Tigecycline Coverage in Pneumonia
Tigecycline should NOT be used for hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP), and should only be considered for community-acquired pneumonia (CAP) in hospitalized patients when fluoroquinolones cannot be used, with the critical caveat that it carries an FDA boxed warning for increased mortality. 1, 2
FDA-Approved Indication and Critical Warnings
Tigecycline is FDA-approved for community-acquired bacterial pneumonia (CABP) in adults ≥18 years, but is explicitly NOT indicated for hospital-acquired pneumonia or ventilator-associated pneumonia. 2
The FDA issued a boxed warning due to increased all-cause mortality compared to control antibiotics in meta-analyses of phase III and IV clinical trials, particularly in severe infections. 1
Consultation with an infectious disease specialist is recommended when considering tigecycline use. 1
Microbiological Coverage Spectrum
Tigecycline provides broad coverage against CAP pathogens, including:
Gram-positive organisms: Streptococcus pneumoniae (including penicillin-resistant strains), methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA/MRSA), Streptococcus pyogenes. 2, 3
Gram-negative organisms: Haemophilus influenzae, Moraxella catarrhalis (including β-lactamase producers), Klebsiella pneumoniae, Enterobacter species. 2, 4
Atypical pathogens: Legionella pneumophila, Mycoplasma pneumoniae, Chlamydophila pneumoniae. 3, 4
Anaerobes: Bacteroides fragilis and other anaerobic species. 2
Clinical Efficacy Data in CAP
In two phase III randomized controlled trials comparing tigecycline (100 mg loading dose, then 50 mg IV q12h) versus levofloxacin in hospitalized CAP patients, clinical cure rates were non-inferior: 89.7% versus 86.3% in clinically evaluable populations and 81.0% versus 79.7% in modified intent-to-treat populations. 2, 5
For Streptococcus pneumoniae specifically (including penicillin-susceptible strains), cure rates were 95.7% with tigecycline versus 88.6% with levofloxacin, including cases with concurrent bacteremia (90.9% versus 72.2%). 2
Eradication rates for S. pneumoniae were 92% for tigecycline versus 89% for levofloxacin. 6
Explicit Contraindications in HAP/VAP
For HAP/VAP, tigecycline is strongly contraindicated:
The IDSA/ATS 2016 guidelines provide a strong recommendation against tigecycline use in patients with HAP/VAP caused by Acinetobacter species, based on low-quality evidence showing inferior outcomes. 1
Tigecycline is notably absent from all empirical treatment algorithms for HAP/VAP in both low-risk and high-risk MDRO settings, where antipseudomonal β-lactams, fluoroquinolones, aminoglycosides, and polymyxins are preferred. 1, 7, 8
The FDA label explicitly states tigecycline is not indicated for hospital-acquired pneumonia, including ventilator-associated pneumonia. 2
Limited Role in CAP
When tigecycline might be considered for CAP (with extreme caution):
As an alternative parenteral monotherapy option in hospitalized patients with moderate-severity CAP (CURB-65 score 2-3) who cannot receive fluoroquinolones due to contraindications or allergies. 1, 4
The Taiwan pneumonia guidelines note that tigecycline use is associated with increased all-cause mortality and recommend infectious disease consultation before use. 1
Tigecycline should not be used in severe CAP requiring ICU admission, where combination therapy with β-lactam plus macrolide or fluoroquinolone is strongly preferred. 1, 9
Dosing and Administration
Standard dosing: 100 mg IV loading dose, followed by 50 mg IV every 12 hours for 7-14 days total therapy duration. 2, 10
Tigecycline achieves effective lung tissue penetration with a prolonged post-antibiotic effect and long serum elimination half-life. 3
Common Pitfalls to Avoid
Never use tigecycline for HAP/VAP – this is explicitly contraindicated by FDA labeling and major guidelines. 1, 2
Avoid in severe CAP – recent mortality data suggest increased risk in severe infections; reserve for mild-to-moderate hospitalized CAP only. 1, 4
Do not use as first-line therapy – tigecycline should only be considered when standard agents (β-lactam/macrolide combinations or fluoroquinolones) cannot be used. 1
Anticipate gastrointestinal adverse effects – nausea (20.8%) and vomiting (13.2%) occur significantly more frequently than with comparators like levofloxacin (6.6% and 3.3% respectively). 2, 5
Recognize lack of Pseudomonas coverage – tigecycline has poor activity against Pseudomonas aeruginosa and should never be used when this pathogen is suspected. 4