evaluation of a molecular point of care testing for viral and atypical pathogens on CORD-Papers-2021-10-25 (Version 1)

Title: Evaluation of a molecular point-of-care testing for viral and atypical pathogens on intravenous antibiotic duration in hospitalized adults with lower respiratory tract infection: a randomized clinical trial
Abstract: OBJECTIVES: The primary objective was to evaluate whether a molecular point-of-care test (POCT) for viral and atypical pathogens added to routine real-time PCR could reduce duration of intravenous antibiotics in hospitalized patients with lower respiratory tract infection (LRTI) compared with routine real-time PCR. METHODS: In this single-centre, open-label, randomized controlled study, we enrolled hospitalized adults diagnosed with LRTI. Patients were randomized to an intervention group (POCT FilmArray Panel for 20 viruses, atypical pathogens and bacteria plus routine real-time PCR) or a control group (routine real-time PCR for ten pathogens). The primary outcome was duration of intravenous antibiotics during hospitalization. The secondary outcomes included length of stay, cost of hospitalization and de-escalation within 72 hours and between 72 hours and 7 days. Intention-to-treat analysis was used. RESULTS: Between October 2017 and July 2018, we enrolled 800 eligible patients (398 in the intervention group and 402 in the control group). Duration of intravenous antibiotics in the intervention group was shorter than in the control (7.0 days (interquartile range (IQR) 5.09.0) versus 8.0 days (IQR 6.011.0); p <0.001). Length of hospital stay in the intervention group was significantly shorter (8.0 days (IQR 7.011.0) versus 9.0 days (IQR 7.012.0; p <0.001) and the cost of hospitalization in the intervention group was significantly lower ($1804.7 (IQR 1298.42633.8) versus $2042.5 (IQR 1427.42926.2); p 0.002) than control group. More patients in the intervention group achieved de-escalation within 72 hours (7.9%, 29/367 versus 3.2%, 12/377; p 0.005) and between 72 hours and 7 days (29.7%, 109/367 versus 22.0%, 83/377; p 0.024). CONCLUSIONS: Use of molecular POCT testing for respiratory viruses and atypical pathogens might help to reduce intravenous antibiotic use in hospitalized LRTI patients. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03391076.
Published: 6/20/2019
Journal: Clin Microbiol Infect
DOI: 10.1016/j.cmi.2019.06.012
DOI_URL: http://doi.org/10.1016/j.cmi.2019.06.012
Author Name: Shengchen, D
Author link: https://covid19-data.nist.gov/pid/rest/local/author/shengchen_d
Author Name: Gu, X
Author link: https://covid19-data.nist.gov/pid/rest/local/author/gu_x
Author Name: Fan, G
Author link: https://covid19-data.nist.gov/pid/rest/local/author/fan_g
Author Name: Sun, R
Author link: https://covid19-data.nist.gov/pid/rest/local/author/sun_r
Author Name: Wang, Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/wang_y
Author Name: Yu, D
Author link: https://covid19-data.nist.gov/pid/rest/local/author/yu_d
Author Name: Li, H
Author link: https://covid19-data.nist.gov/pid/rest/local/author/li_h
Author Name: Zhou, F
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zhou_f
Author Name: Xiong, Z
Author link: https://covid19-data.nist.gov/pid/rest/local/author/xiong_z
Author Name: Lu, B
Author link: https://covid19-data.nist.gov/pid/rest/local/author/lu_b
Author Name: Zhu, G
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zhu_g
Author Name: Cao, B
Author link: https://covid19-data.nist.gov/pid/rest/local/author/cao_b
sha: c764cd38d032dac75b9a86b3d26877570b55dc14
license: no-cc
license_url: [no creative commons license associated]
source_x: Elsevier; Medline; PMC
source_x_url: https://www.elsevier.com/https://www.medline.com/https://www.ncbi.nlm.nih.gov/pubmed/
pubmed_id: 31229593
pubmed_id_url: https://www.ncbi.nlm.nih.gov/pubmed/31229593
pmcid: PMC7173318
pmcid_url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173318
url: https://doi.org/10.1016/j.cmi.2019.06.012 https://www.ncbi.nlm.nih.gov/pubmed/31229593/ https://www.sciencedirect.com/science/article/pii/S1198743X19303374 https://api.elsevier.com/content/article/pii/S1198743X19303374
has_full_text: TRUE
Keywords Extracted from Text Content: nasopharyngeal swab OC43 CIs HL adenovirus blood urea nitrogen ! BioM oxygen EpsteineBarr virus 245.8 (138.1e397.8 C reactive protein herpes simplex virus oral SD, LRTI patients haematological cancer tetracycline macrolide UT LRTI [3 1e2 moxifloxacin participants e1.5 parainfluenza virus cephalosporin human cytomegalovirus interstitial lung sputum 1804.7 (1298.4e2633.8) USA solid tumour HKU1 erythrocyte c 2 organ pulmonary b-lactamase/b-lactamase-inhibitors Pulmonary NL63 carbapenem enterovirus 2042.5 (1427.4e2926.2 nasopharyngeal swabs H7N9 upper respiratory infections human metapneumovirus Lower respiratory tract serum procalcitonin ChinaeJapan e1.6 intravenous e2.1 CJFH blood LRTI Patients Mycoplasma pneumoniae Plasmodium falciparum parainfluenza virus types 1 4 H1N1 Laboratory-developed patients BL bone marrow ± XG lung procalcitonin nasopharyngeal swab samples levofloxacin 5e7 penicillins human immunodeficiency virus coronaviruses https://doi.org/10.1016/j.cmi.2019.06.012 patients ChinaeJapan
