ESCMID Online Lecture Library. by author

Transcription

1 Clostridium difficile an old foe in new clothes. Diagnostics, epidemiology and therapy Torbjörn Norén MD, Ph D Dept. Infectious Diseases & Infection Control Örebro University Hospital, Sweden National reference laboratory for clinical CDI isolates torbjorn.noren@orebroll.se

2 Old foe defichele transforming /Bartlett CID 2008, 46 S 4-11 Anatomic studies 1893, pseudomembranous changes in the intestinal tract (PMC) of a 22-yearold postoperative patient Finney JMT. Bull Johns Hopkins Hosp 1893; 4:53 5. Clostridium difficile and its toxin (?) first described in newborn children / Hall and O Toole Am J Dis Child 1935; 49: ies postoperative and AB 14-27% PMC C difficile era 1974 Tedesco PMC post clindamycin colitis C difficile and clinical correlate established / Bartlett J Infect Dis 1977 and N Engl J Med 1978; Penicillins, tetracyclins, clindamycin cephalosporins fluoroquinolones carbapenems.. NAP1/027 North-American-European CDI epidemic Leading cause of infectious nosocomial bacterial diarrhoea in industrialised countries / Crobach CMI 2009

3 C. difficile Spores in soil Al Saif J Med Micro 1996 Cardiff UK 2580 samples: River water 87% soil 21% Hospital wards 20% swimmingpools 50% drinking water 5% Dogs 10% cats 2% humans 2% vegetables 2.4% fish gut 0% Gram positive rod 3 Enterotoxins von Eichel Streiber, 1996, Trends Micro TJ ADP ribosyltransferas CDT A/B Rho Aktincytoskeleton apoptos 1. Toxin A 2. Toxin B 3. Binary toxin CTD ++ B A

4 Clostridium difficile major pathogen (AAD) 25% of CDI 4% Healthy carriers (PCR 53%) C. perfringens. B. fragilis ETBF K. oxytoca Antibiotic therapy Toxin A + B + (CDT) CDI Antibiotic associated diarrhoea (AAD) PMC 1-3%

5 ÖREBRO LÄNS LANDSTING CDI clinical picture /Owen, CID 2008:46 (Suppl 1)

6 ÖREBRO LÄNS LANDSTING Antimicrobials and risk of CDI -All AB can precipitate CDI Broadspectrum and anaerobe activity 1. Clindamycin 2. Cephalosporins* 3. Fluoroquinolones } } Constitutes 90% of CDI /Spencer JAC 1998 All merited in outbreaks and restrictions results in CDI decline /Johnson NEJM 1999; Thomas CID 2002, Pepin CID 2005 *Slimings JAC 2014 Less proposed risk: Aminoglycosides, Tazobactam/Tigecyklin Fidaxomycin Tetracyclines /Doernberg CID 2012 Spore inhibition Garneau BMC 2014 Bebakhani CID 2012 /Owen, CID 2008:46 (Suppl 1)

7 ÖREBRO LÄNS LANDSTING Risk of CDI Primary/recurrence how can we tell? Altered enteric flora /Jernberg Microbiology 2010 Old age /Kelly CMI 2012 Lack of immune response /Wilcox Lancet 2001 Concomittant AB during CDI therapy/garey J Hosp Inf 2008 Prophylactic vancomycin, Carignan, ICCAC 2013 K 334, Fidaxomycin Cornely, CID 2012 Hospital stay /McFarland Inf Control Hosp Epi 1999 PPI /Janarthanan Am J Gastro 2012 Prior severe CDI (LPK eller CRP) /Eyre CID 2012

8 The Spores I love them (Autoclave 110 ) Lawley 2010 Resistant to: Alkohols peroxides detergents Boiling 2 h Radiation 400 rad (4 x letal dose human)

9 Prevention: Isolation for how long? Clostridium difficile Survival år? /Sethi Inf Control Hosp Epi 2010

10 Bedstudy Cd Bed study 52 numbered beds enrolled by index CDI case resident. Sampling four times/month CD 40% positive and 20% at follow-up 2, 3 or 4 weeks Sjöberg M APMIS Jan 30. doi: /apm touch surfaces swabbed from 10 single rooms Singleroom pos (85%) Before cleaning Bed overhead handle 5 1 Call button 3 0 Bed table 4 0 Bedrail 4 1 Toilet tap 3 0 Flushknob 1 0 Toilet seat 3 2 Armrest toilet 3 1 Door handle toilet 1 0 Disinfectant device 1 0 Door handle inside 1 0 Stethoscope 1 0 bed front lining 2 0 Door handle outside 0 0 After cleaning* * Current CDI clean routine: Wipe EtOH+tenside touch sufaces and Virkon 3% toilet+floor

11 Epidemiology in the era of NAP1/027 Toxin production A 16x B 23x Warny Lancet 2005 High sporulation Åkerlund Increased morbidity Severe CDI = SCDI 7% % Mortality 4.7%-13.8% (Pepin CMAJ 2004) Cure p=0.02 Zar et al,cid Therapeutic failure Metronidazole Failures 9% 2002 to 25% 2004 Relapse (> 65 år) 28% to 58% (Musher CID 2005) Va Mz

