Tigecycline (Tygacil)

Indications

Complicated Skin/Skin Structure Infections (see Cellulitis, [[Cellulitis]])

Community-Acquired Pneumonia (CAP) (see Pneumonia, [[Pneumonia]])

  • Haemophilus Influenzae (see Haemophilus Influenzae, [[Haemophilus Influenzae]]): beta lactamase-negative isolates
  • Legionella Pneumophila (see Legionellosis, [[Legionellosis]])
  • Streptococcus Pneumoniae (Pneumococcus) (see Streptococcus Pneumoniae, [[Streptococcus Pneumoniae]]): penicillin-susceptible isolates

Complicated Intra-Abdominal Infections


Pharmacology

  • Glycylcycline Antibiotic
    • Structural similarity with tetracyclines (see Tetracyclines, [[Tetracyclines]]): tigecycline is a derivative of minocycline and may share some tetracycline-associated class adverse effects
    • Mechanism: binds to 30s bacterial ribosomal subunit, inhibiting protein synthesis
      • Bacteriostatic: in most cases
      • Bacteriocidal: in some cases (certain isolates of Streptococcus Pneumoniae and Legionella Pneumophila)

Metabolism

  • Hepatic: via glucuronidation, N-acetylation, and epimerization
    • 59% excreted in feces (as unchanged drug)
  • Renal
    • 33% excreted in urine (mostly as unchanged drug)
  • Pharmacokinetics
    • Elimination Half-Life: 27 hrs (after single dose) -> 42 hrs (after multiple doses)

Administration

  • IV (Complicated Skin/Skin Structure Infections, Community-Acquired Pneumonia, Complicated Intra-Abdominal Infections): 100 mg, then 50 mg q12hrs

Dose Adjustment

  • Hepatic
    • Mild-Mod Impairment (Child-Pugh Class A or B): none
    • Severe Impairment (Child-Pugh Class C): 100 mg, then 25 mg q12 hrs
  • Renal: none

Adverse Effects

Gastrointestinal Adverse Effects

  • Abdominal Pain (see Abdominal Pain, [[Abdominal Pain]]): occurs in 6% of cases
  • Acute Pancreatitis (see Acute Pancreatitis, [[Acute Pancreatitis]]): cases have been reported
  • Diarrhea (see Diarrhea, [[Diarrhea]]): occurs in 12% of cases
  • Nausea (see Nausea and Vomiting, [[Nausea and Vomiting]])
    • Nausea: 26% of cases
    • Vomiting: 18% of cases
  • Elevated Liver Function Tests (LFT’s) (see Drug-Induced Hepatotoxicity, [[Drug-Induced Hepatotoxicity]])
    • Elevated Alk Phosph: occurs in 3% of cases
    • Elevated Total Bilirubin: occurs in 2% of cases
    • Transaminitis: occurs in 4-5% of cases

Neurologic Adverse Effects

Renal Adverse Effects

  • Increased Blood Urea Nitrogen (BUN): occurs in 3% of cases

Other Adverse Effects

  • Increased All-Cause Mortality (of Unclear Etiology): reported in phase 3 and 4 trials
  • Thrombophlebitis: occurs in 3% of cases

References

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