You are on page 1of 3

Clinical Infectious Diseases

I N V I T E D C O M M E N TA R Y

2017 Infectious Diseases Society of America Infectious


Diarrhea Guidelines: A View From the Clinical Laboratory
Ferric C. Fang1,a and Robin Patel2,a
1
Departments of Laboratory Medicine and Microbiology, University of Washington School of Medicine, Seattle; and 2Division of Clinical Microbiology, Department of Laboratory Medicine and
Pathology, Mayo Clinic, Rochester, Minnesota

Keywords.  gastroenteritis; culture-independent diagnostic tests; multiplex panels; IDSA guidelines; diagnosis.

An estimated 2–4 billion episodes of daycare. Moreover, a specific diagnosis DIAGNOSTIC TESTING SHOULD
BE SELECTIVELY UTILIZED
acute diarrhea occur worldwide each can facilitate public health surveillance IN APPROPRIATE CLINICAL
year. The 2017 Infectious Diseases Society efforts; authors of the earlier guideline SETTINGS
of America (IDSA) guidelines on the expressed hope that the development of
Although culture-independent diag-
diagnosis and management of infectious rapid diagnostic tests would eventually
nostic tests (CIDTs) offer laboratory
diarrhea [1] provide a welcome update improve the diagnosis, management,
workflow advantages over conven-
of previous guidelines published in 2001 and prevention of infectious diarrhea.
tional testing [11] and efficiencies in
[2]. We would like to underscore selected Importantly, both the 2001 and 2017
establishing a diagnosis, reagent costs
aspects of the new guidelines from the guidelines acknowledge that the ability
are undeniably greater. Hence it is im-
perspective of the clinical microbiology to accurately predict a specific micro-
portant to limit diagnostic testing for
laboratory. bial etiology on the basis of epidemio-
infectious diarrhea to settings in which
logical or clinical features is limited.
CULTURE-INDEPENDENT the tests are likely to yield the most clin-
The hope expressed in 2001 has become
DIAGNOSTIC TESTS ARE A ically useful results. The 2017 guide-
GAME-CHANGER a reality in 2017. Multiple US Food
lines include individuals with fever,
and Drug Administration–approved
As noted in the 2001 guidelines, a spe- bloody or mucoid diarrhea, severe ab-
or–cleared multiplex gastrointestinal
cific diagnosis can benefit a patient dominal cramping, or signs of sepsis,
panels are now available to rapidly de-
with infectious diarrhea by directing as well as immunocompromised hosts
tect a broad range of bacterial, viral, and
appropriate therapy and allowing the [1]. Additional specific criteria for diag-
parasitic causes of diarrhea from a single
judicious use of antimicrobial agents nostic testing can be found in the 2016
fecal specimen [3, 4]. With few excep-
[2]. A  specific diagnosis can provide American College of Gastroenterology
tions, these molecular assays are consid-
information regarding the likely course guidelines for acute diarrhea, which
erably more sensitive than conventional
of illness, which can be important for specify patients with dysentery, those
nonmolecular methods [5–9] and fre-
patient satisfaction and life planning, with moderate to severe disease, or
quently identify pathogens unsuspected
as well as guide management in special those with symptoms lasting >7  days,
by clinicians [10]. Furthermore, their
circumstances, such as when diarrhea and in the setting of outbreaks involv-
ease of use makes such testing available
occurs in food workers or children in ing food handlers, healthcare workers,
to patients in a variety of healthcare set-
daycare attendees or employees, and
tings, many of whom would previously
residents of institutions [12].
Received 7 August 2017; editorial decision 7 August 2017; have waited for days to have their diag-
accepted 10 August 2017; published online October 19, 2017.
a
nosis confirmed, if it was confirmed DETECTION OF BACTERIAL
F. C. F. is the Deputy Editor and R. P. an Associate Editor of
Clinical Infectious Diseases.
at all. Conveniently, a single stool spe- PATHOGENS BY CIDTS SHOULD
Correspondence: F.  C. Fang, Department of Microbiology, cimen is all that is required, abrogating BE FOLLOWED BY DIRECTED
Box 357735, University of Washington School of Medicine, CULTURES
1959 NE Pacific St, Seattle, WA 98195-7735 (fcfang@uw.edu).
the need for invasive procedures such
Clinical Infectious Diseases®  2017;65(12):1974–6 as a duodenal aspirate for diagnosis of The 2001 and 2017 guidelines both em-
© The Author 2017. Published by Oxford University Press for giardiasis, or for the aliquoting of stool phasize that bacterial isolates are essential
the Infectious Diseases Society of America. All rights reserved.
For permissions, e-mail: journals.permissions@oup.com.
into multiple containers for different to allow typing studies that inform public
DOI: 10.1093/cid/cix730 tests. health outbreak investigations. For some

