Tigecycline

Published: 17.7.21

Nature: Glycylcycline, a member of the tetracycline family. Semisynthetic derivative of minocycline.
Molecular weight: 585.6

Mechanism of action

1. Bind to 30S ribosomal subunit and inhibit protein synthesis – It inhibits the attachment of aminoacyl tRNA to the A site and prevents chain elongation, i.e. block the translation process.

2. Inhibit mitochondrial protein synthesis by binding to 70 S ribosome (parasites).

Mechanism of resistance

Two major mechanisms of resistance exist –

1. Overexpression of efflux pump – help to remove tigecycline from the bacterial cell:

  • mepA -MATE family of efflux pump –in Staph aureus.

  • Multidrug efflux pump (AcrAB/AcrEF/AdeABC) – in gram-negative bacteria.

  • Multdrug efflux pump (MexXY) – in Pseudomonas

2. Enzymatic modification – inactivates tigecycline: tetX gene-mediated.

Caution/contraindication

1. Avoid in children <18 years of age – no data, similar adverse effect as tetracycline (bone growth abnormality, tooth discolouration).

2. Dose adjustment in severe hepatic impairment.

3. Avoid in pregnancy.

4. May increase INR when used with warfarin. May increase PT, aPTT.

PK/PD

1. Protein binding: 80%

2. Food improves tolerability.

3. Tissue to plasma concentration ratio is high—low concentration in serum.

4. T1/2 = 37-66hr

5. Route – IV

6. Excretion: Mainly excreted through the liver. Renal clearance is only <15%.

7. It doesn’t interact with CYP450.

Adverse effect

GI side effects (nausea, vomiting)- commonest.

Transient increase in ALT, AST, alk phosphatase.

Potential tooth discolouration and inhibition of bone growth if used in children (or pregnancy) – no data.

Rare: Hyperpigmentation, electrolyte imbalance, dizziness, vaginitis etc.

Use

Complicated skin and soft tissue infection.

Complicated intraabdominal infection.

MHRA update 2014 – Use only when other antibiotics are unsuitable

Spectrum

Gram-positive:

  • MSSA, MRSA, Streptococcus, Enterococcus including VRE, Listeria, Corynebacterium – Susceptible.

Gram-negative:

  • Most enterobacterales (except – Proteus, Providencia, Morganella), Acinetobacter, Stenotrophomonas, Neisseria -Susceptible.

  • Pseudomonas is resistant,

  • Burkholderia -may be resistant.

  • Proteus, Providencia, Morganella has high MIC/resistant.

Anaerobe:

  • Susceptible, including C difficile.

  • Some strains of B fragilis could be resistant.

Atypical bacteria:

  • Mycoplasma, Chlamydia -Susceptible,

  • Rapid growing mycobacteria: fortutum, abscessus, chelonae, smegmatis – Susceptible.

  • Legionella may have high MIC.

Tetracycline and Tigecycline – similarities and difference

  1. Tigecycline belongs to the tetracycline family, it is a minocycline derivative.

  2. It attaches to 30S ribosome like tetracycline and prevents protein synthesis, however, it also binds to the ribosomal binding site and binding is much stronger than tetracycline.

  3. It is not affected by ribosomal binding site protection (tetM, tetO mediated) which confers tetracycline resistance.

Possible questions

  1. Tigecycline – SAQ

  2. Mechanism of action and mechanism of resistance.

  3. MCQ based on Mechanism of action/resistance

  4. Mutations and efflux pumps involved in resistance

  5. MCQ/OSPE based on susceptibility profile, esp. learn those that are resistant.

  6. Management of Multi-drug resistant gram-negative bacteria, like NDM-1