The "new" "Superbug": one of many antibiotic resistant β-Lactamases ?

[Gert van der Hoek]

If you go to PubMed and do some searches you wil find a long list of "multiresistant" or "panresistant" or "carbapenem-resistant" Metallo-β-Lactamase genes.

Here just 1 example from Greece.

But you can find a lot more: from Spain, Japan, Poland, Mexico, you name it. Too much to post here.

It seems the "new" "Superbug" is just one of many and had a better PR campaign?.

At the same time we can conclude some real serious attention is needed regarding the use of anti-biotics.

This is an understatement.




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J Hosp Infect. 2010 Sep;76(1):70-73. Epub 2010 Jun 17.

Hospital outbreak caused by Klebsiella pneumoniae producing KPC-2 beta-lactamase resistant to colistin.

Kontopoulou K, Protonotariou E, Vasilakos K, Kriti M, Koteli A, Antoniadou E, Sofianou D.

Department of Clinical Microbiology, G. Gennimatas General Hospital, Thessaloniki, Greece.

Abstract
We describe a hospital outbreak caused by colistin-resistant Klebsiella pneumoniae producing KPC-2 beta-lactamase in two distinct medical centres.

Seven clinical isolates of K. pneumoniae exhibiting resistance to carbapenems were collected from patients with hospital-acquired infection.

All isolates were phenotypically positive for carbapenemase activity but negative for metallo-beta-lactamase production.

PCR analysis using specific primers for bla(KPC), bla(SHV), bla(TEM) and bla(CTX-M) demonstrated that all clinical strains of K. pneumoniae from hospital A and one isolate from hospital B were genetically related and carried bla(KPC-2) in addition to bla(SHV-12). In contrast, the remaining isolate carried bla(S)(HV-5) with bla(K)(PC-2) and yielded a different profile.

These results indicate the clonal spread of KPC producers between hospitals as well as the acquisition of KPC genes by different K. pneumoniae strains.

All isolates were resistant to carbapenems, beta-lactams, ciprofloxacin, aminoglycosides and colistin, but intermediately susceptible to tigecycline and susceptible to gentamicin.

The infection was fatal in five cases. The emergence of colistin-resistant K. pneumoniae possessing bla(KPC)(-2) underscores the implementation of strict control measures to prevent their dissemination of these organisms in hospitals.

http://www.ncbi.nlm.nih.gov/pubmed/20705205

[Vibrant62]

Re: The "new" "Superbug" is one of many antibiotic resistant Metallo-β-Lactamases

I beleive that the particular concern associated with this most recent pan resistant form is its ability to transmit its resistance characteristics between different types of bacteria via plasmid formation and exchange, rather than being specific to a particular bacterial strain. I dont know if this is also a characteristic of the examples above, and will need to do some more reading before commenting further.

[Gert van der Hoek]

Re: The "new" "Superbug" is one of many antibiotic resistant Metallo-β-Lactamases

I beleive that the particular concern associated with this most recent pan resistant form is its ability to transmit its resistance characteristics between different types of bacteria via plasmid formation and exchange, rather than being specific to a particular bacterial strain. I dont know if this is also a characteristic of the examples above, and will need to do some more reading before commenting further.

Good point, which deserves to be investigated by members who know much more about this than I do .

According to a report in this post another Metallo-β-Lactamase gene called "VIM-7" is "highly mobile", also located on a plasmid.

I don't know what a plasmid is, but Maryn McKenna does:

- snip -

As the Lancet ID paper reports, NDM-1 resides on a plasmid — a snippet of DNA, not on a chromosome, that reproduces on its own and can move freely between organisms. Intuitively, you would think that bacteria either inherit resistance from their progenitors or develop it on their own when they encounter a drug. Plasmids short-circuit both those processes, allowing resistance to spread rapidly within a single bacterial generation to organisms that have never experienced the drug they are acquiring defenses against.

http://www.superbugtheblog.com/

[Roehl_JC]

Re: The "new" "Superbug": one of many antibiotic resistant Metallo-β-Lactamases ?

