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Clostridium difficile-a new Disease?Dr Mike CooperConsultant Microbiologistand DIPCNew Cross HospitalWolverhamptonOxoid Infection Control Team of the Year Awards 2006/2007 Winners AnnouncedBASINGSTOKE,UK,26 April 2007-Oxoid,a world leader in microbiology,is pleased to announce the winners of the 2006/2007 Oxoid Infection Control Team of the Year Awards:1st Prize:Royal Wolverhampton Hospitals NHS Trust,UK2nd Prize:Cho Ray Hospital,VietnamJoint 3rd Prize:Southampton University Hospitals NHS Trust,UK and Aminu Kano Teaching Hospital,Nigeria.C.difficilel1935-discoveredlObligate anaerobelMotilelGram positive bacilluslOval,sub-terminal sporeslOccasional case reports-infected wounds(1960s)C.difficilel1977-C.difficile identified as causelBirmingham General HospitallAAD-20-30%lAAC-50-75%l90%-pseudomembranous colitisC.difficile ToxinslToxigenic strains produce 2 major toxins:ltoxin A(enterotoxin)ltoxin B(cytotoxin)lNeutralised by C.sordellii antitoxinToxin AlBinds to specific CHO receptors on intestinal epitheliumlToxin induced inflammatory process:lneutrophilslinflammatory mediatorslfluid secretionlaltered membrane permeabilitylhaemorrhagic necrosisToxin BlBinding site not yet identifiedlDepolymerization of filamentous actinldestruction of cell cytoskeletonlrounding of cellsClinical ManifestationslAsymptomatic carriage(neonates)lDiarrhoeal5-10 days after starting antibioticslmaybe be 1 day after startinglmay be up to 10 weeks after stoppinglmay be after single doselspectrum of disease:lbrief,self limitinglcholera-like-20X/day,watery stoolClinical ManifestationslAdditional symptoms:labdominal pain,fever,nausea,malaise,anorexia,hypoalbuminaemia,colonic bleeding,dehydrationlAcute toxic megacolonlacute dilatation of colonlsystemic toxicitylsigns of obstructionlhigh mortality(64%)lColonic perforationPathogenesislDisruption of normal colonic floralColonisation with C.difficilelProduction of toxin A+/-BlMucosal injury and inflammationPathogenesislMicroflora of gut:l1012 bacteria/graml400-500 specieslcolonisation resistancelTransmission-faecal/orallsporeslLate log/early stationary phaseltoxin productionPathologylColonic mucosa-raised yellow/white plaqueslinitially smalllenlarge and coalescelInflamed mucosaMortalitylAll cause 28/7 mortality for CDT positive:l1.12.03 31.3.0418/6030.0%l1.12.05 31.3.0671/18338.8%lRR 1.29(CI 0.84 1.98)What Changed?lHand hygiene?lEnvironmental cleanliness?lAntimicrobial prescribing?lOther factors?What Changed?l?Different organismIndependent 6-8th June 2005PCR Ribotype 027 lIn North America PFGE Type NAP1lInternational=NAP1/027lMajor problems in Montreal and several states in the USPCR Ribotype 027lMontreal 30/7 mortality increasedl4.7%in 1991/2l8.6%in 2002l13.8%in 2003lIncidence per 100,000 individuals aged 65l102(1991-2)l866(2003)PCR Ribotype 027lFirst UK isolate Preston 1999lSecond UK isolate Birmingham 2002lNext seen March 2004 Stoke MandevillelWolverhampton 8 isolates from Oct Dec 2005 sent for typinglall 027!PCR Ribotype 027lNorth American outbreak strain:l8 to 16 X production of toxins A and B in-vitro lHyper-toxin production:l18bp deletion in the TcdC genelregulates toxin productionlStrong association with fluoroquinolone uselThe Lancet 24th Sept 2005:lWarny,Pepin,Fang,Killgore,Thompson,Brazier,Frost and McDonald:“Toxin production by an emerging strain of C.difficile associated with outbreaks of severe disease in North America and Europe”RWHT ResponseAlso major problems with MRSA bacteraemiasRWHT ResponseDoH MRSA HCAI Improvement ProgrammeDisband ICCForm IPB:chaired by Chief Executiveperformance management for Divisions and WardsRWHT Response to C.difficilelRegular commode auditinglReplacement of 100 old/damaged commodeslReplacement of 300 mattresseslIntroduction of Saving Lives HII Number 6 following every case of CDADlRoot cause analysis on every caselIntroduction of hotel style bed space check lists following discharge of every patientRWHT Response to C.difficilelMatron led ward de-clutter programmelIntroduction of monthly clutter collectionl200 domestics trained in CDAD and the role of the environmentlMedical division nurse