Wüstenschiff

Experts have warned that a new type of drug-resistant superbug is emerging in UK hospitals.

Mehr hier: http://www.bbc.co.uk/news/health-10930031


Sorry Kuno

Antibiotika-resistente Keime aus Indien auch in Deutschland
13.08.2010 - tagesspiegel

Sogar Antibiotika bleiben machtlos: Im Juli wurden erstmals Keime mit einem Resistenzgen in Deutschland entdeckt. Bakterien, die gegen Antibiotika resistent sind, nehmen weltweit an Häufigkeit zu. Nun haben britische und indische Forscher eine neue Gefahr ausgemacht: Ein Resistenzgen mit dem Namen Neu Delhi Metallo-beta-lactamase-1 (NDM-1) ... mehr
__________________

Resistente Bakterien: Entwicklung "absehbar"
13.08.2010 - orf

Wenig überrascht ist der Wiener Infektionsspezialist Wolfgang Graninger (AKH Wien) von Meldungen über neue Stämme von Bakterien, die praktisch gegen alle verfügbaren Antibiotika resistent sind. "Diese Entwicklung war absehbar" ... mehr


Gruß
Birgitt

GRAM NEGATIVE BACILLI, RESISTANT,UPDATE (01): NDM-1
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In this update:
[1] China (Ningxia, Fujian): NDM-1
[2] Israel ex India: NDM-1


******
[1] China (Ningxia, Fujian): NDM-1
Date: Tue 26 Oct 2010
Source: Xinhua News Agency [edited]
<http://news.xinhuanet.com/english2010/h ... 576388.htm>


China's health authorities Tuesday [26 Oct 2010] announced the
country's 1st 3 cases of NDM-1, a multidrug-resistant "super"
bacterium. Chinese Center for Disease Control and Prevention (China
CDC) official Ni Daxin said at a press conference that 2 cases were
detected from samples submitted by the local CDC in the northwestern
Ningxia Hui Autonomous Region and one from the southeastern Fujian
Province.

The samples from Ningxia were drawn from faeces of 2 infants born on 8
Mar 2010 and 11 Mar 2010. Both were born underweight and showed
symptoms of diarrhea and respiratory infections 2 days after birth.
One suffered an oxygen deficiency. One of the babies recovered after 9
days in hospital and the other after 14 days. They remained healthy,
said Ni. Although the 2 babies were diagnosed as carrying the NDM-1
bacteria, there was no link between the bacteria and their illnesses,
said Ni.

The other sample from Fujian was identified from an 83-year-old, who
died on 11 Jun 2010. Ni said the primary cause of death was late-term
lung cancer, and the role of the drug-resistant bacteria in the
development of the illness was unclear.

The bacteria were identified in laboratories of the China CDC and
Academy of Military Medical Sciences from among 3500 samples. Ni told
Xinhua the detection rate was still low. Ni said it was impossible to
trace the origin of the bacteria, because it had been a long time
since samples were collected. Ni said there was no cause for panic
because the bacteria did not spread among people. "It is only
contagious through medical activities, so hospitals and clinics must
be on high alert." Ni said China CDC would expand the pool of samples
for NDM-1 testing.

Xiao Yonghong, director of national drug-resistant bacteria
surveillance network run by the Ministry of Health, said hospitals
should step up monitoring and sterilization. Xiao said the network,
established in 2005, covered 170 top-level hospitals across China.

NDM-1 is most prevalent in South Asia, but has also been found in
Britain, the Netherlands, Australia, Canada, the United States, and
Sweden.

[Byline: Zhang Xiang]

--
Communicated by:
ProMED-mail Rapporteur Mary Marshall

[The HealthMap/ProMED-mail interactive map of China is available at
<http://healthmap.org/r/00dj>.
A map showing the provinces can be seen at
<http://www.sacu.org/provmap.html>. Sr.Tech.Ed.MJ]

******
[2] Israel: NDM-1
Date: Wed 27 Oct 2010
Source: Haaretz [edited]
<http://www.haaretz.com/print-edition/ne ... n-1.321340>


For the 1st time, an Israeli patient has been diagnosed with a
"superbug" -- one that is resistant to antibiotics.

The 50-year-old woman was involved in a traffic accident in India and
hospitalized in New Delhi for 5 days before being transferred to the
Sheba Medical Center, Tel Hashomer. There, she was found to have
intestinal bacteria containing the enzyme New Delhi
metallo-beta-lactamase-1, better known as NDM-1. The enzyme, which is
found in a variety of intestinal bacteria, breaks down [beta-lactam]
antibiotics, thereby rendering the carrier bacteria immune
[non-susceptible] to them.

The woman was immediately quarantined to prevent her from infecting
anyone else. Sheba also tested all the staff who had treated her and
the other patients in the ward, but did not find any who had been
infected with the bug. The hospital said the woman is due to be
released in a few days, once it confirms that the bug has left her
system.

2 months ago, the Health Ministry ordered all hospitals to test any
patient who had undergone any type of medical treatment in India since
2008 for NDM-1. The order was issued because the bug has been detected
in several other Western countries in recent months.

[Byline: Dan Even]

--
Communicated by:
ProMED-mail Rapporteur Mary Marshall

NDM-1 CARRYING ENTEROBACTERIACEAE - INDIA: (NEW DELHI) WATER SUPPLY
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Date: Wed 6 Apr 2011
Source: Reuters [edited]
<http://www.reuters.com/article/2011/04/ ... W920110406>


A gene that makes bugs highly resistant to almost all known
antibiotics has been found in bacteria in water supplies in New Delhi
used by local people for drinking, washing, and cooking, scientists
said. The NDM 1 gene, which creates what some experts describe as
"super superbugs," has spread to germs that cause cholera and
dysentery, and is circulating freely in other bacteria in the Indian
city capital of 14 million people, the researchers said.

"The inhabitants of New Delhi are continually being exposed to
multidrug-resistant and NDM 1-positive bacteria," said Mark Toleman of
Britain's Cardiff University School of Medicine, who published the
findings in a study on Thursday, 7 Apr 2011.

A "substantial number" of them are consuming such bacteria on a daily
basis, he told a briefing in London. "We believe we have discovered a
very significant underlying source of NDM 1 in the capital city of
India," he said.

NDM 1, or New Delhi metallo-beta-lactamase 1, makes bacteria
resistant to almost all antibiotics, including the most powerful
class, called carbapenems.

It first emerged in India 3 years ago and has now spread across the
world. It has been found in a wide variety of bugs, including familiar
pathogens like _E. coli_.

No new drugs are on the horizon for at least 5-6 years to tackle it
and experts are concerned that only a few major drug companies, such
as GlaxoSmithKline and AstraZeneca, still have strong antibiotic
development programs.

Experts say the spread of superbugs threatens whole swathes of modern
medicine, which cannot be practiced if doctors have no effective
antibiotics to ward off infections during surgery, intensive care, or
cancer treatments like chemotherapy.

The WHO has designated April 7 as World Health Day and under the
slogan "No action today, no cure tomorrow" it is campaigning about the
risks of life-saving antibiotics losing their healing power. "We are
at a critical point in time where antibiotic resistance is reaching
unprecedented levels," said Zsuzsanna Jakab, the WHO's regional
director for Europe.

"Given the growth of travel and trade in Europe and across the world,
people should be aware that until all countries tackle this, no
country alone can be safe."

[Byline: Kate Kelland]

--
Communicated by:
ProMED-mail Rapporteur Mary Marshall

[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): 5046-54 (<http://aac.asm.org/cgi/reprint/53/12/5046>).
The plasmid carrying NDM-1 also carries several other resistance genes
and appears to easily transmit itself to other organisms. The authors
state "the dissemination of this plasmid among clinical bacteria would
be a nightmare scenario." Clearly, inadequate sanitary systems make
spread of enteric bacteria of any sort quite easy.

This gene cassette of wide-spectrum antimicrobial resistance appears
to have developed in the Indian subcontinent where the use of
antimicrobial agents is quite poorly controlled. Organisms carrying
this resistance combination have already been introduced into western
Europe, the USA, and Canada. The best methods of control are rapid
recognition by standard microbiologic methodology in patients having
the appropriate medical/travel history and aggressive handwashing
techniques.

The amazing overuse of our current antimicrobial armamentarium that I
am currently observing in my clinical practice in the USA will no
doubt serve as an efficient multiplier of these isolates just as
intravenous drug abuse and sexual promiscuity facilitated the
explosion of HIV 30 years ago. This misuse, in my opinion, is directly
related to the lack of control of antimicrobial usage in intensive
care units and emergency care settings by intensivists and ER
physicians who often react with unwisdom and "cookbook" protocols
instead of using common sense and rational prescribing patterns. Once
the patient moves out of the ICU or ER, these physicians do not even
see the products of their unwise labors.

