Netherlands: Large Nosocomial KPC Outbreak

 

 

K. pneumoniae on a MacConkey agar plate.

# 5717

 

For nearly two months a hospital in Rotterdam in the Netherlands has been battling an outbreak of CRKP - Carbapenem-Resistant Klebsiella pneumoniae – which may have been linked to as many as 27 deaths.

 

The exact cause of death has yet to be determined in all of these cases.

 

Klebsiella pneumoniae is a Gram negative, rod shaped bacterium commonly found in the flora of the human intestinal tract. Most of the time, it resides harmlessly in the intestines.

 

But when K. pneumoniae moves beyond the intestinal tract – particularly in people with weakened immune systems – it can cause cause severe pneumonia, urinary tract infections (UTI), septicemia, and soft tissue infections.

 

Complicating matters, over the past decade doctors have seen the emergence of antibiotic resistant forms of K. pneumoniae – known as CRKP or  KPC (K. pneumoniae carbapenemase).

 

Bacteria resistant to the Carbapenem class of antibiotics – called carbapenemases – are of particular concern since Carbapenems are often used as the drug of last resort for treating difficult bacterial infections

 

K. Pneumoniae’s opportunistic qualities – attacking those with weakened immune systems - makes it an important, and difficult to control, hospital acquired (nosocomial) infection.

 

First a report from Xinhua News, and then I’ll return with more, including a press release from the hospital.

 

Multiple-resistant bacteria likely cause 27 deaths in Netherlands: hospital

2011-07-27 02:26:27

THE HAGUE, July 26 (Xinhua) -- Klebsiella bacterie Oxa-48, a kind of multi-resistant bacteria, may have caused 27 deaths in the Netherlands since June 1, a hospital source said Tuesday.

 

Though the 27 people died have all been infected with the bacteria, it didn't mean that all the deceased have died as a result of the bacteria, added the Maastad hospital in Rotterdam.

 

Research is under way to show the link between the deaths and the multiple resistant bacteria.

 

The hospital announced the first two death cases on June 1, while the latest report said 78 people are carrier of the bacteria and another 1,967 people are suspected carriers for the time being.

(Continue . . .)

 

 

According to the following (machine translated) press release from the Maastad hospital, there have been no new infections detected since July 18th, and while more infections may be discovered, the situations is `under control’.

 

Press Release: Update multi-resistant bacteria in Rotterdam Hospital: July 26, 2011

On July 26, 2011, the Hospital Rotterdam the next situation that: 78 carriers of multiresistant bacteria, 27 in 1967 and deceased persons suspected patients.

 

Compared to July 21 this represents an increase of 8 carriers, two deceased persons and 143 suspected patients.

 

An increase of carriers automatically means more suspected patients, as they have been in the vicinity of the carriers.  Given the current culture tests and examinations will increase the numbers in the near future.

 

At present, the Hospital Rotterdam, since July 18, no infections in patients receiving for the first time hospitalized. On this basis we can conclude that the outbreak is still under control.

 

This is the current state of affairs until July 26, 2011:

• The number of carriers of the bacteria increased from 70 to 78 patients
• • Of these 78 patients, a total of 27 deceased patients.
  • It does not mean these 27 patients were deceased by the bacterium.
  • Investigated the role of bacteria in the death of patients.
  • -Of the 78 patients are currently only 8 patients in the hospital, which cared isolated.

• The number of people in a room located in the 78 carriers of the bacterium has increased from 1824 to 1967 people.
  • The 143 additional people receive today a culture test by mail.
  • At present there are 43 patients included isolated and tested.
  • If it appears that more patients are infected, should be monitored in any patient with whom they have been in contact. This allows the number of infections is increasing.

 

 

While this is an unusually large nosocomial outbreak, it is by no means an isolated incident.

 

In 2010, 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.

 

Similarly, Brazil reported a substantial outbreak of KPC in 2010, which has been identified in more than 200 patients, and blamed for 22 deaths last year.

 

There have been outbreaks in many other countries, including Italy, Israel, France, Germany, the United Kingdom, Argentina, Lebanon, Israel, Morocco and Tunisia, and Ireland.

 

The gene that gives K. Pneumoniae its carbapenem resistance 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.

 

One of the big concerns is that that we will see a transfer of carbapenem drug-resistance into a highly fit E. coli clone that could spread widely around the world. 

 

From EID Journal Dispatch I referenced above, 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.

 

Which is why such an emphasis is being placed on the proper stewardship over our dwindling arsenal of effective antibiotics.