Extracted Text Content in Record: First 5000 Characters:Lower respiratory tract infection (LRTI) is the leading infectious disease in the world [1] . It is also the fourth commonest cause of death globally, accounting for about 3.0 million deaths worldwide in 2016 [2] . Viral infection is one of the most important causes of LRTI [3] . Because of large overlap in symptoms and clinical presentation between bacterial and viral LRTI, antibiotics are inappropriately prescribed to patients with viral infection. This may result in potential risks of antimicrobial resistance with a corresponding financial burden and environmental pollution [4] . Furthermore, inappropriate prescription of antibiotics is even more critical in China, which ranks as the world's most frequent user of antibiotics [5, 6] . Overuse of intravenous antibiotics in patients hospitalized with LRTI constitutes an important part of the inappropriate prescription of antibiotics [7] . In one retrospective study in a teaching hospital in Beijing [8] , the median duration of intravenous antibiotics was 10 days (interquartile range 8e14 days) among hospitalized individuals with mild to moderate communityacquired pneumonia (CAP). Diagnostic uncertainty regarding the lack of microbiological evidence may be one of the most important reasons. Laboratory-developed PCR testing is highly accurate for the diagnosis of microbial aetiology, with the turnaround time generally being 1e2 days [9e11]. However, experienced specialists are required for this test and the instruments have to be installed in a central laboratory. FilmArray Respiratory Panel (BioFire; Salt Lake City, UT, USA) is a new molecular point-of-care test (POCT) platform, which can simultaneously detect 20 viruses and atypical pathogens and provide results in about 1 hour [12, 13] . The sensitivity and specificity of this new molecular POCT for detecting pathogens were high, with the sensitivity and specificity ranging from 92.3% to 97.9% and 96.1% to 99.1%, respectively [12, 13] . A recently published randomized controlled trial showed that use of the FilmArray Respiratory Panel was associated with reduction in proportion of antibiotic use among patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and asthma [9] . We speculated that molecular POCT for the detection of viruses might reduce the duration of antibiotic use in adult LRTI patients [14, 15] . Considering predominant overuse of intravenous antibiotics in China, the aim of this study was to evaluate whether combination of POCT and routine real-time PCR for pathogen detection could reduce duration and improve deescalation of intravenous antibiotics in individuals with LRTI compared with routine real-time PCR only. This was a single-centre, open-label, parallel randomized controlled study that took place between October 2017 and July 2018 in the ChinaeJapan Friendship Hospital (CJFH), Beijing, China (clinicaltrials.gov identifier: NCT03391076). CJFH is a large teaching hospital with 1600 beds. Patients were recruited from the general ward of the Department of Pulmonary and Critical Care Medicine, Department of Traditional Chinese Medicine Lung Disease and Department of Infectious Disease in CJFH. Hospitalized patients aged !18 years who were preliminarily diagnosed as radiographically confirmed CAP, AECOPD or acute exacerbation of bronchiectasis were recruited on the day of hospitalization. Patients were excluded if they were <18 years old, pregnant, had hospitalacquired pneumonia, or lung tuberculosis. We also excluded patients with human immunodeficiency virus infection, haematological cancer or solid tumour treated with chemotherapy or radiotherapy in the previous 3 months, organ or bone marrow transplantation, splenectomy, or autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, rheumatic polymyalgia and interstitial lung disease treated with immunosuppressive therapy for >3 weeks. In addition, patients with any other condition that may have increased serum procalcitonin levels, including severe burns, major surgical procedures, major trauma, long-term or severe cardiogenic shock, invasive fungal infection, or an acute attack of Plasmodium falciparum, were also excluded. This study was conducted in accordance with the Declaration of Helsinki. The study was approved by the ethics committee of CJFH (2017-29). Written informed consent was obtained from each participant after meeting inclusion criteria and before randomization. Random allocation sequence was generated using SPSS 22.0 software (Statistical Product and Service Solutions, IBM Co. Ltd, Armonk, NY, USA) with a fixed random seed. Simple randomization was conducted subsequently by sealing the group allocation cards into envelopes according to the sequence number. Each envelope was opened only when patients met inclusion criteria and signed informed consent, with allocation of patients to intervention or control group accordingly. Study participants, research staff and clinical
Keywords Extracted from PMC Text: –0.8 herpes simplex virus Lower respiratory tract human immunodeficiency virus nasopharyngeal swab samples parainfluenza virus types 1 4 SD, UT NL63 HL human metapneumovirus haematological cancer HKU1 CJFH USA [16], 10–14 blood Pulmonary interstitial lung BL cephalosporin tetracycline –1.5 Patients parainfluenza virus SD and DY narrower-spectrum XG β-lactamase/β-lactamase-inhibitors, macrolide erythrocyte Plasmodium falciparum OC43 Mycoplasma pneumoniae H1N1 bone marrow serum procalcitonin C reactive protein penicillins levofloxacin upper respiratory infections oxygen LRTI 245.8 (138.1–397.8 human cytomegalovirus 2042.5 (1427.4–2926.2); p 0.002). Epstein–Barr virus adenovirus [17] sputum LRTI [3 intravenous solid tumour China– organ 1804.7 (1298.4–2633.8 LRTI patients coronaviruses carbapenem, H7N9 procalcitonin 5–7 patients nasopharyngeal swabs pulmonary moxifloxacin lung 1–2 oral Laboratory-developed participants parts enterovirus –2.1 acute bronchiectasis [18 nasopharyngeal swab CIs
