6. Medicine II_Acute Diarrhea_2014A

ACUTE Dr. Solante DIARRHEA I.

II. III. IV.

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OUTLINE Diarrhea: Definition a. Pathophysiology of Infectious Diarrhea b. High-risk Groups c. Three types of Enteric Infection d. Clinical Features of Infectious Agents e. Other causes of Acute Diarrhea Approach to a patient with diarrhea a. Assessment b. Stool Laboratory Examination Diagnostic Tests Preventive Measures a. Food and Beverage selection b. Non-antimicrobial drugs for Prophylaxis c. Prophylactic antibiotics d. Vaccines Treatment a. Antibiotics b. Anti-motility agents c. Oral rehydration therapy Appendix: TABLE: Types if Diarrheal Infection

DIARRHEA: Definition  Definition: Passage of abnormally liquid or unformed stools, with increased frequency (if you are going to quantify the frequency it should be more than once)  Stool weight > 200 g/day  Acute < 2 weeks (vs. Chronic >4 weeks)  A commonality in patients with infectious diarrhea is that it is usually a result of the imbalance between the host and the microorganism. The microorganism has the capacity to overwhelm both of the host’s mucosal and non-mucosal defenses.  The most important aspect that dictates the severity of the clinical manifestations is the volume of the inoculum of the microorganism in the water or food. (The larger the volume, the more severe the manifestations.) The immune defenses and the virulence of the microorganism have a smaller role in dictating the severity of the manifestations. Acute Diarrhea: Infectious Diarrhea  More than 90% of acute diarrhea are caused by infectious agents; often accompanied by vomiting, fever and abdominal pain. The remaining 10% or so are

2.

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High-risk Groups  Travelers o As a traveler sometimes you do not know the source of water and the hygienic nature of the food you are eating. o

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Traveler’s diarrhea - most commonly due to E. coli, and also Campylobacter, Shigella, Aeromonas, Coronavirus, Salmonella

 Consumers of certain foods o o o o o o

These are the individuals who love to eat outside, like students. [Harrison’s] Vibrio species, Salmonella, or acute Hepatitis A from seafood, especially if raw Fried rice - Bacillus cereus Eggs - Salmonella Undercooked hamburger – Enterohemorrhagic E.coli (0157:H7) Mayonnaise, Creams – S. aureus, Salmonella

 Immunodeficient persons o

or

immunocompromised

[Harrison’s] Persons with primary immunodeficiency – IgA immunodeficiency, common variable hypogammaglobulinemia, chronic granulomatous disease

 Daycare attendees and family members o

Shigella, Giardia, Cryptosporidium, and rotavirus are very common.

 Institutionalized persons o

caused by medications, toxic ingestion, ischemia, and other conditions [Harrison’s]

 Infection occurs when the ingested agent overwhelms the host’s mucosal immune and non- immune defenses such as: o Gastric acid o Digestive enzymes o Mucus secretion o Peristalsis o Suppressive resident flora  The different pathophysiologic alterations in patients with diarrhea: 1. Altered normal intestinal physiology o Shift in the delicate balance (imbalance) of the bidirectional water and electrolyte fluxes in the upper small bowel by intraluminal toxins or minimally invasive organisms. o Exemplified by Giardia lamblia,

Cryptosporidium which are protozoans Inflammation at the site of infection or cytotoxic destruction of the ileal or colonic mucosa o The cells within the mucosa will be destroyed because of the inflammatory reaction caused by the microorganism o Destruction may be due to toxins, or the organism itself Direct penetration of the microorganism through an intact mucosa to the reticuloendothelial system

o

Infectious diarrhea one of the most frequent nosocomial infections in many hospitals and long-term care facilities Most commonly caused by Clostridium difficile

Three types of enteric infection (See APPENDIX for the table)

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TYPE 1: Non-inflammatory type Brought about by the toxins produced by the microorganisms like Vibrio cholera, E.coli, C. perfringens, Bacillus aureus, Staphylococcus aureus Giardia lamblia, Rotavirus, Norwalk-like virus do not produce enterotoxins but they adhere to the tissue and cause superficial invasion. Most of these patients present with watery diarrhea When you do stool examination, there is absence of leukocytes Patients in this group are prone to dehydration because the diarrhea here involves the proximal

