Despite a broad spectrum covering MRSA, ESBL producers, and anaerobes, tigecycline carries a boxed warning against empiric use in serious infections with documented or suspected bloodstream involvement. The pharmacokinetic reason is:
- A It is highly protein bound and displaced by other antibiotics, lowering free serum levels
- B The drug undergoes extensive first-pass metabolism making IV levels unpredictable
- C Serum concentrations achieved are low because the drug distributes rapidly and extensively into tissues ✓
- D It is cleared so rapidly by glomerular filtration that trough levels fall below the MIC within hours
Correct answer: C. Serum concentrations achieved are low because the drug distributes rapidly and extensively into tissues
Explanation
Tigecycline has a very large volume of distribution exceeding 7 L/kg because it avidly penetrates and accumulates in tissues, leaving peak serum concentrations of only about 0.5 to 1 mg/L, below the MIC90 of many bacteremic pathogens. Meta-analyses showed increased mortality when it was used for severe infections including bacteremia, prompting the warning. It is given intravenously, so first-pass metabolism is irrelevant, and rapid renal clearance is incorrect since fecal-biliary excretion predominates.
Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.