1、Clostridium difficile - a new Disease?,Dr Mike Cooper Consultant Microbiologist and DIPC New Cross Hospital Wolverhampton,Oxoid Infection Control Team of the Year Awards 2006/2007 Winners Announced,BASINGSTOKE, UK, 26 April 2007 - Oxoid, a world leader in microbiology, is pleased to announce the win
2、ners of the 2006/2007 Oxoid Infection Control Team of the Year Awards: 1st Prize: Royal Wolverhampton Hospitals NHS Trust, UK 2nd Prize: Cho Ray Hospital, Vietnam Joint 3rd Prize: Southampton University Hospitals NHS Trust, UK and Aminu Kano Teaching Hospital, Nigeria.,C. difficile,1935 - discovered
3、 Obligate anaerobe Motile Gram positive bacillus Oval, sub-terminal spores Occasional case reports - infected wounds (1960s),C. difficile,1977 - C. difficile identified as cause Birmingham General HospitalAAD - 20-30% AAC - 50-75% 90% - pseudomembranous colitis,C. difficile Toxins,Toxigenic strains
4、produce 2 major toxins: toxin A (enterotoxin) toxin B (cytotoxin) Neutralised by C. sordellii antitoxin,Toxin A,Binds to specific CHO receptors on intestinal epithelium Toxin induced inflammatory process: neutrophils inflammatory mediators fluid secretion altered membrane permeability haemorrhagic n
5、ecrosis,Toxin B,Binding site not yet identified Depolymerization of filamentous actin destruction of cell cytoskeleton rounding of cells,Clinical Manifestations,Asymptomatic carriage (neonates) Diarrhoea 5-10 days after starting antibiotics maybe be 1 day after starting may be up to 10 weeks after s
6、topping may be after single dose spectrum of disease: brief, self limiting cholera-like - 20X/day, watery stool,Clinical Manifestations,Additional symptoms: abdominal pain, fever, nausea, malaise, anorexia, hypoalbuminaemia, colonic bleeding, dehydration Acute toxic megacolon acute dilatation of col
7、on systemic toxicity signs of obstruction high mortality (64%) Colonic perforation,Pathogenesis,Disruption of normal colonic flora Colonisation with C. difficile Production of toxin A +/- B Mucosal injury and inflammation,Pathogenesis,Microflora of gut: 1012 bacteria/gram 400-500 species colonisatio
8、n resistance Transmission - faecal/oral spores Late log / early stationary phase toxin production,Pathology,Colonic mucosa - raised yellow / white plaques initially small enlarge and coalesce Inflamed mucosa,Mortality,All cause 28/7 mortality for CDT positive:1.12.03 31.3.04 18/60 30.0% 1.12.05 31.3
9、.06 71/183 38.8%RR 1.29 (CI 0.84 1.98),What Changed?,Hand hygiene? Environmental cleanliness? Antimicrobial prescribing? Other factors?,What Changed?,?Different organism,Independent 6-8th June 2005,PCR Ribotype 027,In North America PFGE Type NAP1 International = NAP1/027 Major problems in Montreal a
10、nd several states in the US,PCR Ribotype 027,Montreal 30/7 mortality increased 4.7% in 1991/2 8.6% in 2002 13.8% in 2003 Incidence per 100,000 individuals aged 65 102 (1991-2) 866 (2003),PCR Ribotype 027,First UK isolate Preston 1999 Second UK isolate Birmingham 2002 Next seen March 2004 Stoke Mande
11、villeWolverhampton 8 isolates from Oct Dec 2005 sent for typing all 027!,PCR Ribotype 027,North American outbreak strain: 8 to 16 X production of toxins A and B in-vitro Hyper-toxin production: 18bp deletion in the TcdC gene regulates toxin production Strong association with fluoroquinolone useThe L
12、ancet 24th Sept 2005: Warny, 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 Response,Also major problems with MRSA bacteraemias,RWHT Response,DoH MRSA
13、HCAI Improvement ProgrammeDisband ICCForm IPB: chaired by Chief Executive performance management for Divisions and Wards,RWHT Response to C. difficile,Regular commode auditing Replacement of 100 old/damaged commodes Replacement of 300 mattresses Introduction of Saving Lives HII Number 6 following ev
