Gastrointestinal Infections 2023 PDF

Gastrointestinal infections Dhara Surati, PharmD, BCPS Clinical Associate Professor University of Houston-College of Pharmacy PHAR 5337 – ID 1 module [email protected] 10-25-2023 Objectives: • Recognize the types and common pathogens associated with gastrointestinal infections • Choose an app...

Gastrointestinal infections Dhara Surati, PharmD, BCPS Clinical Associate Professor University of Houston-College of Pharmacy PHAR 5337 – ID 1 module [email protected] 10-25-2023 Objectives: • Recognize the types and common pathogens associated with gastrointestinal infections • Choose an appropriate general plan for the management of gastrointestinal infections • Recognize the main factors in the pathogenesis of Clostridium difficile infection (CDI) • Select clinical presentation, diagnostic tests, and therapeutic goals associated with CDI • Select appropriate measure(s) to minimize/prevent transmission • Formulate a therapeutic regimen based on clinical presentation of a patient with CDI • Choose an efficacy and safety monitoring plan for patients with CDI Format: • Slide deck • Interactive/active learning component Main references • Textbook: Roecker A, Bates B. Chapter 131: Gastrointestinal Infections and Enterotoxigenic Poisonings. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 11e New York, NY: McGraw-Hill; • Textbook: Roecker AM, Bates BN. Chater 136:Gastrointestinal Infections and Enterotoxigenic Poisonings. In: DiPiro JT, Yee GC, Michael Posey LL, Haines ST, Nolin TD, Ellingrod VL. eds. DiPiro: Pharmacotherapy A Pathophysiologic Approach, 12e. McGraw Hill; 2021. • Guidelines: Johnson S, et al. CID. 2021 (focused updates) – www.idsociety.org (Practice guidelines) • Guidelines: McDonald LC, et al. CID. 2018;66(7):e1-e48. (2017 guidelines) – www.idsociety.org GI infections Infectious diarrhea Viruses Bacteria Protozoans Two types of infectious diarrhea Types: Common pathogens Watery or enterotoxigenic Viruses; enterotoxigenic E. coli Bloody or dysenteric Campylobacter species; Salmonella species, Shigella species Infectious diarrhea • Food poisoning: Staphylococcus; Salmonella; Shigella; and Clostridium species; should Listeria be added? • Traveler’s diarrhea: Enterotoxigenic E. coli, Shigella spp., Campylobacter jejuni; Salmonella; viruses • Clostridioides (Clostridium) difficile infection (CDI) General key points – management of infectious diarrhea Fluid and electrolyte replacement ------------------------------------------------------- Antibiotic therapy recommended if • • • • Loperamide • Symptomatic relief • Avoid in watery and dysentery diarrhea diphenoxylate/atropine Severe diarrhea Moderate-to-severe traveler’s diarrhea Febrile dysenteric diarrhea Bacterial diarrhea General points about antibiotic therapy • Selection of an antibiotic based on a pathogen(s) – Some options: • • • • • Ciprofloxacin Levofloxacin Azithromycin Rifaximin Ceftriaxone • Duration – Varies Clostridioides (Clostridium) difficile Infection (CDI) Impact of CDI C. difficile is responsible for Antibiotic-associated diarrhea Antibiotic-associated colitis Pseudo-membraneous colitis Complications of CDI • Recurrence(s) of CDI • Toxic megacolon • Perforations of the Colon • Colectomy • Sepsis/Septic shock • Death http://www.cdc.gov/HAI/organisms/cdiff/Cdiff_faqs_HCP.html#a2 What factors play a role? Patient (Host factors) C. difficile Toxigenic C. difficile: toxins A/B present Medication use /Breakdown in infection control http://www.cdc.gov/HAI/organisms/cdiff/Cdiff_faqs_HCP.html#a2 Rupnik M, et al. Nature Reviews. 2009. Vol. 7. 526-36. C. difficile colonization vs. CDI Toxigenic C. difficile; IgG response Toxigenic C. difficile; no IgG response → symptomatic CDI Colonization • Positive for C. difficile and/or its toxins • NO clinical symptoms • More common Infection • Positive for C. difficile and/or its toxins • Clinical symptoms How does C. diff spread? Bobulsky et al. CID. 2008;46:447–50 Which of the following is the most likely risk factor for Clostridium difficile infection? a. Use of Pepcid® AC 1 week ago b. Use of Levaquin® 1 week ago c. Properly managed type 2 diabetes d. Proper hand hygiene Overview of assessment – CDI Symptoms/signs Physical assessment • Diarrhea Vitals (smelly) • Abdominal pain • Abdominal • Nausea tenderness • Vomiting • Loss of appetite Laboratory findings Microbiology Other diagnostics • Elevated SCr Stool test • Electrolyte imbalance • Elevated WBC • Decreased albumin Other diagnostics: Colonoscopy 20 CDI diagnostics tools Stool culture • Most sensitive • False positive (as it could also have non-toxigenic) • Labor intensive and long turn-around time • Toxigenic culture is considered gold standard Toxin Testing for C. difficile • Tissue culture cytotoxicity assay: • Technical expertise • Long turn-around time • Less sensitive than PCR or toxigenic culture Toxin Testing for C. difficile • Enzyme immunoassay (EIA) • Toxin A • Toxin B • Toxin A and B • Low sensitivity CDI diagnostics tools Molecular tests • Real-time PCR • Highly sensitive and specific • Two step approach: Antigen • Glutamate dehydrogenase detection (GDH) → toxin detection, PCR, for C. difficile or toxigenic culture Therapeutic goals • To alleviate signs and symptoms • To minimize complications of CDI • To prevent spread of CDI Management of CDI • Supportive care – Fluid and electrolyte replacement therapy, if needed • Infection control • Therapeutic agents Infection Control: How to prevent C. difficile spread? For good hand hygiene after seeing patients with CDI, which of the following should you do? A. Remove gloves and go see your next patient B. Exit the room with gloves on and trash it in the biohazard waste at the nurses’ station; wash hands with water C. Remove gloves and wash hands with soap and water Mainstay treatment options for CDI (based on 2021 guidelines) Options Initial treatment response Recurrence risk Evidence supporting efficacy Cost Fidaxomicin Route: Highest Lowest FDA approved; Multiple RCTs (compared to vancomycin) $$$$ Vancomycin Route: Highest Intermediate FDA approved; Multiple RCTs $ - $$ Metronidazole Route: Intermediate Intermediate Multiple RCTs $ Efficacy and safety monitoring Efficacy • Monitor signs/symptoms, lab values • Not recommended: _____________________ Safety: • Metronidazole: • Oral vancomycin: • Fidaxomicin: Monoclonal antibody for secondary prevention • Bezlotoxumab – Adjunct therapy – To reduce risk of recurrence of CDI – Not addressed in the 2017 guidelines – Addressed in the 2021 guidelines Caution: In patients with congestive heart failure (CHF) FDA warning – “in patients with congestive heart failure (CHF), bezlotoxumab should be reserved for use when the benefit outweigh the risk” Factors to consider for appropriate treatment (based on 2017/2021 guidelines) Factors to consider: Details: CDI Episode # Initial First recurrence Second or subsequent recurrent CDI severity Non-severe Severe Fulminant Severity determination: (based on 2017 / 2021 guidelines) • Non-severe CDI: – Leukocytosis with a WBC ≤ 15, 000 cells/ml, AND – SCr < 1.5 mg/dL • Severe – Leukocytosis with a WBC ≥ 15, 000 cells/ml, OR – SCr > 1.5 mg/dL • Fulminant – Hypotension or shock, ileus, megacolon Guideline navigation – Table 1 • Guidelines: Johnson S, et al. CID. 2021 (focused updates) – www.idsociety.org (Practice guidelines) Guideline Navigation – Table 1 • Read/highlight • Pair-Share: Share with your classmate what points did you find essential in this table? • We will discuss the key points together Case vignette • PP is a 68-year-old female diagnosed with first episode of CDI. Vitals: BP 118/78; HR 64; RR 16; Temp 39.1 degrees Celsius. BMP (fasting labs): Sodium 138 mEq/L; Potassium 2.9 mEq/L; Chloride 107 mEq/L; Bicarbonate 22 mEq/L; SrCr 1.2 mg/dL (baseline 1 mg/dL); BUN 24 mg/dL; and glucose 120 mg/dL. CBC: Hgb 13.1 g/dL; Hct 44%; WBC 19,000 cells/ µL; and platelets 170 X 103. • According to the 2017 (2021) IDSA/SHEA Clostridium difficile infection (CDI) guidelines, which of the following PP’s parameters accurately determines PP’s severity of CDI? Example of vancomycin PO tapered/pulsed regimen • • • • 125 mg every 6 hours for 10-14 days, 125 mg every 12 hours for 7 days, 125 mg once daily for 7 days, 125 mg every 2 or 3 days for 2-8 weeks Gastrointestinal infections Dhara Surati, PharmD, BCPS Clinical Associate Professor University of Houston-College of Pharmacy PHAR 5337 – ID 1 module [email protected] 10-25-2023