In the USA, reimbursements for medical care are based on procedures,
not thought processes. Until the power of therapeutic nihilism is
recognized, that is, using these agents only when rational, in
combinations that make sense, and in settings where therapeutic
interventions can have the ability to produce measurable and
meaningful improvement in a patient's life, the medical community will
continue down the slippery slope into an era where no therapeutic
options will exist. - Mod.LL]

NDM-1 CARRYING ENTEROBACTERIACEAE - INDIA, CHINA: GOVERNMENT RESPONSE
*********************************************************************
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<http://www.isid.org>

*******
[1] India
Date: Mon 11 Apr 2011
Source: IGovernment.in [edited]
<http://igovernment.in/site/no-superbug- ... stry-39614>


There is no major health threat by the presence of multi-drug
resistant bacteria in Delhi's environment, the Union Health Ministry
said on Mon 11 Apr 2011.

A UK based prestigious medical journal has accused the Indian
government of "suppressing the truth" about the presence of the
superbug. "We have rejected it and we still reject it," Director
General Health Service RK Srivastava said, reports IANS. However, he
said that a final statement can be made only after the research wing
of the Health Ministry (Indian Council of Medical Research) completes
its study.

"The research wing will examine everything, the protocol and the
method of research, all will be examined and only after that, a final
statement can be given by the concerned authorities," he said.

Days after Health Ministry rejected the study on the presence of the
superbug in Delhi's environment, published in British journal The
Lancet, study co-author Mark Toleman accused the government of India
of "suppressing the truth."

The study, published last week, said the New Delhi
metallo-beta-lactamase (NDM-1) gene, which makes bacteria resistant to
an array of antibiotics, including the most powerful ones, has been
found in open water pools, water from overflowing sewage and even a
couple of drinking water samples in the Indian capital.

The health ministry, however, said such bacteria existed all over the
world and the study was targeting India.

Delhi Chief Minister Sheila Dikshit also reiterated Monday that water
in the city was safe for drinking and there was nothing to panic
about.

--
Communicated by:
Dr. Omesh Kumar Bharti
OSD, Emergency Medical Response and Transport,
Directorate of Health, Kasumpati,
SHIMLA, Himachal Pradesh, India
<bhartiomesh@yahoo.com>

[ProMED thanks Dr. Bharti for this report. Indeed, panic should not
be the response to the report. While it is the truth that NDM-1 gene
containing bacteria have been found around the world, most of the
cases have been traced back to the Indian subcontinent where, in New
Delhi, the gene cassette was 1st identified. Furthermore, the danger
represented by such antimicrobial-resistant bacteria needs to be
stratified. That is, an extremely resistant _E. coli_ in the
intestines of a healthy individual is not an immediate danger to the
host. Indeed, it can be part of the microflora of the gut which serves
a positive role in health. How well the NDM-1-containing
enterobacteriacae compete in the gut is not clear and may not be able
to survive well against their drug-sensitive 'cousins.'

Those points must be taken in perspective should the
polydrug-resistant organism escape the nurturing environment of the
gut and cause a urinary tract infection by traversing the urethra or
enter the sterile peritoneum via a ruptured appendix or diverticulum.
In such circumstances, appropriate antimicrobial intervention is
extremely limited and can certainly lead to increased morbidity and
mortality.

As discussed in the ProMED posting NDM-1 carrying Enterobacteriaceae
- India: (New Delhi) water supply 20110411.1145, the widespread misuse
of antimicrobial agents, plays a large role in the selection on such
isolates. The recognition and some of the creative causes of the
misuse in China are discussed below. An inadequate sanitary system,
allowing human waste to contaminate water supplies, further serves to
spread the resistant strains. - Mod.LL]

*****
[2] China
Date: Tue 12 Apr 2011
Source: XinHuaNet [edited]
<http://news.xinhuanet.com/english2010/c ... 824833.htm>


The Ministry of Health is set to further curb the overuse of
antibiotics, mainly at large hospitals, to fight rising drug
resistance.

By 2011's end, the rates of antibiotics use among inpatients and
outpatients on the mainland are expected to be lowered from 70 percent
and 50 percent to around 50 percent and 20 percent, which are in line
with international standards, the ministry told a regular news
conference on Mon 11 Apr 2011.

"The long-time overuse is related to factors including bad morality
of some medical workers and the current system whereby hospitals rely
on drug sales for revenue," said Zhao Minggang, deputy director of the
department of medical administration under the ministry. Experts
estimate that only 20 percent of the total antibiotics administered on
the mainland are necessary. Others are prescribed mainly for financial
benefit.

Apart from the economic burden caused for patients, "the misuse of
antibiotics. primarily the overuse, creates antibiotic-resistant
germs, which might cost human lives," warned Professor Xiao Yonghong
from the First Hospital of Zhejiang province.

According to Xiao, about 30 to 50 percent of the infections acquired
in hospitals on the mainland are caused by bacteria that are highly
resistant to antibiotics. And the rate is on the rise, he said.

In October 2010, China confirmed its 1st 3 cases of the NDM-1
superbug in 2 infants in northwestern Ningxia Hui autonomous region,
and an elderly resident of the eastern Fujian province. Originally
found in India in 2008, the new bacterium carrying the NDM-1 gene,
which is resistant to almost all antibiotics and could only be treated
with a combination of antibiotic drugs, was briefly spreading
globally.

--
Communicated by:
ProMED Rapporteur Mary Marshall
<promed@promedmail.org>

Antibiotika-Resistenz rechtzeitig enttarnt
Strukturaufklärung ermöglicht erstmals rechzeitigen Umbau des betroffenen Antibiotikums
26.04.2011 - scinexx

Zum ersten Mal ist es Forschern gelungen, die molekulare Ansatzstelle einer Antibiotika-Resistenz aufzuklären, bevor resistente Krankheitserreger die klinische Anwendung des Wirkstoffs wirkungslos machen. Wie sie in der Fachzeitschrift „FEBS Letters“ berichten, vermittelt die Struktur des Proteins Monooxygenase TetX den Bakterien eine Resistenz gegen neue Tetracyclin Antibiotika. Damit ist nun ein schpützender Umbau des gefährdeten Antibiotikas Tigecyclin möglich ... mehr

Gruß
Birgitt

NDM-1 CARRYING ENTEROBACTERIACEAE - INDIA (02): NOSOCOMIAL INFECTIONS
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[1] Neonatal ICU
Date: Wed 5 Oct 2011
Source: IBN Live [edited]
<http://ibnlive.in.com/news/drug-resista ... 42-17.html>


India is hosting a global summit on antibiotic resistance in New Delhi
this week [week of 3 Oct 2011], even as the NDM-1 bacterial resistance
factor has now made its way into neonatal ICUs in the country and is
affecting and killing newborn babies.

Because of antibiotic resistance, nearly 60 000 newborn babies are
dying every year in India of sepsis, a treatable blood infection,
despite getting lifesaving antibiotics. "The organisms in the
hospitals have become multidrug resistant. Even the strongest
antibiotics may not work. Invariably, the baby ends up losing the
battle," said Dr Vishal Singh, Sr Consultant, Pediatric Critical Care
Unit, Neonatal ICU.

According to the Public Health foundation of India, one million babies
die every year in India within the 1st 4 weeks of birth, and 190 000
are dying of sepsis, often due to lack of access to medicines, and 30
percent of these deaths are due to antibiotic resistant bacteria.

There is now the threat from NDM-1 containing bacteria, as 4 infants
at a hospital in Birbhum district in rural West Bengal affected with
these bacteria died within 72 hours.

"When we abuse antibiotics or don't use them appropriately, we are
basically strengthening the bacteria that work against these babies,"
said Dr Ramanan of PHFI. "To change this, all we need to do is to use
antibiotics according to prescribed guidelines.

--
Communicated by:
ProMED-mail Rapporteur Mary Marshall
<promed@promedmail.org>

******
[2] General hospital
Date: Wed 5 Oct 2011
Source: India Today [edited]
<http://indiatoday.intoday.in/story/stud ... 53810.html>


A study conducted at Delhi's famous Sir Ganga Ram Hospital has found a
worryingly high prevalence of bacteria containing a resistance factor
gene named New Delhi metallo-beta-lactamase 1 (NDM-1). The study,
conducted over the last 5 months, found patients positive for bacteria
containing the antibiotic drug-resistance factor.

