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Zorluk: OrtaInfectious Disease Mechanisms

A 54-year-old woman is evaluated in the intensive care unit for worsening respiratory status. She was admitted 14 days ago for management of extensive third-degree burns covering 40% of her total body surface area. Over the past 24 hours, she has developed a new-onset fever, tachycardia, and increased purulent endotracheal secretions requiring higher ventilator settings. Her temperature is 39.4°C (102.9°F), blood pressure is 90/55 mmHg, and heart rate is 118/min. A Gram stain of the endotracheal aspirate reveals numerous neutrophils and Gram-negative bacilli. The organism is non-lactose-fermenting, oxidase-positive, and produces a blue-green pigment on culture. Antimicrobial susceptibility testing results for the isolate are shown below:

Antimicrobial AgentSusceptibility
CeftazidimeSusceptible
CefepimeSusceptible
CiprofloxacinSusceptible
ImipenemResistant

Which of the following cellular mechanisms best explains this isolate's specific antimicrobial resistance profile?

  1. Mutational loss or downregulation of a specific outer membrane porin channelCevap
  2. B
    Acquisition of a plasmid-encoded metallo-beta-lactamase
  3. C
    Overexpression of a multidrug efflux pump system
  4. D
    Target site modification through the synthesis of altered penicillin-binding proteins
  5. E
    Structural alteration of terminal D-alanyl-D-alanine peptidoglycan precursors

Cevap

Mutational loss or downregulation of a specific outer membrane porin channel
The patient has developed a healthcare-associated pneumonia secondary to Pseudomonas aeruginosa. The microbiological description (non-lactose-fermenting, oxidase-positive, Gram-negative rod producing a blue-green pigment) is highly characteristic of this organism. The antimicrobial susceptibility testing reveals a classic pattern: isolated resistance to imipenem with preserved susceptibility to antipseudomonal cephalosporins (ceftazidime, cefepime) and fluoroquinolones. Imipenem is unique among beta-lactams in that it traverses the outer membrane of P. aeruginosa almost exclusively via the OprD porin channel. Consequently, mutational loss, structural alteration, or transcriptional downregulation of OprD prevents imipenem from reaching its target penicillin-binding proteins (PBPs) in the periplasmic space, conferring resistance. Because cephalosporins and other beta-lactams utilize different porins or pathways for entry, they retain their efficacy against OprD-deficient strains.

Adım Adım Çözüm

1
Identify the causative pathogen from the clinical and microbiological data.
The patient has ventilator-associated pneumonia caused by Pseudomonas aeruginosa, evidenced by a non-lactose-fermenting, oxidase-positive Gram-negative bacillus producing a blue-green pigment (pyocyanin) in a burn patient.
Correct identification of the organism is required to interpret species-specific resistance patterns accurately.
2
Analyze the provided antimicrobial susceptibility profile.
The isolate demonstrates isolated resistance to imipenem, while retaining susceptibility to other antipseudomonal beta-lactams (ceftazidime, cefepime) and fluoroquinolones (ciprofloxacin).
Different resistance mechanisms confer distinct phenotypic patterns of antimicrobial susceptibility.
3
Determine the molecular mechanism that explains isolated carbapenem resistance in this specific pathogen.
Imipenem uniquely relies on the OprD outer membrane porin to penetrate the cell envelope of P. aeruginosa. Loss of this porin confers resistance to imipenem while sparing agents that use alternative entry pathways.
Linking the unique phenotypic profile to the precise cellular mechanism identifies the correct answer.

Anahtar Kavram

Isolated imipenem resistance in Pseudomonas aeruginosa is classically mediated by the mutational loss or downregulation of the OprD outer membrane porin channel.
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Infectious Disease Mechanisms

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