Plasmid-carried genes are much easier to transmit BETWEEN BACTERIAL species...and this one is a doozy. If this gene NDM-1 for total antibiotic resistance is not species-specific but is quite easily plasmid-shared , then the days of antibiotic use to treat diseases may be a thing of the past soon.
I feel this is like the shot heard 'round the world. It means that nasocomial disease organisms in hospital settings and in the wider community are highly likely and soon to pick up this gene, making treatment regimens all the more problematic. If we learn that NDM-1 can be taken up by MRSA, and TB mycobacteria, and Streptococci and E. coli variants already causing disease, it's going to become the world's greatest menace to public health. Just goes to prove that we've overused antibiotics for mild illnesses, and some countries illegally used antibiotics on animals that were solely intended for humans, and this is the result. I'm so thankful we've got the super FluTrackers and wider medical community and WHO already onto this. Good luck and thank you Sharon and Dutchy and Vibrant62 for your valuable efforts.

[Gert van der Hoek]

Re: The "new" "Superbug": one of many antibiotic resistant Metallo-β-Lactamases ?

Superbug yet another hospital bug, no panic

Express News Service First Published : 17 Aug 2010

KOCHI: There is a no cause for panic as the newly identified superbug is a variant of the several bugs or MultiDrug Resistant (MDR) bacteria that have been identified the world over.

"Earlier also, bacteria, which are resistant to certain class of medicines, had been identified. What we need to develop is a regulatory mechanism which prevents the sale of antibiotics without prescription," Dr Prem Nair, medical director of the Amrita Institute of Medical Sciences, Kochi said.

On the recent controversy generated by the superbug 'New Delhi metalloßlactamase,' he told reporters that 'hospital acquired infections' (HAI) can be controlled to a large extent if a proper policy and procedure is in place. "Our hospital has the lowest HAI which is almost on a par with the West. I can tell this because we keep a data of all the infections reported from patients in the hospitals," he said.

"We are probably one of the few hospitals in India to keep a record of data on infection control, and recently a paper on the same was presented at the Centre for Disease Control, Atlanta, the US," Dr Sanjeev Singh, Head of Department, Infection Control, AIMS said.

"The identified bug 'New Delhi metalloßlactamase 1 (NDM1)' is just a new variant of the normally prevalent 'hospital bugs.' They have just named it to the city they have identified in India. Earlier, such bugs were identified in Germany, Sao Paulo, Verona, Australia and they have been named after these places also," Anil Kumar V, microbiologist, AIMS said.

He said since the strain has been identified, it would not be long before the actual place of origin of the bug is identified, especially if these are traced to people who have not visited or been treated in India.

The most difficulttotreat bacteria called MethicillinResistant Staphylococcus Aureus (MRSA) has been identified in Britain which has been responsible for several difficulties in treating infections.

More:

http://expressbuzz.com/cities/kochi/superbug-yet-another-hospital-bug-no-panic/198662.html

[Gert van der Hoek]

Re: The "new" "Superbug": one of many antibiotic resistant Metallo-β-Lactamases ?

Another "superbug" variant , this time from the Netherlands, called "DIM-1" (Dutch Imipenemase). Seems to be equally antiresistant and seems potentially to be able to spread the resistance as easily as the infamous "new superbug": having "gene cassettes" and being "located on a plasmid" .


Antimicrob Agents Chemother. 2010 Jun;54(6):2420-4. Epub 2010 Mar 22.

Characterization of DIM-1, an integron-encoded metallo-beta-lactamase from a Pseudomonas stutzeri clinical isolate in The Netherlands.

Abstract

A carbapenem-resistant Pseudomonas stutzeri strain isolated from a Dutch patient was analyzed in detail.

This isolate produced a metallo-beta-lactamase (MBL) whose gene, with 43.5&#37; GC content, was cloned and expressed in Escherichia coli. beta-Lactamase DIM-1 (for Dutch imipenemase) was weakly related to other Ambler class B beta-lactamases, sharing <52% amino acid identity with the most closely related MBL, GIM-1, and 45% identity with IMP-type MBLs.

The beta-Lactamase DIM-1 significantly hydrolyzed broad-spectrum cephalosporins and carbapenems and spared aztreonam.

This MBL gene was embedded in a class 1 integron containing two other gene cassettes, encoding resistance to aminoglycosides and disinfectants, that was located on a 70-kb plasmid.

http://www.ncbi.nlm.nih.gov/pubmed/20308383

[Diane Morin]

Re: The &quot;new&quot; &quot;Superbug&quot;: one of many antibiotic resistant Metallo-β-Lactamases ?

Superbug: 'Lancet doesn’t publish rubbish, threat is real'



Posted: Sat Aug 14 2010, 06:16 hrs Updated: Sat Aug 14 2010, 08:13 hrs New Delhi/Lucknow:

/.../

Countering the criticism over naming the bug after New Delhi — New Delhi metallo-beta-lactamase-1 — Walsh said that this wasn’t an unusual practice.