A total of 10 889 samples were collected from the hospital. Out of
these, over 2500 positive samples were found in the intensive care
unit (ICU) and around 2700 more in the general ward. The positive
samples came mostly from patients with _E. coli_ infection and
pneumonia. However, doctors at the hospital said that since Ganga Ram
was a tertiary care hospital, patients could already have been
infected when they came to the hospital.

Senior physician and cardiologist Dr K.K. Aggarwal said: "The bacteria
are present. There are 3 studies now which confirm that [they are]
present in the hospitals; they are present in multiple hospitals,
present in India. They are present in water. Now, Ganga Ram says they
are present in their ward. It's a matter of serious concern. All
hospitals should check it, should come out with a new antibiotic
policy, and should absolutely implement hygiene maintenance," Aggarwal
added.

--
Communicated by:
ProMED Rapporteur Mary Marshall
<promed@promedmail.org>

[Originating in India, NDM-1 containing bacteria have spread to the
developed world. As reported in the 25 Jun 2010 Morbidity and
Mortality Weekly Report (2010;59:750), during the 1st half of 2010, 3
isolates of _Enterobacteriaceae_, an _E. coli_, a _Klebsiella
pneumoniae_, and an _Enterobacter cloacae_, were identified at CDC to
carry NDM-1, which confers resistance to all beta-lactams except
aztreonam (a monobactam) and were also resistant to aztreonam. All 3
isolates were from patients who received recent medical care in
India.

Yong and colleagues (Yong D, Toleman MA, Giske CG, et al:
Characterization of a new metallo-beta-lactamase gene, bla-NCm-1, and
novel erythromycin esterase gene carried on a unique genetic structure
in _Klebsiella pneumoniae_ sequence type 14 from India. Antimicrob
Agents Chemother. 2009;53: 5046-54) found that the plasmid carrying
NDM-1 also carries several other resistance genes and appears to
easily transmit itself to other organisms. The authors state that "the
dissemination of this plasmid among clinical bacteria would be a
nightmare scenario."

This NDM-1 gene cassette of wide-spectrum antimicrobial resistance
appears to have developed in the Indian subcontinent, as in the above
report, where the use of antimicrobial agents is quite poorly
controlled. Organisms carrying this resistance combination have
already been introduced into western Europe, the USA, and Canada. The
best methods of control are rapid recognition by standard
microbiologic methodology in patients having the appropriate
medical/travel history and aggressive hand washing techniques.

The amazing overuse of our current antimicrobial armamentarium that I
am currently observing in my clinical practice in the USA will no
doubt serve as an efficient multiplier of these isolates, just as
intravenous drug abuse and sexual promiscuity facilitated the
explosion of HIV 30 years ago. This misuse, in my opinion, is directly
related to the lack of control of antimicrobial usage in intensive
care units and emergency care settings by intensivists and ER
physicians who often react with a lack of wisdom and "cookbook"
protocols instead of using common sense and rational prescribing
patterns. Once the patient moves out of the ICU or ER, the physicians
do not even see the products of their unwise labors.

In the USA, reimbursements for medical care are based on procedures,
not thought processes. Until the power of therapeutic nihilism is
recognized -- that is, using these agents only when rational, in
combinations that make sense, and in settings where therapeutic
interventions can have the ability to produce measurable and
meaningful improvement in a patient's life -- the medical community
will continue down the slippery slope into an era where no therapeutic
options will exist. - Mod.LL]

GRAM NEGATIVE BACILLI, MULTIDRUG RESISTANT - SOUTH AFRICA, NDM-1,
NOSOCOMIAL
*****************************************************************************

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ProMED-mail is a program of the
International Society for Infectious Diseases
http://www.isid.org


Date: Mon 17 Oct 2011
Source: Deccan Herald, Agence France-Presse (AFP) report [edited]
http://www.deccanherald.com/content/198 ... erbug.html


A South African outbreak of a multidrug resistant ''superbug'' has
been contained after it infected 9 patients of whom 3 were still in
quarantine, a hospital group said today [17 Oct 2011].

Two patients infected with the NDM-1 (New Delhi metallo-beta-lactamase
1) died but were suffering from other chronic diseases, said Joy
Cleghorn, infection prevention risk manager at Life Healthcare. "4
have been discharged and 3 remain isolated," she told AFP about the
patients at the hospital east of Johannesburg.

The NDM-1, first detected in 2009, is a gene that enables some types
of bacteria to be highly resistant to almost all antibiotics.

Only 2 other cases have been recently reported in South Africa.
"Around the same period, one month ago, there has been an outbreak in
a public hospital of Johannesburg," said Cleghorn. The patients at the
private Life Glynnwood Hospital, in Benoni east of Johannesburg, had
not travelled to India and the illness was "a secondary contact," she
said.

The 1st African infections were reported in Kenya and they have also
been found around the world including in Australia, Britain, Japan,
and the United States.

--
communicated by:
ProMED-mail rapporteur George A Robertson

[NDM-1 (New Delhi metallo-beta-lactamase 1) is a carbapenemase, which
is a beta-lactamase that degrades and thereby confers resistance to
carbapenem antibiotics. Carbapenems are a class of beta-lactam
antibiotics that includes imipenem and meropenem. These carbapenems
historically have been antibiotics of last resort to treat many
infections due to carbapenem-sensitive multidrug-resistant Gram
negative bacilli.

The carbapenemases fall into several molecular classes, A, C, B, and
D. Classes A, C, and D have serine at the active site and class B,
zinc at the active site. KPC (_Klebsiella pneumoniae_ carbapenemase)
are class A carbapenemases; IMP (imipenemase), NDM-1, and VIM (Verona
integron-encoded metallo-beta-lactamase) are class B carbapenemases;
and OXA-types (oxacillin-hydrolyzing) are class D carbapenemases.

NDM-1 confers resistance to carbapenems, as well as resistance to all
other beta-lactam antibiotics, except aztreonam (a monobactam).
Nevertheless, isolates that produce NDM-1 are commonly resistant to
aztreonam, presumably by a different mechanism. The gene that encodes
NDM-1 also can co-exist with genes that determine resistance to other
classes of antibiotics, including the fluoroquinolones and
aminoglycosides. Colistin and tigecycline may retain activity against
NDM-1-producing bacteria, but these antibiotics either have
significant side effects, are potentially inferior to more
conventional therapies, or can be costly.

_Enterobacteriaceae_ that produce NDM-1 have been reported from the
UK, the US, Canada, Australia, Japan, Sweden, Belgium, the
Netherlands, Taiwan, China, Israel, and now South Africa. Many
patients who are either infected or colonized with bacteria that
produce NDM-1 had initially gone abroad to India and Pakistan for
treatments such as cosmetic surgery, and carried these organisms back
to their home countries. Once these patients were hospitalized in
their home countries, NDM-1-producing bacteria could then spread
locally to other hospitalized patients.

Community spread of these fecal organisms is facilitated in developing
countries by unsanitary disposal of human excrement, fecal
contamination of the drinking water supply, coupled with heavy and
unregulated antibiotic use. Indeed, NDM-1 has been found in the
drinking water and sewage in New Delhi (Walsh TR, Weeks J, Livermore
DM, Toleman MA: Dissemination of NDM-1 positive bacteria in the New
Delhi environment and its implications for human health: an
environmental point prevalence study. The Lancet Infectious Diseases,
2011; 11(5): 355-62; available at
http://www.thelancet.com/journals/lanin ... 7/abstract).

The gene encoding NDM-1 is located on mobile genetic elements, which
facilitates their spread between bacteria of the same or even
different species. Consequently, NDM-1 is not only found in
_Enterobacteriaceae_ such as _K. pneumoniae_ and _Escherichia coli_,
NDM-1 has been found in other Gram negative bacilli such as
_Acinetobacter_. (See ProMED-mail NDM-1 carrying Enterobacteriaceae -
worldwide ex India, Pakistan (02) 20100914.3325.) However, the
bacterial species involved in the South African NDM-1 outbreak is not
stated in the news release above.

Infection control interventions in healthcare facilities aimed at
preventing transmission of carbapenemase-producing isolates include
recognition of carbapenem-resistant _Enterobacteriaceae_ when cultured
from clinical specimens, placement of patients colonized or infected
with these isolates on contact precautions, and in some circumstances,
conducting point prevalence surveys or active-surveillance testing
among high-risk patients (CDC: Guidance for control of infections with
carbapenem-resistant or carbapenemase-producing _Enterobacteriaceae_
in acute care facilities. MMWR 2009; 58(10): 256-60; available at
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5810a4.htm).

