What is tigecycline?
Tigecycline, known commercially as Tygacil®, is an intravenous glycylcycline antibiotic. Derived from minocycline, it's designed to overcome common antibiotic resistance mechanisms. Its broad-spectrum activity includes many multidrug-resistant strains, making it important for complex infections.
Approved uses of tigecycline
Tigecycline is approved for adults with specific, serious bacterial infections, typically when alternatives aren't viable. Approved uses include:
- Complicated skin and soft tissue infections (cSSTIs): Such as abscesses, cellulitis, and surgical site infections from susceptible pathogens, including MRSA.
- Complicated intra-abdominal infections (cIAIs): Including complicated appendicitis, intra-abdominal abscesses, and peritonitis caused by susceptible bacteria.
- Community-acquired bacterial pneumonia (CAP): For CAP caused by certain susceptible bacteria like Streptococcus pneumoniae and Haemophilus influenzae.
Tigecycline is not approved for hospital-acquired pneumonia, ventilator-associated pneumonia (VAP), or diabetic foot infections due to observed higher mortality rates in some trials.
Mechanism of action
Tigecycline inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit. This blocks aminoacyl-tRNA binding, preventing protein chain formation. Its modified structure enhances ribosome binding and helps overcome resistance mechanisms like efflux pumps and ribosomal protection.
Role in treating multidrug-resistant bacteria
Given rising antibiotic resistance, tigecycline is a crucial option for difficult-to-treat pathogens. It is effective against many MDR strains:
- MRSA
- VRE
- CRE
- ESBL-producing bacteria
- Multi-drug resistant Acinetobacter baumannii
However, some bacteria like Pseudomonas aeruginosa, Proteus spp., and Morganella spp. are naturally resistant. Acquired resistance is also a concern.
Important warnings and considerations
The FDA issued a boxed warning for tigecycline in 2010 due to increased all-cause mortality risk compared to other antibiotics, particularly in hospital-acquired pneumonia patients. Therefore, it should be reserved for approved uses when other options are unavailable.
Other considerations and side effects include:
- Gastrointestinal Issues: High rates of nausea and vomiting are common, potentially leading to treatment discontinuation.
- Pancreatitis: Fatal acute pancreatitis has been reported.
- Liver Problems: Liver injury and hepatic failure can occur.
- Pregnancy and Pediatric Use: Avoid use in the second or third trimester of pregnancy and in children under 8 due to risks of tooth discoloration and bone growth inhibition.
- Drug Interactions: Tigecycline can reduce hormonal contraceptive effectiveness and increase warfarin effects.
How tigecycline compares to other antibiotics
Tigecycline's profile distinguishes it from other antibiotics. Here's a comparison:
| Feature | Tigecycline | Imipenem/Cilastatin | Vancomycin | Colistin |
|---|---|---|---|---|
| Drug Class | Glycylcycline | Carbapenem (β-Lactam) | Glycopeptide | Polymyxin |
| Spectrum | Very broad (Gram+, Gram-, Anaerobes), including MDR strains like MRSA, VRE, CRE | Broad (Gram+, Gram-, Anaerobes) | Narrow (primarily Gram+) | Narrow (primarily Gram-) |
| Mechanism | Inhibits protein synthesis (30S ribosome) | Inhibits cell wall synthesis | Inhibits cell wall synthesis | Disrupts cell membrane |
| Administration | Intravenous only | Intravenous only | Intravenous, Oral (for C. diff) | Intravenous, Inhaled |
| Mortality Warning | FDA Boxed Warning for increased all-cause mortality | No | No | No (but significant renal toxicity) |
| MDR Pathogens | Effective against many MDR Gram+ and Gram- | Limited effectiveness against CRE | Effective against MRSA, VRE | Effective against many CRE |
| Adverse Effects | High rates of nausea, vomiting | Gastrointestinal upset, seizures | Nephrotoxicity, ototoxicity | Nephrotoxicity, neurotoxicity |
| Last-Resort Use | Often used as last resort for MDR strains | Less commonly due to resistance | Reserved for specific resistant Gram+ | Often reserved for highly resistant Gram- |
Common and serious side effects
Tigecycline can cause various side effects. Common issues include significant nausea, vomiting, and diarrhea. Injection site reactions are also frequent. Less common but serious side effects can include allergic reactions, liver injury, fatal pancreatitis, increased intracranial pressure, and hematologic changes. Photosensitivity is also a possibility.
Conclusion
Tigecycline is a vital antibiotic for treating specific serious infections, especially those caused by multidrug-resistant bacteria. Its approved uses include complicated skin and soft tissue infections, complicated intra-abdominal infections, and certain community-acquired pneumonias. However, its use is limited by an FDA boxed warning regarding increased all-cause mortality risk, particularly in severe infections like hospital-acquired pneumonia. Its unique mechanism helps overcome resistance, making it a valuable option against challenging pathogens. Due to common side effects and the potential for serious complications, tigecycline is reserved for cases where other treatments are unsuitable.
This article provides general information and is not a substitute for professional medical advice. Always consult a healthcare provider for diagnosis and treatment.
