Shiga-like Toxin Producing E. coli Identified in Patients with Multiple Myeloma (MM) Hospitalized Due to Acute Onset Diarrhea; First Report on the Clinical Use of the Biofire Film Array Gastrointestinal Panel
Authors: Kreiniz Natalia , Tadmor Tamar , Polliack Aaron , Abu-Ahmad Asala , Golan-Shani Orit , Alona Paz 
Published: October 2019

Abstract
Introduction:
Infections are a major cause of morbidity and mortality in patients with multiple myeloma (MM) and of these, one of the most frequent is gastroenteritis. This can be explained by immunoparesis, a known manifestation of MM and immunosuppression due to multiple lines of treatment.
Other causes of diarrhea such as drugs or gastro-intestinal infiltration by plasma cells should also be excluded.
Immunoglobulin A(IgA) is a major immunoglobulin on mucosal surface and defends the bowel from pathogens invasion. Data exists in literature about the protective role of IgA against Shiga toxin.
Early isolation of pathogen and correct therapeutic intervention are important and can be lifesaving for MM myeloma patients.
Until recently, diagnostic clinical laboratories utilized different methodologies to detect bacterial, parasitic, and viral causes of gastroenteritis. These tests have a number of disadvantages, including poor sensitivity, potentially long turnaround times, and complicated workflows. In addition, there are limited or almost no testing methods routinely available for most strains of Escherichia coli causing diarrhea.
The Film Array GI Panel, is a relatively new method introduced recently, which provides comprehensive, simultaneous detection of 22 different enteric pathogens on stool specimens with a turnaround time as short as 1 hour . Because of its high cost it is not used routinely in all patients presenting to the emergency room with acute diarrhea.
Here we summarize our real-life experience, using the BioFire PCR-Arrayfor 4 patients with relapsed /refractory MM who were admitted to our medical center with an acute presentation of gastroenteritis
Methods:
The Infectious Diseases Unit at our medical centre decided to introduce a strategic approach of the use of BioFire PCR-Array for the examination of stool samples, in immunocompromised patients who present to the emergency room with acute diarrhea.
The panel used includes the following 22 pathogens: Campylobacter spp., Clostridium difficile(toxin A/B), Plesiomonas shigelloides, Salmonella spp., Vibriospp., Vibrio cholerae, Yersinia enterocolitica, enteroaggregative E. coli, enteropathogenic E. coli, enterotoxigenic E. coli, Shiga-like toxin-producing E. coli (stx1 and stx2) (including specific detection of E. coli O157), Shigella spp./enteroinvasive E. coli, Cryptosporidium spp., Cyclospora cayetanensis, Entamoeba histolytica, Giardia lamblia, adenovirus F 40/41, astrovirus, norovirus GI/GII, rotavirus A, and sapovirus.
The assay is sent on the first day of patient admission, and results are reported to the Infectious Diseases Unit within one hour.
Here we summarize the results obtained in four patients with MM treated at the Hemato-Oncology Unit in Bnai Zion Medical Centre , Haifa , who were hospitalized in 2018 due to acute diarrhea and had positive PCR-Biofire results;
Results:
All patients examined had relapsed/refractory MM and had received 2-5 treatment lines for MM.
Two of the four patients had neutropenia on admission, two had low IgG level, three had low IgM level and all four had low IgA levels. Of the four patients with MM and acute diarrhea, evaluated by BioFire Film Array, one had two episodes of acute diarrhea on different occasions and was evaluated twice.
Five pathogens were detected by BioFire FilmArray, STEC (Shiga-like toxin producing E. coli) was the most common bacteria encountered and was detected 3 times: EPEC (Enteropathogenic E. coli) and ETEC (Entertoxogenic E. coli) were detected one time each.
Careful review of the literature did not identify any previous case report of patients with multiple myeloma who had Shiga-like toxin producing E. coli.
All patients received antibiotics-Azithromycin and improved.
Conclusion: In our experience using the PCR- Biofire assay we show that this approach is feasible and can be used safely to tailor therapy in immunocompromised patients. In all cases, E.Coli was found, most frequently STEC (Shiga-like toxin producing E. coli). Using this approach enable us to identify new pathogens causing diarrhea in immunocompromised patients, extremely quickly. These preliminary results reveal the need for more clinical experience using the Biofire FilmArray as a diagnostic test for patients with MM and other haematological malignancies, who present acutely with severe diarrhea.

Disclosures
Tadmor: NOVARTIS: Consultancy; ABBVIE: Consultancy; JNJ: Consultancy; PFIEZER: Consultancy; ROCHE: Research Funding. Polliack:ABBVIE: Consultancy; ROCHE: Research Funding.