Johannesburg, the largest city in South Africa, with a population of
almost 4 million, is the provincial capital of Gauteng
(http://en.wikipedia.org/wiki/Johannesburg). For a map of Gauteng
with Johannesburg highlighted, see
http://en.wikipedia.org/wiki/File:Map_o ... (2011).svg.
For the interactive HealthMap/ProMED map of South Africa, see
http://healthmap.org/r/1lDO. - Mod.ML]

NDM-1 CARRYING ENTEROBACTERIACEAE - INDIA (03): COMMENT
*******************************************************

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Date: Fri 30 Dec 2011
Source: DNA India [edited]
http://www.dnaindia.com/india/report_th ... ut_1631397


There is an epidemic coming. The gram negative bacteria that produces
the NDM1 (New Delhi mettalo-beta-lactamase-1) enzyme, making it
resistant to powerful antimicrobials like the carbapenems, is
developing a resistance to the last line of antimicrobial defense.

It will develop resistance to old drugs such as Colistin and
Tigacycline in a couple of years, say doctors, and the process has
already started. Dr Bharat Shah, a senior nephrologist in the city,
says: "There are already cases where drugs like colistin are not
proving to be as effective as earlier."

Dr Abdul Ghafur, an infectious disease expert who was one of the 1st
in India to raise the NDM-1 alarm a couple of years back, says: "Once
the bacteria become resistant, thousands in ICUs all over the country,
those undergoing complex procedures like transplants, or even those
infected by the relatively harmless _Klebsiella_ or _E. coli_, will be
at huge risk."

Dr Mark Toleman, a senior research fellow at the Department of
Infection, Immunity and Biochemistry at Cardiff University [UK], was
part of a team that conducted a study which found that 30 percent of
all water samples tested in New Delhi contained bacteria carrying
NDM-1. In a carrier test done by the team in Rawalpindi, they found
the presence of NDM1-producing bacteria in 14 percent of the people
and 27 percent of the patients. "Based on the results, we estimate
that 100 million Indians are already carrying bacteria harboring the
gene," he said.

The risk of infection is highest in hospitals because of a mix of
unhygienic conditions as well as the fact that the sick are generally
more prone to this particular infection. "The gram negative bacteria
in hospitals acquire genetic characteristics from other bacteria
present there," says Dr Abhay Chaudhary, director of Haffkine
Institute.

Toleman says: "Once Colistin is gone, there is little if anything that
can be done. Studies in the UK have shown that combinations of
different drugs can be used successfully against the bacteria, but
this is really hit-or-miss. The future looks especially bleak for East
Asia, and the Indian government is utterly complacent at the moment."

One problem in India is the lack of control on use of anti-infectives.
Toleman says this unrestricted use will make any new drug useless
rapidly. "It seems unfair that companies in the West should invest
heavily in development just to have their drug copied in India and
then rendered useless because the Indian government has failed to put
down restrictions," he adds.

So what's the solution? We need to take precautionary measures, says
Chaudhary. "We need to have a serious antimicrobial and infection
control policy at our hospitals. We must have a stringent disinfectant
policy that makes sure that hospital staff scrupulously disinfect
medical apparatus."

However, in a country where most government hospitals have dogs
roaming in and about and open bins with swarming flies, it remains to
be seen whether a proper sanitation policy is implemented.

[Byline: Rito Paul]

--
Communicated by:
ProMED Rapporteur Mary Marshall
promed@promedmail.org

[Originating in India, NDM-1 containing bacteria have spread to other
parts of the world. As reported in the 25 Jun 2010 Morbidity and
Mortality Weekly Report (2010;59:750), during the 1st half of 2010, 3
isolates of _Enterobacteriaceae_, an _E. coli_, a _Klebsiella
pneumoniae_, and an _Enterobacter cloacae_, were identified at CDC to
carry NDM-1, which confers resistance to all beta-lactams except
aztreonam (a monobactam) and were also resistant to aztreonam. All 3
isolates were from patients who received recent medical care in
India.

Yong and colleagues (Yong D, Toleman MA, Giske CG, et al:
Characterization of a new metallo-beta-lactamase gene, bla-NCm-1, and
novel erythromycin esterase gene carried on a unique genetic structure
in _Klebsiella pneumoniae_ sequence type 14 from India. Antimicrob
Agents Chemother. 2009;53: 5046-54) found that the plasmid carrying
NDM-1 also carries several other resistance genes and appears to
easily transmit itself to other organisms. The authors state that "the
dissemination of this plasmid among clinical bacteria would be a
nightmare scenario."

This NDM-1 gene cassette of wide-spectrum antimicrobial resistance
appears to have developed in the Indian subcontinent, as in the above
report, where the use of antimicrobial agents is quite poorly
controlled. Organisms carrying this resistance combination have
already been introduced into western Europe, the USA and Canada. The
best methods of control are rapid recognition by standard
microbiologic/nucleic acid methodology in patients having the
appropriate medical/travel history and aggressive hand washing
techniques.

The amazing overuse of our current antimicrobial armamentarium that I
am currently observing in my clinical practice in the USA will no
doubt serve as an efficient multiplier of these isolates, just as
intravenous drug abuse and sexual promiscuity facilitated the
explosion of HIV 30 years ago. This misuse, in my opinion, is directly
related to the lack of control of antimicrobial usage in intensive
care units and emergency care settings by intensivists and ER
physicians who often react with a lack of wisdom and "cookbook"
protocols instead of using common sense and rational prescribing
patterns. Once the patient moves out of the ICU or ER, the physicians
do not even see the products of their unwise labors.

In the USA, reimbursements for medical care are based on procedures,
not thought processes. Until the power of therapeutic nihilism is
recognized -- that is, using these agents only when rational, in
combinations that make sense, and in settings where therapeutic
interventions can have the ability to produce measurable and
meaningful improvement in a patient's life -- the medical community
will continue down the slippery slope into an era where no therapeutic
options will exist. - Mod.LL

A HealthMap/ProMED-mail map can be accessed at:
http://healthmap.org/r/1pSH.]

NDM-1 CARRYING ACINETOBACTER - CZECH REPUBLIC ex EGYPT
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Date: Thu 17 Feb 2012
Source: Eurosurveillance, Volume 17, Issue 7 [edited]
http://www.eurosurveillance.org/ViewArt ... leId=20085.


We describe the isolation of an NDM-1-producing _Acinetobacter baumannii_ in a Czech patient repatriated in July 2011 from Egypt. The infection spread to another patient on the same ward. Both isolates showed the same resistance pattern and were susceptible only to colistin. They had an identical PFGE [pulse feild gel electrophoresis] pattern and belonged to the same sequence type ST 1. Sequencing of the blaNDM gene identified the NDM-1 variant of the carbapenemase, surrounded by two copies of insertion sequence ISAba125.

The index patient was hospitalized in Egypt, and then transferred to a hospital in the Czech Republic. The patient developed ventilator-associated pneumonia caused by _A. baumannii_ in addition to a primary neurological diagnosis. A carbapenem-resistant _A. baumannii_ strain (V509) was isolated from bronchoalveolar lavage and an oral cavity swab. He was initially treated by meropenem and metronidazole. Due to progression of the primary disease, the patient was transferred to a long term intensive care unit (ICU). Although the antibiotic regimen was not changed, the patient recovered according to the biochemical markers of inflammation within 7 days and the antibiotic therapy was then stopped. The available data are not conclusive as to whether this patient was infected or colonized. However, the resistant isolate has been detected in low quantity in oral swab and bronchoalveolar lavage until the transfer to the long term ICU. The ICU was informed about the epidemiological risk associated with this patient so that they could prepare for appropriate measures upon transfer.

A second _A. baumannii_ isolate (V566) with the same resistance pattern was recovered 6 days later from the airways of another ventilated patient sharing the same room. The patient was treated with amoxicillin/clavulanic acid, chloramphenicol, and ciprofloxacin. He died due to respiratory failure 4 days after the 1st isolation of NDM-1-producing _A. baumannii_.

Laboratory analysis
-------------------
The isolates from both patients were identified as _A. baumannii_ by biochemical testing and by matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometry. The minimum inhibitory concentrations (MICs) to 14 antibiotics were tested and the results were interpreted according to the EUCAST recommendation (1). The isolates from both patients were resistant to all beta-lactams tested including carbapenems and other antibiotics (Table, see URL above. - Mod.LL]).

Typing performed by PFGE (2) showed that the isolates had indistinguishable macrorestriction patterns. Carbapenemase production was confirmed by MALDI-TOF mass spectrometry (3). Production of metallo-beta-lactamase (MBL) activity was verified by ethylenediaminetetraacetic acid (EDTA) double-disk synergy test (4).

