This organism was grown from an endotracheal tube (ETT) aspirate of a 67-year-old male with pneumonia.
Light growth of Klebsiella pneumoniae
What are the enzymes potentially responsible for antibiotic resistance? (10% marks)
How would you manage this clinical scenario? (90% marks)
Klebiella pneumoniae carbapenemase (KPC)
Metallo-beta-lactamases (MBL’s – e.g. New Delhi metallo-beta-lactamase)
(Only one required)
i. Resuscitation and supportive treatment as indicated
ii. Antimicrobial Therapy
Use of antimicrobial dependant on clinical status of patient – avoid treatment if possible
If treatment required recommendation is combination antimicrobial therapy Optimal combination is uncertain
Depends on further resistance pattern and enzyme present. Specialist ID opinion should be sought
iii. Infection control procedures
Isolate patient in negative pressure room
Avoid unnecessary movement in and out of room
Have anteroom available
Dedicated equipment within room
Contact precautions in addition to standard precautions:
Strict hand hygiene
Wear gloves/gowns on entering room
Appropriate disposal of contaminated equipment
Appropriate infectious clean of surfaces and room post discharge Screening of other patients in unit.
Closed suction circuit if ventilated
Public health notification
Not well answered, with most attempts lacking structure, or understanding of all the relevant issues.
The fact that the college asked specifically which enzymes are responsible strongly implied that the college only wanted to hear the keywords "β-lactamase" or "carbapenemase", even though the Klebsiella strain they gave us was also resistant to aminoglycosides, fluoroquinolones, tetracyclines and cotrimoxazole. β-lactamase enzymes are classified according to a system called the Bush-Jacoby-Medeiros classification:
Management might be summarised as follows:
Determine the result is clinically relevant
Supportive management, if the result is clinically relevant
Prevent contamination of other patients
The college in their answer mention that "recommendation is combination antimicrobial therapy" but do not specify whose recommendation that is. Presumably they were not referring to Hawkey et al (2018), as that statement came out approximately two weeks before the written paper. The authors admit that "most of the current evidence for the advantage of combination therapy ...derives from observational studies and reports". It is not totally clear that combination therapy is better than monotherapy, and studies tend to come up with wildly different contradictory conclusion, thereby generating some very confused systematic reviews (eg. Paul et al, 2014). The recommendations from Hawkey (2018) are:
Nordmann, Patrice, Gaelle Cuzon, and Thierry Naas. "The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria." The Lancet infectious diseases 9.4 (2009): 228-236.
Hawkey, Peter M., et al. "Treatment of infections caused by multidrug-resistant Gram-negative bacteria: report of the British Society for Antimicrobial Chemotherapy/healthcare Infection Society/british Infection Association Joint Working Party." Journal of Antimicrobial Chemotherapy 73.suppl_3 (2018): iii2-iii78.
MacVane, Shawn H. "Antimicrobial resistance in the intensive care unit: a focus on gram-negative bacterial infections." Journal of intensive care medicine 32.1 (2017): 25-37.
Schneider, Elena K., et al. "Antibiotic–non-antibiotic combinations for combating extremely drug-resistant Gram-negative ‘superbugs’." Essays in biochemistry 61.1 (2017): 115-125.