Published Date: 2007-01-12 00:00:00
Subject: PRO/EDR> Clostridium difficile, ribotype 027 - Japan: 2005
Archive Number: 20070112.0146
CLOSTRIDIUM DIFFICILE, RIBOTYPE 027 - JAPAN: 2005
A ProMED-mail post
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International Society for Infectious Diseases
Date: Thu, 11 Jan 2007
From: ProMED-mail <email@example.com>
Source: Eurosurveillance weekly release [edited]
We report the 1st isolation of a variant strain of _Clostridium
difficile_ from a patient with pseudomembranous colitis in Japan. The
strain was chararacterized as North American pulsed field gel
electrophoresis type 1 (NAP1), PCR ribotype 027, toxinotype III. This
strain has been reported previously as the cause of outbreaks in
Canada, USA, the Netherlands, the UK, France, and Belgium. (1-6).
A 30-year-old Japanese woman with no history of previous hospital
admission was admitted to a hospital for ulcerative colitis in
mid-March 2005. She had received medical treatment for ulcerative
colitis as an outpatient since 2004. She had not been abroad just
before this admission. On admission, treatment with antibiotics
(levofloxacin and cefozopran hydrochloride) was started, and one
month after admission, endoscopy detected rectal pseudomembranes. The
intestinal symptoms (mucus in stool) were mild and, after she started
treatment with vancomycin, these symptoms resolved in a few days.
The patient developed a relapse of diarrhea on 10 May 2005, and a
colonoscopy showed pseudomembranes along the entire region of her
colon. Metronidazole therapy was started, but the symptoms were still
present after 6 days, and a further colonoscopy revealed no
improvement. Therapy was switched to vancomycin, and the diarrhea
resolved in 5 days.
Stool culture of specimens taken during both episodes yielded _C.
difficile_. The stool specimen at the relapse was available for toxin
detection, and was positive for toxin A and toxin B by enzyme
immunoassay and cell culture assay. The 2 isolates were toxin
A-positive, toxin B-positive and positive for the binary toxin gene
by PCR. Analysis by PCR ribotyping and slpA sequence typing was
performed on the 2 isolates, and both were identified as the same
type of a strain characterized as _C. difficile_ 027 (2). These
typing results were confirmed by multi-locus variable number tandem
repeats analysis (MLVA).
Sequence analysis of tcdC in these isolates showed a single-base pair
deletion at position 117 as well as a well-documented 18-bp deletion,
which were identical to the sequence results in that of the reference
strain of _C. difficile_ 027. When examined by E-test, both of
isolates were sensitive to gatifloxacin (MIC=0.5), moxifloxacin
(MIC=0.5), clindamycin (MIC=1.0) and metronidazole (MIC=0.25). More
than 150 _C. difficile_ isolates collected between 2003 and 2006 at 5
medical facilities, including the hospital where the patient was
admitted were examined, and none of those isolates was typed as 027.
This is the first report of the 027 strain of _C. difficile_ in
Japan. The infection was most likely hospital-acquired. As far as
investigated to date, _C. difficile_ outbreaks in multiple hospitals
in Japan have been associated with a different strain: PCR ribotype
smz, and outbreaks caused by the 027 strain have not been found in
Japan. It is unknown whether the 027 strain was present in Japan
previously or whether it has come from other countries recently. In
contrast to 027 strains circulating in North America and Europe, the
Japanese isolate was susceptible to the newer fluoroquinolones, as
has been reported in the 027 isolates obtained before 2001 in North
1. MacCannell DR, Louie TJ, Gregson DB, et al: Molecular analysis of
Clostridium difficile PCR ribotype 027 isolates from Eastern and
Western Canada. J Clin Microbiol 2006;44: 2147-52.
2. 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.
3. Kuijper EJ, van den Berg RJ, Debast S, et al: Clostridium
difficile ribotype 027, toxinotype III, the Netherlands. Emerg Infect
Dis 2006;12: 827-30
4. Smith A: Outbreak of Clostridium difficile infection in an English
hospital linked to hypertoxin-producing strains in Canada and the US.
Euro Surveill 2005; 10(6):E050630.2
5. Coignard B, Barbut F, Blanckaert K, et al: Emergence of
Clostridium difficile toxinotype III, PCR-ribotype 027-associated
disease, France, 2006; Euro Surveill 2006; 11(9):E060914.1
6. Delmee M, Ramboer I, Van Broeck J, Suetens C: Epidemiology of
Clostridium difficile toxinotype III, PCR-ribotype 027 associated
disease in Belgium, 2006. Euro Surveill 2006; 11(9):E060914.2;
7. Indra A, Huhulescu S, Hasenberger P, et al: First isolation of
Clostridium difficile PCR ribotype 027 in Austria. Euro Surveill
2006; 11(9): E060914.3; <http://www.eurosurveillance.org/ew/2006/060914.asp#3>
8. Kato, H, Yokoyama T, Arakawa Y: Typing by sequencing the slpA gene
of Clostridium difficile strains causing multiple outbreaks in Japan.
J Med Microbiol 2005;54:167-71.
[Reported by: Kato H (<firstname.lastname@example.org>), Ito Y, van den Berg RJ, et al]
[This 2005 case appears to be due to the same hypertoxin producer.
Its epidemiologic relationship to the North American and European
cases is as yet unknown. - Mod.LL]