Tuesday, November 16, 2010

Carbapenemases Rising




# 5056



Via Arkanoid Legent this morning, we’ve a press release from the Hong Kong SAR government on two patients colonized (but not infected with) with the Klebsiella pneumoniae bacteria carrying the KPC carbapenemase gene.



K. pneumoniae on a MacConkey agar plate.


First some excerpts from this press release, then a discussion on this type of antibiotic resistance.




Two strains of drug resistant bacteria identified

Hong Kong (HKSAR) - The Microbiology Laboratory of the Public Health Laboratory Services Branch (PHLSB) has for the first time identified two strains of Klebsiella pneumoniae harbouring the gene encoding for the KPC carbapenemase.


Similar carbapenem-resistant bacteria, for example, those harbouring IMP gene, have been found in Hong Kong before.


A spokesman for the Centre for Health Protection (CHP) of the Department of Health said the gene confers resistance to the carbapenem group of antibiotics, which are broad-spectrum and usually used as second-line agents.


The finding involved two patients attending public hospitals, whose isolates were referred to PHLSB.
The patient from Queen Mary Hospital was a 66-year-old man with a history of previous hospital admission in China in October 2010. His rectal swab specimen tested positive for the KPC-harbouring K.pneumoniae strain.


He was not infected but only colonised with the strain. The patient is now staying at the Tung Wah Hospital in stable condition.Isolation precautions have been implemented.

The other patient was a 24-year-old man admitted to United Christian Hospital (UCH). His mid-stream urine specimen, which harboured the organism, was obtained as part of work-up for abdominal pain. Laboratory results indicated that the patient did not have urinary tract infection, and that the organism was a coloniser.


The patient had no travel history. His symptoms subsided with conservative management, without antibiotics. He has recovered and was discharged from the hospital.The organism in this patient is sensitive to the antibiotic gentamicin.

(Continue. . . )



Although this sounds similar to the NDM-1 (New Delhi metallo-ß-lactamase-1) gene that made a splash back in August in a Lancet  study called Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study, this particular resistance enzyme has been around, and spreading globally, for more than a decade.


I’m going to try to keep the following geared to the layman (so I can understand it, too), and hope Maryn McKenna – Flublogia’s resident expert in all things antibiotic resistant - will forgive the over-simplification.


Beta Lactam antibiotics are broad spectrum antibiotics characterized by having a a β-lactam ring in their molecular structure. They are the most widely used class of antibiotics, and include many penicillin  derivatives, cephalosporins, and carbapenems.


Over the years some bacteria have developed a class of enzymes - called Beta-lactamases – that have the ability to break open the beta-lactam ring common to these antibiotics, which disrupts or destroys their antimicrobial properties.


In 1940, even before penicillin could be rolled out for clinical use, the first β-lactamase (Penicillinase) was identified by researchers in a sample of Gram-negative E. coli.


Over the next two decades this penicillinase resistance spread to other bacteria, which required the creation of newer generations of penicillin (such as Methicillin in 1959), that were resistant to these enzymes.


Methicillin is no longer used (replaced by newer generation antibiotics), although we retain its name in the term MRSA (Methicillin-resistant Staphylococcus aureus), which was identified in the UK just two years after Methicillin was introduced.


Today, we are seeing an expanding array of β-lactamase enzymes in bacteria, and they are slowly eroding the value of much of our antibiotic arsenal.


Those that inhibit the antimicrobial actions of the (formerly resistant) Carbapenem class of antibiotics – called carbapenemases – are of particular concern. Carbapenems are often used as the drug of last resort for treating difficult bacterial infections, including Escherichia coli (E. coli) and Klebsiella pneumoniae.


While NDM-1 has garnered most of the headlines over the past few months, there are a variety of other carbapenemases out there, including: IMP, VIM, OXA, CMY, and most notably KPC (K. pneumoniae carbapenemase).


First identified in North Carolina fifteen years ago, KPC has since spread globally and is the most widely reported of the carbapenemases.


And like NDM-1, this KPC resistance gene resides on a plasmid — a snippet of transferable DNA – that has the potential to jump to other strains of bacteria.


A trait that was recently demonstrated in an EID Journal dispatch (Transfer of Carbapenem-Resistant Plasmid from Klebsiella pneumoniae ST258 to Escherichia coli in Patient) in June, 2010.



Three weeks ago, a survey presented at the IDSA  conference in Vancouver showed that Chicago was reporting a 42% rise in the number of hospitals and long-term care facilities reporting cases of KPC over last year.


Brazil is currently dealing with a substantial outbreak of KPC, which has been identified in more than 200 patients, and blamed for 22 deaths this year.


Four More Die From Antibiotic Resistant Bacteria In Brazil


As a result, Brazil recently imposed new restrictions on the sale and purchase of antibiotics as of last month, now requiring a doctor’s prescription. 


Similar moves are underway in places like India and Mexico, where antibiotics have traditionally been available over-the-counter.


Returning to the EID Journal Dispatch I referenced earlier, the concern with KPC (and other carbapenemases) is that we will see a transfer of drug-resistance into a highly fit E. coli clone that will spread widely around the world. 


The authors write:


Such an event may have severe public health consequences, leading to elimination of any effective antimicrobial drug treatment against the most common human bacterial pathogens.


Ominous words.


While the end of the antibiotic era is not yet at hand, the fear is we may be drawing closer to that day.  Which is why we watch reports of bacterial resistance with such great interest.



For a far more complete (and eye-opening) discussion of antimicrobial resistance issues, I can think of no better primer than Maryn McKenna’s book SUPERBUG: The Fatal Menace of MRSA.


And Maryn’s SUPERBUG Blog, now part of Wired Science Blogs, continues to provide the best day-to-day coverage of these issues.


This week the CDC is promoting their GET SMART ABOUT ANTIBIOTICS campaign, which I will have more on later.