Clinical Impact of a Multiplex Gastrointestinal Polymerase Chain Reaction Panel in Patients With Acute Gastroenteritis

Clinical Infectious Diseases MAJOR ARTICLE Clinical Impact of a Multiplex Gastrointestinal Polymerase Chain Reaction Panel in Patients With Acute Gastroenteritis Robert J. Cybulski Jr,1,a Allen C. Bateman,1,a,b Lori Bourassa,1 Andrew Bryan,1 Barb Beail,1 Jason Matsumoto,2 Brad T. Cookson,1,3 and Ferric C. Fang1,2,3,4 1 Department of Laboratory Medicine, University of Washington, 2Harborview Medical Center Clinical Microbiology Laboratory, 3Department of Microbiology, University of Washington, and University of Washington School of Medicine, Seattle 4 Accurate and timely diagnosis of acute gastroenteritis is an unmet clinical and public health need [1, 2], as diarrhea remains a leading cause of morbidity and mortality worldwide [3, 4]. Approximately 80% of acute gastroenteritis cases are presently unattributed [4], partly due to insensitive and pathogen-specific diagnostic tests [1, 5, 6]. Multiplex nucleic acid amplification testing provides a rapid turnaround time and allows clinicians to test on the basis of clinical syndromes [7–9], recognizing the overlapping clinical presentations of various gastrointestinal infections [10]. Many pathogens identified by multiplex panels respond to antimicrobial therapy [11–20], offering potential benefits from timely results that enable targeted therapy and the detection of Shiga-like toxin producing E. coli (STEC), for which antibiotics are Received 6 March 2018; editorial decision 17 April 2018; accepted 20 April 2018; published online April 25, 2018. a R. J. C. and A. C. B. contributed equally to the work. b Present address: Communicable Disease Division, Wisconsin State Laboratory of Hygiene, Madison. Correspondence: F. C. Fang, University of Washington School of Medicine, 1959 NE Pacific St, Box 357735, Seattle, WA 98195-7735 (). Clinical Infectious Diseases®  2018;67(11):1688–96 © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: . DOI: 10.1093/cid/ciy357 1688 • CID 2018:67 (1 December) • Cybulski et al contraindicated [21, 22]. Multiplex testing improves laboratory workflow [23] and can enhance infection control by increasing outbreak detection [24] and guiding contact precaution decisions [25]. Questions remain regarding the costs and benefits of multiplex panels. Increasing reliance upon molecular assays may increase public health awareness of disease incidence, but fewer cultured isolates may be available for outbreak investigations [26, 27]. Benefits realized from multiplex syndromic testing may vary among patient populations [28–31]. Whether additional cases of infectious gastroenteritis diagnosed by multiplex polymerase chain reaction (PCR) warrant antimicrobial treatment is also debated, and the clinical impact of multiplex panels is uncertain in the absence of coordinated stewardship efforts [32, 33]. We undertook a 9-month, prospective, multi-center study with parallel testing of stool specimens by the BioFire FilmArray Gastrointestinal PCR panel and conventional methods. The objectives were to determine whether the additional patients detected by multiplex PCR had comparable clinical features to those diagnosed with conventional methods and to measure the impact of more rapid diagnoses on clinical decision-making and therapy. Background. Molecular syndromic diagnostic panels can enhance pathogen identification in the approximately 2–4 billion episodes of acute gastroenteritis that occur annually worldwide. However, the clinical utility of these panels has not been established. Methods. We conducted a prospective, multi-center study to investigate the impact of the BioFire FilmArray Gastrointestinal polymerase chain reaction panel on clinical diagnosis and decision-making, and compared the clinical acuity of patients with positive results obtained exclusively with the FilmArray with those detected by conventional stool culture. A total of 1887 consecutive fecal specimens were tested in parallel by FilmArray and stool culture. Laboratory and medical records were reviewed to determine rates of detection, turnaround times, clinical features, and the nature and timing of clinical decisions. Results. FilmArray detected pathogens in 35.3% of specimens, compared to 6.0% for culture. Median time from collection to result was 18 hours for FilmArray and 47 hours for culture. Median time from collection to initiation of antimicrobial therapy was 22 hours for FilmArray and 72 hours for culture. Patients diagnosed by FilmArray were more likely to receive targeted rather than empirical therapy, compared to those diagnosed by culture (P = .0148). Positive Shiga-like toxin-producing E. coli results were reported 47 hours faster with FilmArray and facilitated discontinuation of empirical antimicrobials. Patients diagnosed exclusively by FilmArray had clinical characteristics similar to those identified by culture. Conclusions. FilmArray markedly improved clinical sensitivity in patients with acute diarrhea, identified cases with clinical acuity comparable to those identified by culture, and enabled clinicians to make more timely and targeted therapeutic decisions. Keywords. acute gastroenteritis; multiplex PCR panel; syndromic testing; culture-independent diagnostic test. METHODS Study Design, Population, and Procedures Record numbers were obtained from the laboratory information system for patients testing positive either by culture from January to September 2016 or by any method from January to September 2017 for chart review. For the 2017 cohort, 14 patients lacking documentation of clinical findings were excluded, although their test results were included in the analyses of clinical sensitivity and time to diagnosis. Electronic chart review was performed by 4 doctoral-level clinical microbiologists and overseen by the corresponding author, who is a physician and infectious disease specialist. For initial training and standardization, 10 charts were reviewed by all 4 reviewers; charts were subsequently reviewed by individual reviewers. Collected information included clinical signs and symptoms of gastroenteritis (fever, nausea, vomiting, diarrhea, abdominal pain, tenesmus, hematochezia, duration of symptoms, mucus, nature of stool, elevated white blood cell count) and antimicrobial treatment. Time of sample collection, arrival in the laboratory, and result reporting were obtained from the laboratory information system. Antibiotics were estimated to be prescribed at 5 pm on the day on which they were ordered. Empirical antimicrobial therapy was defined as therapy initiated prior to the release of results. Targeted therapy was defined on the basis of documentation that the primary clinician received a result and then prescribed an agent with predicted activity against the microbe detected. Statistical Analysis Clinical sensitivity was defined as the ability to detect a pathogen when the pathogen is present in a clinic (...truncated)