Question 30

Discuss the Extended Spectrum Beta-Lactamase producing micro-organisms (ESBL) under thefollowing headings:
a) List six ESBL producing micro-organisms commonly encountered in the ICU.
(30% marks)
b) List four risk factors for ESBL producing micro-organism development. (20% marks)
c) Outline infection control measures for ESBL producing micro-organisms. (50% marks)

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College answer

Aim: To allow the candidate to demonstrate familiarity with multi-resistant organisms.
Key sources include: Papers 2014.1 Q3.3, 2009.1 Q 25.2 CanMEDS Medical Expert.
Discussion: This is a core topic with increasing importance in current ICU practice. The overall standard of response to this question was commendable. Expert answers included a thorough detailing of infection control measures and listing the relevant organisms. Candidates who failed to gain marks did so mainly in part b) with a knowledge deficit in relation to the risks of ESBL development. 

Discussion

a)

The questions listed by the examiners in their answer, Question 3.3 from the first paper of 2014 and Question 25.2 from the first paper of 2009 all asked about ESCAPPM organisms:

  • Enterobacter
  • Serratia
  • Citrobacrter
  • Acinetobacter (and Aeromonas)
  • Proteus
  • Providencia
  • Morganella

As a reader (thank you Saikai Mitra) has pointed out, ESBL and ESCAPPM is not exactly the same thing:

  • ESCAPPM organisms have the ability to express induceable chromosomal AmpC cephalosporinase/β-lactamase enzymes, which may not be immediately present in all the members of a culture, resulting in an apparent sensitivity in vitro but a failure of clinical response in vivo where the clone of resistant variants proliferates under selective pressure from antibiotics.
  • ESBL organisms carry extended spectrum β-lactamase which confers resistance to roughly the same selection of drugs as the AmpC enzyme.  However, ESBl organisms will demonstrate a good honest resistance to cephalosporins and β-lactams in a culture, as the enzyme is non-induceable and plasmid-mediated.
  • Even though the patterns of resistance and sensitivities between ESCAPPM and ESBL organisms can be very similar, there are some broad differences. Specifically, they differ in their response to fourth generation cephalosporins (of which the only commercially available members right now are cefepime and cefpirome). ESCAPPM organisms are usually susceptible to fourth generation cephalosporins, whereas ESBL organisms can hydrolyse them (Paterson & Bonomo, 2005)
  • This statement is something of an oversimplification because there are multiple different  possible ESBL and AmpC enzyme variants and several classification systems exist, all of which are better than just labelling organisms as "ESCAPPM" or "ESBL", which leads to confusion.
  • Even more confusing is the overlap between groups, as nothing stops these organisms from shamelessly expressing both enzymes at you. As the result, the list of ESBLs looks very much like the list of ESCAPPMs:
    • E.coli
    • Enterobacter
    • Salmonella 
    • Citrobacter
    • K. pneumonia and oxytoca
    • Proteus
    • Providentia
    • Morganella morganii

Other organisms that can carry ESBL include  Chromobacterium violaceum,  Hafnia alvei, Lysobacter lactamgenusOchrobactrum anthropiProteus rettgeri,  Pseudomonas aeruginosaPsychrobacter immobilis, Rhodobacter sphaeroides and Yersinia enterocolitica, as well as potentially Neisseria, Burkholderia and Shigella; but they only asked for six. Every article you google has a list of approximately these dimensions.

b)

"risk factors for ESBL producing micro-organism development" could potentially have meant a whole variety of different things, but most probably meant "what are the risk factors for being colonised with an ESBL-producing organism". Otter et al (2019), looking at the data from a universal screening program in London, and Ben-Ami et al (2009) analysing coimmunity patient data identified the following:

  • Number of courses of antibiotics in the last 6 months  (>2)
  • Travel to Asia or Africa in the previosu 12 motnhs
  • Overseas hospital stay in the past 12 months
  • Residence in a long-term care facility
  • Recent hospitalization
  • Age ⩾65 years
  • Male sex
  • Multiple comorbidities

c)

This requires a list of standard contact precautions for critically ill patients:

  • Single rooms
    • Or, cohort patients with the same pathogen in the same room
    • Ensure patients are separated by more than 1m
    • Change protective attire and perform hand hygiene between contact with patients in the same room
  • PPE
    • Wear gloves whenever touching the patient’s intact skin
    • Wear a gown whenever anticipating that clothing will have direct contact with the patient
  • Limit transport and movement of patients outside of the room
  • Use disposable equipment
  • Daily cleaning and disinfection of patient rooms, with a focus on frequently-touched surfaces
  • Hand hygiene before and after all patient contact

References

The CDS test manual has an excellent section on this topic

Paterson, David L., and Robert A. Bonomo. "Extended-spectrum β-lactamases: a clinical update." Clinical microbiology reviews 18.4 (2005): 657-686.

Nakai, Hazuki, et al. "Prevalence and risk factors of infections caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae." Journal of Infection and Chemotherapy 22.5 (2016): 319-326.

Chaudhary, U., and R. Aggarwal. "Extended spectrum β-lactamases (ESBL)–An emerging threat to clinical therapeutics." Indian journal of medical microbiology 22.2 (2004): 75-80.

Otter, J. A., et al. "Individual-and community-level risk factors for ESBL Enterobacteriaceae colonization identified by universal admission screening in London." Clinical Microbiology and Infection 25.10 (2019): 1259-1265.

Ben-Ami, Ronen, et al. "A multinational survey of risk factors for infection with extended-spectrum β-lactamase-producing Enterobacteriaceae in nonhospitalized patients." Clinical Infectious Diseases 49.5 (2009): 682-690.

Eggimann, Philippe, and Didier Pittet. "Infection control in the ICU." Chest 120.6 (2001): 2059-2093.

CDC Guidelines for Isolation Precautions

Garau, Javier, et al. "Fourth‐generation cephalosporins: a review of in vitro activity, pharmacokinetics, pharmacodynamics and clinical utility.Clinical Microbiology and Infection 3 (1997): s87-s101.