Tigecycline

FDA‑approved uses:

• Complicated skin and skin structure infections (cSSSI)
• Complicated intra‑abdominal infections (cIAI)
• Community‑acquired bacterial pneumonia (CABP)

Important off‑label uses (specialist-guided):

• Multidrug-resistant Gram-negative infections (e.g., Acinetobacter baumannii, ESBL-producing Enterobacteriaceae)
• Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) when no alternatives available
• Severe bloodstream infections secondary to intra-abdominal or skin sources (limited evidence)

Adults (≥ 18 years):

• Loading dose: 100 mg IV over 30–60 min
• Maintenance dose: 50 mg IV every 12 h
• Duration: 5–14 days for cSSSI/cIAI; 7–14 days for CABP

Pediatrics (8–17 years):

• 8–11 years: 2.4 mg/kg loading, then 1.2 mg/kg q12 h (max 50 mg/dose)
• 12–17 years: 50 mg IV every 12 h

Renal impairment: No dosage adjustment needed (including dialysis).
Hepatic impairment:

• Mild–moderate (Child-Pugh A/B): no adjustment
• Severe (Child-Pugh C): reduce maintenance dose to 25 mg q12 h after 100 mg loading

Elderly: Same as adults; monitor hepatic/renal status.
Administration tips: Infuse over 30–60 min; flush IV lines before and after infusion.

Tigecycline is a glycylcycline antibiotic that reversibly binds to the 30S ribosomal subunit, blocking aminoacyl‑tRNA entry and inhibiting protein synthesis. It overcomes common tetracycline resistance mechanisms, including ribosomal protection and efflux pumps, providing activity against MRSA, VRE, and many resistant Gram‑negatives (excluding Pseudomonas).

• Absorption: Only administered IV; no oral absorption
• Distribution: Very large volume (~7–10 L/kg), with extensive tissue penetration (lungs, intra‑abdominal tissue), but relatively low serum levels
• Protein binding: 71–89%
• Metabolism: Minimal, via non‑CYP pathways (e.g., glucuronidation); no significant active metabolites
• Elimination: Approximately 59% biliary/fecal, 33% renal (unchanged/metabolites)
• Half-life: ~27 hours (single dose); ~42 hours at steady state; prolonged in hepatic impairment

• Pregnancy: Category D—animal studies show risk to fetus (bone ossification effects). Use only if maternal benefits justify fetal risk.
• Lactation: Unknown if excreted in human milk; potential for effects on infant bone/tooth development. Breastfeeding not recommended during treatment.

• Primary Class: Antibacterial
• Subclass: Glycylcycline (tetracycline derivative)

• Hypersensitivity to tigecycline or tetracyclines
• Children under 8 years old (due to permanent tooth discoloration and bone growth inhibition)
• Severe hepatic impairment without dose adjustment

• Black-box warning: Increased all-cause mortality observed; reserve for serious infections without alternative options
• Hypersensitivity: Severe reactions including anaphylaxis have been reported
• Pancreatitis, hepatic dysfunction, pseudotumor cerebri: Monitor for clinical signs
• Pediatric use: Avoid in children < 8 years due to bone/tooth development risk
• Clostridium difficile–associated diarrhea and superinfections: Monitor for GI symptoms

Common (>10%):

• Nausea (~30%), vomiting (~20%), diarrhea (~13%)

Other (1–10%):

• Headache, fever, abdominal pain, anemia, hypotension, dyspnea, pruritus, rash

Serious/Rare:

• Pancreatitis, liver injury, coagulation abnormalities, severe skin reactions, anaphylaxis, superinfection

• Warfarin: May increase bleeding risk; monitor INR
• Oral contraceptives: Antibacterial effect may reduce efficacy; recommend alternate contraception
• Minimal CYP450 interactions; not a significant substrate, inhibitor, or inducer

• FDA box warning (2010 & 2013): Emphasized increased mortality and restricted indication use
• WHO Watch List: Tigecycline is included due to resistance monitoring
• EMA/NICE guidance: Recommend tigecycline only when alternatives are unsuitable; caution in pediatric use

• Unopened vials: Store at 20–25 °C; protect from light and humidity
• Reconstituted solution: Stable for 6 h at room temperature or 24 h under refrigeration (2–8 °C); do not freeze
• Handling: Use aseptic technique; flush IV lines before and after infusion