Evaluation of a multiplex panel for the diagnosis of acute infectious diarrhea in immunocompromised hematologic patients

RESEARCH ARTICLE Evaluation of a multiplex panel for the diagnosis of acute infectious diarrhea in immunocompromised hematologic patients Izaskun Alejo-Cancho1, Francesc Fernández Avilés2, Alicia Capón1, Cristina Rodrı́guez1, Josep Barrachina1, Pilar Salvador1, Mª Eugenia Valls1, Miriam J. Álvarez-Martı́nez1, Yuliya Zboromyrska1¤, Jordi Vila1, Mª Ángeles Marcos1* a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 1 Microbiology Department, Hospital Clinic, Barcelona, Spain, 2 Hematology Department, Hospital Clinic, Barcelona, Spain ¤ Current address: Yuliya Zboromyrska, Microbiology Department, Hospital de Vilafranca, Barcelona, Spain * Abstract OPEN ACCESS Citation: Alejo-Cancho I, Fernández Avilés F, Capón A, Rodrı́guez C, Barrachina J, Salvador P, et al. (2017) Evaluation of a multiplex panel for the diagnosis of acute infectious diarrhea in immunocompromised hematologic patients. PLoS ONE 12(11): e0187458. https://doi.org/10.1371/ journal.pone.0187458 Introduction Diarrhea is a frequent complication in hematologic patients, being an infectious cause frequently suspected. Rapid and accurate detection of gastrointestinal pathogens is vital in immunocompromised hosts. The aim of this study was to compare routine diagnostic methods versus a multiplex polymerase chain reaction (PCR) assay for the diagnosis of infectious diarrhea in immunocompromised hematologic patients. Editor: Claudia D. Andl, University of Central Florida College of Medicine, UNITED STATES Received: May 5, 2017 Accepted: October 22, 2017 Published: November 3, 2017 Copyright: © 2017 Alejo-Cancho et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Material and methods We conducted a prospective observational study from March 2015 to January 2016 to compare conventional methods for the diagnosis of infectious diarrhea with FIlmArray GI Panel (BioFire-bioMérieux, France). Samples from adult immunocompromised hematologic patients with acute diarrhea were collected. In cases with discordant results, a second multiplex assay was performed (Allplex, Seegene, Korea). The result was considered positive or negative when the same result was obtained by at least two of the methods. Data Availability Statement: All relevant data are within the paper. Results Funding: BioMerieux provided us FilmArray panels in order to be evaluate. However, the funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. When we decided to publish the results, BioMerieux offered to pay for the publishing fares. They did not, however, have any role in writing the manuscript. A total of 95 samples were obtained from 95 patients (median age of 52 years (46–64)). Sixty-one (64%) episodes were hospital-acquired and 34 (36%) were community-acquired diarrhea. Twenty-five (26%) patients had a positive microbiological result, being Clostridium difficile the most frequent pathogen, followed by Campylobacter spp and norovirus. The concordance between FilmArray methods was good (k = 0.79). The FilmArray GI panel showed a sensitivity of 95%, a specificity of 100% for positive results. The time required to obtain results was markedly reduced with the use of multiplex PCR methods. PLOS ONE | https://doi.org/10.1371/journal.pone.0187458 November 3, 2017 1 / 10 Evaluation of a multiplex panel for the diagnosis of acute infectious diarrhea in immunocompromised hematologic patients Competing interests: The authors have declared that no competing interests exist. Conclusions Multiplex molecular panels provide a rapid and sensitive tool for the diagnosis of infectious diarrhea, thereby allowing more timely clinical decisions in immunocompromised hematologic patients. Introduction Diarrhea is a very frequent complication in immunocompromised patients, including hematologic patients. In patients with these underlying conditions diarrhea can be a severe disease, affecting the patient’s quality of life and leading to longer hospitalizations. Diarrhea can be caused by many different community- and hospital-acquired pathogens, including several bacteria, viruses and, less frequently, parasites. However, the etiology of diarrhea in these patients may be multiple, varying from infectious disease, graft-versus-host disease or drug-induced diarrhea [1]. Even though diarrhea in hematologic patients is a frequent and important issue, there is a lack of studies regarding the etiology of diarrhea in these patients. Rapid accurate diagnosis of the etiology of diarrhea is required in order to implement the most adequate treatment in immunocompromised patients. Conventional diagnostic techniques, such as culture, microscopy and antigen detection, as well as one-target polymerase chain reaction (PCR) assays, are often laborious and time-consuming, and are only able to detect a limited number of pathogens. Taking these limitations into account faster and more sensitive molecular tests able to simultaneously detect a wide range of bacterial, viral and parasitic pathogens might be helpful in the case of these patients. Several studies have evaluated these assays in various settings, but their performance in hematological patients has yet to be determined [2][3]. The FilmArray GI panel (BioFire-bioMérieux, France) is a FDA-cleared assay that can detect 22 agents of gastroenteritis by a nested multiplex PCR method directly from stool samples, being a very rapid and easy-to-use technique. The aim of this study was to compare routine diagnostic methods with a multiplex PCR assay (BioFire FilmArray, Gastrointestinal Panel) and to determine the infectious etiology of acute diarrhea in immunocompromised hematologic patients. Material and methods Study design This was a prospective observational study carried out from between March 2015 to January 2016. Stool samples were obtained from immunocompromised adult patients (>18 years-old) admitted to the Hematology Department of the Hospital Clinic of Barcelona with acute diarrhea (increased frequency of soft or liquid stools (>3/day) lasting less than 14 days) [4]. Written consent was not obtained from the patients, as the samples were remmants of what had to be taken for other diagnostic purposes and the results would have no impact on the patients. The Ethics Committee of the Hospital Clinic of Barcelona approved the study. Immunosupression was defined as grades 3–4 neutropenia and/or lymphopenia by the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3.0 following the administration of cytotoxic agents or autologous stem-cell transplantation (auto-SCT) or during the first year after allogenic stem-cell transplantation (allo-SCT) [5]. Demographical data including age and sex, and clinical data (community or hospitalacquired di (...truncated)