Tigecycline is a glycylcycline antibiotic active against tetracycline-resistant organisms. Which resistance mechanisms overcome by tigecycline explain its expanded spectrum compared to earlier tetracyclines?

• A Tigecycline is immune to ribosomal protection proteins (Tet[M], Tet[O]) and major efflux pumps (Tet[A], Tet[B]) that confer tetracycline resistance ✓
• B Tigecycline inhibits both the 30S and 50S ribosomal subunits unlike tetracyclines that only inhibit 30S
• C Tigecycline has a higher affinity for beta-lactamases making it immune to enzymatic degradation
• D Tigecycline penetrates the outer membrane of gram-negatives through OmpF rather than OmpC porins

Explanation

Tigecycline is a 9-glycylamido derivative of minocycline. Its bulky side chain at position 9 sterically prevents binding by tetracycline ribosomal protection proteins (TetM, TetO) and also makes it a poor substrate for major tetracycline efflux pumps (TetA, TetB) — the two principal resistance mechanisms in gram-positives and gram-negatives. This resistance bypass accounts for tigecycline's activity against many tetracycline-resistant organisms. However, Pseudomonas aeruginosa and Proteus spp. possess intrinsic non-tet efflux pumps (MexXY-OprM, AcrAB-TolC) that still export tigecycline, explaining its intrinsic resistance there.

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

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