Acute Gastroenteritis

Transcription

1 Acute Gastroenteritis CME / ABIM MOC / ACCENT Supported by an independent educational grant from BioFire Diagnostics, LLC. Presented through a collaboration between The American Association for Clinical Chemistry (AACC) and Medscape Education. 1

2 This article is a CME / ABIM MOC / ACCENT certified activity. To earn credit for this activity visit: Target Audience This activity is intended for physicians who practice infectious disease, critical care, pediatrics, family medicine, internal medicine, gastroenterology, public health, and emergency medicine, as well as laboratory and point-of-care testing professionals. Goal The goal of this activity is to increase awareness of the benefits and limitations of new and emerging diagnostic tests for acute gastroenteritis. Learning Objectives Upon completion of this activity, participants will: Have increased knowledge regarding the key distinguishing characteristics among laboratory methods for the diagnosis of acute gastroenteritis Have greater competence related to the clinical implications of rapid molecular diagnostics for acute gastroenteritis Credits Available Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s) ABIM Diplomates - maximum of 0.25 ABIM MOC points Laboratory and Point-of-Care Testing Professionals - maximum of 0.25 ACCENT credit hours. Accreditation Statements In support of improving patient care, Medscape LLC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. For Physicians Medscape, LLC designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credit(s). Physicians should claim only the credit commensurate with the extent of their participation in the activity. For Laboratory and Point-of-Care Testing Professionals The American Association for Clinical Chemistry (AACC) will designate this activity for a maximum of 0.25 ACCENT credit hours. AACC is an approved provider of continuing education (CE) for clinical laboratory scientists licensed in states that require documentation of CE, including California, Florida, Louisiana, Montana, Nevada, North Dakota, Rhode Island, Tennessee, and West Virginia. ACCENT credit is also recognized by several organizations: AAB, ABCC, ACS, AMT,ASCLS, ASCP, ASM, CAP, IFCC, and NRCC. Medscape, LLC staff have disclosed that they have no relevant financial relationships. 2

3 Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 0.25 MOC points in the American Board of Internal Medicine s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Aggregate participant data will be shared with commercial supporters of this activity. Instructions for Participation and Credit There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board. This activity is designed to be completed within the time designated; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted. To receive AMA PRA Category 1 Credit, you must receive a minimum score of 75% on the post-test. Follow these steps to earn CME/CE credit*: 1. Read the target audience, learning objectives, and author disclosures. 2. Study the educational content online or printed out. 3. Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as designated at the top of the test. We encourage you to complete the Activity Evaluation to provide feedback for future programming. You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as the certificates from the CME/CE Tracker. *The credit that you receive is based on your user profile. Hardware/Software Requirements To access activities, users will need: A computer with an Internet connection. Internet Explorer 8.x or higher, the latest versions of Firefox or Safari, or any other W3C standards compliant browser. Adobe Flash Player and/or an HTML5 capable browser may be required for video or audio playback. Occasionally other additional software may be required such as PowerPoint or Adobe Acrobat Reader. 3

4 Disclosures Faculty Anne J. Blaschke, MD, PhD Associate Professor Pediatrics and Pediatric Infectious Diseases Director, Molecular Microbiology Laboratory University of Utah School of Medicine Salt Lake City, Utah Disclosure: Anne J. Blaschke, MD, PhD, has disclosed the following relevant financial relationships: Served as an advisor or consultant for: BioFire Diagnostics Received grants for clinical research from: BioFire Diagnostics; Gilead Sciences, Inc. Other: Holds intellectual property for FilmArray technology from BioFire Diagnostics Editors Susan L. Smith, MN, PhD Lead Scientific Director, Medscape, LLC Disclosure: Susan L. Smith, MN, PhD, has disclosed no relevant financial relationships. CME Reviewer Esther Nyarko, PharmD Associate Clinical CME Director, Medscape, LLC Disclosure: Esther Nyarko, PharmD, has disclosed no relevant financial relationships. Peer Reviewer This activity has been peer reviewed and the reviewer has disclosed no relevant financial relationships. 4

