Le infezioni da Clostridium difficile, gravi, ricorrenti e complicate Nicola Petrosillo

Transcription

1 Le infezioni da Clostridium difficile, gravi, ricorrenti e complicate Nicola Petrosillo Istituto Nazionale per le Malattie Infettive «lazzaro Spallanzani», IRCCS-Roma

2

3 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 3. Disruption of normal colonic microflora allows colonisation and overgrowth of C. difficile in the colon 4. Toxin production leads to inflammation and damage to intestinal cells C. difficile 2. Germination into growing (vegetative) cells Toxins 5. Transmission of spores via the faecal-oral route Adapted from Sunenshine RH, et al. Cleve Clin J Med 2006;73: SJ101

4 Bagdasarian N et al. JAMA 2015; 313:

5 Mizumura N et al. Intern Med 2015; 54:

6 Bagdasarian N et al. JAMA 2015; 313:

7 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 colonpreserving techniques.

8 Stewart DB et al. Colorectal Dis 2013;15: 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

9

10 Epidemiology of Recurrent CDI (rcdi) 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. Louie TJ et al. N Engl J Med 2011;364: Johnson S et al J Infect 2009;58: Kelly C et al Clin Microb Infect 2012; 18: 21-27

11 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

12 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

13

14 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.

15 Relapse or reinfection? 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. Wilcox M et al J Hosp Infect 1998; 38: Marsh JW et al. J Clin Microb 2012; 50: Kim J et al. Clin Microb Infect 2014; 20:

16 modifiable

17 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: ) Immunocompromised patients mortality associated with CDAD 11.9% (Magee G et al. Am J Infect Control 2015; 43: ) Abou Chakra CN et al. Plos One 2014: 9; e98400

18 Are risk factors for rcdi different from primary CDI? 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. Deshpande A et al. Infect Control Hosp Epidemiol 2015; 36: Garey KW et al. J Hosp Infect 2008;70: Abou Chakra CN et al. Plos One 2014: 9; e98400.

19 Age Additional antibiotics during follow up Renal insufficiency Proton-Pump Inhibitors during follow up Tube feeding Deshpande A et al. Infect Control Hosp Epidemiol 2015; 36:

20 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

21 Courtesy M. Bassetti

22 C difficile is not invasive. Toxins production is the key to pathogenesis Di Bella S et al. Toxins 2016; 8: 134

23

24 Bagdasarian N et al. JAMA 2015; 313:

25 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 Includes 1,2 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 patients 1 1. Vonberg RP, et al. Clin Micro Infect 2008;14 Suppl 5: UK Department of Health, England. High impact intervention. Care bundle to reduce the risk from Clostridium difficile,

26 Aldeyab MA et al. JAC 2012

27 Feazel LM et al.

28 Feazel LM et al.

29 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