1974 • CID 2017:65 (15 December) •  INVITED COMMENTARY

Downloaded from https://academic.oup.com/cid/article-abstract/65/12/1974/4557074


by Research 4 Life user
on 09 December 2017
organisms, isolates are also needed for anti- have sex with men [35, 36]. Furthermore, 2. Guerrant RL, Van Gilder T, Steiner TS, et  al;
Infectious Diseases Society of America. Practice
microbial susceptibility testing. For these in our opinion, the high fecal concentra- guidelines for the management of infectious diar-
reasons, directed or “reflexive” cultures tions of fluoroquinolones [37] make it rhea. Clin Infect Dis 2001; 32:331–51.
3. Binnicker MJ. Multiplex molecular panels for diag-
should be performed for pathogens such likely that these agents will remain effect- nosis of gastrointestinal infection: performance,
as Salmonella, Shigella, and Campylobacter ive against strains with MICs ≥0.12  µg/ result interpretation, and cost-effectiveness. J Clin
Microbiol 2015; 53:3723–8.
species and Escherichia coli O157:H7 when mL that are still at or below the current
4. Abbott AN, Fang FC. Clinical impact of multiplex syn-
these bacteria are detected by CIDTs [13, susceptibility breakpoint of 1 µg/mL. dromic panels in the diagnosis of bloodstream, gastro-
14]. This testing can be performed by With the increasing availability of intestinal, respiratory and central nervous system
infections. Clin Microbiol Newsl. 2017; 39:133–42.
public health or clinical microbiology lab- rapid and highly sensitive diagnostic pan- 5. Khare R, Espy MJ, Cebelinski E, et al. Comparative
oratories. The greater sensitivity of CIDTs els, a likely microbial etiology can now be evaluation of two commercial multiplex panels
for detection of gastrointestinal pathogens by use
is anticipated to greatly enhance public established in more patients presenting of clinical stool specimens. J Clin Microbiol 2014;
health efforts and has already been useful with acute diarrhea than ever before [8]. 52:3667–73.
6. McAuliffe G, Bissessor L, Williamson D, et al. Use
in identifying an unsuspected outbreak of This can facilitate appropriate treatment, of the EntericBio Gastro Panel II in a diagnostic
Cyclospora infection and in increasing case avoid unnecessary antimicrobial use, microbiology laboratory: challenges and opportu-
nities. Pathology 2017; 49:419–22.
detection during a Shigella outbreak [8, 15]. and expedite recognition of foodborne
7. Spina A, Kerr KG, Cormican M, et  al. Spectrum
and other outbreaks. Many of the goals of enteropathogens detected by the FilmArray GI
articulated in the 2001 IDSA infectious Panel in a multicentre study of community-ac-
ANTIMICROBIAL THERAPY quired gastroenteritis. Clin Microbiol Infect 2015;
SHOULD BE GUIDED BY diarrhea guidelines are now possible in 21:719–28.
DIAGNOSTIC TESTING 2017 as a result of advances in diagnos- 8. Buss SN, Leber A, Chapin K, et  al. Multicenter
evaluation of the BioFire FilmArray gastrointes-
The 2017 guidelines provide a strong tic technology. Configurations of individ- tinal panel for etiologic diagnosis of infectious
recommendation that “antimicrobial ual multiplex gastrointestinal panels will gastroenteritis. J Clin Microbiol 2015; 53:915–25.
9. Huang RS, Johnson CL, Pritchard L, Hepler R, Ton
treatment should be modified or dis- likely evolve over time as experience with TT, Dunn JJ. Performance of the Verigene® enteric
continued when a clinically plausible these new technologies and their perfor- pathogens test, Biofire FilmArray™ gastrointestinal
panel and Luminex xTAG® gastrointestinal patho-
organism is identified.” A number of the mance grows. Hopefully, the costs will
gen panel for detection of common enteric patho-
organisms detected by CIDTs have been also decrease, which would make testing gens. Diagn Microbiol Infect Dis 2016; 86:336–9.
even more accessible. 10. Stockmann C, Rogatcheva M, Harrel B, et al. How well
shown to respond to antimicrobial ther-
does physician selection of microbiologic tests identify
apy, including Campylobacter, Shigella, Clostridium difficile and other pathogens in paediatric