5 Taryn Brill: Hello, and welcome to the second episode of Diagnosis-TV: Timely Identification in Infectious Disease; Informed Patient Care -- Acute Gastroenteritis. I m Taryn Brill. Before we begin, please take a moment to answer the pre-assessment questions. Ms Brill: Acute gastroenteritis -- or diarrheal disease of rapid onset potentially accompanied by nausea, vomiting, fever, or abdominal pain -- is a major cause of illness in the United States and the burden of disease is high. Approximately 179 million episodes of acute gastroenteritis occur annually resulting in approximately 600,000 hospitalizations and 5000 deaths. [1,2] Although viral pathogens are the most common cause of acute gastroenteritis, this disease can also be caused by bacteria or sometimes parasites, making it difficult to rapidly determine the cause and to choose appropriate therapy. To get the latest perspectives on advances in rapid diagnostics for acute gastroenteritis, we visited Anne Blaschke, MD, PhD, Associate Professor in Pediatrics and Pediatric Infectious Diseases, the Edward B. Clark Endowed Chair in Pediatrics, Program Director for the Pediatric Infectious Diseases Fellowship Program, and Director of the Molecular Microbiology Laboratory at the University of Utah School of Medicine in Salt Lake City, Utah. Anne J. Blaschke, MD, PhD: Gastroenteritis is a clinical syndrome that can be caused by a wide range of pathogens. As with some other infectious syndromes, the patient s clinical presentation may offer few specific clues to diagnosis. Diarrhea is often the predominant sign, regardless of the etiology. Successful management of infectious gastroenteritis depends on the ability of clinicians to choose the most likely of a wide range of potential etiologic pathogens. The first step is to take a good history. Epidemiologic clues help us know whether we are dealing with a possible foodborne illness, a travel-associated illness, or an illness related to hospitalization or antibiotic use. Guidelines for testing and treating are somewhat different for each category of disease. Depending on the broad category of illness and character of the diarrhea (watery or bloody), the conventional approach has been to either manage expectantly, treat empirically, or utilize one or more of a number of testing methodologies to identify the offending pathogen (eg, rapid antigen tests, cultures, specialized microscopy, and singleplex molecular assays). 5

6 Standard testing methods can be complicated, however. Some have poor sensitivity, many have long turn-around times, and there are complex workflows for some tests. The diagnostic process can be laborious, slow, and costly, and there are limited or no conventional testing methods routinely available to detect some pathogens, such as many of the diarrheagenic Escherischia coli strains, and viruses such as astroviruses or sapoviruses. And finding the pathogen depends on the physician ordering a test for it, which can sometimes be challenging. Therefore, this approach has the potential to lead to over-treatment or under-treatment in the acute setting. 6

7 Ms Brill: Dr Blaschke highlighted the diagnostic challenges facing clinicians who care for patients with acute gastroenteritis. In Episode 1, Dr Blaschke described the syndromic approach to diagnosis of infectious diseases and in particular, the use of multiplex molecular panels for the rapid diagnosis of meningitis and encephalitis. We asked Dr Blaschke if a syndromic approach is appropriate for the diagnosis of acute gastroenteritis. Dr Blaschke: Epidemiologic and clinical clues help clinicians consider the most likely pathogens of acute gastroenteritis, but they are not specific enough to make a precise diagnosis. And when physicians choose from a range of testing methods that target specific pathogens, they may not choose a test that actually identifies the causative agent. Recent advances are allowing clinical laboratories to utilize multiplex molecular panels to rapidly identify pathogens responsible for acute gastroenteritis. Several commercial multiplex molecular panels are now available that have a number of advantages over culture-based testing. [3] These multipathogen gastrointestinal panels have the potential to improve patient care by allowing clinicians to rapidly identify a broad range of pathogens, some of which they may not have considered, or for which testing is otherwise unavailable. 7

8 A panel-based test can take the place of multiple diagnostic studies that might have been performed and would have to have been ordered separately, if not sequentially, leading to delays in diagnosis. More rapid diagnosis can have a positive impact on patient care. Let me illustrate with a recent study. Cybulski and colleagues conducted a prospective, multicenter study to investigate the impact of a 22-target multiplex molecular gastrointestinal panel on patient care in inpatient and outpatient settings. [4] In the study, the multiplex panel was compared primarily to stool culture. The panel test detected pathogens in 35.3% of specimens vs 6.0% of specimens using stool cultures. 8

9 Median time from specimen collection to result was 18 hours for the panel test vs 47 hours for stool cultures. Median time from collection to initiation of antimicrobial therapy was 22 hours for the panel vs 72 hours for stool cultures, and patients evaluated with the multiplex panel test were more likely to receive targeted therapy vs those diagnosed by stool culture. A specific finding was that results for Shiga toxin-producing E coli were reported 47 hours earlier when the panel test was used, facilitating discontinuation of empiric antimicrobial therapy. Another study showed that some unnecessary imaging studies and antibiotic use could be avoided and that hospitalized patients had a decreased length of stay when a panel test was used. [5] Ms Brill: We asked Dr Blaschke about community-acquired acute gastroenteritis, specifically food-borne illnesses and traveler s diarrhea, and the toll these infections take on persons in the United States. Dr Blaschke: Reports of outbreaks of food-borne gastroenteritis are frequently in the news. We hear about it occurring on cruise ships, college campuses, military bases, and even at the Olympics. The The Centers for Disease Control (CDC) estimates 48 million people in the United States become ill from foodborne illnesses each year. Among these, 128,000 are hospitalized and 3000 die. [6] Foodborne illness, usually a community-acquired illness, is a big problem in the United States. Norovirus and Salmonella species are the most commonly identified pathogens associated with food-borne acute gastroenteritis in the United States. 9

