Lifting the lid on a difficile problem part 2 (Clinical) Evidence Based Practice. Problem in evolution (1) Problem in evolution (1) Interventions (2)

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Lifting the lid on a difficile problem part (Clinical) Dr Philip T Mannion Consultant Microbiologist, Rhyl Evidence Based Practice Antibiotic prescribing guidance Isolation policy Hand hygiene (soap and water with proven cases) PPE (gloves and aprons) Environmental cleaning (separate detergent, additional chlorine based clean) Cell cytotoxin assay Problem in evolution () 6 7 8 January February 6 8 March 6 April 7 7 May 9 6 June 9 July 7 August 6 September 6 7 6 October November 9 December 7 Problem in evolution () Different clinical picture Increased severity: - failure of metronidazole - progression to severe disease - prolonged duration Rapid development of secondary cases (clustering) Interventions () January Major Incident declared Saving lives working group already in process (Integrated care pathway) Regular meetings (PDSA process using wards where cases occurring regularly) Ward closure refurbishment (including mattress covers)/deep clean Medical management guidelines Medical notes inserts

GUIDELINES FOR THE MANAGEMENT OF CLOSTRIDIUM DIFFICILE ASSOCIATED DIARRHOEA Medical staff should suspect that a case may be infective if no clear alternative cause for diarrhoea is apparent. Send a sample for Clostridium difficile toxin testing and routine tests for enteric pathogens. If Clostridium difficile infection is strongly suspected despite a negative initial test, a repeat sample may be sent. In suspected cases of silent Clostridium difficile infection, such as ileus, toxic megacolon or pseudomembranous colitis without diarrhoea, other diagnostic procedures such as white cell count, serum lactate and abdominal CT scan may be required. Occasionally some cases may need discussion with a gastroenterologist to consider other contributory causes to symptoms. Commence the Trust Integrated Care Plan for Clostridium difficile and monitoring of bowel function using Bristol Stool Chart and continue daily until patient has passed normal stool for at least days. Assess and document disease severity: Mild disease or fewer types to 7 stools on Bristol Chart per day and normal white cell count. Moderate disease to of types to 7 stools on Bristol Chart per day and a raised white cell count (<,). Severe disease white cell count >, or a temperature of 8. C or acute rising serum creatinine, e.g. >% increase above baseline or evidence of severe colitis (abdominal or radiological signs). The number of stools may be a less reliable indicator of severity. Life-threatening disease such as hypotension, partial or complete ileus or toxic megacolon or CT evidence of severe disease. Review drug treatment and stop other antibiotics unless to do so would place patient at risk. Other drugs that may also cause diarrhoea should be stopped if possible as well as PPIs. Use ranitidine if acid suppression essential. Antimotility and associated drugs should not be used. Commence treatment according to severity as soon as Clostridium difficile is suspected. Do not wait for a positive toxin result. Mild and moderate disease oral metronidazole mg 8 hourly for to days, as tablets or suspension. IV metronidazole should be used only if oral treatment is not possible. Severe disease oral vancomycin mg 6 hourly for to days. Check pharmacy information sheet regarding administration if oral solution required. Monitoring of serum levels is not normally necessary. In severe cases not responding to the above dose, high dose oral vancomycin (up to mg 6 hourly, instilled via nasogastric tube if necessary) +/- IV metronidazole mg 8 hourly is recommended. The addition of oral rifampicin (mg BD*) or IV immunoglobulin (mg/kg) may also be considered. Life-threatening disease oral vancomycin up to mg 6 hourly for to days via nasogastric tube or rectal installation (guidance available from pharmacy) PLUS IV metronidazole mg 8 hourly. Such patients should be monitored with serum lactate and colectomy considered, especially if caecal dilatation is > cm. Colectomy is best performed before serum lactate rises to > millimoles per litre. Interventions () January Major Incident declared Saving lives working group already in process (Integrated care pathway) Regular meetings (PDSA process using wards where cases occurring regularly) Ward closure refurbishment (including mattress covers)/deep clean Medical management guidelines Medical notes inserts Interventions () Enhanced surveillance (Infection Control and Pharmacy) Sight poster Stool charts incorporating BSC Weekly e-mail to senior staff highlighting all symptomatic patients within the Trust Safety Cross (on each ward) Education of all staff S I G H T High Risk Medium Risk Low Risk Clindamycin Quinolones (e.g. Ciprofloxacin Ceftazidime Ceftriaxone Cefuroxime) Amoxicillin Cefalexin Clarithromycin / Erythromycin Doxycycline Flucloxacillin Imipenem Meropenem Tetracycline e.g. Doxycycline Trimethoprim Co-amoxiclav Benzylpenicillin Gentamicin Metronidazole Penicillin V Rifampicin Tazocin Teicoplanin Vancomycin uspect that a case may be infective where there is no clear alternative for diarrhoea. solate the patient in a side room, with dedicated toilet or commode. Consult with the Infection Control Team. loves and aprons must be used for all contacts with patients and with their immediate environment. and washing with soap and water before and after each contact with patient and the patient s immediate environment. est the stool for toxin immediately, if negative result and patient remains symptomatic, send a repeat specimen. Interventions () Enhanced surveillance (Infection Control and Pharmacy) Sight poster Stool charts incorporating BSC Weekly e-mail to senior staff highlighting all symptomatic patients within the Trust Safety Cross (on each ward) Education of all staff

