ESBL and CRE pathogens

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ESBL Pathogens - The Cephalosporin Crushers

  • Mechanism: Extended-spectrum β-lactamase enzymes hydrolyze and inactivate most penicillins and cephalosporins (1st, 2nd, and 3rd generations).
  • Key Pathogens: 📌 Primarily Klebsiella pneumoniae and Escherichia coli.
  • Treatment of Choice: Carbapenems (e.g., Meropenem, Imipenem).
  • Lab Detection: Confirmed by showing synergy between a 3rd-gen cephalosporin and a β-lactamase inhibitor (e.g., clavulanic acid).

ESBL and CRE detection methods

⭐ ESBL genes are typically located on plasmids, facilitating horizontal gene transfer and rapid spread of resistance between different bacterial species.

CRE Pathogens - Carbapenem's Kryptonite

  • Mechanism: Production of carbapenemase enzymes (e.g., KPC, NDM, OXA-48) that hydrolyze carbapenems.
  • Genetics: Resistance genes are often carried on mobile plasmids, facilitating rapid horizontal transfer among different bacterial species.
  • Key Pathogens: 📌 KEEp resisting Carbapenems: Klebsiella pneumoniae, Enterobacter spp., E. coli.
  • Clinical Impact: Cause severe, high-mortality infections (bacteremia, pneumonia, UTIs), particularly in ICU and immunocompromised patients.
  • Treatment: Requires newer β-lactam/β-lactamase inhibitor combos (e.g., ceftazidime-avibactam) or last-resort agents like polymyxins.

⭐ The blaKPC gene, a common carbapenemase gene, is frequently located on a mobile Tn4401 transposon within plasmids, contributing to its widespread dissemination.

Mechanisms of Antibiotic Resistance

Lab Diagnosis - Unmasking the Resistance

  • ESBL Detection:

    • Screening: Check for resistance to 3rd-gen cephalosporins (e.g., ceftazidime, ceftriaxone).
    • Confirmation: Phenotypic tests use a β-lactamase inhibitor. A ≥5 mm increase in inhibition zone with clavulanate + cephalosporin is positive.
  • CRE Detection:

    • Screening: Test for resistance to any carbapenem (e.g., meropenem).
    • Confirmation (Carbapenemase Production):
      • Carba NP Test: Rapid colorimetric assay detects carbapenemase activity.
      • Molecular Tests (PCR): Gold standard. Identifies specific resistance genes like blaKPC, blaNDM, blaOXA-48.

⭐ The Modified Hodge Test (MHT) is no longer recommended by CLSI due to low specificity and being difficult to interpret.

Treatment Strategies - The Counter-Offensive

  • ESBL Infections: Carbapenems (Meropenem, Imipenem) are the drugs of choice for systemic infections.

    • For uncomplicated cystitis, oral options like Nitrofurantoin or Fosfomycin may be sufficient.
  • CRE Infections: Treatment is guided by the type of carbapenemase produced.

High-Yield: For Metallo-β-lactamases (MBLs) like NDM, Aztreonam is not hydrolyzed by MBLs but is degraded by co-produced ESBL/AmpC. Adding Ceftazidime-avibactam protects Aztreonam by inhibiting these other β-lactamases, creating a potent combination therapy.

  • ESBLs are plasmid-mediated enzymes, primarily in E. coli and Klebsiella, that inactivate most penicillins and cephalosporins.
  • Carbapenems are the empiric treatment of choice for serious ESBL infections.
  • CRE (Carbapenem-Resistant Enterobacterales) are a major threat due to resistance to carbapenems, often via carbapenemase enzymes (e.g., KPC).
  • CRE infections are associated with high mortality and are often acquired in healthcare settings.
  • Treatment for CRE is difficult, requiring newer β-lactam/β-lactamase inhibitor combinations or polymyxins.

Practice Questions: ESBL and CRE pathogens

Test your understanding with these related questions

An investigator is studying the chemical structure of antibiotics and its effect on bacterial growth. He has synthesized a simple beta-lactam antibiotic and has added a bulky side chain to the molecule that inhibits the access of bacterial enzymes to the beta-lactam ring. The synthesized drug will most likely be appropriate for the treatment of which of the following conditions?

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Flashcards: ESBL and CRE pathogens

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What gram negative bug that causes meningococcal meningitis is treated with penicillin G or ceftriaxone?_____

TAP TO REVEAL ANSWER

What gram negative bug that causes meningococcal meningitis is treated with penicillin G or ceftriaxone?_____

Neisseria meningitidis

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