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Published Date: 2012-05-20 14:10:14
Subject: PRO/EDR> NDM carrying bacilli - Canada: (Alberta) nosocomial, fatal
Archive Number: 20120520.1138608

NEW DELHI METALLOBETALACTAMASE CARRYING BACILLI - CANADA: (ALBERTA) NOSOCOMIAL, FATAL
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[1]
Date: Fri 18 May 2012
Source: edmontonjournal.com [edited]
http://www.edmontonjournal.com/health/Health%20officials%20closer%20to%20determining%20source%20of%20antibiotic-resistant%20bacteria%20that%20killed%20patient/6645859/story.html

Health officials suspect a Royal Alexandra Hospital patient died after picking up antibiotic-resistant bacteria brought to Edmonton by an infected traveller. After the infection was discovered, Alberta Health Services closed various Royal Alex wards to new patients, screened more than 300 patients who might have been exposed and identified 7 with confirmed or suspected antibiotic-resistant bacteria.

Dr. Mark Joffe, senior medical director in charge of infection, prevention and control for the provincial health authority, said he suspects there is a link between the unidentified patient who died and a woman who travelled to the Indian subcontinent, where she was injured and required surgery. 5-6 weeks after her return to Edmonton, she went to the Royal Alex with an infection at the surgical site. She was not immediately isolated, as is the protocol, but spent about 3 days receiving treatment before it was determined she had 2 types of bacteria. One, called _Acinetobacter_, has occasionally infected Albertans before. The other bacterium carries genes [producing] New Delhi metallo-beta-lactamase, or NDM, which [confer resistance] to multiple antibiotics. Alberta has had only one confirmed case about one year ago. The female patient at the Royal Alexandra had 2 different strains of NDM.

Following that discovery, various hospital units were closed to additional admissions — one remains so — and more than 300 patients from 5 units were tested for various antibiotic-resistant bacteria; 2 people were confirmed to have _Acinetobacter_ and 2 more have the bacteria that contain NDM.

2 others, including the patient who died in the last 10 days after an infection post-surgery, are still being investigated to determine whether they are linked to the spread in the hospital. “We suspect. We’re concerned. We are investigating further,” Joffe said. He said test results should be complete by next week.

He said Alberta Health Services is also investigating why the female traveller wasn’t immediately isolated when she arrived for emergency care at the Royal Alex, since that is the health authority’s protocol for sick global travellers. The bacteria likely travelled between patients on unwashed hands of nurses, doctors, aides or anyone else with direct patient contact, Joffe said.

“I can tell you that they washed their hands most of the time, maybe almost all the time, but I suspect there was at least one opportunity for cleaning their hands that must have been missed,” Joffe said, noting there are initiatives underway to encourage and track hand-washing before and after patient care.

Of the 7 patients with the suspected bacteria, 3 remain isolated in hospital and will remain so until the bacterium clears itself out, which can take weeks or months. 5 — all except the female traveller and the patient who died — are carriers of the bacteria and haven’t become ill or infected from it. “In general, it’s not dangerous,” Joffe said. But people who have compromised immune systems, who have had surgery and have catheters or intravenous lines put in, are more at risk. If the bacterium enters their bodies, many types of antibiotics won’t work to clear the infection. Our hope is that we have contained these strains for now and, hopefully, indefinitely. But the reality is these bacteria are global travellers,” Joffe said. “This won’t be the last time we’ll see this. … This is a reality of modern health care. This is something we can’t escape from and something we need to be very vigilant about.”

He said patients and visitors to hospitals can help by washing their hands and asking health-care workers if they’ve washed their hands and stethoscopes. “Cleaning of hands is the simplest single most important measure for preventing the spread of bacteria,” Joffe said. “Antibiotics are a precious resource and we all need to use antibiotics responsibly.”

He said Albertans shouldn’t be scared. “There is no such thing as zero risk,” he said of hospital care. But he said, “We’ve been extremely aggressive in our approach to controlling these bacteria. We are confident that it is now controlled. … We work very hard every day to make sure health care is as safe as it possibly can be.”

The investigation to determine why the initial patient wasn’t isolated upon admission is expected to take several weeks.

[Byline: Jodie Sinnema

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[2]
Date: Fri 18 May 2012
Source: CBC News Edmonton [edited]
http://www.cbc.ca/news/canada/edmonton/story/2012/05/18/edmonton-hospital-bacteria-death.html

An antibiotic-resistant bacterium is suspected in the death of a patient at the Royal Alexandra Hospital and of spreading to 4 other patients, according to Alberta Health Services [AHS].

"Infection … was part of the cause of death. We know that there was an antibiotic-resistant bacteria [sic: "bacteria" is plural; singular is "bacterium". -Mod.JW] that was part of this. We don’t know yet whether that bacteria was linked to the others that we’re talking about,” said Dr. Mark Joffe, AHS Medical Director of Infection Prevention and Control.

The bacteria is thought to have been brought to Edmonton by another patient who developed the infection after having surgery overseas. Joffe said the infected patient was not immediately isolated when she entered the hospital, as she should have been under AHS policy. "That is our policy and has in fact been our policy for a number of years. So, we believe it is important and we need to find out why in this particular occasion it did not happen," said Joffe. Instead, she was not isolated until 3 days later. In the meantime, Joffe suspects the bacteria was spread — likely on the hands of medical staff - to at least 5 other patients.

Tests found the presence of New Delhi Metallo-beta-lastamase or NDM, an enzyme that makes bacteria resistant to drugs normally used against antibiotic-resistant strains. It is rarely found in Canada and is extremely rare in Alberta, Joffe said. The patient was also found to be carrying a strain of bacteria known as _Acinetobacter_.