training on CDAD,spread and role of equipmentlGrand Round presentation of case studies and action on CDAD.Mandatory attendance of at least one member of every clinical team.250 attendedRWHT Response to C.difficilelSlide card for infection prevention for all stafflC.difficile management/treatment guidelines lNew antimicrobial guidelineslAntimicrobial prescribing policylMonitoring and antimicrobial prescribing performance management of DivisionslWard refurbishment programmeC.difficile Antibiotic RiskHigh Risk Antibiotics:CefotaximeCeftriaxoneCefalexinCefuroximeCeftazidimeCiprofloxacinMoxifloxacinClindamycin(low dose)Medium Risk Antibiotics:MeropenemErtapenemClindamycin(high dose)Co-amoxiclavTazocinErythromycinClarithromycinC.difficile Antibiotic RiskLow Risk Antibiotics:Benzyl penicillinGentamicinAmoxicillinMetronidazoleFlucloxacillinVancomycinTetracyclinesTeicoplaninTrimethoprimSynercidNitrofurantoinLinezolid Fusidic acidTigecyclineRifampicinDaptomycinSymptomatic Proven or SuspectedC.diff infectionAssess Patient:AXR,CRP,U&Es,FBCStool ChartStool for C.diff&culture(if not done)Consider Flexi Sig if diagnosis in doubtReview AntibioticsTreatment Algorithm For New Cases of C.difficile DiarrhoeaModerate DiseaseWellWCC 20CRP 20*CRP 150*Abnormal AXR*Distended Abdomen*(*=severe if any of these features)(If Deterioratesto Severe)Start treatment without delay-Vancomycin 500mg QDS PO-Metronidazole 500mg TDS IV or 400mg TDS PO-IVI-Consider HDU/ITUColorectal Surgical Referral on day 1Daily Surgical Review until improving:if fails to improve consider surgeryStart treatment without delay-Metronidazole 400mg TDS for 5 days-Daily Review including stool chart-FBC,CRP,AXR if deterioratesModerateSevere(If Deterioratesto Severe)ResponseComplete 14 day course of Vancomycin Complete course of metronidazoleNo Response:-Refer Gastroenterology for flexible sigmoidoscopy&advice.Continue Vanc&Met Treat as for severe if deterioratesResponseComplete 14 day course of metronidazoleNo Response:-Add Vancomycin 500mg QDS PO for 5 daysComplete 14 day course of metronidazoleCan be discharged on metronidazole and vancomycin(125mg QDS)Recurrence:?re-infectionAssess:if severe treat as aboveModerate:metronidazole 400mg TDS and PO vancomycin 500mg QDSIf responds by day 5:14 days of metronidazole+500mg QDS vancomycin,then 6 weeks tapering vancomycinIf no response after 5 days of combined therapy refer to gastroenterologyIf remains symptomatic after 10 days and C.diff/PMC confirmed on flexible sigmoidoscopy then consider IV Immunoglobulin.If this is the third or more recurrence then consider immunoglobulin +2 weeks metronidazole 400mg TDS PO/vancomycin 500mg QDS at the outset followed by 6 weeks of vancomycin.Third Line Drug Regimes for Recurrent Disease:-6 weeks Tapering Vancomycin:125mg every 6 hours for 1 week125mg every 12 hrs for 1 week125mg once daily for 1 week125mg every other day for 1 week125 mg every 3rd day for 2 weeksIV Immunoglobulin400mg/kg single dose with a repeat at 21 days if necessaryYeastYeast preparations are contraindicated.Prebiotic and Probiotics(live yoghurt)No proven benefit of prebiotics or probiotics.Cannot be prescribed and should not be advocated-no quality control over the agents that the patient will receiveMatrons lead Ward Declutter programme Domestics training delivered by IPT Bed space checklists introduced Commode replacement Mattress replacement RCA for all c diff cases introduced Antibiotic review commenced Grand Round presentation High Impact Intervention No 6 introduced Medical division training Commode AuditCommode re-Audit&feedbackMortalitylAll cause 28/7 mortality for CDT positive:l1.12.03 31.3.0418/6030.0%l1.12.05 31.3.0671/18338.8%MortalitylAll cause 28/7 mortality for CDT positive:l1.12.03 31.3.0418/6030.0%l1.12.05 31.3.0671/18338.8%l1.12.06 31.3.0723/8527.1%lRR 0.70(CI 0.47 1.03)ConclusionslNew strain(s)of C.difficile cause more severe diseasel?sub-strainslAppear to spread more readilylMore difficult to controllMulti-factorial approach to control neededlRequires involvement of entire Trustlnot just a medical/nursing solutionlNot just antibiotics!
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