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Published Date: 2006-09-15 00:00:00
Subject: PRO/EDR> Clostridium difficile, ribotype 027 - France, Belgium, Austria
Archive Number: 20060915.2617

CLOSTRIDIUM DIFFICILE, RIBOTYPE 027 - FRANCE, BELGIUM, AUSTRIA
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[1] France
Date: Thu, 14 Sep 2006
From: ProMED-mail<promed@promedmail.org>
Source: Eurosurveillance [edited]
<http://www.eurosurveillance.org/ew/2006/060914.asp#1>

On 27 Mar 2006, the Institut de Veille Sanitaire
(InVS) was alerted to a cluster of [cases of]
_Clostridium difficile_-associated disease (CDAD)
in a health-care facility (HCF) in northern
France through its national nosocomial infection
notification system (1). This first cluster
involved 41 patients (median age 82 years) who
developed CDAD between 24 Jan 2006 and 24 May
2006, of whom 14 (34 percent) died. However, none
of these deaths were found to be attributable to
the CDAD. Of 23 strains isolated from these
patients and sent to a central laboratory for
typing, 17 (74 percent) were found to be the
toxinotype III, PCR-ribotype 027 epidemic strain
which had also been isolated from severe CDAD
outbreaks in North America and Europe (2). This
cluster has now been controlled.
The InVS alerted all French health-care
facilities about this first 027 cluster through
regional infection control coordinating centers
(CClin). After the notification, other CDAD
clusters were notified to the InVS. In northern
France, as of 12 Sep 2006 and including the first
described outbreak, 16 health-care facilities and
2 nursing homes have notified severe CDAD cases
or CDAD clusters to the InVS. A total of 266
cases have been reported which occurred from Jan
to Sep 2006, mostly among elderly patients
hospitalized in acute care or rehabilitation
departments. Two health-care facilities accounted
for 143 (54 percent) of all cases. Among these
266 patients, 71 (27 percent) deaths were
registered, 15 (6 percent) of which were
attributable to CDAD according to mortality review results.
As CDAD diagnosis relies on enzyme immunoassays,
stool culture was not systematically available.
Of the 114 _C. difficile_ strains isolated from
these 266 patients and typed, 81 (71 percent)
were found to be the 027 strain. The 027 strain
was isolated in 11 health-care facilities and 1
nursing home. In other French regions, 13
health-care facilities notified CDAD clusters to
the InVs but none of these were associated with the 027 strain.
Control measures:
-------------------
Local infection control units implemented control
measures for each cluster, assisted by the CClin
when necessary. Control measures included
standard and contact precautions, use of
solutions containing hypochlorite for
environmental cleaning, meticulous hand hygiene,
and closure of wards in 5 facilities. Audits of
antimicrobial prescriptions also were
recommended. By 12 Sep 2006, 7 episodes had been
controlled and 11 were still considered as active
(that is, new cases in these clusters had been notified within the past month).
Discussion:
------------
Our data confirm the emergence and spread of the
027 strain of _C. difficile_ in northern France
since Jan 2006. Clusters can be controlled if
they are detected early and if strict control
measures, which apply for any type of CDAD, are
implemented. However, this strain has a
particular epidemic potential and inter-hospital
transmission is likely to occur when transferring
patients, a similar situation to that which was
observed in a regional outbreak of _Acinetobacter
baumannii_ infection in France in 2003 (3). The
emergence of _C. difficile_ 027 in northern
France could be linked to similar clusters in
northern Europe, although our investigations did
not find any evidence (such as the transfer of an
index patient across borders) to support this hypothesis.
National recommendations for surveillance,
prevention and control of CDAD were disseminated
in France in May 2006 (4). A national laboratory
network consisting of the Anaerobe National
Reference Center and 5 regional laboratories has
been set up in order to characterise isolated
strains. Current efforts are being focused on
reinforcing recommendations in all healthcare
facilities and nursing homes, in order to detect
and control clusters early and limit the spread
of the 027 strain. Surveillance for CDAD will be
instituted at national level in 2007.
More information can be found (in French) at the
web page for the Reseau d'alerte, d'investigation
et de surveillance des infections nosocomiales
(Raisin): <http://www.invs.sante.fr/raisin>.
1. Tachon M, Cattoen C, Blanckaert K, et al:
First cluster of C. difficile toxinotype III,
PCR-ribotype 027 associated disease in France:
preliminary report. Euro Surveill 2006;11:
E060204. <http://www.eurosurveillance.org/ew/2006/060504.asp#1>
2. Kuijper EJ, Coignard B, Tull P, et al:
Emergence of Clostridium difficile-associated
disease in North America and Europe. Clin
Microbiol Infect 2006;12 (S.6):2-18.
