Tigecycline: Indications, Dosage, and Treatment Duration in Adults
FDA-Approved Indications
Tigecycline is FDA-approved for three specific indications in adults ≥18 years: complicated skin and skin structure infections (cSSSI), complicated intra-abdominal infections (cIAI), and community-acquired bacterial pneumonia (CAP). 1
Approved Indications:
Complicated skin and skin structure infections (cSSSI): Caused by susceptible isolates including E. coli, Enterococcus faecalis (vancomycin-susceptible), S. aureus (MRSA and MSSA), Streptococcus species, Enterobacter cloacae, K. pneumoniae, and B. fragilis 1
Complicated intra-abdominal infections (cIAI): Caused by susceptible isolates including Citrobacter freundii, E. cloacae, E. coli, Klebsiella species, Enterococcus faecalis (vancomycin-susceptible), S. aureus (MRSA and MSSA), Streptococcus anginosus group, Bacteroides species, C. perfringens, and Peptostreptococcus micros 1
Community-acquired bacterial pneumonia (CAP): Caused by S. pneumoniae (penicillin-susceptible), H. influenzae, and Legionella pneumophila, including cases with concurrent bacteremia 1, 2
Critical Contraindications:
- NOT approved for diabetic foot infections (clinical trial failed to demonstrate non-inferiority) 1
- NOT approved for hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) due to greater mortality and decreased efficacy in comparative trials 1, 3
Standard Dosage Regimen
The FDA-approved standard dosage is 100 mg IV loading dose, followed by 50 mg IV every 12 hours, administered over 30-60 minutes. 1
Standard Dosing Details:
- Loading dose: 100 mg IV 1
- Maintenance dose: 50 mg IV every 12 hours 1
- Infusion time: 30-60 minutes 1
- No renal adjustment required: Dosing remains unchanged in renal impairment or continuous renal replacement therapy 4
Treatment Duration
For cSSSI and cIAI, treat for 5-14 days; for CAP, treat for 7-14 days, guided by severity, infection site, and clinical response. 1
Duration by Indication:
- Complicated skin and skin structure infections: 5-14 days 1
- Complicated intra-abdominal infections: 5-14 days 1
- Community-acquired bacterial pneumonia: 7-14 days 1, 2
Special Dosing Considerations
Hepatic Impairment:
- Mild to moderate hepatic impairment (Child-Pugh A and B): No dose adjustment needed 1
- Severe hepatic impairment (Child-Pugh C): Reduce maintenance dose by 50% (100 mg loading dose, then 25 mg every 12 hours); monitor closely for treatment response 1
Higher Dosing for Severe Infections (Off-Label):
For severe infections, particularly HAP/VAP or multidrug-resistant organisms, consider high-dose regimen: 200 mg IV loading dose followed by 100 mg IV every 12 hours, which achieves cure rates of 85% versus 69.6% with standard dosing. 4, 5
- Rationale: Standard dosing achieves serum Cmax of only 0.87 mg/L, insufficient for bloodstream infections, and low endothelial lining fluid concentrations (0.01-0.02 mg/L) explain lower efficacy in VAP 4
- Specific scenarios: Carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia or bloodstream infections, carbapenem-resistant Enterobacterales (CRE), and vancomycin-resistant Enterococci (VRE) 4, 5
Off-Label Use for Multidrug-Resistant Organisms
CRAB Infections:
For CRAB pneumonia or bloodstream infections, tigecycline should NEVER be used as monotherapy; combination therapy with colistin and sulbactam is recommended (100 mg loading, then 50 mg every 12 hours). 4
- Pneumonia: Triple combination therapy for at least 7 days 4
- Bloodstream infections: Triple combination therapy for 10-14 days 4
- MIC consideration: Use only if MIC ≤2 mg/L 4, 5
CRE and VRE Infections:
- CRE intra-abdominal infections: 100 mg loading, then 50 mg every 12 hours, preferably in combination with polymyxins or carbapenems 4, 5
- VRE intra-abdominal infections: 100 mg loading, then 50 mg every 12 hours 4, 5
Non-Tuberculous Mycobacterial (NTM) Infections:
- Dosing: 100 mg loading, then 50 mg twice daily (some studies use 50 mg/day for improved tolerance, though once-daily dosing is unproven) 3
- Note: Not licensed for NTM treatment in the UK 3
Critical Safety Warnings
FDA Boxed Warning:
Tigecycline carries an FDA boxed warning for increased all-cause mortality (0.6% absolute risk increase, 95% CI 0.1-1.2%) observed in meta-analysis of Phase 3 and 4 trials; reserve use for situations when alternative treatments are not suitable. 1, 3
Specific Cautions:
- Avoid monotherapy for bacteremia: Poor outcomes with standard dosing due to low serum concentrations 4, 5
- Pregnancy and breastfeeding: Evidence of fetal harm in animal studies 3
- Children <8 years: Risk of tooth discoloration 3
- Coagulation: May prolong PT and aPTT 3
Common Adverse Effects:
- Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain (most common) 3, 6
- Hepatic: Elevated liver function tests 3
- Advantage: Significantly lower nephrotoxicity compared to colistin-based therapy 5
Practical Clinical Algorithm
Step 1: Confirm Appropriate Indication
- Is this cSSSI, cIAI, or CAP? → Use tigecycline 1
- Is this diabetic foot infection or HAP/VAP? → DO NOT USE tigecycline 1
Step 2: Assess for MDR Organisms
- If CRAB, CRE, or VRE suspected → Consider high-dose regimen (200 mg loading, then 100 mg every 12 hours) AND combination therapy 4, 5
- If standard pathogens → Use FDA-approved dosing (100 mg loading, then 50 mg every 12 hours) 1
Step 3: Check Hepatic Function
- Severe hepatic impairment (Child-Pugh C)? → Reduce maintenance to 25 mg every 12 hours 1
- Mild-moderate impairment or normal? → No adjustment needed 1
Step 4: Determine Duration
- cSSSI or cIAI → 5-14 days 1
- CAP → 7-14 days 1
- CRAB pneumonia → At least 7 days 4
- CRAB bloodstream → 10-14 days 4