What is the recommended dose of tigecycline (generic) for treating bloodstream infection sepsis?

Tigecycline Dosing for Bloodstream Infection Sepsis

For bloodstream infections caused by multidrug-resistant organisms, a high-dose tigecycline regimen of 200 mg loading dose followed by 100 mg every 12 hours is recommended due to the poor outcomes associated with standard dosing in bacteremia. 1

Rationale for High-Dose Regimen

Tigecycline presents unique pharmacokinetic challenges in bloodstream infections:

• Standard dosing (100 mg loading, then 50 mg q12h) results in low serum concentrations (Cmax <0.87 mg/L) 1
• Clinical series consistently show poor outcomes with standard-dose tigecycline in bacteremia 1
• Tigecycline has a large volume of distribution that limits its effectiveness in bloodstream infections 1

Specific Dosing Recommendations

For Bloodstream Infections:

• Loading dose: 200 mg IV once
• Maintenance dose: 100 mg IV every 12 hours
• Duration: 10-14 days 1

Important Considerations:

• Due to uncertainties about efficacy in bloodstream infections, tigecycline should be used in combination with another active agent when possible 1
• Combination therapy is particularly important when treating carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infections 1

Evidence Supporting High-Dose Regimen

Multiple studies support the use of high-dose tigecycline for bloodstream infections:

• A population pharmacokinetic study in patients with sepsis or septic shock demonstrated that high-dose tigecycline (200 mg loading, 100 mg q12h) achieved more favorable drug concentrations 2
• An observational cohort study showed significantly longer survival times with high-dose versus standard-dose tigecycline in carbapenem-resistant Klebsiella pneumoniae bloodstream infections (mean: 83 days vs. 28 days; p=0.027) 3
• High-dose tigecycline has been successfully used to treat extensively drug-resistant Acinetobacter baumannii bloodstream infections, with better outcomes observed in non-pulmonary-related BSI 4
• Even in cases of pandrug-resistant organisms with in vitro resistance to tigecycline, high-dose regimens have successfully eradicated bloodstream infections 5

Clinical Pitfalls and Caveats

• Tigecycline is not FDA-approved for bloodstream infections, and its use represents off-label application 6
• Standard-dose tigecycline should be avoided for bloodstream infections due to consistently poor outcomes 1
• The source of infection impacts treatment success - bloodstream infections secondary to pulmonary sources may have worse outcomes with tigecycline compared to non-pulmonary sources 4
• Tigecycline should not be used as monotherapy for serious bloodstream infections 1
• Common adverse effects include nausea, vomiting, and diarrhea, but high-dose regimens have not shown significantly increased adverse events compared to standard dosing 3

Alternative Options

If tigecycline cannot be used or is inappropriate, consider:

• Colistin-carbapenem combination therapy (for CRAB bloodstream infections) 1
• Polymyxin-based combinations for carbapenem-resistant organisms 1
• Newer agents such as ceftazidime-avibactam for specific resistant pathogens 1

Remember that treatment should be guided by susceptibility testing whenever possible, and source control remains a critical component of successful management of bloodstream infections.