Tigecycline is a glycylcycline that overcomes the two most common mechanisms of tetracycline resistance. These mechanisms are:

• A Enzymatic inactivation by tetracycline-acetyltransferase and porin channel downregulation
• B Efflux pumps (TetA-E, TetK/L) and ribosomal protection proteins (TetM, TetO); tigecycline is a poor efflux pump substrate and has high affinity for the protected ribosome ✓
• C Modification of 50S ribosomal binding site and reduced intracellular drug uptake
• D Beta-lactamase co-production neutralizing tetracycline and altered outer membrane permeability

Explanation

Classical tetracycline resistance is mediated by: (1) active efflux via Tet efflux pumps (TetA-E in gram-negatives; TetK/L in gram-positives) that export tetracycline out of the cell, and (2) ribosomal protection proteins (TetM, TetO) that bind to the 30S ribosomal subunit and conformationally protect it from tetracycline binding. Tigecycline has a bulky glycylamido side chain at C9 that makes it a very poor substrate for efflux pumps and allows it to still bind to the ribosome even when TetM/TetO protection proteins are present. This is why tigecycline is active against many MRSA, VRSA, and multidrug-resistant organisms that are resistant to classical tetracyclines.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.