10 Norovirus is highly contagious and takes the biggest toll on young children and the elderly. It is the most common cause of vomiting and diarrhea from infectious gastroenteritis among people of all ages. [7] There are about 5.5 million cases of norovirus infection in the United States each year. Common settings in which norovirus outbreaks occur are healthcare facilities, restaurants, catered events, cruise ships, schools, and other institutional settings. The CDC estimates Salmonella causes about 1.2 million illnesses, 23,000 hospitalizations, and 450 deaths in the United States every year. Food is the source for about 1 million of these illnesses. [8] There have been recent reports of Salmonella outbreaks related to ingesting contaminated cereal and pre-cut melon and contact with live poultry and guinea pigs. Particularly in cases where there is a concern for an outbreak, in the case of food handlers or when disease is severe, diagnostic testing to determine etiology can help in public health investigations, prevention of transmission, and targeted treatment for individual patients. Traveler s diarrhea is an interesting case to consider because it can be caused by a large number of pathogens, and sometimes even multiple pathogens. There are guidelines that recommend which patients with traveler s diarrhea should receive diagnostic testing and which patients should be treated. [9,10] Most guidelines recommend against diagnostic testing in the acute setting, as the majority of mild traveler s diarrhea is self-limited and can be treated by the patient with oral rehydration solutions. If traveler s diarrhea is considered moderate or severe, which means distressing, interfering with activities, or grossly bloody, empiric therapy with a short course of antibiotics is recommended. Stool diagnostic studies may be used for severe or persistent symptoms, for dysentery, or for travelers who fail to respond to empiric therapy. This may allow targeted therapy for specific pathogens or supportive care for those in whom a viral etiology is identified. Ms Brill: We ve discussed some examples of community-acquired acute gastroenteritis. Healthcare-associated diarrhea is also a serious problem in the United States, with the major causative pathogen being toxin-producing Clostridium difficile. [11] C difficile infection is associated with a large clinical burden due to diarrhea and potentially life-threatening complications, such as pseudomembranous colitis, toxic megacolon, perforation of the colon, and sepsis. We asked Dr Blaschke about the use of multiplex molecular panel tests for C difficile infection. 10

11 Dr Blaschke: The use of multiplex molecular panels for C difficile infection is not straightforward. Prior to the introduction of molecular tests for C difficile, conventional diagnostics identified toxigenic C difficile through culture and immunoassays. But these tests could be time consuming, and there was concern that some cases of C difficile infection, also called CDI, were being missed. [12,13] Consequently, many labs now use nucleic acid amplification tests (NAATs) instead that detect the C difficile toxin gene. But NAATs can be positive in patients who are colonized with C difficile, but who do not have disease. This is particularly true when tests are sent on patients who are unlikely to have C difficile infection, such as young children or those taking laxatives. Thus, the interpretation of C difficile toxin detection by polymerase chain reaction (PCR) is complicated. In children, for example, the rate of asymptomatic colonization with toxigenic C difficile is high in those less than 1 year of age, and clinical illness is rare in this group; detection in these patients should largely be discounted. The American Academy of Pediatrics does not recommend routine testing for C difficile in children less than 1 year of age and also suggests that positive C difficile results be interpreted with suspicion in children less than 3 years old as they also can be asymptomatically colonized. [14] With the interpretation of any NAAT for C difficile already complicated, the value of C difficile testing in a multiplex panel is even more so. In some cases, patients colonized with C difficile will be inappropriately diagnosed and treated for CDI, even if another pathogen is detected. Conversely, sometimes patients in whom only C difficile is suspected are found to have an alternative etiology when multiplex molecular testing is used. In a pediatric study, an alternative pathogen was found in 29% of patients using multiplex molecular testing when only C difficile testing was ordered clinically. [15] This included a number of cases of norovirus. The appropriate use of multiplex molecular panel tests for evaluation of C difficile and the appropriateness of C difficile on these panels is hotly debated. Ms Brill: To recap the potential utility of multiplex molecular panel tests, we asked Dr Blaschke who would benefit the most. 11

