A 58-year-old man in the ICU with ventilator-associated pneumonia is started on tigecycline. Blood cultures grow Pseudomonas aeruginosa. Despite appropriate susceptibility-adjusted dosing, he deteriorates. The most important limitation of tigecycline explaining this outcome is:
- A It has no intrinsic activity against Gram-negative bacilli
- B It is rapidly degraded by pulmonary beta-lactamases
- C It achieves very low serum concentrations because it distributes extensively into tissues ✓
- D It antagonizes concurrently administered beta-lactams
Correct answer: C. It achieves very low serum concentrations because it distributes extensively into tissues
Explanation
Tigecycline has a huge volume of distribution because it penetrates tissues avidly, leaving very low serum and urinary concentrations. It is approved for complicated intra-abdominal, skin and community-acquired infections but is not indicated for hospital-acquired or ventilator-associated pneumonia or bloodstream infection, and it has no useful activity against Pseudomonas. Meta-analyses have shown increased mortality when tigecycline is used outside its approved indications.
Reference: Katzung Basic and Clinical Pharmacology, 16th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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