“We named the bacteria NDM-1 because the original patient who was investigated had flown back to Sweden from India with the infection. It was known that the origin of the infection was India and not Sweden. (It was) in the tradition of naming these types of bacteria after the city of origin,” he said.
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For example, the Verona Integron encoded metallo-beta-lactamase 1 (VIM1) was first reported in Verona, Italy, in 1997 in Pseudomonas aeruginosa, a very common bacteria reponsible for hospital-acquired infection, mostly found in burn and post-surgical infections. The gene was later traced in Greece, France, South Korea, Taiwan, Venezuela, Japan, Belgium etc.


The Sao Paulo Metallo-beta-lactamase1 (SPM1) was first isolated in Sao Paulo, Brazil, in 1997 in the same bacteria. The German Imipenemase1 (GIM1) was isolated in Dusseldorf, Germany, in 2002 and was reported in a research paper published in 2004. And the Seoul Imipenemase (SIM) was a gene reported in Seoul.

/.../

http://www.indianexpress.com/news/superbug-lancet-doesnt-publish-rubbish-threat-is-real/660277/0

[Gert van der Hoek]

Re: The &quot;new&quot; &quot;Superbug&quot;: one of many antibiotic resistant β-Lactamases ?

This letter from India published in a medical journal, seems to illustrate my point:

the "new superbug" recently announced seems to be (part of) just one of many antibiotic resistant bacteria developing worldwide.

If I understood it well, in fact were are not talking about a bacteria but about enzymes who carry with them antibiotic resistant properties and "jump" from one bacteria to another. Making the bacteria antibiotic resistant.

These enzymes are called β-lactamases (beta-lactamases), they can be found in 3 distinct groups (see article below).

If you do a search at PubMED with the names of these 3 groups you get a long list of reports, showing antibiotic resistance in bacteria which have 1 or more of these enzymes.

Somehow the recently reported metallo-β-lactamase from India/UK, received more attention than the others and the publication resulted in a wake-up call (let's be optimistic..) regarding antibiotic resistant bacteria, a.k.a. "superbugs".

One reason why this variant could get more attention could be: it seems to be relatively widespread, normally these bacteria/enzymes tend to stay inside the hospitals, this one seems to have "escaped" and can survive "in the wild", could cause more problems.

However: you can find multiresistant bacteria/enzymes all over the world, in some countries more than others, probably related to their policy and procedures of (over)using antibiotics.

In the Table you can find names of bacteria which are typically associated with antibiotic resistance worldwide .

So it seems dozens of β-Lactamases are circulating, able to make pathogenic bacteria (almost completely or totally) resistant for antibiotics.

The resistant bacteria we are talking about are pathogenic, but not virulent. If these bacteria become antibiotic resistant, it doesn't mean the bacteria will be "supervirulent".

Immunocompromised patients, like cancerpatients, etc., are the ones who are vulnerable.

If you are healthy, you don't have to fear the "superbugs".

However anyone can fall ill at some time or live under stress or need an operation and then you can be vulnerable for diseases, including resistant pathogenic bacteria. Most cases occur "nocosomial" : acquired in a hospital.

Please correct me if I'm wrong.




Date of Web Publication 17-Jul-2010

High prevalence of co-expression of newer β-lactamases (ESBLs, Amp-C-β-lactamases, and metallo-β-lactamases) in gram-negative bacilli


Dear Editor,

The newer β-lactamases, including extended-spectrum β-lactamases (ESBLs), Amp-C-β-lactamases, and metallo-β-lactamases (MBLs), have emerged worldwide as a cause of antimicrobial resistance in gram-negative bacteria (GNB). [1]

Genes for all these three enzymes are often carried on plasmids, facilitating rapid spread between microorganisms.

[1] The presence of ESBLs and Amp-C-β-lactamases in a single isolate reduces the effectiveness of the β-lactam-β-lactamase inhibitor combinations, while MBLs and Amp-C-β-lactamases confer resistance to carbapenems.

Often these enzymes are co-expressed in the same isolate.

We conducted this study to detect all three of these newer β-lactamases in GNB.

- snip -

http://www.ijmm.org/article.asp?issn=0255-0857;year=2010;volume=28;issue=3;spage=267;epage=268;aulast=Chatterjee#