<http://www.blackwell-synergy.com/toc/clm/12/s6>
3. Naas T, Coignard B, Carbonne A, et al: VEB-1
extended-spectrum �lactamase-producing
Acinetobacter baumannii, France. Emerg Infect Dis
2006;12: 1214-22. <http://www.cdc.gov/ncidod/EID/vol12no08/05-1547.htm>
4. Reseau d'alerte, d'investigation et de
surveillance des infections nosocomiales
(Raisin). Conduite a tenir : diagnostic,
investigation, surveillance, et principes de
prevention et de maitrise des infections a
Clostridium difficile. Institut de Veille Sanitaire, 2006, 42 p.
<http://www.invs.sante.fr/publications/2006/guide_raisin/index.html>
[Authors: Coignard B(<b.coignard@invs.sante.fr>),
Barbut F, Blanckaert K, et al]
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[2] Belgium
Date: Thu, 14 Sep 2006
From: ProMED-mail <promed@promedmail.org>
Source: Eurosurveillance [edited]
<http://www.eurosurveillance.org/ew/2006/060914.asp#2>

As a result of the reports of outbreaks of
diarrhea due to _C. difficile_ North American
Pulse field type 1 (NAP1), PCR ribotype 027,
toxinotype III in North America, UK, the
Netherlands and Belgium (1-5), 2 different
surveillance systems for _C.
difficile_-associated diarrhea (CDAD) were set up
in Belgium: a laboratory-based surveillance of
clusters (since 1 Jan 2006) and prospective
surveillance of CDAD incidence in acute care
hospitals since 1 Jul 2006 (6). Here we report on
the preliminary results of the 2 surveillance systems.
Laboratory surveillance of clusters:
---------------------------------
A total of 288 strains of _C. difficile_ were
sent to the reference laboratory by 27
laboratories (24 hospitals, 3 peripheral labs)
from 1 Jan to 5 Sep 2006 as part of the
laboratory-based surveillance of CDAD clusters.
Of these, 150 (52 percent) were PCR ribotype
027-strains reported by 16 labs (15 hospitals, 1
peripheral lab). When grouped by trimester, the
percentage of 027 strains increased from 44
percent in Jan-Mar 2006 to 67 percent in Jul-Sep 2006 (p trend=0.004).
Prospective surveillance of CDAD in hospitals:
--------------------------------------------
For the hospital-based surveillance, the
objective is to assess and follow-up the baseline
incidence of CDAD in Belgian hospitals,
independently of an epidemic situation, to
compare incidences between hospitals, to make a
descriptive analysis of the clinical picture of
the CDAD cases, and to do typing of the strains
sent by the hospitals to the reference laboratory.
Approximately 80 percent (n=96) of all Belgian
acute care hospitals are taking part in the
enhanced surveillance. Since 1 Jul 2006, 45 _C.
difficile_ strains were sent to the reference
laboratory by 17 hospitals, 40 percent of which
were 027 strains from 10 (59 percent) hospitals.
However, since hospitals with higher CDAD
incidences are more likely to be confronted to
027 strains and to send surveillance strains more
rapidly to the reference laboratory, these
percentages are probably an overestimate if
interpreted as the national situation.
One patient with 027 CDAD was reported to have
died as the direct consequence. Of the 40 CDAD
cases for which the origin was given, 55 percent
(027=7/non-027=15) were associated with a stay in
the declaring hospital, 7.5 percent (0/3)
originated from another hospital, 20 percent
(4/4) were imported from nursing homes and 12.5
percent (2/3) originated at home. Of all
healthcare-associated cases for which the date of
onset was known (n=28), 32 percent started before
the 3rd day of hospital admission.
The median age of patients was higher for 027
strains than for non-027 strains (83.5 years vs.
72 years, p<0.01). Accordingly, the proportion of
027-strains was highest among patients who stayed
on the geriatric ward (65 percent vs 35 percent
in other wards, p=0.02). The proportion of
recurrent CDAD-cases was higher in 027 cases than
in non-027 CDAD cases. These findings correspond
with earlier reports (7,8). Hospitals reporting
CDAD cases were evenly distributed throughout the country.
Control measures were implemented by the
Infection Control teams in the hospitals, with
the support of the reference laboratory, the _C.
difficile_ working group of the Belgian Infection
Control Society. Guidelines for the control and
prevention of CDAD in health-care institutions
have been compiled by the Belgian Infection
Control Society and were communicated to all
Belgian health-care workers in May 2006
(<http://www.belgianinfectioncontrolsociety.be>).
