Tigecycline 

  • Bacteriostatic (mostly)
  • Time-dependent activity
  • High intracellular penetration

Boxed Warning

U.S. Food and Drug Administration issued a black box warning due to:

Increased all-cause mortality compared to other antibiotics

Seen especially in:

  • VAP
  • Severe sepsis


 Spectrum of Activity

Tigecycline has very broad coverage, especially against resistant gram-positives and gram-negatives.

 Gram Positive

  • MRSA
  • VRE (VanA and VanB)
  • Penicillin-resistant Streptococcus pneumoniae

 Gram Negative

  • ESBL-producing Enterobacteriaceae
  • Carbapenem-resistant Enterobacteriaceae (CRE) (some activity)
  • Acinetobacter baumannii (variable)
  • Stenotrophomonas maltophilia


 No Activity Against:

  • Pseudomonas aeruginosa
  • Proteus species
  • Providencia
  • Morganella


 FDA Approved Indications

Approved by U.S. Food and Drug Administration for:

  1. Complicated intra-abdominal infection (cIAI)
  2. Complicated skin and soft tissue infection (cSSTI)
  3. Community-acquired bacterial pneumonia (CABP)


⚠ Not preferred for:

  • Bloodstream infections (low serum levels)
  • VAP (increased mortality signal)


 Pharmacokinetics 

Absorption

  • IV only

Distribution

  • Excellent tissue penetration:
    • Lung
    • Intra-abdominal tissues
    • Soft tissue

But:

  • Low serum concentration because of Very large Vd→ Not ideal for bacteremia


 PK/PD Target

  • AUC/MIC ratio drives efficacy
  • Time-dependent killing with prolonged post-antibiotic effect


 Adverse Effects

Common

  • Nausea (very common)
  • Vomiting
  • Diarrhea

Serious

  • Hepatotoxicity
  • Pancreatitis
  • Coagulopathy (hypofibrinogenemia – ICU pearl)
  • Increased mortality warning


 Special Situations

1. Hepatic Impairment

  • Child-Pugh C → reduce maintenance dose

2. Renal Failure

  • No dose adjustment required

3. Pregnancy

  • Category D
  • Avoid (teeth discoloration risk)


 Resistance Mechanisms

  • Efflux pump overexpression
  • Tet(X) enzyme mediated degradation (emerging)
  • Ribosomal mutations


 Role in CRE Era

In carbapenem-resistant Enterobacteriaceae:

  • Used as combination therapy
  • Combined with:
    • Colistin
    • Carbapenem (double carbapenem strategy)
    • Fosfomycin

Never preferred as monotherapy in severe CRE sepsis.