What is the recommended dose of Tigecycline (generic name) for a patient with normal renal function and no history of hepatic impairment?

Tigecycline Dosing Recommendations

For patients with normal renal function and no hepatic impairment, the FDA-approved standard dose of tigecycline is 100 mg IV loading dose followed by 50 mg IV every 12 hours, infused over 30-60 minutes. 1

Standard Dosing Regimen

• The recommended initial dose is 100 mg IV, followed by 50 mg IV every 12 hours 1
• Each dose should be infused over approximately 30 to 60 minutes 1
• No dose adjustment is required for renal impairment, including patients on continuous renal replacement therapy 1
• No dose adjustment is needed for mild to moderate hepatic impairment (Child-Pugh A and B) 1

Duration of Therapy by Indication

• Complicated skin and skin structure infections: 5 to 14 days 1
• Complicated intra-abdominal infections: 5 to 14 days 1, 2
• Community-acquired bacterial pneumonia: 7 to 14 days 1

High-Dose Tigecycline for Severe Infections

While the FDA-approved standard dosing remains the official recommendation, emerging evidence supports higher dosing in specific severe infection scenarios:

• For severe hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), a high-dose regimen of 200 mg IV loading dose followed by 100 mg IV every 12 hours has demonstrated superior cure rates (85% vs 69.6% with standard dosing) 3, 4
• For carbapenem-resistant Enterobacterales (CRE) infections, high-dose tigecycline (200 mg loading, then 100 mg every 12 hours) in combination therapy significantly reduced mortality (OR 0.44,95% CI 0.30-0.66) compared to standard dosing 2
• High-dose tigecycline is particularly important when treating multidrug-resistant organisms with MIC values approaching breakpoints 3

Critical Clinical Caveats

Tigecycline should NOT be used as monotherapy for bloodstream infections due to poor serum concentrations and documented treatment failures with standard dosing 3, 4

• Tigecycline is NOT indicated for hospital-acquired or ventilator-associated pneumonia per FDA labeling due to increased mortality in comparative trials 1
• Tigecycline is NOT indicated for diabetic foot infections as clinical trials failed to demonstrate non-inferiority 1
• For bacteremia, tigecycline should only be used in combination therapy with other active agents (such as colistin, meropenem, or aminoglycosides) 2, 3

Specific Infection Scenarios

Community-Acquired Intra-Abdominal Infections (Non-Critically Ill)

• For patients at risk for ESBL-producing Enterobacteriaceae: 100 mg loading dose, then 50 mg every 12 hours 2

Healthcare-Associated Intra-Abdominal Infections

• As carbapenem-sparing regimen: combine piperacillin/tazobactam 4.5 g every 6 hours with tigecycline 100 mg loading dose, then 50 mg every 12 hours 2, 3

Carbapenem-Resistant Enterobacterales (CRE) Infections

• Standard dose (100 mg loading, then 50 mg every 12 hours) in combination therapy for intra-abdominal infections 2, 3
• Consider high-dose regimen (200 mg loading, then 100 mg every 12 hours) for bloodstream infections in combination with colistin or meropenem 2, 3
• Tigecycline should only be used when isolate MIC ≤0.5 mg/L to avoid increased mortality 2

Vancomycin-Resistant Enterococci (VRE)

• Standard dose: 100 mg loading dose, then 50 mg every 12 hours for complicated intra-abdominal infections 3, 4

Pharmacokinetic Considerations

• Standard dosing achieves serum Cmax of only 0.87 mg/L, which may be insufficient for bloodstream infections 3
• Tigecycline has excellent tissue penetration (Vd 7-9 L/kg) but low serum and urinary concentrations, limiting its use in bacteremia and urinary tract infections 2, 5
• The elimination half-life is 42.4 hours, allowing for sustained tissue concentrations 5
• Tigecycline is eliminated primarily by biliary/fecal (59%) and renal (33%) excretion 5

Important Safety Considerations

• The FDA issued a boxed warning noting increased all-cause mortality (0.6% absolute risk difference) in tigecycline-treated patients versus comparators 4
• Consultation with an infectious disease specialist is strongly recommended when considering tigecycline use 4
• Most common adverse events include nausea (28.5%), vomiting (19.4%), and diarrhea (11.6%) 1, 5
• Tigecycline has significantly lower nephrotoxicity compared to polymyxin-based therapy 4