The blaNDM gene of both isolates was amplified and sequenced as described previously [5], and revealed the NDM-1 variant of the enzyme. The blaNDM-1 together with other genes was located between two copies of the insertion sequence ISAba125 in the same orientation as found by Pfeifer and colleagues [6]. Because plasmid preparations from the two isolates did not yield any plasmids visible after electrophoretic separation, and no transformants were obtained after transformation experiments performed as previously described [7], it can be hypothesised that blaNDM-1 is located on the bacterial chromosome.

Multi-locus sequence typing (MLST) was performed [8] and the MLST database available at the website of the Pasteur Institute was used to assign the sequence type (ST). Both isolates belonged to sequence type (ST) 1 (allelic profile 1-1-1-1-5-1-1) which represents the epidemiologically successful European clone I [9].

Discussion and conclusion
-------------------------
Reports describing NDM-type carbapenemase producers isolated from patients previously hospitalised in high-prevalence countries have been increasing. Pfeifer and colleagues detected NDM-1 in _A. baumannii_ isolated from a patient repatriated to Germany from Serbia in 2007 [6]. Importation of NDM-1-producing _A. baumannii_ strain from Serbia has also been described by Poirel and colleagues [10]. Other _A. baumannii_ isolates expressing NDM-1 MBL have been isolated in China and India [11,12]. It is remarkable that blaNDM-1 was also found on a plasmid in _A. lwoffii_ in China [13]. The new NDM-2 variant was first detected in _A. baumannii_ from a patient transferred from Egypt to Germany [5]. Recently, clonal spread of NDM-2-producing _A. baumannii_ strains have been described in a rehabilitation ward in Israel and in the United Arab Emirates [14,15].

Until this report, no NDM-1 producing bacterium had been described in the Czech Republic, a country with a low prevalence of carbapenemase-producing bacteria [16-18]. Although routine procedures were in place in the hospital department, the strain quickly spread within one ward to another patient. After the death of the second patient and the transfer of the first patient to the long term ICU, the department was closed for 2 weeks and general cleaning including decontamination of all equipment was undertaken. No NDM-1-producing strain has been detected after the cleaning. Due to the importance of international travel in the spread of bacterial resistance, fast detection and active surveillance of bacteria producing acquired carbapenemases is needed [5-7,10,16,18,19].

We also tested the new MALDI-TOF mass spectrometry approach [3] for the detection of carbapenemase activity in the isolates. Although phenotypical detection of carbapenem-hydrolyzing enzymes in _A. baumannii_ seems to be difficult by conventional methods [20], we were able to see a clear carbapenemase activity by this assay. Further validation, however, is necessary.

Acknowledgements
----------------
This work was supported by the research project grants NT11032-6/2010 and NS9717-4/2008 from the Ministry of Health of the Czech Republic and MSM0021620819 from the Ministry of Education of the Czech Republic.

References
----------
[See URL above. - Mod.SH]

[byline: J Hrabák, M Štolbová, V Študentová, M Fridrichová, E Chudáčková, H Zemlickova]

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NDM-1 CARRYING VIBRIO CHOLERAE - INDIA
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Date: Sat 28 Jul 2012
Source: Deccan Chronicle [edited]
http://www.deccanchronicle.com/node/144375


In a major cause for concern, a new strain of cholera bacteria resistant to 3rd generation antibiotics has been found to be circulating in India. This cholera bacterial strain contains 2 super bug genes including the notorious New Delhi Metallo beta-lactamase-1 (blaNDM-1). The other super bug gene is plasmid-mediated beta-lactamase-1 (blaDHA-1). Thanks to these 2 super bug genes, the new cholera bacterial strain (O1 El Tor Ogawa) has developed resistance to a majority of known antibiotics.

The blaNDM-1, discovered a couple of years ago from hospitals in New Delhi, created ripples in the health sector worldwide. The gene was then found in _Escherichia coli_ strains. This is the 1st time that doctors have found the super bug gene blaNDM-1 in the cholera bacteria _Vibrio cholerae_.

A team of doctors led by Dr Jharna Mandal from Jawaharlal Institute of Post-graduate Medical Education and Research (Jipmer), Puducherry, isolated the cholera germ strain from the stool of a 2-year-old patient. It reported the findings in the journal of the Centres for Disease Control and Prevention (CDC), USA.

"_Vibrio cholerae_ [have] developed enormous capabilities to combat antimicrobial drug effects. It possesses efflux pumps that act on multiple classes of antimicrobial drugs and elaborates enzymes that can nullify the impact of complex antimicrobial drugs," the team said.

--
Communicated by:
ProMED-mail Rapporteur Mary Marshall

[The news release above refers to a very recent article: Mandal J, Sangeetha V, Ganesan V, et al. Third-Generation Cephalosporin-Resistant _Vibrio cholerae_, India. Emerg Infect Dis 2012;18, (8), 1326-28. Available at http://wwwnc.cdc.gov/eid/article/18/8/pdfs/11-1686.pdf.

Abstract:
"_Vibrio cholerae_ resistance to third-generation cephalosporins is rarely reported. We detected a strain that was negative for extended-spectrum B-lactamase and positive for the AmpC disk test, modified Hodge test, and EDTA disk synergy test and harbored the blaDHA-1 and blaNDM-1 genes. The antimicrobial drug susceptibility profile of V. cholerae should be monitored."

The strain in question was said to be resistant to ampicillin, ceftriaxone, cotrimoxazole, and furoxone and sensitive only to ciprofloxacin and tetracycline. It carried NDM-1 (a gene that encodes a carbapenemase and thereby resistance to carbapenems, as well as other beta-lactam antibiotics) and AmpC beta-lactamase (a gene that encodes for resistance to extended-spectrum cephalosporins e.g., ceftriaxone). However, this pattern of drug resistance is not an issue for treatment of cholera.

Cholera can be successfully treated by immediate replacement of the fluid and salts lost through diarrhea and then maintenance of normal hydration status by replacing ongoing losses. Patients are preferably treated with a prepackaged oral rehydration solution that contains a mixture of sugar and salts to be mixed with water and drunk in large amounts. Patients too ill for oral hydration are given intravenous fluids. With prompt rehydration, less than one percent of cholera patients die (http://www.who.int/cholera/technical/en/).

Use of antibiotics is only an adjunct to rehydration. Antibiotics are not recommended for patients with cholera who have only mild or no diarrhea and dehydration. In severe cases, an effective antibiotic reduces shedding of _Vibrio cholerae_ in feces from over 5 days to 1-2 days and reduces the volume of diarrheic stool and the duration of illness, hastening recovery, and decreasing the chances of disease spread. Doxycycline is recommended as a first-line treatment for adults, while azithromycin is recommended as first-line treatment for children and pregnant women (http://www.cdc.gov/cholera/treatment/an ... tment.html).

Other antibiotics that are effective when _V. cholerae_ are susceptible to them include cotrimoxazole, erythromycin, ciprofloxacin, chloramphenicol and furazolidone. Antimicrobial agents typically are administered for 3-5 days. However, resistance to the tetracyclines and other antimicrobial agents among _V. cholerae_ has been has been increasing. Resistance can be acquired through the accumulation of selected mutations over time, or the acquisition of transmissible genetic elements such as plasmids, which confer rapid spread of resistance. Surveillance for antibiotic resistance among bacterial isolates in a cholera outbreak is essential for maintaining effective therapy and minimizing the spread of resistance.

NDM-1 appears to have developed in the Indian subcontinent where NDM-1 has been found in drinking water and sewage and where cholera is endemic. The highly transmissible plasmid carrying NDM-1 gene, which encodes a carbapenemase, also carries linked genes that encode wide-spectrum antimicrobial resistance that can be transferred at the same time. Many prior isolates of other bacterial species displaying NDM-1 have been resistant to tetracyclines as well as multiple other antibiotics, so it is not surprising that NDM-1 would be found to have caused multidrug resistance in _V. cholera_ in India. - Mod.ML

A HealthMap/ProMED-mail map can be accessed at: http://healthmap.org/r/1pSH.]

NDM-1 CARRYING ENTEROBACTERIACEAE - FRANCE: ex CAMEROON
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Date: Wed 15 Aug 2012
Source: Center for Infectious Disease Research & Policy (CIDRAP) [edited]
http://www.cidrap.umn.edu/cidrap/conten ... sscan.html


A man from Cameroon may represent the 1st reported African case of infection with bacteria carrying [a novel variant of] New Delhi metallo-beta-lactamase [NDM]-4, an enzyme that blocks many antimicrobials, according to a letter yesterday [14 Aug 2012] in Emerging Infectious Diseases [Dortet L, Poirel L, Anguel N, Nordmann P: New Delhi metallo-beta-lactamase 4-producing _Escherichia coli_ in Cameroon [letter]. Emerg Infect Dis [serial on the Internet]. 2012 Sep [date cited]; http://dx.doi.org/10.3201/eid1809.120011].