12 Dr Blaschke: We ve discussed a number of indications for diagnostic testing for acute gastroenteritis. Patients with acute gastroenteritis who would potentially benefit the most from the multiplex molecular panel tests are those with dysentery, meaning grossly bloody stools, those who are ill-appearing with moderate to severe disease, and those who have had symptoms lasting for at least 7 days. In addition, testing is recommended when an outbreak is suspected and in patients with immunocompromising conditions. One of the issues with multiplex molecular panel tests for gastroenteritis pathogens is overuse or maybe a better way to term it, indiscriminate use. This type of test should not be used in all patients who present with acute gastroenteritis, regardless of whether it is community acquired or hospital acquired. For example, it would not be appropriate in a patient who presents from the community with 12 hours of loose stools unless that patient has dysentery, is quite ill-appearing, or is potentially part of an outbreak. Likewise, it would not be appropriate to test for infectious pathogens in the hospitalized patient with diarrhea who has been on laxatives. Clinicians need to be educated on how to appropriately use multiplex molecular panel tests, when to use them, and how to interpret the results when they are positive for pathogens of unclear significance, or when multiple pathogens are detected. Clinicians need to know what to do with the results. For example, if the test is positive for enterohemorrhagic E coli, treating with antibiotics could precipitate hemolytic uremic syndrome, which can be quite dangerous. Antibiotics can also lead to prolonged shedding of Salmonella. 12

13 Multiplex molecular panels tests can equip providers to be good stewards of antibiotics. For the most part, when we use a multiplex molecular panel test in the setting of acute gastroenteritis, the goal is less about saving lives, such as it was with meningitis, but more about making appropriate treatment decisions and providing education to the patient about what to expect in terms of the course of their disease. From a stewardship standpoint, making a diagnosis allows us to treat with a pathogen-specific antibiotic when appropriate, and to provide supportive care when antibiotics are not indicated. Making appropriate treatment decisions is at the heart of antibiotic stewardship. Ms Brill: This brings us to the close of episode 2. We hope you found it to be informative and helpful to your practice. As Dr Blaschke discussed, one of the greatest unmet needs in infectious diseases is availability of rapid and precise diagnostic tests. In out next episode, we will continue our discussion of the use of multiplex molecular panels in patients who present with signs and symptoms of sepsis. To proceed to the online CME/CE test click on the earn CME/CE credit link on this page. And thank you for watching. 13

14 Abbreviations CDC = Centers for Disease Control CDI = Clostridium difficile infection GI = gastrointestinal NAAT = nucleic acid amplification tests PCR = polymerase chain reaction References 1. Shane AL, Moody RK, Crump JA, et al Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea. Clin Infect Dis. 2017;65:e45-e Hall AJ, Rosenthal M, Gregoricus N, t al. Incidence of acute gastroenteritis and the role of norovirus, Georgia, USA, Emerg Infect Dis. 2011;17: Abbott AN, Fang FC. Clinical impact of multiplex syndromic panels in the diagnosis of bloodstream, gastrointestinal, respiratory, and nervous system infections. Clin Microbiol News. 2017;39: Cybulski RJ Jr, Bateman AC, Bourassa L, et al. Clinical impact of a multiplex gastrointestinal PCR panel in patients with acute gastroenteritis. Clin Infect Dis doi: /cid/ciy357. [Epub ahead of print] 5. Beal SG, Tremblay EE, Toffel S, et al. A gastrointestinal PCP panel improves clinical management and lowers health care costs. J Clin Microbiol. 2017;56: e Centers for Disease Control and Prevention. Burden of foodborne illnesses: Findings. Accessed August 5, Centers for Disease Control and Prevention. Burden of norovirus illness in the U.S. trends-outbreaks.html. Accessed August 5, Centers for Disease Control and Prevention. Salmonella. Accessed August 5, Riddle MS, Dupont HL, Connor BA. ACG clinical guideline: Diagnosis, treatment, and prevention of acute diarrheal infections in adults. Am J Gastroenterol. 2016; 111: Riddle MS, Connor BA, Beeching NJ, et al. Guidelines for the prevention and treatment of travelers diarrhea: a graded expert panel report. J Travel Med. 2017; 24(Suppl 1):S63-S Zhang S, Palazuelos-Munoz S, Balsells EM, et al. Cost of hospital management of Clostridium difficile infection in United States -- a metaanalysis and modelling study. BMC Infect Dis. 2016:16: Fang FC, Polage CR, Wilcox MH. Point-counterpoint: What Is the optimal approach for detection of Clostridium difficile infection? Clin Microbiol. 2017;55: Buss SN, Leber A, Chapin K, et al. Multicenter evaluation of the BioFire FilmArray Gastrointestinal Panel for etiologic diagnosis of infectious gastroenteritis. J Clin Microbiol. 2015;53: American Academy of Pediatrics. Policy Statement. Clostridium difficile infection in infants and children. Pediatrics. 2013;131: Stockmann CL, Rogatcheva M, Harrel B, et al. How well does physician selection of microbiologic tests identify Clostridium difficile and other pathogens in paediatric diarrhoea? Insights using multiplex PCR-based detection. Clin Microbiol Infect. 2015;21:179.e9 179.e15. 14