Tedizolid is a second-generation oxazolidinone with improved activity over linezolid. Which feature explains its activity against some linezolid-resistant staphylococci carrying the cfr gene?
- A Tedizolid binds ribosomal protein L3 instead of the 23S rRNA
- B Tedizolid avoids the ribosomal methylation site targeted by the Cfr methyltransferase due to its morpholino side chain ✓
- C Tedizolid is a prodrug activated by tissue phosphatases, achieving higher intracellular concentrations
- D Tedizolid inhibits DHFR in addition to protein synthesis
Correct answer: B. Tedizolid avoids the ribosomal methylation site targeted by the Cfr methyltransferase due to its morpholino side chain
Explanation
The cfr gene encodes a methyltransferase (Cfr) that methylates adenosine at position A2503 of 23S rRNA, the binding site for linezolid. Tedizolid's morpholino side chain results in a slightly different binding geometry at the ribosomal A-site, reducing the impact of Cfr-mediated methylation, conferring partial activity against cfr-positive isolates. Tedizolid is indeed a phosphate prodrug (tedizolid phosphate), but the key mechanistic advantage over cfr resistance is its altered ribosomal contact points.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.