What is the role of tigecycline in the treatment of pneumonia?

Role of Tigecycline in the Treatment of Pneumonia

Tigecycline should not be used as monotherapy for the treatment of pneumonia, particularly hospital-acquired or ventilator-associated pneumonia, due to higher mortality rates and treatment failure compared to alternative therapies. 1

FDA-Approved Indications and Limitations

• Tigecycline is FDA-approved for community-acquired bacterial pneumonia (CAP) caused by susceptible isolates of Streptococcus pneumoniae (penicillin-susceptible isolates), Haemophilus influenzae, and Legionella pneumophila 2
• Tigecycline carries a boxed warning regarding increased all-cause mortality observed in clinical trials compared to alternative treatments 2
• Tigecycline is specifically NOT indicated for the treatment of hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) due to greater mortality and decreased efficacy reported in clinical trials 2

Evidence Against Tigecycline Monotherapy for Pneumonia

• Tigecycline monotherapy has demonstrated a higher rate of treatment failure compared to colistin monotherapy, colistin combination therapy, and sulbactam-based therapy for carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia 1
• A matched cohort study comparing colistin versus tigecycline favored colistin-based therapy for multi-drug-resistant (MDR) pneumonia 1
• The excess mortality with tigecycline may be related to higher A. baumannii MIC of tigecycline (>2 mg/mL) 1
• Guidelines strongly recommend against tigecycline monotherapy for the treatment of CRAB pneumonia 1

Potential Role in Combination Therapy

• For carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia, tigecycline may be considered as part of combination therapy when the MIC is ≤2 mg/L 1
• A randomized study of extensively drug-resistant A. baumannii ventilator-associated pneumonia showed that combination of tigecycline and cefoperazone-sulbactam had synergistic activity and higher clinical response rates than tigecycline monotherapy 1
• For CRAB pneumonia, guidelines suggest colistin with or without carbapenems as the preferred treatment, with tigecycline only as part of combination therapy in specific scenarios 1

Dosing Considerations

• Standard dosing for community-acquired pneumonia is 100 mg IV loading dose, followed by 50 mg IV every 12 hours for 7-14 days 2, 3
• Higher dosing regimens (100 mg IV followed by 50 mg IV every 12 hours or 200 mg IV followed by 100 mg IV every 12 hours) have been studied for hospital-acquired pneumonia with some evidence suggesting better outcomes with the higher dose 4
• In patients with severe hepatic impairment (Child Pugh C), the initial dose should be 100 mg followed by a reduced maintenance dose of 25 mg every 12 hours 2

Pharmacokinetic Considerations

• Tigecycline has good penetration into lung tissue, which theoretically supports its use in respiratory infections 5, 6
• Despite good tissue penetration, tigecycline performs poorly in bacteremic patients due to low plasma concentrations 7
• The clinical efficacy of tigecycline is associated with its MIC value against MDR organisms - comparable to polymyxin when MIC ≤2 mg/L, but inferior when MIC >2 mg/L 7

Alternative Treatment Options

• For CRAB pneumonia, colistin (with or without carbapenems) and adjunctive inhaled colistin therapy is recommended as first-line treatment 1
• Alternative treatments for CRAB pneumonia include high-dose sulbactam (6-9 g/day) or triple therapy with colistin, tigecycline, and sulbactam 1
• For Pseudomonas aeruginosa infections, tigecycline is not recommended due to inadequate activity 8

Adverse Effects and Monitoring

• Common adverse effects include nausea, vomiting, and diarrhea 7, 3
• The FDA has issued a boxed warning regarding increased all-cause mortality with tigecycline compared to alternative treatments 2
• Patients should be monitored for adverse effects, particularly gastrointestinal symptoms and liver function abnormalities 7

Conclusion

Tigecycline has a limited role in pneumonia treatment. While FDA-approved for community-acquired pneumonia, it should not be used as monotherapy for hospital-acquired, ventilator-associated, or carbapenem-resistant Acinetobacter baumannii pneumonia due to higher mortality rates and treatment failure. Its use should be restricted to combination therapy in specific scenarios when alternative treatments are not suitable, and preferably after consultation with an infectious disease specialist.