ACUTE Dr. Solante DIARRHEA small bowel which is responsible for water absorption TYPE 2: Inflammatory type  The common pathology is direct invasion and the production of cytotoxins.  Most of these microorganisms are lodged in the colon that is why the stool exam of most patients with this type of diarrhea present with abundant leukocytes  Examples:  Shigella  E. coli (Enteroinvasive, Enterohemorrhagic)  Vibrio parahemolyticus (causes bloody diarrhea)  Salmonella entiritidis (not all Salmonella are inflammatory)  Clostridium difficile  Campylobacter jejuni  E. histolytica (endemic in the Philippines; does not produce enterotoxins but alters the mucosa which allows invasion of the intestinal mucosa)  Characteristics of stool exam: presence of both red blood cells and white blood cells compared to the non-inflammatory TYPE 3: Penetrating type  Not very common but is very virulent  Salmonella typhi, Yersinia enterocolitica, Campylobacter fetus  These are differential when the patient presents with enteric fever (fever, less of the diarrhea and more of the abdominal cramps, leukocytes in stool examination) Clinical Features of Infectious Agents [Harrison’s]  Ingestion of preformed bacterial toxins, enterotoxin producing bacteria, and enteroadherent pathogens o Profuse watery diarrhea secondary to small bowel hypersecretion o Diarrhea associated with marked vomiting and minimal or no fever may occur abruptly within a few hours after ingestion of preformed bacterial toxins and enterotoxin producing bacteria o Fever is higher in enteroadherent pathogens  Invasive bacteria and entamoeba histolytica often causes bloody diarrhea  Yersinia invades the terminal ileal and proximal colon mucosa and may cause especially severe abdominal pain with tenderness mimicking acute appendicitis  Infectious diarrhea may be associated with systemic manifestations: o Reiter’s syndrome (arthritis, urethritis, and conjuctivitis) may accompany or follow infections by Salmonella, Campylobacter, Shigella, and Yersinia o Yersiniosis may also lead to an autoimmune-type thyroiditis, pericarditis, and glomerulonephritis o Both enterohemorrhagic E.coli (0157:H7) and Shigella can lead to the hemolytic-uremic syndrome o The syndrome of postinfectious Inflammatory Bowel Syndrome has now been recognized as a complication of infectious diarrhea o Acute diarrhea can also be a major symptom of several Garabiles, Garcia J., Garcia F.

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systemic infections including viral hepatitis, listeriosis, legionellosis, and toxic shock syndrome

Other Causes of Acute Diarrhea  Medications o o

Side effect of medications is the most common noninfectious cause of acute diarrhea Antibiotics, cardiac antidysrhythmics, antihypertensives, NSAIDs, certain antidepressants, chemotherapeutic agents, bronchodilators, antacids, laxatives

 Occlusive or non-occlusive ischemic colitis o Typically in persons >50 years old or the elderly with thrombosis in the large intestine which can cause colitis or ischemic colitis o

Often presents as acute lower abdominal pain preceding watery, then bloody diarrhea

 Diverticulitis  Graft-versus-host disease (GVHD) or those who are immunocompromised because of mucosal barrier injury brought about by immunosuppressive drugs  Acute diarrhea, often associated with systemic compromise can follow ingestion of toxins including: o o

Ingestion of organophosphate insecticides, amanita, other mushrooms, arsenic Preformed environmental toxins in seafood such as ciguatera and scombroid

APPROACH TO A PATIENT WITH DIARRHEA

The most important aspect in the management of patients with diarrhea is to first delineate if it is infectious or non-infectious because each entity entails separate interventions. Example: in an infectious diarrhea you should give an antimicrobial. For a noninfectious etiology you just have to withdraw the cause like a medication, or you can improve the patient’s immune system. Assessment

ACUTE Dr. Solante DIARRHEA  Rehydration if indicated  Treatment of symptoms with bismuth subsalicylate or loperamide if diarrhea is not inflammatory or bloody  If it is non-inflammatory, meaning there is absence of WBC in the stool then you can give Loperamide. But if there are WBC then treat accordingly, with an antimicrobial or an anti protozoal because Loperamide is contraindicated in these patients. 2.   3.

 The table above is very important. We should emphasize the importance of stool examination in a patient with diarrhea.  First, you assess the presence of diarrhea. Most of the time when you have a patient with diarrhea, the most important management is to give symptomatic therapy. Usually it entails the use of oral rehydration therapy.  You also have to assess the duration of the diarrhea, severity if it includes signs of dehydration, fever, weight loss, and presence of blood in the stool. If these are present, you have to explore more on the history for you to be able to delineate the etiology.  Was there intake of seafood? Antimicrobials? Sexual experience (E. coli in anal sex)?  Do a stool examination: o WBC count: Absence may mean a noninflammatory type of diarrhea. Presence may mean an inflammatory type of diarrhea and is usually associated with continued systemic illness and for this your differentials are Shigella and Salmonella. o Wet mount: look for presence of microorganisms like Giardia and Cryptosporidium. AGAIN: 1. Provide initial assessment and treatment Garabiles, Garcia J., Garcia F.

