This organism was grown from an endotracheal tube (ETT) aspirate of a 67-year-old male with pneumonia.
Light growth of Klebsiella pneumoniae
- Amp / Amoxycillin R
- Amox/clav acid R
- Cefazolin R
- Cefotaxime R
- Cotrimoxazole R
- Ciprfofloxacin R
- Gentamicin R
- Meropenem R
- Tigecycline R
- Ertapenem R
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
- Polymyxin-based regime (colistin or polymyxin B)
- Meropenem (including high dose infusion) if isolate has acceptable MIC to meropenem as part of combination therapy
- Ceftazidime-avibactam (limited availability in Australia)
- Can consider tigecycline as part of combination therapy
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:
- Class A: resistance to monobactams, third-generation cephalosporins,
but these are inhibited by clavulanate and tazobactam, at least in vitro. To this class belongs KPC, the Klebsielle pneumoniae carbapenemase.
- Class B: resistance to penicillins, cephalosporins and carbapenems. NOT inhibited by clavulanate and tazobactam. These are the ones known as "metallo-beta-lactamases", because their active site contains a divalent metal cation, usually zink. This is the group to which belongs the "New Delhi" NDM-1 enzyme.
- Class C: resistance to cephalosporins; limited inhibition by clavulanate and tazobactam. These are the enzymes induced in ESCAPPM organisms
- Class D: "Oxacillinase"; resistance to carbapenems is slightly inhibited by clavulanate. These are also known as OXA β-lactamase enzymes.
Management might be summarised as follows:
Determine the result is clinically relevant
- Assess the volume of secretions and determine their significance (i.e. is this really an infection, or it just a coloniser? It's a "light" growth)
- Assess the clinical and radiological evidence for infection (is there a pneumonia, or is this result merely reflecting some sort of under-cuff microaspiration?)
- Assess the clinical and biochemical evidence for the systemic effect of this infection (are the inflammatory markers rising, is the patient developing haemodynamic instability?)
Supportive management, if the result is clinically relevant
- Optimise nutrition to minimise immunosuppressant effects of protein malnutrition
- Supplement micronutrients including vitamins
- Cease all possible immunosuppressants
- Chest physiotherapy for secretion clearance
- Left and right alternating recovery position, to assist secretion drainage (or even prone)
- Work towards extubation (secretion clearance by cough is usually better than tracheal suction)
- Nebulise saline in addition to humidifying the circuit
- Determine the need for antibiotics
- Antibiotic choice for KPC strains: colistin + meropenem + tigecyline or ceftazidime/avibactam (Hawkey et al, 2018).
- Other options:
- Also it is possible to dose a carbapenem to MIC, eg. Pea et al (2017) who gave up to 13g/day of meropenem and had good success rates in killing carbamenemase producers
- Give the agents as an infusion to maintain a steady above-MIC concentration (for time-dependent killers)
Prevent contamination of other patients
- Hand hygiene
- Soap and water for visibly contaminated hands
- Alcohol-based rub for routine pre-and-post-contact hygiene
- Monitoring of compliance should be performed
- Disposable gloves
- Disposable gowns
- Contaminated areas should be identified by obvious cautionary signs
- Routine disinfection of equipment between patient contacts
- Wherever possible, individualised equipment for every patient
- Screening of all patients to identify reservoir for spread
- Routine surveillance cultures
- Decontamination of colonised health care workers
- Infection control specialty team, composed of ICU specialists, infectious diseases specialists, senior nursing staff, laboratory staff and administration staff.
- Allocated resources to MRO surveillance, compliance monitoring and education
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:
- For KPC strains, colistin + meropenem + tigecyline or ceftazidime/avibactam
- For OXA strains, aztreonam or ceftazidime/avibactam as monotherapy
- For metallo-β-carbapenemase producers, colistin + fosfomycin, +/- tigecycline
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.