Carbapenem-Resistant Enterobacteriaceae

Aka: Carbapenem-Resistant Enterobacteriaceae, Carbapenem-Resistant Klebsiella, CRKP

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II. Pathophysiology: General

  1. Enterobacteriaceae are Facultative Anaerobic Gram Negative Rods and are common human pathogens
    1. Cause Meningitis, Pneumonia, peritonitis, cystitis and other bacteremia
  2. Enterobacteriaceae are grouped into subtypes
    1. EKP: Escherichia coli, Klebsiella, Proteus
    2. ESP: Enterobacter (Aerobacter), Serratia, Providencia (often grouped with Proteus)
    3. SS: Salmonella, Shigella
    4. Other: Citrobacter (Escherichia freundii), Morganella, Yersinia, Erwinia
  3. Resistance conferred via enzymes known as Carbapenemases that degrade Beta Lactams (including Carbapenems)
    1. Klebsiella PneumoniaeCarbapenemase (KPC) is most common, with Prevalence 47 to 90% in U.S.
    2. Metallo-Beta-Lactamases (zinc containing) are more recently described
  4. Carbapenem resistant organisms (Carbapenemase producers)
    1. Carbapenem-Resistant Klebsiella Pneumoniae (see below)
    2. Enterobacter
    3. Escherichia coli

III. Pathophysiology: Carbapenem-Resistant Klebsiella Pneumoniae

  1. Carbapenem-Resistant Klebsiella Pneumoniae (CRKP) is the first CRE (described in early 2000s)
  2. Klebsiella Pneumoniae Carbapenemase (KPC) is the most common Carbapenemase
  3. CRKP strains are resistant to multiple Antibiotics
    1. Resistance to Aztreonam, Ceftazidime, Ciprofloxacin and Amikacin have all significantly increased
    2. Quinolone and Aminoglycoside resistance has also significantly increased
    3. Colistin and Tigecycline appear to still be active against most strains of CRKP
    4. Some strains are resistant to all known Antibiotics
    5. Mortality rates for CRKP have approached 50%

IV. Risk Factors: Transmission of Carbapenem-Resistant Enterobacteriaceae (via fecal-oral route)

  1. Health care exposure
  2. Longterm Care facility (e.g. Nursing Home)
  3. Immunocompromised state (high risk)
    1. Solid Organ Transplant recipient
    2. Bone Marrow Transplant
    3. Chemotherapy
  4. Recent Mechanical Ventilation
  5. Hemodialysis
  6. Intensive Care unit stay
  7. Recent Urinary Catheterization
  8. Recent Antibiotic use
    1. Carbapenems
    2. Cephalosporins
    3. Fluoroquinolones
    4. Vancomycin

V. Management

  1. Antibiotics for mild CRKP infections
    1. Doxycycline
  2. Antibiotics for severe CRKP infections
    1. Tigecycline (Tygacil)
  3. Other Antibiotic options that may be effective against CRKP infections
    1. Polymyxin used in combination with other agents
    2. Aminoglycosides (e.g. Gentamicin, Amikacin)
    3. Colistin (polymyxin E)
    4. Ceftazidime-Avibactam
    5. Meropenem-Vaborbactam
    6. Plazomicin
    7. Eravacycline

VI. Complications

  1. Mortality with Carbapenem-Resistant Enterobacteriaceae (CRE) infections approaches 23%
    1. High Antibiotic clinical failure rates

VII. Prevention: Healthcare Transmission of Carbapenem-Resistant Enterobacteriaceae (CRE)

  1. Hand Hygiene with waterless Alcohol-based hand rub before and after each patient
  2. Contact precautions with gowns and gloves when exposed to colonized or infected sites
  3. Decontaminate healthcare equipment
  4. Minimize invasive devices as much as possible (e.g. central venous catheters, Endotracheal Intubation, Urinary Catheters)
  5. Cohort infected patients in shared rooms, or better, in single rooms
  6. Lab should notify staff in a timely manner of CRE
  7. Practice antimicrobial stewardship and limit Antibiotic use and duration to appropriate indications
  8. Review hospital culture results every 6-12 months to identify CRE
  9. Screen patients at risk for CRE and those in close proximity to patients positive for CRE
    1. Perianal or rectal cultures are best source of surveillance cultures
    2. Oral Gentamicin can be used to eradicate CRE in carriers
    3. Zuckerman (2011) Bone Marrow Transplant 46(9): 1226-30 [PubMed]

VIII. References

  1. Carvey and Glauser (2023) Crit Dec Emerg Med 37(11): 23-9
  2. Glauser (2014) Crit Dec Emerg Med 28(11): 2-10

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