ANMC Gastrointestinal (GI) Pathogen Panel Guidance

(Created 5/2024, Last Updated 5/28/2024)

Background:
Many pathogens, including bacteria, parasites, and viruses can cause infectious diarrhea. Previously, many of the pathogens responsible could only be isolated
using traditional techniques such as stool culture or ova and parasite exam that were often time consuming and lacked sensitivity. To improve the detection of
intestinal pathogens, the microbiology lab has introduced multiplex PCR testing using the FilmArray Gastrointestinal (GI) panel, which detects 22 common
viruses, bacteria, and parasites that may cause infectious diarrhea.

Testing:
This panel will replace traditional stool culture, Giardia and Cryptosporidium antigen screen, and Rotavirus antigen. Stool cultures for identification and
susceptibility will only be performed by provider request when enteric pathogens are detected by the GI panel. C. difficile testing is part of the panel but will not
be reported. The microbiology lab and antimicrobial stewardship teams have determined that PCR testing alone is inadequate for accurately identifying those
with C. difficile infection (CDI) who require treatment.1,2 If CDI is suspected the C. difficile toxin assay is recommended in combination with PCR testing as it is the
preferred method to diagnose CDI, please continue to order “C difficile PCR with reflex to EIA toxin” in Cerner. See the ANMC C. difficile Testing & Treatment
Guidelines.

Restriction:
The GI panel may only be ordered for patients who have been hospitalized for less than 5 days; otherwise it will require approval from the microbiology director
(or their designee) who will consult with the antimicrobial stewardship program or the infectious disease service when needed. The panel may also only be
ordered once per admission. These restrictions will be put in place as data show that routine stool cultures from patients with diarrhea that develops after 72
hours of hospitalization are typically low yield for standard bacteria and parasites.3,4

Interpretation:
Results of PCR testing for stool pathogens must be taken into clinical context when making treatment decisions and treatment decisions should be based upon
clinical presentation. PCR testing is much more sensitive than traditional techniques and allows for the detection of low numbers of pathogens.5,6,7 The clinical
correlation of PCR results with the need for treatment and clinical outcomes has not been established. Studies evaluating stool PCR testing frequently detect
more than one enteric pathogen in patient’s stool and data are not available to determine the causative organism in these situations.5,7 Additionally low levels of
stool pathogens have been detected in healthy persons and all decisions regarding need for treatment must be taken into clinical context of the patient.

Treatment Recommendations:
Most GI infections due to common bacterial and viral causes are self-limited in nature and do not require antimicrobial therapy. Symptoms typically resolve
within 7 days in a normal host and therapy should focus on providing supportive care by replacing fluid and electrolyte losses. The use of antimicrobial therapy
must be carefully weighed against unintended and potentially harmful consequences, including antimicrobial-resistant infections, side effects of treatment with
antimicrobial agents, super-infections when normal flora are eradicated by antimicrobial agents, the prolongation of a carrier state (particularly in Salmonella)
and the possibility of induction of disease-producing phages by antibiotics (such as Shiga-toxin phage induced by quinolone antibiotics).

These recommendations apply to generally healthy persons unless otherwise noted. There is a paucity of data regarding the efficacy of antimicrobials in a
number of the pathogens detected on the panel and in these cases, antibiotics are generally only recommended in severe or non-resolving cases or those at risk
for severe disease such as immunocompromised patients. In cases where data are lacking, clinical judgment and the assessment of the risk verses benefit must
be considered.