Infections with New Delhi metallo-beta-lactamase-1-producing (NDM-1) bacteria were first described in 2010 in India [actually 2009: Yong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K: Characterization of a new metallo-beta-lactamase gene, blaNDM-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): 5046-54. Available at http://aac.asm.org/content/53/12/5046.full.pdf+html]. Since then, NDM-2, NDM-4, and NDM-5 variants have been identified, with NDM-4 having a higher carbapenemase activity than NDM-1.

Yesterday's [14 Aug 2012] letter details the case of a man with Hodgkin lymphoma who was treated with chemotherapy 1 year before his current 1 month hospitalization for an inflammatory disorder with kidney failure. After transfer to a hospital in France, a rectal swab revealed NDM-4 [-carrying] _Escherichia coli_. The strain was resistant to all beta-lactam antimicrobial drugs, including imipenem, meropenem, ertapenem, and doripenem, and to fluoroquinolones. It was also resistant to all aminoglycosides except amikacin. A literature search turned up only one previously reported NDM-4 case, in a patient from India.

--
communicated by:
ProMED-mail rapporteur Mary Marshall

[In 2008, a novel carbapenemase, the New Delhi metallo-beta-lactamase (NDM)-1 was first detected in a _Klebsiella pneumoniae_ isolated in Sweden from an Indian patient hospitalized previously in New Delhi, India (1). Variants of the NDM-1 carbapenemase, such as NDM-2, NDM-4, and NDM-5, have subsequently been described.

Cases of colonization or infection with NDM-producing Gram negative bacilli have been reported worldwide as either imported cases in patients with a travel history to, or contact with healthcare systems on the Indian subcontinent, and less frequently as cases following secondary transmission or as autochthonous cases with no history of travel to the Indian subcontinent (2). NDM has been predominantly found in _Enterobacteriaceae_, mostly in _K. pneumoniae_ and _Escherichia coli_ isolates. However, NDM carbapenemases have also been found in non-fermentative Gram negative bacteria such as _Acinetobacter_ spp. and _Pseudomonas_ spp.

Plasmids that carry the NDM gene can also carry a number of genes that encode resistance to other classes of antimicrobial drugs such as aminoglycoside and fluoroquinolones, in addition to beta-lactams. Many NDM producers remain susceptible only to tigecycline and colistin. The fact that NDM gene is carried by a highly transmissible plasmid is thought to account for its rapid, widespread dissemination.

The variant NDM-4 was first described in a patient hospitalized in India (3). However, the patient described in the news report above had no history of travel to India (4). This patient was transferred from Cameroon, where he had previously completed chemotherapy for Hodgkin's disease, to a hospital in Paris. A rectal swab specimen collected from the patient on transfer grew an _Escherichia coli_ strain that was fully resistant to all beta-lactam antibiotics, aminoglycosides, except amikacin, and fluoroquinolones (4). Several plasmid-encoded carbapenemases, including both NDM-1 and the variant NDM-4, were identified in this strain. Fecal carriage in this patient of _E. coli_ carrying plasmid-encoded NDM-1 and NDM-4 genes was attributed by the authors to its selection following multiple courses of antibacterial drugs that included carbapenems in Cameroon (4).

References
----------
1. Yong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K. Characterization of a new metallo-beta-lactamase gene, blaNDM-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): 5046-54. Available at http://aac.asm.org/content/53/12/5046.full.pdf+html.
2. Nordmann P, Naas T, Poirel L. Global Spread of Carbapenemase- producing _Enterobacteriaceae_. Emerg Infect Dis. 2011; 17(10): 1791-8. Available at http://wwwnc.cdc.gov/eid/content/17/10/pdfs/v17-n10.pdf.
3. Nordmann P, Boulanger A, Poirel L. NDM-4 metallo-beta-lactamase with increased carbapenemase activity from _Escherichia col_. Antimicrob Agents Chemother. 2012; 56(4): 2184-6. Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22252797.
4. Dortet L, Poirel L, Anguel N, Nordmann P: New Delhi metallo-beta-lactamase 4-producing _Escherichia coli_ in Cameroon [letter]. Emerg Infect Dis. [serial on the Internet]. 2012 Sep [date cited]. Available at: http://dx.doi.org/10.3201/eid1809.120011.

A HealthMap/ProMED-mail map of Cameroon can be accessed at http://healthmap.org/r/1Cfw. - Mod.ML]

NDM-1 CARRYING ACINETOBACTER - FRANCE: ex ALGERIA, ICU OUTBREAK
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Date: Thu 1 Aug 2013
Source: Eurosurveillance Edition 2013, 18(31) [edited]
http://www.eurosurveillance.org/ViewArt ... leId=20547


Outbreak of NDM-1-producing _Acinetobacter baumannii_ in France, January to May 2013
---------------------------------------------------------------------------
J W Decousser, Jansen C, Nordmann P, Emirian A, Bonnin RA, Anais L, Merle JC, Poirel L

We report the 1st outbreak of carbapenem-resistant NDM-1-producing _Acinetobacter baumannii_ in Europe, in a French intensive-care unit in January to May 2013. The index patient was transferred from Algeria, leading to the infection/colonisation of 5 additional patients. Concurrently, another imported case from Algeria was identified. The 7 isolates were genetically indistinguishable, belonging to ST85. The blaNDM-1 carbapenemase gene was part of the chromosomally located composite transposon Tn125. This report underscores the growing concern about the spread of NDM-1-producing _A. baumannii_ in Europe.

Background
----------
The emergence and spread of New-Delhi metallo-beta-lactamase (NDM)-producing Gram-negative isolates constitutes a new wave of multidrug-resistant (MDR) bacteria [1]; 1st identified from Enterobacteriaceae, the blaNDM gene has since been identified in non-fermenting bacterial species such as _Pseudomonas aeruginosa_ and _Acinetobacter baumannii_ [2,3]. Considering its ability to be the source of nosocomial outbreaks, carbapenem-resistant _A. baumannii_ (AB) represents a threat for critically ill hospitalised patients [4]. We report here the 1st outbreak of NDM-1-producing AB in Europe, which occurred in a French surgical intensive-care unit in January to May 2013.

Outbreak description
--------------------
The index case (Patient 1) was a female patient in her early 80s suffering from end-stage cirrhosis. She originated from Algeria but lived mostly in France. During a stay in Algeria in December 2012, she was admitted into a private hospital in the city of Tizi Ouzou following renal failure, which required dialysis. After one month in hospital, she was repatriated to France due to liver decompensation. On 18 Jan 2013, she was admitted to a 15-bed surgical intensive-care unit of a tertiary care university hospital in a Paris suburb. In accordance with local and national policy, she was screened on admission for carriage of MDR bacteria. Rectal screening revealed MDR-_A. baumannii_ (MDR-AB) (Isolate 1) that was susceptible only to amikacin, netilmicin and colistin (Table). The same day, she was intubated for respiratory failure. Protected distal bronchial brushing yielded a culture of MDR-AB with the same antibiotic resistance profile. A combination of intravenous tigecycline and amikacin was given. On 24 Jan 2013, she developed multivisceral failure and died 4 days later. During the following days, 3 additional patients with MDR-AB infection and/or colonisation were identified in the same unit. A cirrhotic male patient in his mid-60s (Patient 2) -- who had been hospitalised since 3 Jan 2013 and confirmed free of MDR bacteria on admission -- developed a ventilator-associated pneumonia on 26 Jan 2013. Culture of a distal protected specimen yielded MDR-AB (Isolate 2). This patient was successfully treated by a combination of tigecycline and amikacin and was extubated 2 days later. Patient 3 was a male liver-transplant patient in his mid-60s who was not colonised on admission but developed a dialysis catheter-related bloodstream infection due to a MDR-AB on 28 Jan 2013 (Isolate 3). Imipenem and amikacin combination was prescribed but the patient died of haemorrhagic shock before antibacterial susceptibility results could be obtained. Patient 4 was a dual renal- and liver-transplant female patient in her late 40s from whom an abdominal drain yielded an MDR-AB culture on 2 Feb 2013 (Isolate 4). This patient recovered without receiving any antibiotic therapy and was discharged from the hospital on 11 Feb 2013.

Then 2 weeks after the admission of the index case, a woman in her early 80s (Patient 5) suffered from a cerebrovascular accident and was repatriated from the same Algerian county that Patient 1 was repatriated from (but from a different healthcare facility) to the emergency unit of our hospital. A screening test performed on admission identified MDR-AB (Isolate 5).