Extracted PMC Text Content in Record: First 5000 Characters:Lower respiratory tract infection (LRTI) is the leading infectious disease in the world [1]. It is also the fourth commonest cause of death globally, accounting for about 3.0 million deaths worldwide in 2016 [2]. Viral infection is one of the most important causes of LRTI [3]. Because of large overlap in symptoms and clinical presentation between bacterial and viral LRTI, antibiotics are inappropriately prescribed to patients with viral infection. This may result in potential risks of antimicrobial resistance with a corresponding financial burden and environmental pollution [4]. Furthermore, inappropriate prescription of antibiotics is even more critical in China, which ranks as the world's most frequent user of antibiotics [5], [6]. Overuse of intravenous antibiotics in patients hospitalized with LRTI constitutes an important part of the inappropriate prescription of antibiotics [7]. In one retrospective study in a teaching hospital in Beijing [8], the median duration of intravenous antibiotics was 10 days (interquartile range 8–14 days) among hospitalized individuals with mild to moderate community-acquired pneumonia (CAP). Diagnostic uncertainty regarding the lack of microbiological evidence may be one of the most important reasons. Laboratory-developed PCR testing is highly accurate for the diagnosis of microbial aetiology, with the turnaround time generally being 1–2 days [9], [10], [11]. However, experienced specialists are required for this test and the instruments have to be installed in a central laboratory. FilmArray Respiratory Panel (BioFire; Salt Lake City, UT, USA) is a new molecular point-of-care test (POCT) platform, which can simultaneously detect 20 viruses and atypical pathogens and provide results in about 1 hour [12], [13]. The sensitivity and specificity of this new molecular POCT for detecting pathogens were high, with the sensitivity and specificity ranging from 92.3% to 97.9% and 96.1% to 99.1%, respectively [12], [13]. A recently published randomized controlled trial showed that use of the FilmArray Respiratory Panel was associated with reduction in proportion of antibiotic use among patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and asthma [9]. We speculated that molecular POCT for the detection of viruses might reduce the duration of antibiotic use in adult LRTI patients [14], [15]. Considering predominant overuse of intravenous antibiotics in China, the aim of this study was to evaluate whether combination of POCT and routine real-time PCR for pathogen detection could reduce duration and improve de-escalation of intravenous antibiotics in individuals with LRTI compared with routine real-time PCR only. This was a single-centre, open-label, parallel randomized controlled study that took place between October 2017 and July 2018 in the China–Japan Friendship Hospital (CJFH), Beijing, China (clinicaltrials.gov identifier: NCT03391076). CJFH is a large teaching hospital with 1600 beds. Patients were recruited from the general ward of the Department of Pulmonary and Critical Care Medicine, Department of Traditional Chinese Medicine Lung Disease and Department of Infectious Disease in CJFH. Hospitalized patients aged ≥18 years who were preliminarily diagnosed as radiographically confirmed CAP, AECOPD or acute exacerbation of bronchiectasis were recruited on the day of hospitalization. Patients were excluded if they were <18 years old, pregnant, had hospital-acquired pneumonia, or lung tuberculosis. We also excluded patients with human immunodeficiency virus infection, haematological cancer or solid tumour treated with chemotherapy or radiotherapy in the previous 3 months, organ or bone marrow transplantation, splenectomy, or autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, rheumatic polymyalgia and interstitial lung disease treated with immunosuppressive therapy for >3 weeks. In addition, patients with any other condition that may have increased serum procalcitonin levels, including severe burns, major surgical procedures, major trauma, long-term or severe cardiogenic shock, invasive fungal infection, or an acute attack of Plasmodium falciparum, were also excluded. This study was conducted in accordance with the Declaration of Helsinki. The study was approved by the ethics committee of CJFH (2017-29). Written informed consent was obtained from each participant after meeting inclusion criteria and before randomization. Random allocation sequence was generated using SPSS 22.0 software (Statistical Product and Service Solutions, IBM Co. Ltd, Armonk, NY, USA) with a fixed random seed. Simple randomization was conducted subsequently by sealing the group allocation cards into envelopes according to the sequence number. Each envelope was opened only when patients met inclusion criteria and signed informed consent, with allocation of patients to intervention or control group accordingly. Study participants, research staff and
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