What is the use and dosage of Tigecycline (generic name) in treating infections?

Tigecycline: Uses, Dosage, and Clinical Applications

Tigecycline is a glycylcycline antimicrobial agent primarily indicated for complicated skin and skin structure infections, complicated intra-abdominal infections, and community-acquired bacterial pneumonia in adults 18 years and older, with specific dosing of 100 mg IV loading dose followed by 50 mg IV every 12 hours. 1

FDA-Approved Indications

Complicated Skin and Skin Structure Infections

• Effective against susceptible isolates of:
  • Escherichia coli
  • Enterococcus faecalis (vancomycin-susceptible)
  • Staphylococcus aureus (methicillin-susceptible and -resistant)
  • Streptococcus species (including S. agalactiae, S. anginosus group)
  • Enterobacter cloacae
  • Klebsiella pneumoniae
  • Bacteroides fragilis 1

Complicated Intra-abdominal Infections

• Effective against susceptible isolates of:
  • Multiple Enterobacteriaceae (C. freundii, E. cloacae, E. coli, K. oxytoca, K. pneumoniae)
  • Gram-positive cocci (E. faecalis, S. aureus, S. anginosus group)
  • Anaerobes (B. fragilis, B. thetaiotaomicron, B. uniformis, B. vulgatus, C. perfringens) 1

Community-Acquired Bacterial Pneumonia

• Effective against susceptible isolates of:
  • Streptococcus pneumoniae (penicillin-susceptible)
  • Haemophilus influenzae
  • Legionella pneumophila 1

Important Limitations of Use

• Not indicated for diabetic foot infections
• Not indicated for hospital-acquired or ventilator-associated pneumonia due to increased mortality and decreased efficacy compared to other agents 1

Standard Dosing Regimen

• Initial dose: 100 mg IV
• Maintenance dose: 50 mg IV every 12 hours
• Infusion duration: 30-60 minutes
• Treatment duration:
  • Skin/skin structure infections: 5-14 days
  • Intra-abdominal infections: 5-14 days
  • Community-acquired pneumonia: 7-14 days 1

Dosage Adjustments

Hepatic Impairment

• Mild to moderate impairment (Child-Pugh A and B): No adjustment needed
• Severe impairment (Child-Pugh C): 100 mg loading dose, then 25 mg every 12 hours 1

Renal Impairment

• No dosage adjustment necessary, even in patients undergoing hemodialysis 1

Pediatric Considerations

• Safety and efficacy not established in pediatric patients
• Use should be avoided unless no alternative antibacterial drugs are available
• If necessary:
  • Ages 8-11 years: 1.2 mg/kg every 12 hours IV (maximum 50 mg per dose)
  • Ages 12-17 years: 50 mg every 12 hours IV 2, 1

Role in Multidrug-Resistant Infections

Vancomycin-Resistant Enterococci (VRE)

• Recommended for intra-abdominal infections caused by VRE
• Not recommended for VRE bacteremia due to low serum levels 2

Carbapenem-Resistant Enterobacteriaceae (CRE)

• May be used in combination therapy for CRE infections
• Standard dose may be insufficient for bloodstream infections
• High-dose tigecycline (200 mg loading, 100 mg every 12 hours) may be considered for severe infections 2

Carbapenem-Resistant Acinetobacter baumannii (CRAB)

• May be used for pulmonary and intra-abdominal infections caused by CRAB
• Consider combination therapy with other active agents 2
• Efficacy may depend on MIC values (better outcomes when MIC ≤2 mg/L) 2

Clinical Considerations and Cautions

Safety Concerns

• WARNING: Increased all-cause mortality observed in meta-analysis (0.6% higher than comparators) 1
• Common adverse effects:
  • Nausea (28.5%)
  • Vomiting (19.4%)
  • Diarrhea (11.6%)
  • Local IV-site reactions (8.2%) 3

Pharmacokinetic Properties

• Large volume of distribution (7-9 L/kg)
• Moderate protein binding (71-89%)
• Terminal half-life: approximately 42 hours
• Elimination: primarily biliary/fecal (59%) and renal (33%) 3, 4
• Extensive tissue penetration but low serum concentrations 4

Drug Interactions

• Does not inhibit major CYP450 enzymes
• Monitor prothrombin time when co-administered with warfarin
• Slight decrease in digoxin Cmax (13%) but no significant clinical effect 1

Special Considerations for Resistant Infections

High-Dose Regimen

• For severe infections with resistant pathogens, high-dose tigecycline (200 mg loading dose, 100 mg every 12 hours) may be considered 2
• May improve outcomes in severe infections caused by multidrug-resistant organisms 2

Combination Therapy

• Due to uncertainties about efficacy in off-label indications, combination with another active agent is recommended when possible 2
• Common combination partners include polymyxins, carbapenems, and aminoglycosides 2

Common Pitfalls to Avoid

1. Using tigecycline for bacteremia or urinary tract infections - Low serum and urinary concentrations make it suboptimal for these indications
2. Monotherapy for severe infections - Consider combination therapy for severe multidrug-resistant infections
3. Standard dosing for highly resistant pathogens - Higher doses may be needed for optimal efficacy
4. Use in hospital-acquired pneumonia - Associated with higher mortality compared to other agents

Tigecycline remains an important option for complicated infections caused by multidrug-resistant pathogens, particularly when alternatives are limited, but should be used judiciously with consideration of its limitations and potential risks.