Later, 2 months after this 1st cluster of 5 patients with MDR-AB, 2 additional patients free of MDR bacteria on admission to the surgical intensive-care unit described acquired a MDR-AB during their stay in this unit. A woman in her late 50s (Patient 6) was admitted to the surgical intensive-care unit on 6 Apr 2013 and placed in the room where the index case had stayed. This patient was found positive for MDR-AB on 15 Apr 2013 in specimens from a catheter and the respiratory tract (Isolate 6). She was treated with intravenous tigecycline and aerosolised colistin. She underwent successful liver transplantation on 22 Apr 2013 and recovered well. The last patient (Patient 7) was a man in his late 50s admitted to the surgical intensive-care unit on 3 Apr 2013 for a liver transplant and from whom a rectal swab yielded MDR-AB a month later (Isolate 7). The patients' duration of hospital stay, time of infection and/or colonisation and location in the hospital are reported in Figure 1.

Laboratory analysis
-------------------
Identification of the 7 MDR-AB strains at the species level was confirmed by 16S RNA sequencing (data not shown). Their antimicrobial susceptibilities were tested by minimum inhibitory concentration (MIC) determination (Etest, bioMerieux, France) (Table) and interpreted according to EUCAST guidelines [5]. All isolates exhibited a high level of resistance to penicillins, broad-spectrum cephalosporins, carbapenems, fluoroquinolones and trimethoprim-sulfamethoxazole. Those isolates remained susceptible only to netilmicin, colistin and amikacin. The production of a class B carbapenemase was suspected by the positive results of the imipenem/imipenem plus EDTA [ethylenediaminetetraacetic acid] test using MIC double strips (Etest, bioMerieux, France) (Table 1) and confirmed by UV spectrophotometry [6]. Carbapenemase genes were screened by PCR [polymerase chain reaction] as described and the blaNDM-1 gene was amplified in the 7 isolates [7]. Genotypic comparison by pulsed-field gel electrophoresis using restriction enzyme SmaI revealed an indistinguishable profile (data not shown). Diversilab (bioMerieux, France) analysis and multilocus sequence typing (MLST) typing confirmed that these isolates were clonally related and belonged to the same sequence type, ST85 (Figure 2) [8]. The genetic environment of blaNDM-1 was investigated as previously described [8] and showed that it was located in the composite transposon Tn125 made of 2 copies of insertion sequence (IS) ISAba125.

Discussion
----------
Carbapenem-resistant _A. baumannii_ are a source of deep concern due to their multidrug resistance pattern and the ability of this bacterial species to persist in the environment [4,9,10]. Intensive-care units are particularly susceptible to outbreaks associated with MDR-AB: it is sometimes difficult for them to adhere strictly to infection control measures when patients require a high and persistent care-load. The same hospital faced a hospital-wide outbreak of MDR-AB colonisations and infections due to the importation of an index case from Tahiti 4 years ago [11]. Despite this experience and the implementation in 2010 at the national and local level of strict measures on hospital admission to detect, screen and place under contact-isolation precautions repatriated patients, another outbreak linked to the admission of a patient previously hospitalised abroad again occurred [12].

Since 2010, NDM-producing MDR-AB has been identified in various parts of the world, in particular in North Africa and the Middle East [8,13-17]. A series of imported cases have been identified recently in Europe, such as in the Czech Republic, Germany, Slovenia, Switzerland and Belgium [8,13,14,17]. In France, the emergence of an NDM-1-producing MDR-AB strain originating from North Africa was recently highlighted [15,17]. We describe here the 1st outbreak associated with the importation of this NDM-1-producing _A. baumannii_ clone ST85 in Europe. This report underlines the need for dedicated measures for patients previously treated in a hospital located in a 'high risk' geographical area. Such measures (e.g., screening for colonisation/infection with MDR organisms and isolation nursing) should be maintained until the screening for colonisation/infection (e.g., using rectal, throat and wound swabs) has shown that these patients are free of MDR organisms. Because of intermittent carriage or lack of sensitivity of the current culture-based screening methods, repeated specimen collection and molecular-based methods of detection may help to control such outbreaks.

Taking in account the relationship between North African countries and many European countries, it is possible that the spread of NDM-1 carbapenemase may occur rapidly, mostly through _A. baumannii_ rather than Enterobacteriaceae, since _A. baumannii_ may become much more difficult to eradicate.

[Table, Figures, and References are available at the source URL.]

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[_Acinetobacter baumannii_ (AB), a Gram-negative coccobacillus, has emerged as a significant multidrug-resistant (MDR) nosocomial pathogen. Infection due to multidrug-resistant acinetobacter strains, especially _Acinetobacter baumannii_ (MDR-AB), in critically ill, hospitalized patients and the frequency of clonal nosocomial outbreaks due to these microorganisms has increased worldwide in the past several decades (see Urban C, et al: Considerations in control and treatment of nosocomial infections due to multidrug-resistant _Acinetobacter baumannii_. Clin Infect Dis. 2003; 36(10): 1268-74. Available at: http://www.journals.uchicago.edu/doi/fu ... 086/374847). MDR-AB have also been reported recently to cause infections after natural disasters (e.g., earthquakes) (see Joly-Guillou ML. Clinical impact and pathogenicity of Acinetobacter. Clin Microbiol Infect. 2005 Nov;11(11):868-73. Abstract available at: http://www.ncbi.nlm.nih.gov/pubmed/16216100), and in soldiers severely injured in the war in Iraq.

During nosocomial outbreaks, MDR-AB have been recovered from various sites in the patients' environment and can survive on environmental surfaces for long periods of time, including curtains, furniture, and hospital equipment. MDR-AB has been reported to spread most commonly on the hands of hospital personnel from the contaminated environment or from patients who are either infected or colonized with MDR-AB. In addition, airborne spread of MDR-AB has recently been described in a burn unit (Gao J, Zhao X, Bao Y, et al. Antibiotic resistance and OXA-type carbapenemases-encoding genes in airborne Acinetobacter baumannii isolated from burn wards. Burns. 2013 Jul 22. pii: S0305-4179(13)00185-X. doi: 10.1016/j.burns.2013.06.003. [Epub ahead of print] Abstract available at: http://www.ncbi.nlm.nih.gov/pubmed/2388 ... t=Abstract).

Carbapenems are a class of beta-lactam antibiotics that includes ertapenem, doripenem, imipenem, and meropenem. Carbapenems historically have been antibiotics of last resort to treat many infections due to carbapenem-sensitive, but otherwise multidrug-resistant Gram-negative bacilli, such as those that produce extended-spectrum beta-lactamases (ESBLs) or AmpC beta-lactamases, which are enzymes that destroy most beta-lactams, except for the carbapenems. Carbapenem-resistant isolates are increasingly isolated, as carbapenems have been used widely in clinical practice. Mechanisms of carbapenem resistance include: production of carbapenemases (enzymes that destroy the carbapenems), loss of outer membrane porins, alteration of target, and efflux pumps (see Dijkshoorn L, et al: An increasing threat in hospitals: multidrug-resistant _Acinetobacter baumannii_. Nat Rev Microbiol. 2007; 5(12): 939-51. Abstract available at: http://www.ncbi.nlm.nih.gov/pubmed/18007677).

There are several distinct types of carbapenemase: KPCs (_Klebsiella pneumoniae_ carbapenemases); NDM (New Delhi metallo-beta-lactamases); IMP; VIM (Verona integron-encoded metallo-beta-lactamase); and OXA-types (oxacillin-hydrolyzing carbapenemases). KPCs are the most common carbapenemases in the US, but have also been reported worldwide.

In 2008, a novel carbapenemase, the New Delhi metallo-beta-lactamase (NDM)-1 was 1st detected in a _Klebsiella pneumoniae_ isolated in Sweden from an Indian patient hospitalized previously in New Delhi, India. Variants of the NDM-1 carbapenemase, such as NDM-2, NDM-4, and NDM-5, have subsequently been described. NDM gene is carried by a highly transmissible plasmid that is thought to account for its rapid, widespread dissemination to other Enterobacteriaceae and to other unrelated bacterial species such as _Pseudomonas aeruginosa_ and AB.

Attempts to reduce the frequency of nosocomial infections due to MDR-AB have involved surveillance, restriction of antibiotic use and enhanced infection control interventions (see Urban C, et al (2003): reference above). - Mod.ML

A HealthMap/ProMED-mail map can be accessed at: http://healthmap.org/r/1oxc.]

