extremely low serum concentrations 2

FDA Black Box Warning

The FDA issued a boxed warning noting increased all-cause mortality (0.6% absolute risk difference, 95% CI 0.1-1.2) in tigecycline-treated patients versus comparators in meta-analysis of Phase 3 and 4 trials 3, 1. Consultation with an infectious disease specialist is strongly recommended when considering tigecycline use 3.

Appropriate Clinical Scenarios for Tigecycline Use

Multidrug-Resistant Gram-Negative Infections

For carbapenem-resistant Enterobacteriaceae (CRE) infections:

• Tigecycline is recommended for pulmonary and intra-abdominal infections caused by CRE when newer agents (ceftazidime-avibactam, meropenem-vaborbactam, cefiderocol) are not available or not active 3
• Always use combination therapy (not monotherapy) for severe CRE infections 4, 2
• Standard dosing: 100 mg IV loading dose followed by 50 mg IV every 12 hours 4

For carbapenem-resistant Acinetobacter baumannii (CRAB) pulmonary infections:

• Both tigecycline-based and polymyxin-based combination therapies are equally preferable - choice should be based on patient factors 3
• Check MIC before use: Tigecycline efficacy is comparable to polymyxin when MIC ≤2 mg/L, but inferior when MIC >2 mg/L 3, 4
• Use polymyxin preferentially in patients with liver insufficiency 3
• Use tigecycline preferentially in patients with renal insufficiency (225 fewer nephrotoxicity events per 1000 patients versus colistin) 3

Vancomycin-Resistant Enterococci (VRE)

• Standard dosing (100 mg loading, then 50 mg every 12 hours) is appropriate for VRE complicated intra-abdominal infections 4, 2

Dosing Considerations

Standard Dosing

• Loading dose: 100 mg IV 1
• Maintenance: 50 mg IV every 12 hours 1
• Infusion time: 30-60 minutes 1
• Duration: 5-14 days for skin/intra-abdominal infections; 7-14 days for pneumonia 1

High-Dose Regimen for Severe Infections

For HAP/VAP caused by multidrug-resistant organisms (when no alternatives exist):

• 200 mg IV loading dose followed by 100 mg IV every 12 hours 4
• This high-dose regimen achieves 85% cure rates versus 69.6% with standard dosing 4, 2
• High-dose tigecycline is the only independent predictor of clinical cure in critically ill patients with VAP 3

Hepatic Impairment

• Severe hepatic impairment (Child-Pugh C): Reduce maintenance dose by 50% (50 mg loading, then 25 mg every 12 hours) 4
• Use cautiously in any degree of liver insufficiency 3, 5

Common Pitfalls to Avoid

1. Using tigecycline for complicated urinary tract infections - Aminoglycosides are superior to tigecycline for cUTI caused by CRE (moderate certainty evidence) 3

2. Underdosing for pneumonia - Standard dosing has poor pulmonary efficacy due to extremely low endothelial lining fluid concentrations (0.01-0.02 mg/L); always use high-dose regimen if treating pneumonia 2

3. Using as monotherapy for bacteremia - Poor serum concentrations lead to treatment failure 4, 2

4. Ignoring MIC values - Always determine MIC against the isolate before treatment, especially for CRAB 3, 5

5. Using when newer agents are available - For CRE, newer β-lactam/β-lactamase inhibitors (ceftazidime-avibactam, meropenem-vaborbactam) should be used preferentially when susceptible 5

Safety Profile

Advantages over polymyxins:

• Significantly lower nephrotoxicity (RR 0.23,95% CI 0.11-0.46) 3
• Lower incidence of nausea/vomiting (6.3% vs 35.9%) 3

Disadvantages:

• Higher incidence of abdominal pain (18.8% vs 2.6% with polymyxins) 3
• Potential for thrombocytopenia and elevated liver enzymes 3
• Numerically higher mortality and clinical failure rates versus polymyxins (though not statistically significant with very low certainty evidence) 3