Tedra D. D Gray, Gray BSN BSN, MS, MS ACNPACNP-BC Sinai Health Systems Internal Medicine Department Division of Gastroenterology
Diarrhea Evaluation & Management Diarrheal disease represents 1 of 5 leading causes of death worldwide Bacterial enteropathogens lead to an estimated 46,000 hospitalizations and 1500 deaths in the United States www.uptodate.com 4/2011
Diarrhea Evaluation& Management Diarrhea is defined by the World Health Organization as having three or more loose or liquid stools per day, or as having more stools than is normal for that person. www.who.int/topics/diarrhoea
Categories of Diarrhea Secretory - increase in the active secretion, or there is an inhibition of absorption. There is little to no structural damage. Osmotic - too much water is drawn into the bowels. Exudative - presence of blood and pus in the stool. Motility - related - hypermotility Inflammatory - occurs when there is damage to the mucosal lining or brush border, which leads to a passive loss of protein-rich fluids, and a decreased ability to absorb these lost fluids. www.en.wikipedia.org
Duration of Symptoms Acute less than 14 days Persistent more than 14 days Chronic more than 30 days www.uptodate.com 4/2011
Culprits of Acute Diarrhea Viral Bacterial Protozoa Norovirus Salmonella Giardia Rotavirus E. Coli Cryptosporidium Adenovirus Astrovirus Campylobacter C. Diff Entamoeba Cyclospora
Bacterial Culprits & Symptoms Enteropathogen Clostridium difficile Shigella Nontyphoid Salmonella t Clinical & Epidemiologic Features Diarrhea, often with fever and dysenteric characteristics and dfever Severe Diarrhea, often with fever or dysenteric characteristics, high risk person to person spread Acute watery diarrhea, often with fever occasionally with dysenteric characteristics; foodborne transmission Diagnostic Evaluation Stool test for C. difficile toxin (enzyme immunoassay for toxins A & B Stool Culture Stool Culture NEJM 2009;361:1560-1569
Bacterial Culprits & Symptoms Enteropathogen Clinical & Epidemiologic Features Diagnostic Evaluation Campylobacter Jejuni Acute watery diarrhea, often with fever or dysenteric symptoms; foodborne transmission & international travel Stool Culture C.perfringes Watery diarrhea without Stool cultures or in fever or vomiting infected foods Staphylococcus aureus Vomiting lasting,12 hr Food cultured for staphylococcus or enzyme immunoassay Yersinia Enterocolitica Acute watery diarrhea, may cause fever and dysentery Organism identified in selective gram negative media such as MacConkey agar NEJM 2009;361:1560-1569
Types Escherichia coli Type Enteropathogenic Ecoli E.coli Clinical Features Most important cause of Traveler s diarrhea. Important cause of pediatric diarrhea in the developing world. Enteroinvasive i E.coli Common cause of acute shigella like pediatric diarrheas in Brazil and eastern Europe Enterotoxigenic E.coli Classic type causes hospital nursery outbreaks and pediatric diarrhea worldwide. d NEJM 2009;361:1560-1569
Types Escherichia hi coli Types Enteroaggregative E.coli Clinical Features Most important cause of diarrhea in children. 2 nd most common cause of Travelers diarrhea. Cause of AIDS associated diarrhea. Shiga toxin producing E. coli Important cause of watery diarrhea progressing to bloody diarrhea in 1 5 days. Hemolytic uremic syndrome follows colitis in children and elderly. Diffusely adherent E.coli Cause of diarrhea in children older than 1 yr in developed countries and travelers diarrhea NEJM 2009;361:1560-1569
Diarrhea Evaluation& Management When do you order diagnostic work up for diarrhea? Severe diarrhea (>6 stools per day) Diarrhea > 1 week Presence of Fever Presence of Dysentery Presence of Outbreak NEJM 2009;361:1560-1569
Case Presentation ti # 1 52 yr old Hispanic female with PMHx of DM type II (on Metformin) & HL presents with 3 day history of moderate volume bloody diarrhea, ABD pain but no fever. Diarrhea between 6 8 per day. ABD pain intermittent diffuse that cramps in nature. Pt. recently returned from Mexico 5 days ago. She denies sick contacts, antibiotic use or recent hospitalization. Pt. has NKDA or prior colonoscopy.
