Multicenter evaluation of a syndromic rapid multiplex PCR test for early adaptation of antimicrobial therapy in adult patients with pneumonia

Monard et al. Critical Care (2020) 24:434 https://doi.org/10.1186/s13054-020-03114-y RESEARCH Open Access Multicenter evaluation of a syndromic rapid multiplex PCR test for early adaptation of antimicrobial therapy in adult patients with pneumonia Céline Monard1, Jonathan Pehlivan2, Gabriel Auger3,4, Sophie Alviset5, Alexy Tran Dinh6,7, Paul Duquaire1, Nabil Gastli8, Camille d’Humières9,10, Adel Maamar11,12, André Boibieux13, Marion Baldeyrou14, Julien Loubinoux15, Olivier Dauwalder16,17, Vincent Cattoir3,18,19, Laurence Armand-Lefèvre9,10, Solen Kernéis 5,10* and the ADAPT study group Abstract Background: Improving timeliness of pathogen identification is crucial to allow early adaptation of antibiotic therapy and improve prognosis in patients with pneumonia. We evaluated the relevance of a new syndromic rapid multiplex PCR test (rm-PCR) on respiratory samples to guide empirical antimicrobial therapy in adult patients with communityacquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-acquired pneumonia (VAP). Methods: This retrospective multicenter study was conducted in four French university hospitals. Respiratory samples were obtained from patients with clinical and radiological signs of pneumonia and simultaneously tested using conventional microbiological methods and the rm-PCR. A committee composed of an intensivist, a microbiologist, and an infectious diseases specialist retrospectively assessed all medical files and agreed on the most appropriate antimicrobial therapy for each pneumonia episode, according to the results of rm-PCR and blinded to the culture results. The rm-PCR-guided antimicrobial regimen was compared to the empirical treatment routinely administered to the patient in standard care. Results: We included 159 pneumonia episodes. Most patients were hospitalized in intensive care units (n = 129, 81%), and episodes were HAP (n = 68, 43%), CAP (n = 54, 34%), and VAP (n = 37, 23%). Conventional culture isolated ≥ 1 microorganism(s) at significant level in 95 (60%) patients. The syndromic rm-PCR detected at least one bacteria in 132 (83%) episodes. Based on the results of the rm-PCR, the multidisciplinary committee proposed a modification of the empirical therapy in 123 (77%) pneumonia episodes. The modification was a de-escalation in 63 (40%), an escalation in 35 (22%), and undetermined in 25 (16%) patients. In microbiologically documented episodes (n = 95), the rm-PCR increased appropriateness of the empirical therapy to 83 (87%), as compared to 73 (77%) in routine care. (Continued on next page) * Correspondence: 5 Equipe Mobile d’Infectiologie, APHP, Hôpital Cochin, Centre Université de Paris, Paris, France 10 IAME, INSERM, Université de Paris, Paris, France Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Monard et al. Critical Care (2020) 24:434 Page 2 of 11 (Continued from previous page) Conclusions: Use of a syndromic rm-PCR test has the potential to reduce unnecessary antimicrobial exposure and increase the appropriateness of empirical antibiotic therapy in adult patients with pneumonia. Keywords: Antimicrobials, Antimicrobial stewardship, Pneumonia, Multiplex PCR, Syndromic tests, Biofire® FilmArray® Background Inadequate and delayed empirical treatments are strong predictors of mortality in sepsis [1, 2]. Therefore, in pneumonia patients, international guidelines state that an attempt should be made to obtain respiratory samples and recommend to start early empirical treatment while awaiting for the results of culture and antimicrobial susceptibility testing (AST) [3]. For severe patients or those with risk factors of multidrug-resistant organisms (MDRO), the empirical treatment should include a broad-spectrum antibiotic [4, 5]. However, conventional microbiological techniques have a low sensitivity, particularly on microbiological samples collected in non-intubated patients and in case of prior exposure to antibiotics [6, 7]. The lack of a reliable microbiological diagnosis thus prevents from deescalating the empirical regimen in a large proportion of patients [8]. Identification of causative microorganisms provides the potential to target antibiotic therapy, but the turnaround time from microbiological sampling to AST usually requires at least 48 h. New molecular diagnostic tools aim at shortening this time. Syndromic rapid multiplex PCR (rm-PCR) can be used for simultaneous detection of multiple organisms and resistance markers in a specific clinical context, within a few hours [9]. Alongside with antimicrobial stewardship (AMS), the use of rm-PCR has been shown to significantly decrease time-to-appropriate therapy and optimize clinical and economic outcomes [10, 11]. During a previous evaluation in community-acquired pneumonia, a rm-PCR assay achieved pathogen detection in 87% of patients compared to 39% using culture-based methods [12]. In addition, in this population, molecular testing had the potential to lead to a de-escalation in the number and/or spectrum of initial empirical antibiotics in 77% of patients. The BioFire® FilmArray® Pneumonia Panel (bioMerieux S.A., Marcy-l’Etoile, France) is a novel assay able to simultaneously identify 27 of the most common pathogens involved in lower respiratory tract infections (semi-quantitative results for 11 Gram-negative and 4 Gram-positive bacteria, qualitative results for 3 atypical bacteria and 9 viruses) as well as 7 antibiotic resistance genes (Fig. 1). Two studies have found excellent agreement between this molecular method and standard culture [13, 14]. Our main objective was to estimate the potential impact of this new syndromic rm-PCR assay on early adaptation of empirical antimicrobial therapy in adult patients with pneumonia. Methods Settings and participants Between July and December 2018, 11 French university hospitals participated in a pre-commercializatio (...truncated)