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Transcript
Journal club 2011.09.21
Type-Specific Risk Factors and Outcome in an
Outbreak With 2 Different Clostridium difficile
Types Simultaneously in 1 Hospital
A. Goorhuis, S. B. Debast, J. C. Dutilh, C. M. van Kinschot, C. Harmanus, S. C.
Cannegieter, E. C. Hagen, and E. J. Kuijper
Clinical infectious disease. (2011) November 1
R2. Yoo, Jung-sun
Introduction
 Clostridium difficile infection (CDI) due to polymerase chain reaction
(PCR) ribotype 027 (type 027) : described worldwide
 This strain harbors the toxin genes tcdA and tcdB as well as binary toxin
genes, and has a deletion at position 117 in the toxin regulatory gene tcdC
 C. difficile strains lacking toxin A (A-/B1) : increasingly found to cause
outbreaks, especially in some Eastern European countries, South America,
and Asia
 The most commonly found A-/B1 strain belongs to PCR ribotype 017
(type 017)
Introduction
 They encountered a unique CDI outbreak due to type 027 and type 017
occurring simultaneously in a 980-bed teaching hospital in the
Netherlands.
 In response, they performed a case-control study to investigate type
specific risk factors and outcome of CDI patients, compared with control
patients without diarrhea.
 They studied clonal dissemination using multilocus variable number
tandem repeat analysis (MLVA).
Methods
 Included all consecutively diagnosed CDI patients with a positive feces
toxin test and culture of C. difficile from May 2005 through January
2007.
 For every CDI patient, they randomly selected a control patient without
diarrhea, matched for ward, age, sex, admission period, and duration of
hospitalization.
 They also included a group of control patients with non CDI diarrhea, as
determined by a negative C difficile toxin assay.
Methods
 Microbiological analysis : They used the number of differing loci and the
summed tandem-repeat difference (STRD) between MLVA types as
coefficients for the genetic distance
 Genetically related complexes were defined by a STRD ≤ 10 and clonal
complexes by a STRD ≤ 2.
 CDI was defined as diarrhea in combination with a positive laboratory
assay for C. difficile toxin A or B in stools
Sever diarrhea : Occurred in combination with 1 or more of the
following (bloody stools, hypovolemia, hypoalbuminemia (<20g/L),
fever (T >38.0 C), leukocytosis and pseudomembranous colitis.
Results
33 type-027 isolates
(in blue circles) and
42 type-017 isolates
(in green circles).
The numbers
between the circles
represent STRD
between MLVA types.
Within the spanning
tree, genetically
related complexes
(STRD ≤ 10) are
marked in grey.
Clonal complexes
(with a STRD ≤ 2) are
marked in yellow.
Figure 1. Minimum spanning tree analysis of Clostridium difficile isolates typed by
multilocus variable-number tandem-repeat analysis (MLVA)
Results
Table 1. Risk Factors Among Clostridium difficile Infection Cases and Non–Clostridium
difficile Infection Diarrheal Patients Compared With Nondiarrheal Control Patients
Results
In the adjusted model, the association with high exposure to
second-generation cephalosporins and clindamycin remained
statistically significant (Case Vs control)
Table 2. Antibiotic Use Among Cases and Non–Clostridium difficile Infection Diarrheal
Patients Compared With Nondiarrheal Controls
Results
Significant risk factors, in both
crude and adjusted models, were
older age and hematological
malignancy
(Type 027 Vs other types)
Significant risk factors, in
adjusted models, were use of
immunosuppressive agents and
hematological malignancy (Type
017 Vs other types)
Table 3. Risk Factors Among Patients With Type 027, Type 017, and Other (Non017/Non-027) Types
Results
High exposure to ciprofloxacin
was specifically associated with
type-027 CDI
(Type 027 Vs other types)
High exposure to clindamycin was
specifically associated with type017 CDI
(Type 017 Vs other types)
Table 4. Antibiotic Use Among Patients With Type 027 or Type 017 Versus Patients With
Other (Non-27/Non-017) Clostridium difficile Infection Types
Results
Patients with CDI had a higher 30-day mortality,
overall in hospital mortality than both non-CDI
diarrheal patients and nondiarrheal control patients.
Table 5. Clinical Outcome Among Cases (All Types Combined), Non–Clostridium
difficile Infection Diarrheal Patients, and Nondiarrheal Controls
Results
Patients with type 027 or 017 had similar overall mortality rates after
30 days, which were significantly higher than the mortality rate
observed among patients with CDI due to other types.
Table 6. Clinical Outcome Among Patients With Clostridium difficile Infection
Due to Different Polymerase Chain Reaction Ribotypes
Conclusion
 Type-specific risk factors were older age for both types 017 and 027,
use of clindamycin and immunosuppressive agents for type 017, and
use of fluoroquinolones for type 027
 Patients with CDI had a higher 30-day mortality than both non-CDI
diarrheal patients and nondiarrheal control patients.
 Patients with type 027 or 017 had similar overall mortality rates after
30 days, which were significantly higher than the mortality rate
observed among patients with CDI due to other types.
 Patients with CDI have type-specific risk factors and mortality rates,
with prolonged clonal spread of type 027 or 017.