Tigecycline

Tigecycline is a glycylcycline given intravenously, with activity against MRSA, vancomycin-resistant enterococci, many ESBL and carbapenem-resistant Enterobacterales, Acinetobacter and anaerobes. Low serum levels and increased mortality in pooled analyses restrict it to infection without a better option.

Classification. Glycylcycline.

Mechanism. Binds the 30S ribosomal subunit with high affinity and overcomes efflux and ribosomal protection resistance; bacteriostatic.

Spectrum. MRSA, MSSA, streptococci, vancomycin-resistant enterococci, ESBL Enterobacterales, carbapenem-resistant Klebsiella and Escherichia coli (variable), Acinetobacter, Stenotrophomonas, anaerobes, atypical bacteria and rapidly growing mycobacteria. Not active against Pseudomonas, Proteus, Providencia or Morganella.

Pharmacokinetics. IV only. Half-life about 42 hours. Large volume of distribution, so serum and urinary concentrations are low (about 22% excreted in urine). Mainly biliary elimination.

Reserve agent; use only when alternatives are unsuitable. Maximum 100 mg every 12 hours (high-dose regimen).

Adults.

• Loading dose 100 mg, then 50 mg IV over 30 to 60 minutes every 12 hours.
• Complicated skin and soft tissue infection, complicated intra-abdominal infection: 5 to 14 days.
• Community-acquired bacterial pneumonia: 7 to 14 days.
• High-dose regimen (specialist use for multidrug-resistant infection, hospital-acquired pneumonia, severe infection): 200 mg loading dose, then 100 mg every 12 hours, usually with a second active agent.
• Not suitable for bacteraemia, urinary infection, diabetic foot infection or ventilator-associated pneumonia as monotherapy.

Children. Only when no alternative exists: 8 to under 12 years 1.2 mg/kg every 12 hours (maximum 50 mg a dose); 12 to under 18 years 50 mg every 12 hours.

Alternatives. Eravacycline, omadacycline, colistin-based regimens, ceftazidime avibactam, meropenem.

Boxed-warning level risk. Higher all-cause mortality than comparator drugs in pooled analyses; use only when other options are not suitable.

Contraindications. Hypersensitivity to tetracyclines; pregnancy; children under 8 years except in life-threatening disease.

Adverse effects. Nausea and vomiting (very common, up to 30%), diarrhoea, raised bilirubin and liver enzymes, hypofibrinogenaemia with coagulopathy, pancreatitis, photosensitivity, tooth staining. Serious: hepatotoxicity and cholestasis, anaphylaxis, Clostridioides difficile infection, severe skin reactions.

Interactions. Warfarin (INR rise); oral contraceptives (possible reduced efficacy); other tetracyclines; no cytochrome P450 interactions of clinical significance.

Common prescribing errors. Using it for bacteraemia or urinary infection, using it for Pseudomonas or Proteus, using the low dose for resistant Acinetobacter, and not slowing the infusion in nausea.

Special groups. - Pregnancy: avoid (foetal tooth and bone effects). Breastfeeding: avoid. - Older adults: usual dose. - Kidney impairment: no adjustment, including haemodialysis. - Liver impairment: Child-Pugh A or B no change; Child-Pugh C 100 mg loading dose then 25 mg every 12 hours. - Region: availability in East Africa is limited.

Preparation. Reconstitute each 50 mg vial with 5.3 mL of 0.9% sodium chloride or 5% glucose (10 mg/mL), then add to a 100 mL bag; infuse over 30 to 60 minutes. Antiemetics can reduce nausea; slow the infusion if needed.

Baseline and monitoring. - Baseline: liver tests, fibrinogen, prothrombin time, lipase if abdominal pain, pregnancy test. - During treatment: liver tests and fibrinogen twice weekly; INR in warfarin users; lipase if pain.

Stop rules. Stop for pancreatitis, severe hepatotoxicity, anaphylaxis or severe skin reaction.

Referral and escalation. Infectious diseases consultation is needed before use and for any off-label regimen.