Diarrhea: Infectious Disease Society of America’s New Guidelines

Molecular diagnostic testing and other culture-independent diagnostic tests have recently pushed culture diagnostic testing for diarrheal illness diagnosis and treatment to the sidelines.  Culture can always play a role in confirmation testing and can offer additional antibiotic sensitivity information not completely available in molecular tests, but molecular and other non-culture methods seem to be growing in popularity for a reason.

With all of this new information, physicians and health care providers are faced with more information than they ever have been before.  Additionally, with these new and improved tools come new and improved guidelines for treatment.  The Infectious Diseases Society of America (ISDA) released a list of guidelines late 2017 that updates their previous guidance released in 2001. This new document, published in Clinical Infectious Diseases (CID) highlights that not all patients with diarrheal illness need to be tested. New guidance indicates a focus on alternatives to culture based diagnostic testing, provides seven tables complete with recommendations, and emphasizes the critical role that culture-based diagnostic tests continue to play in detecting food poisoning outbreaks in public health investigations.

Case by Case Diagnostic Testing Recommendation

ISDA recommends treatment of dehydration symptoms for those who may benefit from it, but reserves molecular testing for people meeting certain criteria.  Testing is recommended, for those who fall into higher risk categories such as the more vulnerable groups.  This includes children 5 years of age and under, the elderly, and those with a compromised immune system. Additionally, patients presenting symptoms of bloody diarrhea, severe abdominal tenderness or pain, or signs of sepsis should be tested.

These higher risk populations are more likely to contract a pathogen causing diarrheal illness as well as experience more severe complicates associated with the illness.  Severe symptoms indicated in the guidance recommendations demonstrate infection that should be treated immediately, often with antibiotics.  According to Andi L. Shane, MD, MPH, MSc and lead author of the ISDA guidelines, “Diagnostic testing combined with clinical expertise is helpful in identifying a cluster of infections that may signal an outbreak.”

Due to the cost of these tests, “it is important to limit diagnostic testing for infectious diarrhea to setting in which the tests are likely to yield the most clinically useful results,” says commentators Ferric C. Fang, MD of the Department of Laboratory Medicine and Microbiology at University of Washington in Seattle and Robin Patel, MD of Department of Laboratory Medicine and Pathology at Mayo Clinic in Rochester, Minnesota.

Focus on Culture Independent Diagnostic Tests

Many diagnostic tests do not rely on culturing clinical specimens are sometimes referred to as “culture-independent diagnostic tests” or CIDTs.  In fact, FoodNet sites indicated the diagnosis of Campylobacter diarrheal illness by CIDTs without culture confirmation at 13% in 2012 – 2014 nearly doubling to 24% in 2015.  CIDTs currently include molecular tests and antigen-based testing, though technology is quickly evolving to include additional options.  Benefits often include the speed at which a result can be obtained.  A faster answer to what ails the patient allows health care professionals to treat illness more quickly and specifically than with older culture based diagnostic tests.  While these new methods are a bit higher in cost than their culture counterparts, the increase in demand and reduced labor overhead are quickly driving down the cost of performing these alternative methods.

Molecular Diagnostic Testing

Molecular diagnostic tests have rapidly been adopted as a diagnostic tool for health care providers and rely on nucleic acid amplification assays such as Polymerase Chain Reaction (PCR).  These molecular diagnostic testing methods allow for faster results, the ability to simultaneously detect multiple pathogens in a single sample, and greater sensitivity that allows a smaller bacterial load to be detected using technology that targets pathogen DNA.

Antigen-based Diagnostic Testing

Molecular testing is not the only CIDT tool health care providers can use.  Antigen-based diagnostic tests require less technical expertise to perform, allowing a greater number of people to be trained in interpreting the results.  Antigen-based tests rely on the antigens that certain bacteria produce to generate a positive test result.  These often include a color changing liquid that responds to a particular bacteria type. 

Tables Created to Assist Clinician Diagnosis

Newer technology allows health care professionals the ability to order test panels that might detect harmful organisms with which they didn’t suspect or are unfamiliar with.  The multi-plex options may also indicate more than one infection present.  This allows health care professionals to provide more direct treatment and facilitate ongoing public health efforts.

The new guidelines include 7 tables that can be consulted that include how infections are acquired, conditions for exposure, post-infection symptoms, clinical presentation, and recommended treatment that includes antimicrobial treatment, fluid administration, and even nutritional management suggestions.  Under new guidelines that only patients that meet certain criteria should be tested, the table also includes information that allows health care providers asses the need for testing.

With respect to fluid administration and hydration therapy, guidance explains that “physicians should ensure that children with mild to moderate dehydration, and children and adults with acute diarrhea and those with mild to moderate dehydration associated with vomiting or severe diarrhea be given oral rehydration solution if tolerated, progressing to intravenous rehydration if oral rehydration is not tolerated.”

ISDA notes that most pathogens responsible for diarrheal illness respond to antimicrobial treatment, blind administration of antibiotics may be more harmful than good.  Shiga toxin-producing E. coli for example may trigger or exacerbate hemolytic uremic syndrome (HUS) if antibiotics are taken.  According to commentators Fang and Patel, “antimicrobial treatment should be modified or stopped when a ‘clinically plausible organism is identified’.”

Additional guidelines include travel-related diarrheal illness and Clostridium difficile diarrhea.  This information is referred to in separate guidelines specifically for these conditions that are not elaborated in the tables.

Culture Methods are Not Dead

While CIDTs are a faster method for diagnostic purposes and treatment options, culture methods are still important.  Benefits of culture-based diagnostic tests include the ability to determine if the culture is alive and reproducing, any antimicrobial resistance that might impede complete infection treatment, as well as obtaining important isolates needed for serotyping studies often used in disease outbreak investigations.  “For these reasons, directed or ‘reflexive’ cultures should be performed for pathogens such as Salmonella, Shigella, Campylobacter species and Escherichia coli O157:H7 when these bacteria are detected by CIDTs,” says Fang and Patel.

Diagnostics Evolve Alongside Diagnostic Tools

Researchers continue to look for faster and smarter methods to detect and direct treatment to those afflicted with diarrheal illness and other pathogens.  The ISDA and other organizations like it will continue to evolve alongside these diagnostic tools to ensure correct recommendations accompany these new procedures.

By: Heather Williams, Contributing Writer (Non-Lawyer)