Conclusions:
In total, 168 cases of ribotype 027 CDAD have
been reported by 23 health-care facilities via
the 2 surveillance systems in 2006. One should be
very careful when interpreting these results, as
they are preliminary and incomplete. Confirmation
of our findings as well as more details, such as
nationwide incidence figures per 10 000 patient
days in the hospitals and previous antibiotic use
will be available in Mar 2007, after the 1st full
semester of the hospital-based incidence
surveillance. Nonetheless, it is clear that the
ribotype 027 strain of _C. difficile_ is
increasingly posing problems in Belgian
health-care institutions. Whether the strain was
imported from North America, from other European
countries or whether it is capable of arising de
novo as the result of the exposure to newer
antibiotics such as fluoroquinolones (9) is unknown.
1. Eggertson L: C. difficile: by the numbers. CMAJ 2004;171: 1331-32.
2. Outbreak of Clostridium difficile in a
hospital in south east England. Comm Dis Rep CDR
Weekly 2005;15: 828-30 (<http://www.hpa.org.uk/cdr/archives/2005/cdr2405.pdf>)
3. McDonald C: Clostridium difficile: responding
to a new threat from an old enemy. Infect Control
Hosp Epidemiol 2005. 26: 672-75.
4. Kuijper EJ, van den Berg RJ, Debast S, Visser
CE, Veenendaal D, Troelstra A et al. Clostridium
difficile Ribotype 027, Toxinotype III, the
Netherlands. Emerg Infect Dis 2006; 12[5]
<http://www.cdc.gov/ncidod/eid/vol12no05/05-1350.htm>)
5. Joseph R, Demeyer D, Vanrenterghem D, et al:
First isolation of Clostridium difficile PCR
ribotype 027, toxinotype III in Belgium. Euro
Surveill 2005;10 (10):E051020.4.
(<http://www.eurosurveillance.org/ew/2005/051020.asp#4>)
6. Surveillance des infections �lostridium
difficile - Protocole. 2006. (<http://www.iph.fgov.be/nsih>)
7. Poutanen SM, Simor AE: Clostridium
difficile-associated diarrhea in adults. CMAJ 2004;171: 51-58.
8. Pepin J, Valiquette L, Cossette B: Mortality
attributable to nosocomial Clostridium
difficile-associated disease during an epidemic
caused by a hypervirulent strain in Quebec. CMAJ 2005 25;173: 1037-42.
9. Pepin J, Saheb N, Coulombe MA, et al:
Emergence of fluoroquinolones as the predominant
risk factor for Clostridium difficile-associated
diarrhea: A cohort study during an epidemic in
Quebec. Clin Infect Dis 2005; 41: 1254-60.
[Authors: Delmee M (<Delmee@mblg.ucl.ac.be>),
Ramboer I, Van Broeck J, Suetens C]
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[3] Austria ex UK
Date: Thu, 14 Sep 2006
From: ProMED-mail <promed@promedmail.org>
Source: Eurosurveillance [edited]
<http://www.eurosurveillance.org/ew/2006/060914.asp#3>

A hypervirulent epidemic strain of _C. difficile_
- PCR ribotype 027 has been recently found in
England, Belgium, France and the Netherlands
(1-6). This PCR ribotype causes more severe
disease than the more frequent type and is
associated with a higher mortality. We report the
1st isolate of _C. difficile_ 027 documented in Austria.
On 9 Mar 2006, in a local hospital in Tyrol, west
Austria, a 69-year-old British woman was admitted
to hospital with a 5-day history of nausea,
watery diarrhea and lower abdominal pain. She had
been vomiting on the day she was admitted. The
patient was a tourist who arrived in Austria on 5
Mar 2006 from England. The day before the onset
of diarrhea, she was reportedly taking
antibiotics prescribed by her physician to treat
bronchitis. An abdominal x-ray revealed fluid
levels consistent with paralytic ileus (paralysis
of the intestine) without indication of perforation.
Antimicrobial therapy was started with
ciprofloxacin (500 mg orally, twice per day for 4
days), but the patient's condition did not
improve. On 10 Mar 2006, computerised tomography
revealed a massive edematous thickening of the
entire colon wall with excess fluid in the
peritoneal cavity. A stool specimen was obtained,
therapy was switched to metronidazole (500 mg
orally twice per day) on 10 Mar 2006, followed by
500 mg orally, 3 times per day for 10 days, again
without noticeable improvement. On 11 Mar 2006,
test results revealed that the patient was infected with _C. difficile_.
By 20 Mar 2006, the patient had developed an
urticarial rash and her poor response to
treatment (further diarrhea and feeling unwell),
led to a change of therapy to vancomycin (125 mg
orally, 4 times per day for 10 days). Within a
few days, the frequency of bowel movements was
reduced and fluid in the abdomen also diminished.
Results of a colonoscopy on 20 Mar 2006 showed
that there was still active pseudomembranous
colitis reaching to the sigmoid part of the
colon. Histopathology revealed infiltration of
neutrophils through the damaged mucous layer,
compatible with pseudomembranous colitis. The
patient was discharged from the hospital and
returned to England on 29 Mar 2006.