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Manage subsequently according to clinical findings and epidemiology. Clinical findings: fever, severe and/or bloody diarrhea, abdominal pain Epidemiology: travel, food and water exposure, adventure travel, season Stool laboratory exams if diarrhea is severe, bloody, or persistent.

Indications for evaluation [Harrison’s]  Profuse diarrhea with dehydration  Grossly bloody stools  Fever >/= 38.5 C  Duration > 48 hours without improvement  Recent antibiotic use  New community outbreaks  Associated severe abdominal pain in patients >50 years old  Elderly (>/=70 years old)  Immunocompromised patients

Stool Laboratory Examination

For Traveler’s diarrhea you just have to identify the common etiology. For example, if diarrhea is less than

ACUTE Dr. Solante DIARRHEA 7 days then the possible etiologic agents are Salmonella, Shigella and Campylobacter. You then do stool culture to identify which of these 3 is the pathogen. Do Shiga toxin assay for E. coli 0157:H7 if there is bloody stool. If there is history of seafood intake then culture for Vibrio. For diarrhea after antimicrobial therapy (like beta lactams, ampicillin, amoxicillin, co-trimoxazole) the common etiologic agent is C. difficile. Do an assay using blood to identify the presence of the C.difficile toxins A and B. For persistent diarrhea, there is commonly the presence of ova and parasites. Do a wet mount for antigen detection. DIAGNOSTIC TESTS There are specific staining methods for you to identify specific microorganisms: PROCEDURE Microscopy of fresh unstained wet prep of stool

PURPOSE Detection of live actively motile protozoan trophozoites (E. histolytica, Giardia) and helminth larvae (Strongyloides), Helminth eggs and RBCs, WBCs also observed Many WBCs suggests bacterial infection

WBCs by microscopy, use of Methylene blue or presence of lactoferrin Microscopy of Detection of helminth concentrated sediment eggs and larvae, of preserved stool protozoan cysts Microscopy of Detection of protozoan trichrome-stained fecal cysts, trophozoites smear Microscopy w/ special Detection of stains (modified Cryptosporidium, Kinyoun/afb, trichrome microsporidia, Cyclospora blue, safranin) Fecal antigen detection Specific identification for by EIA or fluorescent Giardia, Cryptosporidium, antibody E. histolytica Bacterial culture of Detection of enteric stool pathogens The most common is microscopy of fresh unstained wet preparation of stool. It is very important in the identification of protozoan eggs or cysts.

PREVENTIVE MEASURES Food and Beverage selection o Eat only freshly cooked foods, served hot o Avoid beverages diluted in non-potable water Garabiles, Garcia J., Garcia F.

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o o o

o

 Reconstituted fruit juice  Ice  Milk Avoid food washed in non-potable water Avoid risky foods: raw, undercooked meat, seafood, unpeeled raw fruits and vegetables Drink safe beverages  Bottled, sealed, carbonated  Boiled or treated with iodine or chlorine Restaurant hygiene?

Non-antimicrobial drugs for prophylaxis  Bismuth subsalicylate (BSS) o Anti-diarrheal (non-bloody, non-mucosal, noninflammatory) o Reduces incidence of traveler’s diarrhea from 40% to 14% o Taken as either 2 oz. of liquid or 2 chewable tablets 4x/day o Adverse reactions: nausea, vomiting, blackening of tongue and stool, constipation, tinnitus o Contraindications: aspirin allergy, renal insufficiency, gout o Drug interactions: Probenecid, anticoagulants, antiplatelets, Methotrexate  Probiotics (Lactobacillus spp., Saccharomycesboulardii) o Inconclusive results as to its benefits o Purpose is to enhance the growth of good bacteria o Not highly recommended o Yogurt, Yakult, etc.  Bovine colostrum o Enhance the growth of colonizers (Lactobacillus) o Commercially available preparations not FDAapproved o No data from rigorous clinical trials that it is highly beneficial Prophylactic Antibiotics  NOT RECOMMENDED; Antibacterial prophylaxis is not recommended in infectious diseases  No protection against non-bacterial pathogens  We do not know if there are allergic or adverse reactions if these are given.  Use should be weighed against result of using prompt, early treatment  [Harrison’s] Antibiotic prophylaxis is indicated for certain patients traveling to high-risk countries in whom the likelihood or seriousness of acquired diarrhea would be especially high, including those with immunocompromise, inflammatory bowel disease, or gastric achlorhydria. Use of trimethoprim/sulfamethoxazole or ciprofloxacin may reduce bacterial diarrhea such travelers by 90%.

