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Soru

Zorluk: OrtaInfectious Disease Mechanisms

An infection control consultation is requested for a 55-year-old male patient in the surgical intensive care unit who recently developed a catheter-related bloodstream infection. The patient was admitted three weeks ago following a high-speed motor vehicle collision that required multiple exploratory laparotomies and bowel resections. During his hospitalization, he received prolonged courses of empiric broad-spectrum antibiotics. Today, blood cultures drawn from his central venous catheter are positive for Gram-positive cocci arranged in pairs and short chains. The pathogen is confirmed to be highly resistant to both ampicillin and vancomycin. Which of the following molecular mechanisms most likely explains this pathogen's resistance to the glycopeptide antibiotic?

  1. Substitution of a terminal D-lactate for D-alanine in the peptidoglycan precursorCevap
  2. B
    Acquisition of a mobile genetic element encoding an altered penicillin-binding protein
  3. C
    Plasmid-mediated production of an acetyltransferase enzyme that covalently modifies the antibiotic
  4. D
    Methylation of the 23S ribosomal RNA binding site by an acquired methylase
  5. E
    Upregulation of an active transmembrane efflux pump preventing intracellular accumulation

Cevap

Substitution of a terminal D-lactate for D-alanine in the peptidoglycan precursor
The correct answer accurately describes the mechanism of vancomycin resistance in Enterococcus species. Vancomycin normally binds to the terminal D-alanyl-D-alanine of cell wall precursor peptides. Enterococci can acquire mobile genetic elements (vanA or vanB operons) that encode enzymes to synthesize precursors terminating in D-alanyl-D-lactate instead. This structural change removes a critical hydrogen bond, dramatically lowering vancomycin's binding affinity and conferring resistance.

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1
Identify the likely pathogen based on the clinical vignette and microbiological data.
The patient has a hospital-acquired infection with Gram-positive cocci in pairs and short chains, strongly suggesting Enterococcus species.
Enterococci commonly cause infections in patients with prolonged ICU stays, prior abdominal surgery, and heavy exposure to broad-spectrum antibiotics.
2
Analyze the specific resistance profile provided in the stem.
The pathogen is resistant to ampicillin and vancomycin, identifying it as Vancomycin-Resistant Enterococcus (VRE).
The question specifically asks for the mechanism of resistance to the glycopeptide antibiotic (vancomycin).
3
Recall the molecular mechanism of vancomycin resistance in VRE.
Resistance occurs via alteration of the terminal amino acids of the peptidoglycan precursor from D-alanyl-D-alanine to D-alanyl-D-lactate.
Vancomycin works by binding strongly to the D-alanyl-D-alanine terminus, inhibiting cell wall cross-linking. The D-alanyl-D-lactate alteration decreases vancomycin's binding affinity by a factor of 1,000, allowing cell wall synthesis to continue.

Anahtar Kavram

Vancomycin-Resistant Enterococcus (VRE) resistance mechanism
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Konular

Infectious Disease Mechanisms

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