and Salmonella species; enterotoxigenic/ Note diarrhoea? Insights using multiplex PCR-based detec-
Potential conflicts of interest.  F. C. F. has par- tion. Clin Microbiol Infect 2015; 21:179.e9–15.
enteropathogenic/enteroaggregative/ 11. Halligan E, Edgeworth J, Bisnauthsing K, et  al.
ticipated in research studies supported by BioFire,
enteroinvasive E.  coli; Yersinia enteroco- Cepheid, ELITech, and Luminex (formerly
Multiplex molecular testing for management of in-
fectious gastroenteritis in a hospital setting: a com-
litica; Vibrio species; Clostridium diffi- Nanosphere). R.  P.  has participated in research parative diagnostic and clinical utility study. Clin
cile; Cryptosporidium, Cyclospora, and studies supported by CD Diagnostics, BioFire, Microbiol Infect 2014; 20:O460–7.
Curetis, Merck, Hutchison Biofilm Medical 12. Riddle MS, DuPont HL, Connor BA. ACG clin-
Giardia species; and Entamoeba histolyt- Solutions, Accelerate Diagnostics, Allergan, ical guideline: diagnosis, treatment, and preven-
ica [16–32]. In addition, antibiotics are and The Medicines Company; is a consultant to tion of acute diarrheal infections in adults. Am J
Curetis; receives travel reimbursement from the Gastroenterol 2016; 111:602–22.
contraindicated when Shiga toxin–pro-
American Society for Microbiology (ASM), an 13. Gebrehiwot SA, Rucinski SL, Schwab JJ, et  al.
ducing E. coli is detected, to avoid precip- “Reflexive culture”—a strategy for laboratories
editor’s stipend from ASM, and honoraria from the
itating or exacerbating hemolytic uremic adopting molecular testing for enteric pathogens.
National Board of Medical Examiners, UpToDate,
In: American Society for Microbiology General
syndrome [33]. Thus, the rapid detection and the Infectious Diseases Board Review Course; Meeting, Boston, Massachusetts, 2014. Poster 2034.
of pathogens in patients with infectious has a patent on Bordetella pertussis/parapertussis 14. Shea S, Kubota KA, Maguire H, et  al. Clinical
polymerase chain reaction issued, has a patent microbiology laboratories’ adoption of culture-in-
diarrhea can benefit patients by opti- on a device/method for sonication with royalties dependent diagnostic tests is a threat to food-
mizing the selection of an antimicrobial paid by Samsung to Mayo Clinic, and a patent on borne-disease surveillance in the United States. J
an antibiofilm substance issued; and serves on an Clin Microbiol 2017; 55:10–9.
agent and reducing unnecessary ther- 15. Prakash VP, LeBlanc L, Alexander-Scott NE, et al.
Actelion data monitoring board. Both authors
apy. Of note, the new guidelines include receive editors’ stipends from IDSA. Both authors Use of a culture-independent gastrointestinal
multiplex PCR panel during a shigellosis outbreak:
a recent Centers for Disease Control and have submitted the ICMJE Form for Disclosure
considerations for clinical laboratories and public
Prevention recommendation to avoid of Potential Conflicts of Interest. Conflicts that health. J Clin Microbiol 2015; 53:1048–9.
the editors consider relevant to the content of the 16. Thorén A, Wolde-Mariam T, Stintzing G,
fluoroquinolones for the treatment of
manuscript have been disclosed. Wadström T, Habte D. Antibiotics in the treat-
Shigella infections if the minimum inhibi- ment of gastroenteritis caused by enteropathogenic
tory concentration (MIC) of ciprofloxacin Escherichia coli. J Infect Dis 1980; 141:27–31.
References 17. Lolekha S. Consequences of treatment of gastroin-
is ≥0.12  µg/mL [34]. However, this may 1. Shane AL, Mody RK, Crump JA, et  al. 2017 testinal infections. Scand J Infect Dis Suppl 1986;
prove to be impractical in view of rapidly Infectious Diseases Society of America clinical 49:154–9.
practice guidelines for the diagnosis and manage- 18. Zheng H, Sun Y, Lin S, Mao Z, Jiang B. Yersinia
rising rates of azithromycin resistance in ment of infectious diarrhea. Clin Infect Dis 2017; enterocolitica infection in diarrheal patients. Eur J
Shigella isolates obtained from men who 65:1963–73. Clin Microbiol Infect Dis 2008; 27:741–52.