Detection of _C. difficile_ PCR ribotype 027:
After a request from the European Centre for
Disease Prevention and Control to European member
states in Jan 2006 to look for _C. difficile_ 027
in their countries, a prospective _C. difficile_
typing facility was set up, and regional
hospitals were invited to send in specimens for PCR ribotyping.
Between Jan and Jun 2006, 102 _C. difficile_
isolates were collected from 14 healthcare
facilities in all 9 provinces of Austria. An
isolate from the above case was typed in Sep 2006
and found positive for 027. This is the first
time that ribotype 027 has been documented in
Austria. PCR was used to detect the binary toxin
CDT and a deletion in the pathogenicity locus
gene, tcdC. The identified 027 isolate contained
an 18bp deletion in the gene (tcdC) which
normally regulates toxin production. The strain
was positive for binary toxin genes. This strain
was resistant to fluoroquinolone antibiotics such
as ciprofloxacin and moxifloxacin (MIC greater
than 32), and metronidazole (MIC greater than 256) (7).
Conclusions:
--------------
Among outpatients exposed to antibiotics,
clinically recognised _C. difficile_-associated
diarrhoea due to PCR ribotype 027 is uncommon.
_C. difficile_ is known to colonise the colon in
3 percent of healthy adults and in up to 20-30
percent of patients in hospital (8). We believe
that the patient initially acquired the strain in
her home country. This case demonstrates how _C.
difficile_ ribotype 027 can spread between
European countries. All _C. difficile_ isolates
coming from this hospital will be typed for some months.
1. McDonald LC, Killgore GE, Thompson A, et al:
An epidemic, toxin gene-variant strain of
Clostridium difficile. N Engl J Med. 2005;353: 2433-41.
2. Tachon M, Cattoen C, Blanckaert K, et al:
First cluster of C. difficile toxinotype III,
PCR-ribotype 027 associated disease in France:
preliminary report. Euro Surveill
2006;11:E060504.1. (<http://www.eurosurveillance.org/ew/2006/060504.asp#1>)
3. van den Hof S, van der Kooi T, van den Berg R,
et al: Clostridium difficile PCR ribotype 027
outbreaks in the Netherlands: recent surveillance
data indicate that outbreaks are not easily
controlled but interhospital transmission is
limited. Euro Surveill 2006;11: E060126.2.
(<http://www.eurosurveillance.org/ew/2006/060126.asp#2>)
4. Joseph R, Demeyer D, Vanrenterghem D, et al:
First isolation of Clostridium difficile PCR
ribotype 027, toxinotype III in Belgium. Euro
Surveill 2005;10 (10):E051020.4.
(<http://www.eurosurveillance.org/ew/2005/051020.asp#4>)
5. van Steenbergen J, Debast S, van Kregten E, et
al: Isolation of Clostridium difficile ribotype
027, toxinotype III in the Netherlands after
increase in C. difficile-associated diarrhoea.
Euro Surveill 2005;10(7):E050714.1.
(<http://www.eurosurveillance.org/ew/2005/050714.asp#1>)
6. Outbreak of Clostridium difficile in a
hospital in south east England. CDR weekly
2005;15(24): <http://www.hpa.org.uk/cdr/archives/archive05/News/news2405.htm>
7. Bolmstrom A. Susceptibility testing of
anaerobes with Etest. Clin Infect Dis 1993;16(S4): S367-370
8. Bartlett JG: Clostridium difficile. In: The
PDR/Johns Hopkins ABX Guide: Diagnosis &
Treatment of Infectious Diseases. Bartlett J,
Auwaerter PG, Pham P(eds): Medical Economics Data, New Jersey, USA, p. 580-81.
[Authors: Indra A, Huhulescu S, Hasenberger P, et
al (<Franz.Allerberger@ages.at>]
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[Image at
<http://jcs.biologists.org/cgi/content-nw/full/114/23/4307/FIG5> - Mod.JW]
[This emerging strain of _C. difficile_ continues
to be recognized. Warny, et al, from the 24 Sep
2005 issue of Lancet, reported that the strain,
also referred to as North American PFGE type 1 or
NAP1/027, produces 16 times more toxin A and 23
times more toxin B than control strains due to a
deletion in a regulatory gene. These toxins
appear to be the major virulence factors in this
disease, with toxin B being apparently 10 times
more toxic than A in colonic explants. Although
the strain is sensitive to metronidazole,
clinical observations suggest that both the
metronidazole failure and post-metronidazole relapse rates are higher with 027.
1. Warny M, Pepin J, Fang A, et al: Toxin
production by an emerging strain of Clostridium
difficile associated with outbreaks of severe
disease in North America and Europe. Lancet. 2005; 366:1079-84. - Mod.LL]

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