Tigecycline: glycylcycline reserve antibiotic
Tigecycline (brand name Tygacil) is the first clinically used glycylcycline antibiotic, an evolution of the tetracyclines. Approval in 2005 made available a reserve antibiotic active against many multi resistant pathogens including MRSA, ESBL producers and some carbapenem resistant Enterobacteriaceae. Because of an increased mortality in trials versus comparator antibiotics, tigecycline is used under tight indications and primarily in specialised centres.
Tigecycline is given exclusively intravenously and is approved for specific infection types, mainly complicated skin, soft tissue and intra abdominal infections. Use in nosocomial pneumonia is restricted after safety reviews and only justified in exceptional situations.
Mechanism of action
Like all tetracyclines, tigecycline binds to the 30S subunit of the bacterial ribosome and blocks attachment of aminoacyl tRNA to the A site. Protein synthesis is inhibited and bacterial growth is arrested. The action is primarily bacteriostatic.
The decisive difference compared with classical tetracyclines is the N alkyl glycylamido side chain at position 9. This modification bypasses the most important tetracycline resistance mechanisms, namely efflux pumps (Tet A to Tet E) and ribosomal protection proteins (Tet M, Tet O). The result is a markedly broader spectrum, with activity against MRSA, VRE, ESBL producers, many carbapenemase producing Enterobacteriaceae, Stenotrophomonas, Acinetobacter and some anaerobes.
Tigecycline is not orally bioavailable and is administered intravenously. Elimination is mainly biliary, so no adjustment is needed in renal impairment.
Indications
- Complicated skin and soft tissue infections (cSSTI): including deep infections, polymicrobial cases and MRSA infections when other options are unsuitable
- Complicated intra abdominal infections (cIAI): after hollow organ perforation or sepsis of abdominal origin
- Reserve therapy in multi resistant pathogens: particularly in carbapenem resistant Enterobacteriaceae, mainly in combination therapy
- Nosocomial pneumonia: not approved for community acquired pneumonia and only with particular caution in nosocomial pneumonia because of mortality data
Dosing and administration
Standard dose: initial dose 100 mg intravenously, then 50 mg every 12 hours over 30 to 60 minutes.
Duration: depending on infection and clinical course, generally 5 to 14 days. Severe infections may require longer therapy.
Renal impairment: no dose adjustment required.
Severe hepatic impairment (Child Pugh C): initial dose 100 mg, then 25 mg every 12 hours.
Use is in the clinical setting under medical supervision. Careful indication and resistance testing are standard.
Adverse effects
Very common: nausea, vomiting, diarrhoea, abdominal pain.
Common: raised liver transaminases, hyperbilirubinaemia, dizziness, headache, anaemia, pruritus, rash, phlebitis at the infusion site.
Uncommon: pancreatitis, seizures, hypoglycaemia, prolonged prothrombin time, anaphylactoid reactions.
Rare and very rare: Stevens Johnson syndrome, severe liver reactions, bone or tooth discolouration with use in pregnancy or in children under 8 years, antibiotic associated colitis from Clostridioides difficile.
Important safety aspects:
- Increased mortality in pooled studies versus comparator antibiotics; review the indication strictly
- Caution in nosocomial pneumonia, where mortality in trials was clinically meaningfully increased
- Exclude pancreatitis if sudden abdominal pain occurs
- Close monitoring of liver enzymes
Interactions
- Vitamin K antagonists (warfarin, phenprocoumon): potentiation, INR monitoring
- Oral contraceptives: theoretically reduced efficacy through gut flora effects; clinical relevance limited
- Calcium containing solutions: incompatibility, separate infusion line
- Other myelotoxic or nephrotoxic agents: caution in combination, individual assessment
Special considerations
Pregnancy: not recommended because of possible effects on fetal bone development and tooth discolouration. Only in life threatening situations without alternative.
Breastfeeding: not recommended.
Children under 8 years: contraindicated because of tooth discolouration. In adolescents over 8 years use is possible after individual evaluation.
Liver disease: dose reduction in severe hepatic impairment. Close monitoring of liver enzymes.
Antibiotic stewardship: tigecycline is a reserve antibiotic. Use is justified only when less toxic and better established alternatives are not possible. Resistance testing is standard.
Patient communication: in patients in critical care or with complex infections, realistic information about treatment duration, possible adverse events and the risk of increased mortality is important. The decision is often taken in an interdisciplinary team of infectious diseases, intensive care and microbiology.
Related substances
- Oxytetracycline, classical tetracycline
- Aztreonam, monobactam reserve antibiotic
- Tazobactam, beta lactamase inhibitor
- Sulbactam, beta lactamase inhibitor
- Imipenem, broad spectrum carbapenem
Frequently asked questions
When is tigecycline used?
Tigecycline is a reserve antibiotic in complicated skin, soft tissue and intra abdominal infections, particularly when multi resistant pathogens are involved. Wide or casual use is avoided because of the mortality data.
Why restricted use in pneumonia?
Clinical trials showed an increased mortality in nosocomial pneumonia compared with comparator antibiotics. Plasma levels and tissue penetration in lung tissue were discussed as causes. Tigecycline is therefore used in pneumonia only in exceptional cases.
Does tigecycline work against MRSA?
Yes, tigecycline has very good activity against MRSA. In complicated skin and soft tissue infections with confirmed MRSA and intolerance of other agents tigecycline is an option. Therapy is generally chosen after resistance testing.
What checks are required?
Before therapy: blood count, liver enzymes, pancreatic enzymes, resistance testing. During therapy: liver enzymes and clinical assessment. Exclude pancreatitis with sudden abdominal pain. INR monitoring with concurrent anticoagulation.
Sources
- EMA Tygacil (tigecycline) EPAR
- BfArM German Federal Institute for Drugs and Medical Devices
- AWMF guidelines sepsis and intra abdominal infections
- Gelbe Liste tigecycline monograph
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