Case 1 21 yr old HIV +ve, Cd4-100 HAART naïve Profuse diarrhoea for 3/52. Stool MC&S ve Which of the following would be next appropriate investigation/s regarding the pts diarrhoea? Repeat stool MC&S Stool for C Diff Gastroscopy plus D2 Bx Colonoscopy Sigmoidoscopy Contrast study-enema
Case 2 55 yr old diarrhoea for 5/7 recent surgery for knee replacement about a week ago Clinically well. Not on any current Abics haemodynaically normal Abdo soft LFT/U&E/FBC normal Vancomycin 125 qid po Vancomycin 500 qid po Metronidazole 500 tds po interflora Metronidazole 500 ivi Vancomycin 500 ivi Vancomycin enema Metronidazole 500 po plus vancomycin 125 po Metronidazole 500 ivi tds plus vancomycin 500 po plus vancomycin enema surgery
Case 3 65 yr old Transfer from ward to ICU CDI on admission to ward No diarrhoea on transfer WCC 50 albumin 20 On inotropes. Vancomycin 125 qid po Vancomycin 500 qid po Metronidazole 500 tds po interflora Metronidazole 500 ivi Vancomycin 500 ivi Vancomycin enema Metronidazole 500 po plus vancomycon 125 po Metronidazole 500 ivi tds plus vancomycin 500 po plus vancomycin enema surgery
Case 4 45 yr old, treated for CDI 4 weeks ago Now with diarrhoea. Ambulatory Initial treatment metronidizole Vancomycin 125 qid po Vancomycin 500 qid po Metronidazole 500 tds po interflora Metronidazole 500 ivi Vancomycin 500 ivi Vancomycin enema Metronidazole 500 po plus vancomycon 125 po Metronidazole 500 ivi tds plus vancomycin 500 po plus vancomycin enema surgery
Clostridium Difficile Infection (CDI) an everyday approach Dr Adam Mahomed Head of the Division of Gastroenterology and Hepatology Charlotte Maxeke Johannesburg Academic Hospital
Objectives Review microbiology and epidemiology Review risk factors for transmission Discuss testing methods and diagnosis Review clinical classification and Management Discuss preventive strategies
Microbiology Gram positive spore forming bacillus (rods) Obligate anaerobe Part of the GI Flora Some strains produce toxins A & B Toxins-producing strains cause C. diff Infection (CDI)
Epidemiology Incidence in US adults 1996 30/100 00 vs 2005 85/100 000 2005 75% in previously hospitalised 3 5% of all hospitalised antibiotic treated patients Incidence Surpassing MRSA: recent literature Zilberberg MD. et al. Emerging Infectious Diseases. 2008 Miller BA, et al. Infection Control and Hospital Epidemiology. 2011
Spectrum of disease Asymptomatic Diarrhoea Colitis Pseudomembranous colitis Fulminant colitis Recurrent CDI
Risk Factors Exposure to antimicrobials (prior 2-3 months) Exposure to healthcare (prior 2-3 months) Infection with toxogenic strains of C. difficile Old age > 64 years Underlying illness Immunosuppression & HIV Chemotherapy (immunosuppression & antibiotic-like activities) Tube feeds and GI surgery Exposure to gastric acid suppression meds??
Antimicrobials Predisposing to CDI
Testing modalities
Best Strategy for C. difficile Testing Testing should be performed only on diarrheal stool Testing asymptomatic patients is not indicated Testing for cure is not recommended
Multi-Step Approach Glutamate DeHydrogenase Toxin A & B EIA + - OR NAAT PCR -As a Stand Alone Test Treat for C-Diff NAAT PCR Surawicz CM, et al. American Journal of Gastroenterology. ACG Guidelines. 2013
Clinical classification Mild-moderate disease Diarrhoea with no other symptoms Management Metronidizole 500mg tds 10 days Intolerant Vancomycin 125mg qid Severe disease Albumin <30 PLUS WCC > 30 or Abdominal tenderness Management Vancomycin 125mg qid 10days
Severe and complicated CDI Hypotension +/- vasopressors WCC > 30 or <2 Lactate >2.2 ICU admission End organ failure (eg renal/ventilation) Mental status Ileus abdominal distension
Severe Complicated CDI Medical Management 1. I/V Flagyl 500mg iv 8hrly 2. Oral Vancomycin 500mg 6hrly 3. Vancomycin 500mg in 500ml normal saline by retention enema 6hrly Surawicz CM, et al. American Journal of Gastroenterology. ACG Guidelines. 2013
Complicated CDI Surgical Mx Patient Selection 1. Hypotension + vasopressor 2. Sepsis and Organ dysfunction 3. Mental Status changes 4. WCC 50 000 cells/microliter 5. Lactate 5mmol/l 6. Failure to improve after 5 days of medical therapy Surawicz CM, et al. American Journal of Gastroenterology. ACG Guidelines. 2013
Recurrence of CDI first Metronidazole 500mg tds 10days Alternate Vancomycin 125mg qid 10 days second Vancomycin 125mg qid 10/7 125mg bd 7/7 125mg daily 7/7 125mg eod 7/7 125mg every 3 rd 7/7
3rd Recurrence Fecal Microbiota Transplant Safe High Acceptance rate: 97% of treated patient would have a repeat therapy 53% would choose FMT as initial therapy Effective: 91% primary cure rate 98% secondary cure rate
FMT Screen for transmissible viral and bacterial infections Administration: Upper GI tract via NasoDuodenal or Gastroscopy Lower GI tract via Rectal enema or Colonoscopy All equally efficacious Re-Establised Colonization Resistance
Hypervirulent strain More resistant to fluoroquinolones Produces extra toxin called binary toxin BI/NAP1/027, toxinotype III More virulent
Prevention Contact Precautions for duration of diarrhea Hand hygiene (HH) in compliance with CDC/WHO Cleaning and disinfection of equipment and environment Laboratory-based alert system for immediate notification of positive test results Educate HCP, housekeeping, admin staff, patients, families, visitors, about CDI
Prevention Extend contact precautions beyond duration of diarrhea (48 hours) Presumptive isolation for symptomatic patients Implement soap and water for hand hygiene before exiting room of a patient with CDI Implement universal glove use on units with high CDI rates Use sodium hypochlorite (bleach) - containing agents for environmental cleaning Implement an antimicrobial stewardship program
Environment Risk
Alternative Therapies Probiotics - lactobacilus and S boulardii Fidaxomicin IVIG Rifampin/rifaximin Tigecycline
Take home messages Testing should be performed only on diarrheal stool Testing asymptomatic patients is not indicated Testing for cure is not recommended NAAT superior to EIA or alternative is multi-step Clinical classify disease severity Early surgical intervention Recurrences risk and treatment!!fmt Prevention contact with pts, environment (Gloves)