Case Presentation ti # 1 V/S: T 99.8, HR 110, RR 24, B/P 120/58 PE: A & O X 3. Dehydrated, Resp: CTA, CV: RRR, GI: soft, non distended, mod diffuse ABD tenderness but no masses guarding or rebound. CBC: WBC 17k, Hg 14.8, Hct 44.2, Plts 179 CMP: Na 131, K 4.8, Bun 43, Creat. 2.7, Glucose 210, Lactate 2.7,LFTs WNL
Case Presentation ti # 1 What diagnostic test do you order? Stool cultures, WBC, O&P, C.diff Do you start any empiric treatment? Yes No If it is already started to you continue it? Yes No
Case Presentation ti # 1 What causative organisms do you need to specifically test for in her differential diagnosis? Specifically E.coli O157:H7 E.coli O157:H7; only 10 to 100 organisms required for infection Transmission via food borne, person to person, animal contact www.uptodate.com 4/2012
Enterohemorrhagic E. coli (EHEC) What major complication requires your vigilance il during her care? Hemolytic Uremic Syndrome HUS complicates 6-9% of EHEC infections with mortality of 1-2% (3 5 % if HD needed) Rx supportive care; may need HD during acute phase www.uptodate.com 4/2012
Enterohemorrhagic E. Coli (EHEC) SHIGA TOXIN CIRCULAT ES BOUND TO PMNs AND TARGETS ENDO CELLS VASCULAR DAMAGE & PRO- THROMBIC STATE OCCURS UP- REGULATE D of TNFa, (IL)-1b HEMOLYTIC UREMIC SYNDROME www.uptodate.com 4/2012
SHIGA TOXIN- Producing E. Coli Why is this a consideration? Fluoroquinolones & Bactrim may precipitate the induction of Shiga toxin producing E.coli which in turn increases the risk of HUS. Human studies pending; data from mouse model Azithromycin inhibits the Shiga toxin induced inflammatory response and prevented death. Rifaximin does not appears to increase production. NEJM 2009;361:1560-1569
Antimicrobial Therapy in Bacterial Diarrhea Diarrheal Disease Organism Treatment Shiga toxin producing E.coli O157:H7 Nontyphoid Salmonellosis NONE Levofloxacin 500 mg daily X7-10 D OR Azithromycin 500 mg daily X 7 d immuno-compromised Pt give for 14 D. Enteric, fever including typhoid fever Levofloxacin 500mg daily X7 d OR Azithromycin 500 mg daily X 7 d NEJM 2009;361:1560-1569
Antimicrobial Therapy in Bacterial Diarrhea Diarrheal Disease Organism Treatment Cholera (de to Vibrio cholerae 01) Enterotoxigenic E.coli diarrhea, enteroaggregative Ecolidiarrhea E.coli or Travelers diarrhea Campylobacter jejuni Doxycycline 300 mg X1 OR Tetracycline 500 mg 4X/d X3 d OR E- mycin 250 mg 3X/D or Azithromycin 500 mg daily X3 d Cipro 750 mg daily X3 d OR Azithromycin 1GM X1 OR Rifaximin 200 mg 3X/d X3 d Azithromycin 500 mg daily X 3 d OR Erythromycin y 500mg 4X/dX 3 d NEJM 2009;361:1560-1569
Antimicrobial Therapy in Bacterial Diarrhea Diarrheal Disease Organism Treatment Shigellosis Aeromonas species diarrhea Plesiomonas shigelloides diarrhea Diarrhea due to noncholeraic vibrios Enteroinvasive Ecoliinfection E.coli infection Ciprofloxacin 750 mg daily X3 d OR Azithromycin 500mg daily X 3 days Treat as Shigellosis Treat as Shigellosis Treat as Shigellosis Treat as Shigellosis NEJM 2009;361:1560-1569
Case Presentation ti # 1 Stool tests positive for E. Coli - O157:H7 strain, many WBC, FOBT positive Treatment What progressive symptoms should you look for in your follow up assessment?