Vaccines  Cholera, Rotavirus, HAV  The best intervention Philippines)

(including

travel

to

the

ACUTE Dr. Solante DIARRHEA TREATMENT

Oral Rehydration Therapy  Mainstay, cheapest form  Fluid replacement alone may suffice for mild diarrhea: Beneficial in patients with non-inflammatory type of diarrhea who are prone to dehydration. The most common derangement in dehydrated patients is electrolyte imbalance (usually hyponatremia and hypokalemia).  Relatively unpalatable (salty)  Oral sugar-electrolyte solutions (sports drinks, designed formulations) should be instituted promptly with severe diarrhea to limit dehydration  Profoundly dehydrated patients require IV rehydration especially infants and the elderly

 Add 1 packet to appropriate volume of boiled or treated water

Antibiotics  Should be given as a treatment and not as prophylaxis. Given to inflammatory and penetrating types of diarrhea to decrease toxin production and tissue invasion. Non-inflammatory diarrhea is usually selflimiting and only rehydration is needed.  Fluoroquinolones: Treatment of moderately to severely ill patients with febrile dysentery without diagnostic evaluation e.g. Ciprofloxacin (500 mg bid for 3-5days)  Azithromycin  Rifaximin o Overall usefulness has to be determined  Metronidazole, Tinidazole, Nitazoxanide  Metronidazole – for suspected Entamoeba histolytica, giardiasis (250 mg qid for 7 days) Antimotility agents  Should be given together with antimicrobials  Symptomatic relief as it decreases peristalsis of small and large bowel. But this may not be enough as the transit time for excretion of the microorganism is also decreased, that is why you have to give antibiotics at the same time.  Adjuncts in moderately severe, nonfebrile, nonbloody diarrhea (Loperamide)  Synthetic opiates – Loperamide, Diphenoxylate o Reduce bowel movement frequency o Antisecretory properties (Loperamide)  Should be avoided with febrile dysentery, which may be exacerbated or prolonged

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ACUTE Dr. Solante DIARRHEA Composition Rehydration illness

Garabiles, Garcia J., Garcia F.

of Salts

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WHO Oral for Diarrheal

ACUTE Dr. Solante DIARRHEA Ingredient Sodium Chloride Potassium Chloride Glucose anhydrous Trisodium citrate, dehydrate Water

Amount 2.6 g/L 1.5 g/L 13.5 g/L 2.9 g/L (or 2.5 g/L) 1L

1. 5. A

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SAMPLE QUESTIONS  Which of the following organism produces diarrhea by producing toxins? a. Bacillus cereus b. Rotavirus c. Giardia d. Clostridium difficile Which of the following is an indicator for further work up in a patient with diarrhea? a. Duration >24 hours with improvement of symptoms b. Elderly >70 years old c. Patients with low grade fever d. Watery, mucoid stools Antibiotic prophylaxis is recommended for the following patients travelling to high risk countries a. Elderly b. Patients with mechanical heart valves c. Patients with gastric achlorhydria d. Patients with recent vascular graft Garabiles, Garcia J., Garcia F.

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55 year old male with diabetes was admitted because of respiratory tract infection. A few days after antibiotics were started, patient developed abdominal pain, with fever, vomiting and bloody diarrhea. Most probable cause of the patient’s bloody diarrhea is a. Salmonella typhi b. Shigella sp c. Clostridium difficile d. E. histolytica 6.

Diagnostic test that would confirm the diagnosis of the above patient would be a. Blood culture b. Stool exam c. C. difficile toxin assay d. Colonoscopy

7. a. b. c.

Treatment for the above patient would be Ciprofloxacin Ceftriaxone Amoxicillin

ACUTE Dr. Solante DIARRHEA d. 8.

9.

Metronidazole

A 35 year old missionary from Australia developed abdominal pain with 2-3 episodes of bloody diarrhea for 2 days after arrival to the Philippines. Patient has no signs of dehydration on examination. Most likely etiology of patient’s symptoms is a. Rotavirus b. Escherichia coli c. Entamoeba coli d. Helminthes Aside from hydration, management for the above patient would include a. Viral culture b. Antibiotics c. Admit patient for observation d. Urgent colonoscopy

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10. A 20 year old male patient developed diarrhea occurring >10x per day amounting to >1L/episode. Stools were characterized as rice-water appearance. Most likely etiology of diarrhea is a. Vibrio cholera b. Salmonella infection c. Entamoeba histolytica d. Bacillus cereus 11. A 30 year old businessman developed watery stools,