Le infezioni da Clostridium difficile, gravi, ricorrenti e ... CDI_Pisa2016.pdffollow up and PPI...
Transcript of Le infezioni da Clostridium difficile, gravi, ricorrenti e ... CDI_Pisa2016.pdffollow up and PPI...
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Nicola Petrosillo
Istituto Nazionale per le Malattie Infettive
«lazzaro Spallanzani», IRCCS-Roma
Le infezioni da Clostridium difficile, gravi,
ricorrenti e complicate
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The infectious cycle of transmission and recurrence of CDI
1. Ingestion of spores transmitted from
other patients, via
hands of healthcare
personnel and
the environment
2. Germination
into growing
(vegetative) cells
5. Transmission
of spores via the
3. Disruption of normal
colonic microflora
allows colonisation
and overgrowth of
C. difficile in the colon
C. difficile
4. Toxin production
leads to
inflammation
and damage to
intestinal cells
Toxins
faecal-oral route
Adapted from Sunenshine RH, et al. Cleve Clin J Med 2006;73:187-97. SJ101
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Bagdasarian N et al. JAMA 2015; 313: 398-408
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Mizumura N et al. Intern Med 2015; 54: 1559-62
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Bagdasarian N et al. JAMA 2015; 313: 398-408
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Surgical evaluation in CDI
• Prompt surgical evaluation should be
obtained in patients with complicated CDI
• Early intervention can reduce mortality
• Subtotal or total colectomy with end
ileostomy is often performed when surgery
is required, although there are newer colon-
preserving techniques.
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Stewart DB et al. Colorectal Dis 2013;15:798-804
Fulminant CDC is defined as disease of such severity
as to require any one of the following:
1.Admission to the ICU;
2.Consideration for surgery, or
3.Death due to CDC
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• Recurrence of symptomatic disease following initial
resolution of symptoms is a frequent complication, with
rCDI occurring in 20-30% of CDI patients.
• In hospitalised patients, rCDI is responsible for
increased mortality and decreased quality of life.
• The risk of subsequent recurrences after a first one
doubles after 2 or more recurrent episodes.
• Finally the patient could be trapped in a ‘recurrent CDI
cycle’, which is problematic to resolve, and further
increases the burden to healthcare facilities.
Epidemiology of Recurrent CDI (rCDI)
Louie TJ et al. N Engl J Med 2011;364: 422-31
Johnson S et al J Infect 2009;58: 403-410
Kelly C et al Clin Microb Infect 2012; 18: 21-27
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How much a rCDI costs?
• 540 hospitalized patients (62±17 years) with
primary CDI 95 patients (18%) experienced 101
rCDI episodes.
• CDI-attributable median LOS and costs
increased from 7 days and $13,168 for patients
with primary CDI only versus 15 days and
$28,218 for patients with rCDI (P<0.0001, each).
Shah DN et al. J Hosp Infect 2016 ;93:286-9
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How much a rCDI costs?
•Total hospital median LOS and costs increased
from 11 days and $20,693 for patients with primary
CDI only versus 24 days and $45,148 for patients
with rCDI (P<0.0001, each).
•The median cost of pharmacological treatment
while hospitalized was $60 for patients with
primary CDI only (N=445) and $140 for patients
with rCDI (P=0.0013).
Shah DN et al. J Hosp Infect 2016 ;93:286-9
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Recurrence: when is Reinfection and when is Relapse?
Recurrence of Clostridium difficile infection can occur within
two contexts
•the recrudescence of C. difficile spores persisting in the gut
(relapse), or
•reinfection with spores obtained from the environment.
Distinguishing between the two, however, is challenging.
Molecular assays could be helpful, but not often feasible.
A temporal criterium could be helpful.
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• The greatest risk of recurrence due to relapse is
during the first 14 days after successful treatment.
• Greater time periods between initial and recurrent
episodes tend to be associated with.
• One study reported that the median time to a
recurrent episode of CDI was 26 days for relapse vs
67.5 days for reinfection.
Relapse or reinfection?
Wilcox M et al J Hosp Infect 1998; 38:93-100.
Marsh JW et al. J Clin Microb 2012; 50: 4078-4082.
Kim J et al. Clin Microb Infect 2014; 20: 1198-1204.
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modifiable
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rCDI: a matter of severity, morbidity and mortality
Elderly more than 90% of CDI-related deaths occur in
people aged over 65 years (Garey KW et al. J Hosp Infect 2008;70:298-304)
Immunocompromised patients mortality associated
with CDAD 11.9% (Magee G et al. Am J Infect Control 2015; 43:1148-53)
Abou Chakra CN et al. Plos One 2014: 9; e98400
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• Advanced age, additional antibiotic therapy during
follow up and PPI therapy are the most frequent
independent risk factors for rCDI.
• However, meta-analysis and systematic reviews have
shown that the risk factors for recurrent CDI are similar
to those of initial CDI.
• Moreover, patients with chronic renal insufficiency and
those previously receiving fluoroquinolones have
higher risks for rCDI.
• Finally, also CDI strain has been reported as a risk
factor.
Are risk factors for rCDI different from primary CDI?
Deshpande A et al. Infect Control Hosp Epidemiol 2015; 36: 452-460.
Garey KW et al. J Hosp Infect 2008;70:298-304.
Abou Chakra CN et al. Plos One 2014: 9; e98400.
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Deshpande A et al. Infect Control Hosp Epidemiol 2015; 36: 452-460
Age
Additional antibiotics during follow up
Proton-Pump Inhibitors during follow up
Renal insufficiency
Tube feeding
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Immunity and recurrence
• It is well known that humoral immunity plays a
crucial role in protecting from severe and/or
recurrent CDI
• Patients that acquire CD and become
asymptomatic carriers have higher serum IgG
antibody levels against TcdA vs symptomatic CDI.
• Low anti-TcdA IgG has been reported to be
associated with higher mortality rates among CDI
patients.
Di Bella S et al. Toxins 2016; 8:134
Kyne L et al. NEJM 2000; 342:390-7
Warny M et al. Infect Immun 1994; 62: 384-9
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Courtesy
M. Bassetti
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C difficile is not invasive. Toxins’ production is the key to pathogenesis
Di Bella S et al. Toxins 2016; 8: 134
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Bagdasarian N et al. JAMA 2015; 313: 398-408.
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Antibiotic stewardship and CDI
• CDI is usually an adverse effect of
antibiotic use – Cannot be completely prevented
– However, good antibiotic stewardship may help reduce it
• Includes1,2
– Antibiotics used according to guidelines
– Avoiding the use of multiple antibiotics and prolonged therapy
– Reducing the use of agents most frequently implicated in CDI
– Stopping the use of antibiotics (other than those used to treat
CDI) as soon as possible in CDI-infected patients1
1. Vonberg RP, et al. Clin Micro Infect 2008;14 Suppl 5:2–20.
2. UK Department of Health, England. High impact intervention. Care bundle to reduce the risk from Clostridium difficile, 2010
25
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Aldeyab MA et al. JAC 2012
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Feazel LM et al.
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Feazel LM et al.
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Take home messages
• Recurrence of symptomatic disease following initial resolution
of symptoms is a frequent complication, with rCDI occurring in
20-30% of CDI patients.
• The risk of subsequent recurrences after a first one doubles
after 2 or more recurrent episodes.
• The patient is trapped in a ‘recurrent CDI cycle’, which is
problematic to resolve
• Advanced age, additional antibiotic therapy during follow up
and PPI therapy are the most frequent independent risk factors
for rCDI.
• Antimicrobial stewardship programs can reduce the
occurrence of CDI cases in the healthcare settings