Mgmt. & Follow Up MENTAL STATUS THROMBO- CYTOPENIA ACUTE RENAL FAILURE HEMO- LYTIC ANEMIA
Diarrhea Evaluation& Management Do you need to take prophylaxis antibiotics when traveling? Rifaximin 200 mg PO daily or BID with meals Bismuth Subsalicylate 525 mg (or 2 tabs) with each meal and q HS NEJM 2009;361:1560-1569
Case Presentation ti #2 An otherwise healthy 28 yr old man presents to your office for persistent diarrhea. He was seen in PCP office 3 weeks ago when s/s began. Pt denies sick contacts, recent antibiotic use or hospitalizations. Pt recently returned from a 1 week hiking trip in Canada. PCP empirically started Azithromycin for Traveler s diarrhea.
Case Presentation ti #2 H & P Findings acute onset of 6 8 episodes/d of foul smelling; non bloody watery diarrhea, abdominal pain, N/V and low grade fever. Pt compliant with meds S/S of diarrhea the same but he has lost 8 pounds since going to PCP
Case Presentation ti #2 Do you need to send stool cultures? PCP visit no need. Yes, due to duration of s/s, frequency of stools and of presence abdominal pain and fever. What further inquiries would you make as the specialist? Would you send anything else? Yes. O & P & C. diff
Case Presentation ti #2 Stool Cultures & C. diff Negative Stool WBC Positive O & P Positive for Giardia
Case Presentation ti #2 Start Tinidazole 2 gm as a single dose Actually FDA approved (Flagyl is not) Efficacy > 90% S/E Metallic taste, N/V and disulfiram like S/S www.uptodate.com 4/2012
Case Presentation ti #2 Instruct to avoid lactose containing food for at least 1 month after Rx Lactose Intolerance occurs in 20-40% and may last a few months www.uptodate.com 4/2012
Case Presentation ti #2 F/U visit Documented weight gain & resolution of S/S No improvement repeat O&P and check EGD with duodenal biopsy Prevention
Case Presentation ti # 3 47yr old male with HIV/AIDS presents to ER with small volume, watery stools 5-6/day, abdominal pain, night sweats and fever for 2 weeks. He has noticed weight loss but unsure of quantity. He was on therapy for 8 months taking Combivir 1 tab BID and Nelfinavir 1gm TID and Bactrim for PCP (pneumocyctitis carinii pneumonia) prophylaxis but quit 3 months ago. His last CD4 count was 84 cells/mm 3 which is improved from 12 cells/mm 3 1yr ago. He was arrested 3wks ago for attempting to smuggle drugs in from Mexico.
Case Presentation ti # 3 V/S: Temp 102.0, HR 110, RR 24, B/P 118/64 (orthostatic) CBC: WBC 4.0 K, Hbg 10.4 gms, Plts 200K CMP: NA 133 Meq/L, K 3.3 Meq/L, BUN 48 mg/dl, Creat11 1.1mg/dl
Case Presentation ti # 3 What are some elements of the differential diagnosis? Opportunistic infections are of concern due to CD4 count <180 cell/mm Organisms that cause Travelers Diarrhea (E.coli, Vibrio parahaemolyticus, Yersinia, Rotavirus and Norwalk virus) Query length of time on HAART therapy. www.uptodate.com 12/2010
Case Presentation ti # 3 In addition to cultures, WBC, O& P and C. diff, What test do you order? Send stools for MAC (Mycobacterium avium complex), CMV (Cytomegalovirus), AFB to look for Cryptosporidium parvum, Isospora, Microsporidium and Cyclospora Due to travel history also send stools for Entamoeba and Giardia www.uptodate.com 12/2010
Case Presentation ti # 3 When is an endoscopic work up needed and what would it provide? Endoscopy w/u for persistent diarrhea or diarrhea with fever. EGD with SB biopsies to look for MAC, lymphoma or microsporidiosis Colonoscopy with biopsy to look for CMV and Kaposi s sarcoma www.uptodate.com 12/2010
Case Presentation ti # 3 Stool studies,blood culture and CMV IgM are positive for CMV Colonoscopy showed visualization of ulcers and deep erosions. Pathology showing tissue destruction and viral inclusion bodies Treatment of choice would be Gancyclovir for 3 6 weeks, restart HAART and ID follow up www.uptodate.com 6/2009
Diarrhea Evaluation & Management