2017 Infectious Diseases Society of America Infectious Diarrhea Guidelines: A View From the Clinical Laboratory

An estimated 2–4 billion episodes of acute diarrhea occur worldwide each year. The 2017 Infectious Diseases Society of America (IDSA) guidelines on the diagnosis and management of infectious diarrhea [1] provide a welcome update of previous guidelines published in 2001 [2]. We would like to underscore selected aspects of the new guidelines from the perspective of the clinical microbiology laboratory. As noted in the 2001 guidelines, a specific diagnosis can benefit a patient with infectious diarrhea by directing appropriate therapy and allowing the judicious use of antimicrobial agents [2]. A specific diagnosis can provide information regarding the likely course of illness, which can be important for patient satisfaction and life planning, as well as guide management in special circumstances, such as when diarrhea occurs in food workers or children in daycare. Moreover, a specific diagnosis can facilitate public health surveillance efforts; authors of the earlier guideline expressed hope that the development of rapid diagnostic tests would eventually improve the diagnosis, management, and prevention of infectious diarrhea. Importantly, both the 2001 and 2017 guidelines acknowledge that the ability to accurately predict a specific microbial etiology on the basis of epidemiological or clinical features is limited. The hope expressed in 2001 has become a reality in 2017. Multiple US Food and Drug Administration–approved or–cleared multiplex gastrointestinal panels are now available to rapidly detect a broad range of bacterial, viral, and parasitic causes of diarrhea from a single fecal specimen [3, 4]. With few exceptions, these molecular assays are considerably more sensitive than conventional nonmolecular methods [5–9] and frequently identify pathogens unsuspected by clinicians [10]. Furthermore, their ease of use makes such testing available to patients in a variety of healthcare settings, many of whom would previously have waited for days to have their diagnosis confirmed, if it was confirmed at all. Conveniently, a single stool specimen is all that is required, abrogating the need for invasive procedures such as a duodenal aspirate for diagnosis of giardiasis, or for the aliquoting of stool into multiple containers for different tests. Although culture-independent diagnostic tests (CIDTs) offer laboratory workflow advantages over conventional testing [11] and efficiencies in establishing a diagnosis, reagent costs are undeniably greater. Hence it is important to limit diagnostic testing for infectious diarrhea to settings in which the tests are likely to yield the most clinically useful results. The 2017 guidelines include individuals with fever, bloody or mucoid diarrhea, severe abdominal cramping, or signs of sepsis, as well as immunocompromised hosts [1]. Additional specific criteria for diagnostic testing can be found in the 2016 American College of Gastroenterology guidelines for acute diarrhea, which specify patients with dysentery, those with moderate to severe disease, or those with symptoms lasting >7 days, and in the setting of outbreaks involving food handlers, healthcare workers, daycare attendees or employees, and residents of institutions [12]. The 2001 and 2017 guidelines both emphasize that bacterial isolates are essential to allow typing studies that inform public health outbreak investigations. For some organisms, isolates are also needed for antimicrobial susceptibility testing. For these reasons, directed or “reflexive” cultures should be performed for pathogens such as Salmonella, Shigella, and Campylobacter species and Escherichia coli O157:H7 when these bacteria are detected by CIDTs [13, 14]. This testing can be performed by public health or clinical microbiology laboratories. The greater sensitivity of CIDTs is anticipated to greatly enhance public health efforts and has already been useful in identifying an unsuspected outbreak of Cyclospora infection and in increasing case detection during a Shigella outbreak [8, 15]. The 2017 guidelines provide a strong recommendation that “antimicrobial treatment should be modified or discontinued when a clinically plausible organism is identified.” A number of the organisms detected by CIDTs have been shown to respond to antimicrobial therapy, including Campylobacter, Shigella, and Salmonella species; enterotoxigenic/enteropathogenic/enteroaggregative/enteroinvasive E. coli; Yersinia enterocolitica; Vibrio species; Clostridium difficile; Cryptosporidium, Cyclospora, and Giardia species; and Entamoeba histolytica [16–32]. In addition, antibiotics are contraindicated when Shiga toxin–producing E. coli is detected, to avoid precipitating or exacerbating hemolytic uremic syndrome [33]. Thus, the rapid detection of pathogens in patients with infectious diarrhea can benefit patients by optimizing the selection of an antimicrobial agent and reducing unnecessary therapy. Of note, the new guidelines include a recent Centers for Disease Control and Prevention recommendation to avoid fluoroquinolones for the treatment of Shigella infections if the minimum inhibitory concentration (MIC) of ciprofloxacin is ≥0.12 µg/mL [34]. However, this may prove to be impractical in view of rapidly rising rates of azithromycin resistance in Shigella isolates obtained from men who have sex with men [35, 36]. Furthermore, in our opinion, the high fecal concentrations of fluoroquinolones [37] make it likely that these agents will remain effective against strains with MICs ≥0.12 µg/mL that are still at or below the current susceptibility breakpoint of 1 µg/mL. With the increasing availability of rapid and highly sensitive diagnostic panels, a likely microbial etiology can now be established in more patients presenting with acute diarrhea than ever before [8]. This can facilitate appropriate treatment, avoid unnecessary antimicrobial use, and expedite recognition of foodborne and other outbreaks. Many of the goals articulated in the 2001 IDSA infectious diarrhea guidelines are now possible in 2017 as a result of advances in diagnostic technology. Configurations of individual multiplex gastrointestinal panels will likely evolve over time as experience with these new technologies and their performance grows. Hopefully, the costs will also decrease, which would make testing even more accessible. Potential conflicts of interest. F. C. F. has participated in research studies supported by BioFire, Cepheid, ELITech, and Luminex (formerly Nanosphere). R. P. has participated in research studies supported by CD Diagnostics, BioFire, Curetis, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, Allergan, and The Medicines Company; is a consultant to Curetis; receives travel reimbursement from the American Society for Microbiology (ASM), an editor’s stipend from ASM, and honoraria from the National Board of Medical Examiners, UpToDate, and the Infectious Diseases Board Review Course; has a patent on Bordetella pertussis/parapertussis polymerase chain reaction issued, has a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an antibiofilm substance issued; and serves on an Actelion data monitoring board. Both authors receive editors’ stipends from IDSA. Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.