12 CDI & NAP1/027 i Scandinavia 50/ CDI/year 027 Norge 3 cases 2008 PMC 1 Oslo / CDI/year 027 Denmark Sjaelland SWEDEN 81/ CDI/years / CDI/year 027 Finland Oct SCDI Cure p=0.02 South: 49% 027 Tot 36% 2011(6/13 counties) Other % 001, 002 / Kotila CMI 2011 Outbreak 027 Växjö 2013/14 9 Odd clinical cases 027 moxi R Other Mx res PCR ribotypes 012, 046, Outbreak Eksjö

13 Clustering of multiresistant CD PCR ribotypes

14 Online Lecture Library Slide withheld at request of author

15 Current diagnosis of Clostridium difficile infection (CDI) 2. Odling+toxintest 3. Toxin snabbtest A/B, A Typical clinical picture 3 loose stools AB treatment Hospital stay Old age Immunosuppression Exclusion of other causes Diarré Buksmärta Feber Toxigenic Culture TC Cytotoxicity assay CTA Reference standard EIA - toxin A and B GDH (glutamate dehydrogenase) RT-PCRs tcda tcdb, 2010 TC + Illumigene/GeneXpert

16 Online Lecture Library Slide withheld at request of author

17 Crucial to a more sensitive test True clinical picture and diagnostic verification Awareness of asymptomatic carriage (Toxin (CTBA) in faeces correlate with mortality)/planche Wilcox the Lancet sep Environmental load (current 046 outbreak southern Sweden) of infective spores

18 Online Lecture Library Slide withheld at request of author

19 Two step algorithm /Crobach CMI 2009,ESGMID recommendations Wilcox JCM 2010 Screening step GDH (glutamate dehydrogenase) High Sensitivity NAAT (Nucleic acid amplification test) NEG Specificity 99% -non-tox PCR ribotypes sensitivity 72% (Swindells JCM 2010) +Crossreaction C bifermentans, C sordelii Non toxigenic Cd POS Toxin genes tcda or tcdb EIA (membrane or microwell type) POS NEG? Clinical evaluation

20 CDI therapy 2013 ESCMID treatment guidance document /Debast CMI Okt 2013; doi: / Mild CDI stopping the inciting AB 25% spontaneous resolution / Bartlett 1984, Rev Inf Dis 1. Metronidazole + cheap low concetrations in gut lumen / Bolton Gut Vancomycin First line therapy NA and EU (027)- risk of VRE selection? 3. Fidaxomycin New agent + reduces recurrences by 50% microflora saving and sporeinhibition Expensive. / Louie NEJM 2011 Cornely The Lancet 2012 What is severe CDI?

21

22 ÖREBRO LÄNS LANDSTING ESCMID, When surgery? (colectomy) Mortality19-71% Early intervention = pre-chock, organ failure (renal/resp)) and s-lactate <5 mmol/l Perforation, peritonitis, Clinical decline WBC, creatinin, lactoferrin, crp? Lapraskopic Loop-ileostomy with Lavage (polyethylene) and vancomycin sol postop + Mz iv Neal, Ann Surg, 2011 Total Colectomy

23 ÖREBRO LÄNS LANDSTING Recurrent CDI (RCDI) 20-50% Majority of RCDI 10 days post end of CDI therapy 80% of RCDI occur within 60 days /Eyre CID 2012 Recurrent episodes of CDI (53/272=19%) related to PCR ribotype in Örebro County, Sweden PCR ribotype Number of patients Number of patients with the following number of recurrences UK UK UK UK UK UK UK UK UK UK UK Other Total /Norén JCM 2004

24 ÖREBRO LÄNS LANDSTING Multipel recurrent CDI Probiotics Biotherapy FMT IBD Andersson 2012 Alim Pharm ther) Saccharomyces boulardii (yeast) 5 publications with low efficacy (Surawicz McFarland Lewis, Bleichner, Kotowska) Lactobacilli (GG plantarum rhamnosus) No convincing evidence/ Pillai A, Cochrane Database Syst Rev Rectal fecal enema/endoscope or Gastro-jej. tube 500 ml post oral Vancomycin (50-80% permanent Cure) Schwan Lancet 1983, Bowden Am.Surg Faecal flora cocktail commensal enema(tvede Lancet 1989, Jorup Läkartidningen ) van Nood NEJM 2013 randomized trial, Colonoscope Mattila Gastro 2012 Silverman Clin Gastro 2010 Non-toxinproducing CD (Viropharma) Immunotherapy Monoclonals Davies Clin Vacc Imm 2013 Whey protein (Numan Gut 2007) CFs(Ag) C. difficile Poultry IgY-protection Hamsters (Mulvey) Vaccin (Sougioultzis Gastroent. 2005)

25 ÖREBRO LÄNS LANDSTING Faeces transplantation (FMT) Gastrojejunal tube van Nood E et al. N Engl J Med 2013;368: Colonoscope/Mattila Gastro pat (89% cure 12 weeks) Nasogastrisk tube McConnachie, Glascow 90% cure 30g faeces/150 NaCl coffeefilter Silverman Can CG 2010 at home-do it your self Cure 100% 14 weeks n=7. Mixbag-enema 200 ml

26 Thank you!!

27 Online Lecture Library Slide withheld at request of author