ANTIMICROBIAL RESISTANCE - NETHERLANDS ex EGYPT: FAMILY
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Date: Thu 17 Oct 2013
Source: Eurosurveillance, Volume 18, Issue 42 [edited]
http://www.eurosurveillance.org/ViewArt ... leId=20610


Latent introduction to the Netherlands of multiple antibiotic resistance including NDM-1 after hospitalization in Egypt, August 2013
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We describe the introduction of various multi-drug resistant bacterial strains, including an NDM-1-producing _Klebsiella pneumoniae_, through a traveler returning from Egypt, where the traveler had been admitted to a private hospital. All family members of the patient were colonized with 1 or more extended-spectrum beta-lactamase producing strains. These findings emphasise the importance of adherence to isolation precautions for returning patients and suggest the need for inclusion of _Enterobacteriaceae_ in admission screening.

We here report a patient who had been hospitalised in Egypt for appendicitis in July 2013, and was colonized with various multiresistant _Enterobacteriaceae_ including strains producing NDM-1, oxacillinase-48 (OXA-48) and extended spectrum beta-lactamase (ESBL). Explorative screening for multiresistant microorganisms among the patient's family members also yielded several ESBL-producing microorganisms. This report addresses the need for heightened awareness of patients and family members who have recently been exposed to healthcare environments in countries with high levels of antibiotic resistance.

Patients repatriated after hospitalization abroad are a risk for introducing multiresistant microorganisms into hospitals in their home countries. In 2008, New Delhi metallo-beta-lactamase (NDM), which hydrolyses last-line carbapenem antibiotics, has been for the first time described in a Swedish patient returning from India [1]. Most reports on NDM are related to travelers returning from Pakistan and India. However, the global dispersal of NDM is of growing concern [2]. In the past 2 years, NDM-producing strains have been reported in patients returning from the African continent without obvious links to the Indian subcontinent [3,4].

Case description
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A Dutch patient in his 40s [age group] was admitted to our hospital for fever and abdominal pain. On admission, computed axial tomography showed a periappendicular abscess. 4 days earlier, the patient had returned from holidays in Egypt with his spouse and 2 children. A week into their holiday (2 weeks before presentation at our hospital) the patient had complained about right lower abdominal pain and was admitted to a private hospital in Egypt where 400 mg ciprofloxacin twice a day and 500 mg metronidazole 3 times a day were given intravenously for 2 weeks. The patient was discharged after 13 days without having undergone any surgical intervention, and subsequently returned to the Netherlands. In our hospital, the abscess was drained and the patient was treated with piperacilin/tazobactam 4500 mg 3 times a day intravenously for 5 days with good clinical response.

A perianal screening swab taken on admission grew _Klebsiella pneumoniae_ which was resistant to meropenem (minimum inhibitory concentration: 32 mg/L). Molecular testing of the strain by PCR and sequencing of the PCR product revealed that the strain harbored the gene encoding NDM-1. Molecular testing of feces detected OXA-48, and culture of this sample grew _E. coli_ and _K. pneumoniae_ positive for OXA-48.

We also screened the patient's spouse and children, who had been visiting the patient in the hospital in Egypt. Stool samples were obtained 14 days after admission of the index patient. The Table [see original URL] shows an overview of the screening results for multiresistant microorganisms of the family. The patient, his spouse and the youngest child carried ESBL-producing strains with CTX-M1. The older child carried 2 different ESBL-producing _E. coli_ strains positive for CTX-M9. A gene encoding _K. pneumoniae_ carbapenemase (KPC) was detected by molecular tests from feces of the youngest child. The culture of this sample remained negative for carbapenemase-producing strains. Screening of contact patients on the ward where the index patient was treated did not reveal further dissemination of any resistant strains.

Discussion
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High prevalence of ESBL-producing bacteria with rates of over 60 percent in Egyptian hospitals has been reported [5,6]. Also outbreaks involving OXA-48- and VIM-1 carbapenemase-producing strains have been described in the southern Mediterranean region including Egypt [7]. The occurrence of an NDM-1-producing _Acinetobacter_ in Egypt has previously been reported, but so far no reports of NDM-1-producing _Enterobacteriaceae_ could be found in the literature [8]. This is in contrast to other countries in the area such as Morocco and the United Arab Emirates where these bacteria have already been isolated [9-11].

Highly sensitive and rapid screening methods are the mainstay to prevent introduction of multiresistant microorganisms in hospitals in low prevalence countries by repatriated patients. Molecular tests that allow detection of carbapenemase-encoding genes directly from clinical samples are promising when used in addition to conventional culturing [12].

In the youngest child, we detected a KPC gene by 2 molecular testing methods directly from feces, but we were not able to confirm these findings by culture. The bacterial load of the KPC- producing strain was probably too low to be cultured.

It is well recognized that repatriated patients are a risk for introducing multiresistant microorganisms. Family members attending patients hospitalized abroad may also be at risk of acquiring multiresistant bacteria, as our case illustrates. Although we cannot be sure that the family members picked up all strains in the hospital in Egypt, the diversity of multiresistant microorganisms including strains rarely found in the Netherlands makes this highly plausible. Neither can we rule out that the strains were acquired in Egypt outside the hospital, since traveling to African countries has been described as a risk factor for ESBL carriage [13].

Based on these findings, we recommend alertness and compliance with isolation precautions. Infection control guidelines may need to be expanded to include admission screening for resistant _Enterobacteriaceae_ in low prevalent counties for a growing number of international travellers, including family members who have visited a patient abroad.

References
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1. 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;53:5046-54.
2. Kumarasamy K, Kalyanasundaram A: Emergence of Klebsiella pneumoniae isolate co-producing NDM-1 with KPC-2 from India. J Antimicrob Chemother. 2012;67:243-4.
3. Brink AJ, Coetzee J, Clay CG, et al: Emergence of New Delhi metallo-beta-lactamase (NDM-1) and Klebsiella pneumoniae carbapenemase (KPC-2) in South Africa. J Clin Microbiol. 2012;50: 525-7.
4. Poirel L, Benouda A, Hays C, Norman P: Emergence of NDM-1-producing Klebsiella pneumoniae in Morocco. J Antimicrob Chemother. 2011;66:2781-3.
5. Mohamed Al-Agamy MH, El-Din Ashour MS, Wiegand I: First description of CTX-M beta-lactamase-producing clinical Escherichia coli isolates from Egypt. Int J Antimicrob Agents. 2006;27:545-8.
6. Talaat M, Hafez S, Saied T, et al: Surveillance of catheter-associated urinary tract infection in 4 intensive care units at Alexandria university hospitals in Egypt. Am J Infect Control. 2010;38:222-8.
7. Poirel L, Abdelaziz MO, Bernabeu S, Nordmann P: Occurrence of OXA-48 and VIM-1 carbapenemase-producing Enterobacteriaceae in Egypt. Int J Antimicrob Agents. 2013;41:90-1.
8. Hrabak J, Stolbova M, Studentova V, et al: NDM-1 producing Acinetobacter baumannii isolated from a patient repatriated to the Czech Republic from Egypt, July 2011. Euro Surveill. 2012;17(7):pii=20085.
9. Poirel L, Benouda A, Hays C, Nordmann P: Emergence of NDM-1-producing Klebsiella pneumoniae in Morocco. J Antimicrob Chemother. 2011;66: 2781-3.
10. Sonnevend A, Al Baloushi A, Ghazawi A, et al: Emergence and spread of NDM-1 producer Enterobacteriaceae with contribution of IncX3 plasmids in the United Arab Emirates. J Med Microbiol. 2013;62: 1044-50.
11. Dash N, Panigrahi D, Al Zarouni M, et al: High incidence of New Delhi Metallo-Beta-Lactamase Producing Klebsiella pneumoniae Isolates in Sharjah, United Arab Emirates. Microb Drug Resist. 2013 Aug 30. Epub ahead of print.
http://dx.doi.org/10.1089/mdr.2013.0040
12. Miriagou V, Cornaglia G, Edelstein M, et al: Acquired carbapenemases in Gram-negative bacterial pathogens: detection and surveillance issues. Clin Microbiol Infect. 2010;16:112-22.
13. Peirano G, Laupland KB, Gregson DB, Pitout JD: Colonization of returning travelers with CTX-M-producing Escherichia coli. J Travel Med. 2011;18:299-303.

[Authors: Bathoorn E, Friedrich AW, Zhou K, et al]

--
Communicated by:
ProMED-mail Rapporteur Mary Marshall
<promed@promedmail.org>

[Continued vigilance is needed to identify imported multiply antimicrobial resistant organisms in patients who had received medical care in other countries, as shown here. It is noteworthy that [apparently healthy] family members also harbored resistant enteric flora.
- Mod.LL

A HealthMap/ProMED-mail map can be accessed at: http://healthmap.org/r/1r1l.]

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Sorge vor Rückkehr in "Vor-Antibiotika-Zeiten"

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Grüsse
Alexander