INVITED COMMENTARY • CID 2017:65 (15 December) • 1975

Downloaded from https://academic.oup.com/cid/article-abstract/65/12/1974/4557074


by Research 4 Life user
on 09 December 2017
19. Butler T, Lolekha S, Rasidi C, et  al. Treatment of traveler’s diarrhea: clinical response to ciprofloxa- 32. DuPont HL. Persistent diarrhea: a clinical review.
acute bacterial diarrhea: a multicenter international cin. Clin Infect Dis 1999; 29:335–8. JAMA 2016; 315:2712–23.
trial comparing placebo with fleroxacin given as 25. Oldfield EC 3rd, Wallace MR. The role of anti- 33. Freedman SB, Xie J, Neufeld MS, et  al. Shiga tox-
a single dose or once daily for 3  days. Am J Med biotics in the treatment of infectious diarrhea. in-producing Escherichia coli infection, antibiotics,
1993; 94:187S–194S. Gastroenterol Clin North Am 2001; 30:817–36. and risk of developing hemolytic uremic syndrome:
20. Gayraud M, Scavizzi MR, Mollaret HH, Guillevin 26. Rossignol JF, Ayoub A, Ayers MS. Treatment a meta-analysis. Clin Infect Dis 2016; 62:1251–8.
L, Hornstein MJ. Antibiotic treatment of Yersinia of diarrhea caused by Giardia intestinalis and 34. Centers for Disease Control and Prevention. CDC
enterocolitica septicemia: a retrospective review of Entamoeba histolytica or E.  dispar: a randomized, recommendations for diagnosing and managing
43 cases. Clin Infect Dis 1993; 17:405–10. double-blind, placebo-controlled study of nitazox- Shigella strains with possible reduced susceptibility
21. Mattila L, Peltola H, Siitonen A, Kyrönseppä H, anide. J Infect Dis 2001; 184:381–4. to ciprofloxacin. Available at: https://emergency.
Simula I, Kataja M. Short-term treatment of trav- 27. Rossignol JF, Ayoub A, Ayers MS. Treatment of diar- cdc.gov/han/han00401.asp. Accessed 5 August
eler’s diarrhea with norfloxacin: a double-blind, rhea caused by Cryptosporidium parvum: a prospec- 2017.
placebo-controlled study during two seasons. Clin tive randomized, double-blind, placebo-controlled 35. Bowen A, Grass J, Bicknese A, Campbell D, Hurd
Infect Dis 1993; 17:779–82. study of nitazoxanide. J Infect Dis 2001; 184:103–6. J, Kirkcaldy RD. Elevated risk for antimicrobial
22. Hoge CW, Shlim DR, Ghimire M, et  al. Placebo- 28. Okeke IN, Nataro JP. Enteroaggregative Escherichia drug-resistant Shigella infection among men who
controlled trial of co-trimoxazole for Cyclospora coli. Lancet Infect Dis 2001; 1:304–13. have sex with men, United States, 2011–2015.
infections among travellers and foreign residents in 29. Nelson RL, Suda KJ, Evans CT. Antibiotic treat- Emerg Infect Dis 2016; 22:1613–6.
Nepal. Lancet 1995; 345:691–3. ment for Clostridium difficile-associated diar- 36. Murray K, Reddy V, Kornblum JS, et al. Increasing
23. Wanke CA, Gerrior J, Blais V, Mayer H, Acheson D. rhea in adults. Cochrane Database Syst Rev 2017; antibiotic resistance in Shigella spp. from infected
Successful treatment of diarrheal disease associated 3:CD004610. New York City residents, New York, USA. Emerg
with enteroaggregative Escherichia coli in adults 30. Granados CE, Reveiz L, Uribe LG, Criollo CP. Infect Dis 2017; 23:332–5.
infected with human immunodeficiency virus. J Drugs for treating giardiasis. Cochrane Database 37. Pecquet S, Ravoire S, Andremont A. Faecal excre-
Infect Dis 1998; 178:1369–72. Syst Rev 2012; 12:CD007787. tion of ciprofloxacin after a single oral dose and
24. Glandt M, Adachi JA, Mathewson JJ, et  al. 31. Marie C, Petri WA Jr. Amoebic dysentery. BMJ Clin its effect on faecal bacteria in healthy volunteers. J
Enteroaggregative Escherichia coli as a cause of Evid 2013. pii:0918. Antimicrob Chemother 1990; 26:125–9.

1976 • CID 2017:65 (15 December) •  INVITED COMMENTARY

Downloaded from https://academic.oup.com/cid/article-abstract/65/12/1974/4557074


by Research 4 Life user
on 09 December 2017

You might also like