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Clostridium difficile - CD
• Tarmbakterie– Sporedannende
• Reservoir– Tarmflora– Omgivelser
• Kontaktsmitte– Fæko-orale rute
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Forekomst
• CD forekommer i normal tarmflora hos – Børn < 2 år 50 %– Raske voksne 3 %
• Hos indlagte patienter – 10 – 25 % koloniserede– > 60 % asymptomatiske
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Infektion med CD (CDI)
• Ændring af den normale tarmflora giver mulighed for kolonisering
• Anden behandling– kemoterapi– syrehæmmende mavesårsmedicin
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Infektion med CD (CDI)
• 15-25 % af tilfælde med antibiotika-udløst diaré skyldes C. difficile
• > 90 % af CDI opstår i relation til antibiotisk behandling
• 90 % af pseudomembranøs colitisskyldes C. difficile
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Risikofaktorer
• Alder > 65 år
• Andre konkurrerende sygdomme– Maligne lidelser– Mave-tarm kirurgiske patienter– Immun suppression
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Symptomer• Asymptomatisk
• Diarre og mavesmerter
• Pseudomembranøs colitis
• Toksisk megacolon
• Mortalitet på ca. 5 % (historisk set)
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Clostridium difficile virulens
• Sporedannende
• Toksin-producerende– Toksin A – Toksin B– Binære toksin
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Sporer• Græsk = kim / frø
• Hvilende bakterieform
• Dannes under ugunstige forhold
• Yderst modstandsdygtig
Overlever i miljøet
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Toksiner
• Toksin A og B– slimhindebeskadigelse– inflammation– vandsekretion
• Binære toksin– funktion ukendt– binding til epitelceller ?
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Patogenese
• Udryddelse af normalflora og kolonisation
• Cellebeskadigelse
• Inflammation
• Pseudomembraner
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Udbrud med CD027• En succesrig klon
– CD PCR ribotype 027– NAP1 (North American pulsed-field type 1)
• Mere virulent – Danner større mængde af toxiner ?
• Større smittepotentiale– Flere sporer ?
• Højere morbiditet og mortalitet
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CD027 og toksinproduktion
Figure 3. In vitro production of toxins A and B by C difficile isolates. Median concentration and IQRs are shown. C difficile strains included 25 toxinotype 0 and 15 NAP1/027 strains (toxinotype III) from various locations.
Warny. Lancet 2005, 366 :1079-1084.
X 16
X 23
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Pathogenicity island
Kelly. N Engl J Med 2008; 359: 1932-40.
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CD027 i Region Midt
• Regionshospitalet Randers– 2 Patienter, sommeren 2009
• Århus Universitetshospital – 7 patienter, efteråret 2010– Aktuelt sporadiske tilfælde
• Silkeborg/Viborg– Efteråret 2011 – vedvarende udbrud?
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Recidiv ved CD027
• Hyppigst inden for 4 uger
• Risiko for 1. recidiv ca. 20 %
• Risiko for 2. recidiv ca. 40 %
• Risiko for 3. recidiv ca. 60 %
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CD og mortalitet 2006
Eur J Clin Microbiol Infect Dis. 2012 Feb;31(2):185-92. Clinical features of Clostridium difficile infection and molecular characterization ofthe isolated strains in a cohort of Danish hospitalized patients.Søes LM, Brock I, Persson S, Simonsen J, Pribil Olsen KE, Kemp M.
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CD og 30-dages mortalitet i Danmark 2008-2009
• CD 027• CD toxin A, B, binært• CD toxin A og B• CD uspecificeret
• 28,0 % (54 / 193)• 27,8 % (20 / 72)• 17,0 % (36 / 212)• 13,6 % (247 / 1.822)
Bacci S, Mølbak K, Kjeldsen MK, Olsen KEP. Binary toxin and death afterClostridium difficile infection. Emerg Infect Dis. 2011.
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CD og mortalitet i Danmark2008-2009
Kaplan Meier curves showing the probability of patient survival after diagnosisof Clostridium difficile infection according to the 4 different infection groups (log-rank test, p<0.001).Blue line, C. difficile PCR ribotype 027; black line, C. difficile PCR ribotype non-027; green line, C. difficile with toxins A and B without binary toxin; red line, C. difficile unselected strains not referred for typing.
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CD og mortalitet i Danmark2008-2009
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Behandling
• Seponér udløsende antibiotika• Metronidazol• Vancomycin• Nye lægemidler• Fæces mikrobiota transplantation• Kirurgi
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Behandling• Svær infektion
– Pseudomembraner– Intensiv afdeling– 2 af følgende:
• > 60 år• > 38,3°C• Hypoalbuminæmi• Leucocytose > 15x109/L
• Vancomycin– 125 mg x 4 p.o.
• Metronidazol– 250 mg x 4 p.o.
Kelly. N Engl J Med 2008; 359: 1932-40.
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Indikationer for diagnostik
• Fæces fra hospitalsindlagte patienter bliver undersøgt for CD
• Undtagen børn < 2 år– Afdelingen kan rekvirere undersøgelse
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Diagnostik
• Dyrkning af C. difficile fra fæces– Identifikation– Resistens-undersøgelse– Svartid 2-4 hverdage
• PCR direkte fra fæces (hurtigtest)– Toxin-undersøgelse– Svar samme dag– Begrænset kapacitet
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Forebyggelse
• Fornuftig antibiotikapolitik
• Infektionshygiejniske forholdsregler
• Isolation ved CD027 – og begrundet mistanke om CD027
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C. difficile konklusion
• Særlig opmærksomhed på CD027– Større sygelighed ved infektion
– Epidemisk på Sjælland
• Antibiotikabehandling øger risiko for sygdom
• Nosokomiel smitte