Joffe declined to provide details about the person who died, except that the death occurred within the past 10 days. He said the cause of death is still under investigation but it is suspected that bacteria may have played some role in the person's death.

Immediately after the bacteria was discovered, 5 units at the Royal Alex were isolated, which means no new patients were accepted. About 300 patients on those 5 units were tested and from those, 5 were found to be carrying the bacteria [7 according to report above. - Mod.JW]. They are not ill from the bacteria. 4 remain at the hospital in isolation. One has gone home.

Joffre said there is an investigation underway to find out exactly why staff did not immediately isolate the woman who entered the hospital with infection from a foreign country. He would not say where she was travelling at the time of the accident, only that it was a country in the Indian subcontinent. Joffe said the bacteria, in general, is not dangerous and that the outbreak has been contained.

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[The data presented in these 2 news reports concerning this nosocomial outbreak at the Royal Alexandra Hospital in Edmonton, Canada are somewhat confusing. The index case is a woman who was hospitalized at the Royal Alexandra Hospital for a surgical site infection 5-6 weeks after her return from the Indian subcontinent, where she was injured and required surgery. The woman apparently was infected by 2 different bacteria, an _Acinetobacter_ spp. and another unnamed bacterial species that carries the NDM (New Delhi Metallo-beta-lactamase) [resistance] gene.

One of the articles says that there were “2 different strains of NDM” identified in this woman. I am unsure whether this refers to 2 different types of NDM or 2 different bacterial strains carrying the same NDM. A variant of NDM-1, called NDM-2, has been described in the medical literature; but NDM-2 has only been detected in _Acinetobacter_ and in patients who had acquired the organism in the Middle East, not the Indian subcontinent to my knowledge (http://www.ncbi.nlm.nih.gov/pubmed/21427107 and http://onlinelibrary.wiley.com/doi/10.1111/j.1469-0691.2011.03726.x/abstract).

Another patient at this hospital developed a fatal infection apparently with the NDM-producing organism. After this 2nd infection was discovered, more than 300 patients in the Royal Alexandra Hospital were screened and either 4 or 5 additional non-infected patients were apparently found to be colonized with either _Acinetobacter_ or NDM-producing bacteria. Another 2 patients apparently are suspected, but not as yet confirmed carriers of one of these bacteria.

NDM is a beta-lactamase that degrades and thereby confers resistance to carbapenem antibiotics. The carbapenems, a class of beta-lactam antibiotics that includes ertapenem, doripenem, imipenem, and meropenem, historically have been antibiotics of last resort to treat many infections due to carbapenem-sensitive multidrug-resistant Gram-negative bacilli. Carbapenemases are a diverse group of mostly plasmid-encoded beta-lactamases that either have serine, e.g., _Klebsiella pneumoniae_ carbapenemases (KPC), or zinc at their active site, i.e., the metallo-beta-lactamases, which include NDM (New Delhi Metallo-beta-lactamase), IMP (Imipenemase), and VIM (Verona Integron-encoded Metallo-beta-lactamase).

NDM-1 was first detected in a _Klebsiella pneumoniae_ isolated from a Swedish patient of Indian origin who had traveled to New Delhi, India and acquired a urinary tract infection in 2008, ref.:

(Yong D, Toleman MA, Giske CG, et al. Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother 2009; 53 (12): 5046–5054. Available at: http://aac.asm.org/content/53/12/5046.full?view=long&pmid=19770275).

NDM-1 was later detected in bacteria in India, Pakistan, the United Kingdom, the United States, Canada, Japan and Brazil.

The most common bacteria that make this enzyme are Enterobacteriaceae such as _Escherichia coli_ and _K. pneumoniae_, but NDM has also been found in _Acinetobacter baumanii_ and _Pseudomonas aeruginosa_ ref.:

(Karthikeyan K, Thirunarayan MA, Krishnan P. Coexistence of blaOXA-23 with blaNDM-1 and armA in clinical isolates of _Acinetobacter baumanii_ from India. J Antimicrob Chemother 2010; 65 (10): 2253–2254. Available at: http://jac.oxfordjournals.org/content/65/10/2253.full).

NDM-producing organisms can degrade all beta-lactams, except for the monobactam, aztreonam, but many NDM-producers are resistant to aztreonam, owing to other mechanisms. For the most part, beta-lactamase inhibitors, such as clavulanic acid, tazobactam, and sulbactam, are not active against carbapenemases. The genes encoding the carbapenemases are frequently associated with genes that encode resistance to other classes of antibiotics (e.g., aminoglycosides and fluoroquinolones). Colistin and tigecycline may retain activity against carbapenemase-producing bacteria, but these antibiotics either have significant side effects, are potentially inferior to more conventional therapies, or can be costly, ref.:

(Queenan AM, Bush B. Carbapenemases: the Versatile β-Lactamases. Clin Microbiol Rev. 2007; 20(3): 440–458.)

In 2010, a patient in Ontario, Canada was reported to be infected with NDM-1-producing bacteria; the patient was said to have "likely" acquired the infection in India after receiving medical treatment there (http://www.ctv.ca/CTVNews/Health/20100821/superbug-case-confirmed-brampton-100821/). This news report also said that there were other confirmed cases in British Columbia and Alberta.

The Royal Alexandra Hospital, located in Edmonton, is one of the largest and longest serving hospitals in the Canadian province of Alberta; it has 678 beds and cares for 450,000 patients annually (http://en.wikipedia.org/wiki/Royal_Alexandra_Hospital,_Edmonton).
Edmonton, Canada can be found in the HealthMap interactive map at http://healthmap.org/r/20O7. - Mod.ML]

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