Etiology and Treatment Recommendations 8,9,10

Commonly Implicated
Pathogen Common Presentation Treatment Recommendations Treatment (If Indicated)
Sources and Seasonality
Bacteria
Campylobacter Fever, abdominal cramps, and Poultry, unpasteurized milk Most patients recover without • Azithromycin 500 mg daily x3
diarrhea within 6-48 hours, and dairy products antimicrobial therapy. Antibiotics have days
fecal leukocytes often present Peak season – spring, summer been shown to reduce symptom • Fluoroquinolone x3 days*
duration by 1.3 days and are
recommended for severe illness or risk Immunocompromised patients may
factors for complications (elderly, require prolonged therapy (7-14
pregnancy, immunocompromised). days)
Plesiomonas shigelloides Severe abdominal cramps, Fresh water, shellfish, Most patients recover without • Fluoroquinolone x3 days*
and diarrhea within 6-48 international travel antimicrobial therapy. Unclear if • Azithromycin 500 mg daily x3
hours antibiotics shorten the duration of days
illness. Consider treatment in severe • TMP/SMX DS BID x3 days
diarrhea, extremes of age, and
immunocompromised.
Salmonella Fever, abdominal cramps, and Poultry, eggs, dairy products, Antibiotics have no significant effect on • Fluoroquinolone x7 days*
diarrhea within 6-48 hours, produce, reptile contact the length of illness and may prolong • Azithromycin 500 mg daily x7
fecal leukocytes often present Peak season – summer, fall carriage of the organism in the stool. days
Antibiotics should generally be • TMP/SMX DS BID x7 days
avoided, but recommended for severe
illness (>8 stools/day, high fever, Immunocompromised patients
hospitalized) or risk for complications require 14 days of therapy or
(age <1 or > 50, immunocompromised) longer if relapsing
Yersinia enterocolitica Fever and abdominal cramps Unpasteurized milk, Most patients recover without • For immunocompromised
within 1-11 days, with or undercooked pork, antimicrobial therapy. Unclear if patients, ceftriaxone 2 g IV daily
without diarrhea, fecal chitterlings antibiotics shorten the duration of PLUS gentamicin 5 mg/kg daily
leukocytes often present Peak season – winter illness.
Vibrio species Fever, abdominal cramps, and Shellfish Most patients recover without • Azithromycin 1 g x1 dose
(if positive and V. cholera diarrhea within 6-48 hours, antimicrobial therapy. Unclear if • Doxycycline 300 mg x1 dose
negative indicates V. fecal leukocytes often present antibiotics shorten duration of illness.
parahaemolyticus or V. Consider in severe or prolonged
vulnificans is present) diarrhea.
Vibrio cholerae Abdominal cramps and large Shellfish, travel to Haiti or Oral rehydration is the key intervention. • Azithromycin 1 g x1 dose
volume watery diarrhea other areas where cholera is Antibiotics shorten the duration of • Doxycycline 300 mg x1 dose
within 16-72 hours endemic illness and are recommended. • Levofloxacin 500 mg x1 dose
• Ciprofloxacin 500 mg x1 dose
 Diarrheagenic E. coli/Shigella
Enteroaggregative E. coli Abdominal cramps and International travel, infantile Limited data in EAEC and EPEC, many • Fluoroquinolone x3 days*
(EAEC) watery diarrhea within 16-72 diarrhea in developing patients recover without antimicrobial • Rifaximin 200 mg TID x3 days
Enteropathogenic E. coli hours, can be prolonged countries therapy. Antibiotics have been shown to • Azithromycin 1 g x1 dose or 500
(EPEC) shorten the duration of illness in ETEC mg daily x3 days
Enterotoxigenic E. coli and are generally indicated for
(ETEC) lt/st moderate to severe diarrhea (>4
stools/day, fever, or blood or pus in
stool).
Shiga-like toxin-producing Bloody diarrhea with minimal Unpasteurized milk, fresh Antibiotics have no effect on duration Antibiotics and antimotility agents
E. coli (STEC) stx1/stx2 fever within 3-8 days produce, ground beef, petting or severity of symptoms and certain should be avoided.
(shiga-toxin producing E. zoos antibiotics may increase the risk for Supportive care only
coli is present) hemolytic-uremic syndrome.
E. coli O157
(the shiga-toxin
producing E. coli is type
O157)
Shigella/Enteroinvasive E. Fever, abdominal cramps, and Egg salad, lettuce, day care Treatment is recommended if detected. • TMP-SMX 160-800 mg BID x3
coli (EIEC) diarrhea within 6-48 hours, days
fecal leukocytes present • Fluoroquinolone x3 days*

Immunocompromised patients
require 7-10 days of therapy
*Levofloxacin 500mg PO daily or ciprofloxacin 500mg PO BID (should be avoided in pregnancy)

