What is the role of tigecycline in treating sepsis?

Tigecycline in Sepsis: Limited Role with Specific Considerations

Tigecycline should not be used as first-line monotherapy for sepsis due to evidence of inferiority compared to other antibiotics for bloodstream infections and concerns about increased mortality. 1

Efficacy Limitations in Sepsis

• Tigecycline has shown inferior outcomes compared to aminoglycosides and polymyxin-based regimens for bloodstream infections caused by carbapenem-resistant Enterobacteriaceae (CRE) (low certainty evidence) 1
• The FDA drug label specifically warns against monotherapy with tigecycline in patients with complicated intra-abdominal infections secondary to intestinal perforation due to risk of sepsis/septic shock 2
• Tigecycline performs poorly in bacteremic patients due to low plasma concentrations, increasing the risk of failing to clear bloodstream infections 3

Potential Role in Specific Scenarios

• Tigecycline may be considered as part of combination therapy for multidrug-resistant infections, particularly when options are limited 3
• For intra-abdominal infections with severe sepsis or septic shock caused by CRE, tigecycline-based combination therapy with polymyxin or meropenem may be considered (weak recommendation, very low quality evidence) 1
• Higher dosing regimens of tigecycline (200 mg loading dose followed by 100 mg twice daily) should be used if tigecycline is necessary for hospital-acquired pneumonia/ventilator-associated pneumonia with sepsis 1

Safety Concerns

• The FDA drug label includes a boxed warning about increased all-cause mortality risk with tigecycline compared to other antibiotics (adjusted risk difference 0.6%, 95% CI 0.1-1.2%) 2
• Serious adverse reactions of sepsis/septic shock were more frequently reported for subjects treated with tigecycline (2%) versus comparators (1%) 2
• Common adverse effects include nausea (26%), vomiting (18%), diarrhea (12%), and abnormal liver function tests 2
• Acute pancreatitis, including fatal cases, has occurred with tigecycline treatment 2

Recommendations for Clinical Practice

• Aminoglycosides are preferred over tigecycline for urinary tract infections with sepsis (moderate certainty evidence) 1
• For CRE infections causing sepsis, newer agents like ceftazidime-avibactam, meropenem-vaborbactam, or cefiderocol should be considered before tigecycline when available 1
• If tigecycline must be used in sepsis, it should generally be part of combination therapy rather than monotherapy 1
• Determine the MIC value of tigecycline against the causative organism before treatment initiation when possible - efficacy is comparable to polymyxin when MIC ≤2 mg/L, but inferior when MIC >2 mg/L 3

Special Considerations

• In patients with limited treatment options due to multidrug-resistant pathogens, tigecycline may provide a valuable alternative as part of combination therapy 4, 5
• Some observational studies have reported successful outcomes with tigecycline in critically ill patients with severe sepsis or septic shock, particularly when used in combination with other antibiotics 4, 6
• Monitor closely for superinfections from Enterobacteriaceae that are inherently resistant to tigecycline, especially when used as monotherapy 5
• Tigecycline should be avoided in pregnant women due to potential fetal harm 2