Clostridium difficile Infection Overview.pptx

This presentation provides a comprehensive overview of *Clostridium difficile* infection (CDI). It covers the causative organism, pathophysiology, clinical manifestations, and both pharmacological and non-pharmacological management strategies. The content is based on standard references, including *Pharmacotherapy: A Pathophysiologic Approach* by Joseph T. DiPiro et al., along with relevant peer-reviewed articles and clinical guidelines. Designed for healthcare students and professionals, this presentation aims to enhance understanding of CDI and its evidence-based therapeutic approaches.

1. C. DIFFICLE PRESENTED BY: DURGA PRASANNA KUMAR 23352D1008

2. DFINITION: A gram +ve spore forming cocci bacteria which causes diarrhoea and serious inflammation of the intestine. Other names include clostridium difficile, clostridioides difficile etc . Known cause for the infectious diarrhoea in Hospitalised patients, it is also associated with use of broad spectrum antimicrobial agents like: Clindamycin, ampicillin, cephalosporin, flouroquinolones at higher rates. Low incident rate of CDI (clostridioides difficile) with the use of aminoglycosides, erythromycin, Trimethoprim-sulfamethoxazole, vancomycin, mebomidazole . 2

3. Elderly, Cancer patients, Surgical patients, Patients taking antibiotics Patients with Nasogatric tube, Patients who often take Laxatives, Risk of CDI increases with use of PPI’s for about 65%. 3 Risk groups

4. pathogenesis

5. 5 Clostridium difficile Is a spore forming anaerobic bacillus and causes Toxin mediated disease. Antibiotics  Disrupts the colonic flora  colonization by the c. difficile bacteria. c. Difficile produces 2 types of toxins , A Toxin, B Toxin  released to mediate the diarrhea and colitis This toxin production Is essential for disease manifestation. Toxin A: Major pathological factor, Characterized as an enterotoxin Causes intestinal Fluid secretions Mucosal injury Inflammation through actin disaggregation Intracellular calcium release Damage to the neurons.

6. 6 Presentation title 20XX Toxin B Non enterotoxin cytotoxin  depolymerization of filamentous actin. Causes more potent damage to the human colonic mucosa than toxin A Initially raised with white and yellowish plaques surrounding mucosa inflamed with progression of disease  pseudomembranous plaque becomes enlarged  scattered over the colorectal mucosa.

7. symptoms 7 Presentation title 20XX Based on onset of diarrhea during or after use of antimicrobial agents, Associated symptoms Abdominal pain Fever Polymorphonuclear leukocytosis Spectrum of disease ranges from mild diarrhoea  Life threatening toxic megacolon

8. Symptoms colitis Malaise Abdominal pain Nausea Anorexia Watery diarrhea Low grade fever Leukocytosis CDI suspected in Recent hospitalized patients. 8 Presentation title 20XX

9. 9 Presentation title 20XX Diagnosis Detection of toxin A and Toxin B Stool culture for C. Difficile Endoscopy

10. Standard Treatment 10 Presentation title 20XX Discontinuation of offending agents Fluid and electrolyte therapy Some may require antibiotics like; METRONIDAZOLE VANCOMYCIN FIDAXOMICIN

11. 11 Presentation title 20XX Metronidazole 250mg x 4 times a day or 500mg 3 times a day PO it is a choice of drug for mild to moderate diarrhoea. In patients with severe diarrhoea with intolerance or contraindication to metronidazole and inadequate response to metronidazole, oral vancomycin or fidaxomicin is recommended. Vancomycin 125mg x 4 times a day PO Fidaxomicin 200mg x 2 times a day PO It is macrocyclic oral antibiotic Minimal bioavailability Bacteriostatic against C. difficile It also inhibits spore production

12. 12 Presentation title 20XX Recurrence of the disease may occur due to incomplete eradication of the spore forms in the body. Risk factors for recurrent CDI History of recurrence Emergency hospital admission Recent (4-12 weeks) Hospitalization Increasing age Use of additional anti microbial agents Inadequate protective immune responses to C. difficile toxins Treatment of recurrent CDI Prolonged tapered pulse dosing oral vancomycin Alternate regimens Vancomycin + rifampin Vancomycin followed by rifaximin

13. 13 Presentation title 20XX Concern with these regimens include drug interactions and development of resistance, especially if rifampin or rifaximin used as monotherapy. OTHER MODALITIES Fecal Transplantation IVIG Individuals with more IgG antitoxins are susceptible to more severe disease and frequent relapses. In patients with multiple relapses due to impaired antigenic response to toxins , IVIG 400mg/kg Fecal transplantation uses a small amount fresh feces from a healthy donor , suspended inn saline, filtered and administered through nasogastric tube or retention enema.

14. 14 Presentation title 20XX Vaccines SANOFI PASTEUR Toxoid vaccine of c. difficile Received a fast-track status through FDA and is in phase II testing. It is to be taken note that the drugs like Diphenoxylate which inhibit peristalsis or any other antimotility drugs, which cause to slow the fecal transit time which thought to result in extended toxin associated damage.

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17. 17 Presentation title 20XX Probiotics Saccharomyces boulardii Lactobacilli species Involve in augmenting the resistance to colonization of C. Difficile and to prevent recurrent CDI. Newer agents that are in clinical trails Ramoplanin (a new lipoglycodepsipeptide) Rifamycins (including Rifampin, Rifaximin, Rifalazil) Monoclonal antibodies to C. difficile toxins A and B CB-315 ( a lipopeptide) Tolevamer ( a large anionic polymer that binds to c. difficile toxins A and B) which is inferior to metronidazole and vancomycin in the treatment of First episode of CDI.

18. Additional Information 18 Presentation title 20XX METRONIDAZOLE : causes Hypersensitivity highly water soluble Causes metallic taste, it can be masked by using sugar candies. Metallic taste induces vomiting, this induced vomiting is treated by 5-HT3 antagonists. VANCOMYCIN FIDAXOMICIN LOPERAMIDE: Used to reduces fluid loss CHOLESTYRAMINE: Ion exchange resin and it is effective in binding both toxin A and toxin b, slowing bowel motility .

19. 19 Presentation title 20XX Therapeutics recommendations Cholestyramine + vancomycin Vancomycin I the last resort in the patients who are immune compromised IV immunoglobulin therapy is given in non responsive cases IV INJ BEZLOTOXUMAB- a monoclonal antibody act against C. difficile Toxin A and Toxin B and approved for the treatment of recurrent C. Difficile infections. PREBIOTICS, PROBIOTICS, ANTIOXIDANTS Saccharomyces, lactobacilli FMT: Fecal Microbiota Transplantation Also known as stool transplantation It is roughly 85-90% effective in those antibiotics have not worked. It involves infusion of the microbiota acquired from the feces of a healthy donor to reverse the bacterial imbalance responsible for the recurring nature of infection

20. 20 Presentation title 20XX This procedure replenishes normal colonic microbiota that are wiped out by antibiotics and reestablishes resistance to clostridium colonization. Approved FMT live (REBYOTA) NOV 2022 Taken orally In an Unconscious condition, FMT is done by Colectomy. KMnO4 + H2SO4- Fumigation Oxidation agents – oxidizes the microorganism. 70% ethyl alcohol (or) IPA should be used as Hand sanitizer Floor cleaner – sodium hypochlorite

21. References 21 Presentation title 20XX Pharmacotherapy a pathophysiologic approach by Joseph T Dipiro

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