A patient with community-acquired pneumonia fails azithromycin therapy. Sputum culture grows Streptococcus pneumoniae with high-level macrolide resistance (MIC >256 µg/mL). The MOST likely resistance mechanism is:

• A Mutation in the 30S ribosomal protein S12 preventing azithromycin binding
• B Methylation of 23S rRNA adenine at position 2058 by an erm(B) methyltransferase, conferring MLSB phenotype ✓
• C Upregulation of MexAB-OprM efflux pump mediating azithromycin export
• D Enzymatic cleavage of the azithromycin macrolactone ring by an esterase encoded on integron platforms

Explanation

High-level macrolide resistance in Streptococcus pneumoniae is predominantly mediated by erm(B) gene-encoded 23S rRNA methyltransferases (post-transcriptional methylation of A2058 in domain V), which prevents binding of all macrolides, lincosamides, and streptogramins B (MLSB phenotype). MICs >256 µg/mL strongly indicate ribosomal methylation. Efflux (mef genes) produces lower-level resistance (MIC 1–32 µg/mL). MexAB-OprM is a Pseudomonas aeruginosa efflux system. Enzymatic macrolide esterases (ere genes) are rare in pneumococcus.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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