I have recently had the pleasure of interviewing for new Consultant colleagues and I thought it would be good to ask them “what infection keeps you awake at night?” Their answers where all the same: carbapenemases.
So what are carbapenemases and why are they
worrying?
A carbapenemase is a mechanism of resistance used by bacteria to defend themselves against carbapenem antibiotics.
• They are Beta-lactamase enzymes.
• They tend to give resistance to ALL of the Beta-lactam antibiotics such as the penicillins and cephalosporins.
• They mainly occur in Gram-negative bacilli, which tend to cause more episodes of sepsis.
• They are often associated with other resistance mechanisms, giving resistance to other antibiotics such as the quinolones (e.g. Ciprofloxacin) and aminoglycosides (e.g. Gentamicin).
• They cause resistance to carbapenem antibiotics, (Ertapenem, Meropenem, Imipenem and Doripenem) which are often the last line in the fight against Gram-negative infections. Clinically they are therefore very difficult to treat; patients with infections with carbapenemase-producing bacteria have a very high mortality, in excess of 50%. They are true “Superbugs” and keep microbiologists awake at night!
The carbapenemases can be split into 2 broad categories, the reason the categories are important is for infection control purposes:
• Intrinsic
Intrinsic carbapenemases occur inherently in the bacterium but are not transferrable between bacterial species and can only be spread by spreading the bacteria e.g. poor hand hygiene. They occur in bacteria with a low potential to cause infection and cannot be transferred into bacteria with a high potential to cause infection. They have been present in the UK for many years.
• Acquired
Acquired Carbapenemases are relatively new worldwide. Resistance occurs because the bacterium has gained the ability to become resistant (usually via the acquisition of a plasmid containing the genes encoding the carbapenemase). It is more worrying than intrinsic resistance because it can be spread by passing on the plasmid to other bacterial species which can cause severe infections e.g. E. coli, K.
pneumoniae.
worrying?
A carbapenemase is a mechanism of resistance used by bacteria to defend themselves against carbapenem antibiotics.
• They are Beta-lactamase enzymes.
• They tend to give resistance to ALL of the Beta-lactam antibiotics such as the penicillins and cephalosporins.
• They mainly occur in Gram-negative bacilli, which tend to cause more episodes of sepsis.
• They are often associated with other resistance mechanisms, giving resistance to other antibiotics such as the quinolones (e.g. Ciprofloxacin) and aminoglycosides (e.g. Gentamicin).
• They cause resistance to carbapenem antibiotics, (Ertapenem, Meropenem, Imipenem and Doripenem) which are often the last line in the fight against Gram-negative infections. Clinically they are therefore very difficult to treat; patients with infections with carbapenemase-producing bacteria have a very high mortality, in excess of 50%. They are true “Superbugs” and keep microbiologists awake at night!
The carbapenemases can be split into 2 broad categories, the reason the categories are important is for infection control purposes:
• Intrinsic
Intrinsic carbapenemases occur inherently in the bacterium but are not transferrable between bacterial species and can only be spread by spreading the bacteria e.g. poor hand hygiene. They occur in bacteria with a low potential to cause infection and cannot be transferred into bacteria with a high potential to cause infection. They have been present in the UK for many years.
• Acquired
Acquired Carbapenemases are relatively new worldwide. Resistance occurs because the bacterium has gained the ability to become resistant (usually via the acquisition of a plasmid containing the genes encoding the carbapenemase). It is more worrying than intrinsic resistance because it can be spread by passing on the plasmid to other bacterial species which can cause severe infections e.g. E. coli, K.
pneumoniae.
Click for larger image
There are five main carbapenemases currently causing clinical problems; affectionately known as the “Big Five”:
• KPC (Klebsiella pneumoniae carbapenemase)
• IMP (Imipenemase metallo-beta-lactamase)
• NDM (New Delhi metallo-beta-lactamase)
• VIM (Verona integron-encoded metallo-beta-lactamase)
• OXA (Oxacillin carbapenemases)
They can be split into 3 main groups based on the similarity
enzymes.
• KPC (Klebsiella pneumoniae carbapenemase)
• IMP (Imipenemase metallo-beta-lactamase)
• NDM (New Delhi metallo-beta-lactamase)
• VIM (Verona integron-encoded metallo-beta-lactamase)
• OXA (Oxacillin carbapenemases)
They can be split into 3 main groups based on the similarity
enzymes.
Click for larger image
Current Global Spread of Carbapenemase Resistance (http://wwwnc.cdc.gov/eid/)
Click for larger image
Click for larger image
Click for larger image
Click for larger image
Treatment
Carbapenemase-producing bacteria cause infections just as
readily as their non-resistant counterparts. However, the normal first and second line antibiotics used in UK hospitals are unlikely to be effective and the mortality to these infections may be in excess of 50%. If these bacteria are
identified treatment options are limited and the antibiotics often have side-effects and complications (see the book, "Microbiology Nuts & Bolts").
Most carbapenemase-producing bacteria remain sensitive to:
• Polymyxins e.g. Colistin
• Tigecycline
• Nitrofurantoin
• Fosfomycin
The current recommendations for severe infections caused by carbapenemase-producing bacteria are combinations of
antibiotics:
• Colistin PLUS carbapenem
• OR Colistin PLUS Tigecycline
• OR Colistin PLUS aminoglycoside
What does the future hold?
So should my Consultant colleagues be really worrying about
carbapenemases? YES! Are we entering a post-antibiotic era? PROBABLY! What should we be doing to detect and prevent the spread of carbapenemases? How do we preserve the limited active antibiotics we have remaining and how do we manage patients with carbapenemase-producing bacteria from an infection control point of view? GOSH...I’d better blog on that next week, as I’m already late to bed. Don't have nightmares!
Carbapenemase-producing bacteria cause infections just as
readily as their non-resistant counterparts. However, the normal first and second line antibiotics used in UK hospitals are unlikely to be effective and the mortality to these infections may be in excess of 50%. If these bacteria are
identified treatment options are limited and the antibiotics often have side-effects and complications (see the book, "Microbiology Nuts & Bolts").
Most carbapenemase-producing bacteria remain sensitive to:
• Polymyxins e.g. Colistin
• Tigecycline
• Nitrofurantoin
• Fosfomycin
The current recommendations for severe infections caused by carbapenemase-producing bacteria are combinations of
antibiotics:
• Colistin PLUS carbapenem
• OR Colistin PLUS Tigecycline
• OR Colistin PLUS aminoglycoside
What does the future hold?
So should my Consultant colleagues be really worrying about
carbapenemases? YES! Are we entering a post-antibiotic era? PROBABLY! What should we be doing to detect and prevent the spread of carbapenemases? How do we preserve the limited active antibiotics we have remaining and how do we manage patients with carbapenemase-producing bacteria from an infection control point of view? GOSH...I’d better blog on that next week, as I’m already late to bed. Don't have nightmares!
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