14、ery case of CDAD Root cause analysis on every case Introduction of hotel style bed space check lists following discharge of every patient,RWHT Response to C. difficile,Matron led ward de-clutter programme Introduction of monthly clutter collection 200 domestics trained in CDAD and the role of the en
15、vironment Medical division nurse training on CDAD, spread and role of equipment Grand Round presentation of case studies and action on CDAD. Mandatory attendance of at least one member of every clinical team. 250 attended,RWHT Response to C. difficile,Slide card for infection prevention for all staf
16、f C. difficile management / treatment guidelines New antimicrobial guidelines Antimicrobial prescribing policy Monitoring and antimicrobial prescribing performance management of Divisions Ward refurbishment programme,C. difficile Antibiotic Risk,High Risk Antibiotics:Cefotaxime Ceftriaxone Cefalexin
17、 Cefuroxime Ceftazidime Ciprofloxacin Moxifloxacin Clindamycin (low dose),Medium Risk Antibiotics:Meropenem Ertapenem Clindamycin (high dose) Co-amoxiclav Tazocin Erythromycin Clarithromycin,C. difficile Antibiotic Risk,Low Risk Antibiotics:Benzyl penicillin Gentamicin Amoxicillin Metronidazole Fluc
18、loxacillin Vancomycin Tetracyclines Teicoplanin Trimethoprim Synercid Nitrofurantoin Linezolid Fusidic acid Tigecycline Rifampicin Daptomycin,Symptomatic Proven or Suspected C. diff infection,Assess Patient: AXR, CRP, U& Es, FBC Stool Chart Stool for C. diff & culture (if not done) Consider Flexi Si
19、g if diagnosis in doubt Review Antibiotics,Treatment Algorithm For New Cases of C. difficile Diarrhoea,Moderate Disease Well WCC 20 CRP 150 Normal AXR,Severe Disease Unwell WC 20 * CRP 150 * Abnormal AXR * Distended Abdomen * (* = severe if any of these features),( If Deteriorates to Severe ),Start
20、treatment without delay -Vancomycin 500mg QDS PO -Metronidazole 500mg TDS IV or 400mg TDS PO - IVI -Consider HDU / ITU Colorectal Surgical Referral on day 1 Daily Surgical Review until improving : if fails to improve consider surgery,Start treatment without delay -Metronidazole 400mg TDS for 5 days
21、-Daily Review including stool chart - FBC, CRP, AXR if deteriorates,Moderate,Severe,( If Deteriorates to Severe ),Response Complete 14 day course of Vancomycin Complete course of metronidazole,No Response :- Refer Gastroenterology for flexible sigmoidoscopy & advice. Continue Vanc & Met Treat as for
22、 severe if deteriorates,Response Complete 14 day course of metronidazole,No Response :- Add Vancomycin 500mg QDS PO for 5 days Complete 14 day course of metronidazole,Can be discharged on metronidazole and vancomycin (125mg QDS),Recurrence:,?re-infectionAssess: if severe treat as aboveModerate: metr
23、onidazole 400mg TDS and PO vancomycin 500mg QDS If 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
24、 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 Vancomyci
25、n: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 weeks IV Immunoglobulin 400mg/kg single dose with a repeat at 21 days if necessaryYeast Yeast preparations are contraindicated. Prebiotic and Probiotics
26、(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 receive,Matrons lead Ward Declutter programme,Domestics training delivered by IPT,Bed space checklists introduced,Commode replacem
27、ent,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 Audit,Commode re-Audit &feedback,Mortality,All cause 28/7 mortality for CDT positive:1.12.03 31.3.04 18/60 30.0
28、% 1.12.05 31.3.06 71/183 38.8%,Mortality,All cause 28/7 mortality for CDT positive:1.12.03 31.3.04 18/60 30.0% 1.12.05 31.3.06 71/183 38.8% 1.12.06 31.3.07 23/85 27.1%RR 0.70 (CI 0.47 1.03),Conclusions,New strain(s) of C. difficile cause more severe disease ?sub-strains Appear to spread more readily More difficult to control Multi-factorial approach to control needed Requires involvement of entire Trust not just a medical / nursing solution Not just antibiotics!,