Parasites
Cryptosporidium Prolonged watery diarrhea Contaminated water Most patients recover without May use antimotility agents and/or
(recreational and drinking), antimicrobial therapy but antibiotics nitazoxanide 500mg BID x3 days for
unpasteurized apple cider may decrease the duration of illness. prolonged or severe illness.
Immunocompromised patients often ID consult recommended for
develop prolonged symptoms and immunocompromised patients
respond poorly to therapy.
Cyclospora cayetanensis Imported fresh produce Treatment indicated if symptomatic. TMP/SMX DS BID x 7-10 days
ID consult recommended for
immunocompromised patients
Entamoeba histolytica Returning travelers Treatment recommended if detected. • Metronidazole 500 mg TID x 7-10
days
• Tinidazole 2 g daily x3 days
• Nitazoxanide 500 mg PO BID x3
days followed by paromomycin
25 mg/kg/day in 3 divided doses
x7 days
 Giardia lamblia Contaminated recreational Treatment indicated if symptomatic. • Tinidazole 2 g x1 dose
water, daycare, international • Nitazoxanide 500 mg PO BID x3
travelers days
• Metronidazole 500 mg TID x 5-7
days

Viruses
Adenovirus F 40/41 Vomiting and non-bloody Children <2 yrs, day care No therapy available. Treat Antibiotics not indicated
Astrovirus diarrhea within 10-51 hours Children <1 yr, day care symptomatically.
Norovirus GI/GII Salads, shellfish, cruise ships,
epidemic foodborne disease
Peak season – winter
Rotavirus A Infants
Peak season – winter
Sapovirus Children

Pediatric Dosing Chart:

Recommended Dosing
Azithromycin 10 mg/kg PO/IV daily
Ciprofloxacin* 10-15 mg/kg/dose PO BID (max 1.5 g/day)
Doxycycline* ≥ 8years: 2 mg/kg/dose PO BID (max 100 mg/dose)
Levofloxacin* <5 years: 8-10 mg/kg/dose PO/IV twice daily
≥ 5years: 10 mg/kg/dose PO/IV daily (max 750mg/day)
Metronidazole Giardiasis: 5 mg/kg/dose PO/IV TID (max 250mg/dose)
Nitazoxanide 1-3 years: 100 mg PO BID
4-11 years: 200 mg PO BID
≥ 12 years: 500mg PO BID
Paromomycin 10 mg/kg/dose PO TID (max 1500 mg/day)
Rifaximin 3-11 years: 100 mg PO four times daily (limited data)
≥ 12 years: 200mg PO three times daily
Tinidazole 50 mg/kg PO single dose (max 2000 mg/day)
TMP/SMX ≥ 2months: 4-5 mg/kg/dose (TMP component) PO BID
*Fluoroquinolones and doxycycline are not routinely used as first line therapy in pediatrics

Adapted from Nebraska Medical Center Gastrointestinal Pathogen Panel Guidance. [Link]
providers/asp/GI_Panel_Guidance_10-[Link]. Accessed May 22, 2024.
References:
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on enzyme immunoassay and cell culture cytotoxicity assay. J Clin Micro. 2013;51:3624-30.
2. Planche TD, Davies KA, Coen PG, et al. Differences in outcomes according to Clostridium difficile testing method: a prospective multicentre diagnostic validation study of C.
difficile infection. Lancet Infect Dis. 2013;13:936-45.
3. Rohner P, Pittet D, Pepey B, et al. Etiological agents of infectious diarrhea: implications for requests for microbial culture. J Clin Microbiol 1997; 35:1427.
4. Bauer TM, Lalvani A, Fehrenbach J, et al. Derivation and validation of guidelines for stool cultures for enteropathogenic bacteria other than Clostridium difficile in hospitalized
adults. JAMA. 2001;285(3):313-319.
5. Khare R, Espy MJ, Cebelinski E, et al. Comparative evaluation of two commercial multiplex panels for detection of gastrointestinal pathogens by use of clinical stool specimens. J
Clin Micro. 2014;52:3667-73.
6. Liu J, Kabir F, Manneh J, et al. Development and assessment of molecular diagnostic tests for 15 enteropathogens causing childhood diarrhoae: a multicentre study. Lancet
Infect Dis. 2014;14:716-24.
7. Kabayiza JC, Andersson ME, Nilsson S, et al. Real-time PCR identification of agents causing diarrhea in Rwandan children less than 5 years of age. Pediatr Infect Dis J.
2014;33:1037-42.
8. Gilbert DN, Chambers HF, Eliopoulos GM, Saag MS, eds. The Sanford Guide to Antimicrobial Therapy, 39th ed. Sperryville, VA: Antimicrobial Therapy, Inc; 2014.
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Infectious Disease. Vol 2. 8th ed. Philadelphia, PA: Elsevier;2014:1253-1262.
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Philadelphia, PA: Elsevier;2014:1283-1296.