Pharmacology · Antibacterial Spectrum (Aminoglycosides, Macrolides, Tetracyclines, Metronidazole)

The mechanism of macrolide resistance most commonly acquired by Streptococcus pneumoniae in community-acquired pneumonia is:

  • A Efflux pump overexpression (mef gene) removing macrolides from the bacterial cell
  • B Ribosomal methylation of the 23S rRNA at the macrolide binding site (erm gene-encoded methylase), causing cross-resistance to macrolides, lincosamides, and streptogramin B (MLSB phenotype)
  • C Acquisition of a plasmid encoding macrolide esterase that hydrolyses the lactone ring of erythromycin
  • D Downregulation of the LPS outer membrane proteins reducing macrolide penetration into the pneumococcal cell wall
Correct answer: B. Ribosomal methylation of the 23S rRNA at the macrolide binding site (erm gene-encoded methylase), causing cross-resistance to macrolides, lincosamides, and streptogramin B (MLSB phenotype)

Explanation

In S. pneumoniae, the two principal mechanisms of macrolide resistance are: (1) erm(B)-mediated ribosomal methylation of adenine-2058 in domain V of 23S rRNA, conferring high-level resistance to all macrolides AND lincosamides AND streptogramin B (MLS_B phenotype); and (2) mef(A/E)-mediated macrolide efflux pump providing low-level resistance (usually conferring 14/15-membered macrolide resistance only). The erm(B) mechanism predominates in Southeast Asia and is more clinically important for treatment failure. Macrolide esterase is found in certain Enterobacteriaceae, not pneumococci. Pneumococcus has no outer LPS membrane.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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