Interventions () Regular Severity Assessment by Medical Staff Wash your hands posters Introduction of chlorine releasing cleaning agent (single clean) Period of Increased Incidence action plan (ward audit by ICN s, daily ward visits, change to chlorine releasing cleaning agent) MDT walkabouts (ICN s/antibiotic pharmacist/consultant microbiologist) Cases where mortality attributable to C difficile (post-mortem data) 6 C difficile attributable mortality Nov- Dec- Jan- Feb- Mar- Apr- May- Jun- Jul- Aug- IPCT Enhanced Surviellance Data Performance against Cl Difficile reduction target / % % 8% 6% % % Aug-Dec Pre- Interventions Jan-Aug Post- Interventions % Isolated Isolated Compliance Compliance <hrs post <hrs Post with with stool symptoms Result treatment chart & PPE Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar regime Cum / -% Cum /

Comparative data (ICT database) Pilot Ward (COTE) Dec Jan-May Jun-Sep Total number of episodes 6 69 69 Death within 8 days (%).. 7. Mild symptoms (%) 67. 6. 6.8 Moderate symptoms (%) 7.6 6. Severe symptoms (%)... Previous C difficile infection (%).. Jul- Aug- Nov- Dec- Jan- Feb- Mar- Apr- May- Community onset (%) 7.6 8.9.9 Ribotyping of C.difficile cases June /September clusters 6 medical, surgical, ITU 6 mixed ribotype 7 ribotype 6 mixed 78 x, 6 x x, 6 x, x 7 x, 6 x, x 7 x 6, 6 x, x 7 x, x, x x, 6 x, x Suspected ward transmission (August -Septmber ) Date Medical Surgical Ribotype Aug- 6, 7 6 Nov- 7 Dec- Jan- 7 Feb- Mar- 7 Apr- 7 May- Jun- 7, Mixed Jul- Aug- Mixed

Further ribotyping data no. GDH TEST GDH VE GDH +VE Negative report issued no Interim report (if issued) further testing on the sample GDH reactive - C.difficile not detected C.difficile infection may send a further sample in be present 8 hrs if symptoms persist TOXIN ASSAY Perform a combined toxin A+B assay R6 R7 R R R R R6 R R8 R R R7 R78 R R6 R78 R R R6 TOXIN VE GDH reactive, Toxin assay negative. C.difficile infection may be present send a further sample in 8 hrs if symptoms persist. TOXIN +VE Final report issued GDH reactive, Toxin assay positive - C.difficile infection present Figure - Proposed testing algorithm for C.difficile infection Eastwood K et al (J Clin Micro, October, p.-7, Vol 7,no ) The optimum rapid single test was PCR for toxin B gene, as this had the highest negative predictive value. Diagnostic algorithms that optimize test combinations for the diagnosis of C difficile infection need to be defined. Compared to cytotoxigenic culture: Toxin B gene PCR NPV of 99.7% and 98.6% (at % and % prevalence respectively) GDH screen NPV of 99.7% and 98.6% (at % and % prevalence respectively) Conclusions GDH screening may increase case ascertainment (surveillance/improvement targets) Clinical management is multidisciplinary Re-educate the clinical staff (disease severity/urgency of response) Testing and treatment out of hospital (especially nursing homes) the poor relative? GDH screening should be introduced rapidity of results, high NPV, ability to provide a seven day service Improved patient management (benefits individuals and hospitals) Currently no single test algorithm is perfect