 

Some recent blogs on this subject include:

 

Going, Going, Gonorrhea

The Path Of Increased Resistance

Carbapenemases Rising

WHO: The Threat Of Antimicrobial Resistance

 

Perhaps the single best place I can direct you to learn about the dangers and impact of antimicrobial resistance is our favorite `scary disease girl’ Maryn McKenna’s SUPERBUG BLOG  and her terrific book on the subject  SUPERBUG: The Fatal Menace Of MRSA.

ECDC/EMEA: Joint Report On Resistant Bacteria

 

 

 

# 5064

 

Just as the CDC on this side of the pond is promoting their GET SMART about antibiotics campaign, countries across Europe each year promote European Antibiotic Awareness Day during the week of November 18th.

 

This year the European campaign is promoting the prudent use of antibiotics in hospitals; meaning that antibiotics are only used when they are needed, with the correct dose, dosage intervals and duration of the course.

 

To coincide with this campaign, the ECDC and EMEA have released a 54 page joint technical report called:

 

The Bacterial Challenge: Time To React

 

 

The main findings from the executive summary include:

Executive summary

Main findings:

• There is a gap between the burden of infections due to multidrug-resistant bacteria and the development of new antibiotics to tackle the problem.
• Resistance to antibiotics is high among Gram-positive and Gram-negative bacteria that cause serious infections in humans and reaches 25% or more in several EU Member States.
• Resistance is increasing in the EU among certain Gram-negative bacteria such as recently observed for Escherichia coli.
• Each year, about 25 000 patients die in the EU from an infection with the selected multidrug-resistant bacteria.
• Infections due to these selected multidrug-resistant bacteria in the EU result in extra healthcare costs and productivity losses of at least EUR 1.5 billion each year.
• Fifteen systemically administered antibacterial agents with a new mechanism of action or directed against a new bacterial target were identified as being under development with a potential to meet the challenge of  multidrug resistance. Most of these were in early phases of development and were primarily developed against bacteria for which treatment options are already available.
• There is a particular lack of new agents with new targets or mechanisms of action against multidrug-resistant Gram-negative bacteria. Two such agents with new or possibly new targets and documented activity were identified, both in early phases of development.
• A European and global strategy to address this gap is urgently needed.

 

The ECDC posted the following press release on their website, regarding this awareness campaign, and release of information.

 

Multidrug resistant bacteria remain a public health issue in Europe

Brussels, 16 November 2010

On the occasion of the European Antibiotic Awareness Day, ECDC is releasing new European-wide surveillance data on antibiotic resistance from the European Antimicrobial Resistance Surveillance Network (EARS-Net).

 

With annually up to 400,000 patients [1]reported to suffer from infections resistant to multiple antibiotics, the data show that antibiotic resistance remains a public health problem across the European Union. In Klebsiella pneumoniae, a common cause of infection amongst hospital patients, an emerging trend is the proportion of resistance to powerful last-line antibiotics, such as carbapenems.

 

Proportions of resistance range from less than 1% to more than 25%. Without effective last-line antibiotics, doctors face the dilemma of not having any treatment options left.

 

Speaking today at the launch event for European Antibiotic Awareness Day in the European Parliament, ECDC Director, Marc Sprenger, said:
“Antibiotic resistance remains a serious threat to patient safety, reducing options for treatment and increasing lengths of hospital stay, as well as patient morbidity and mortality.

 

However the news is not all gloomy. European-wide surveillance data from EARS-Net – a network coordinated by ECDC – show that a significant number of countries have reported decreasing trends for MRSA for the second consecutive year.

 

Notwithstanding, we are seeing increasing multi-drug resistance and the emergence of resistance to last-line antibiotics in European hospitals which we must take urgent action to address.”

(Continue . . . )

 

Reuters has a good report today on all of this, including an interview with Dominique Monnet of the ECDC who expressed deep concern over the spread of NDM-1 (New Delhi metallo-beta-lactamase) and other resistant bacteria.

 

He is quoted as saying, "I know people are calling this NDM-1 a superbug, but for me NDM-1 and bacteria like it are more than superbugs. We're talking about super superbugs."

 

"Super superbug" NDM-1 spreads in Europe

By Kate Kelland, Health and Science Correspondent

LONDON | Wed Nov 17, 2010 6:27pm IST

 

The concern over these resistant bugs was palpable and increasing practically every day - even before NDM-1 appeared on the scene.

Now, with many of these new resistance genes residing on a plasmid — a snippet DNA  that has the potential to jump to other strains of bacteria – concerns are escalating even faster than before.

 

You can read my recent report on KPC and NDM-1 in Carbapenemases Rising.

 

For more on the CDC’s  GET SMART program, visit their website at http://www.cdc.gov/getsmart/.

 

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.