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Rafiei N, Subedi S, Harris PN, Paterson DL. Clinical and cost implications of Biofire FilmArray® meningitis / encephalitis panel testing: a systematic review. Diagn Microbiol Infect Dis 2025; 112:116823. [PMID: 40158249 DOI: 10.1016/j.diagmicrobio.2025.116823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 03/18/2025] [Accepted: 03/21/2025] [Indexed: 04/02/2025]
Abstract
BACKGROUND Meningitis and encephalitis are diseases with high case fatality rates and serious long-term sequalae. A significant percentage do not receive an aetiological diagnosis, in part due to limitations of conventional testing methods. The Biofire FilmArray® Meningitis / Encephalitis Panel (MEP) is the first commercially approved multiplex PCR panel for diagnosis of infectious meningoencephalitis. It provides rapid results and has the potential to reduce empiric antimicrobial use and length of hospitalisation when compared to conventional testing. METHODS We conducted a systematic review to evaluate the impact of MEP implementation by searching the Medline and Embase databases. The outcomes of interest were duration of acyclovir treatment, duration of antimicrobials, length of stay and healthcare cost. RESULTS A total of 23 studies satisfied the inclusion criteria, the majority of which were retrospective studies comparing cohorts before and after MEP implementation. The included studies were very heterogenous, with variation in MEP implementation strategies, standard of care diagnostics and study populations. MEP testing resulted in reduction in acyclovir use in 75 % of studies with an average reduction of 39 h (range 11-144 h). Antimicrobial use and length of stay was reduced in 44 % and 40 % of studies respectively. Five studies looked at healthcare costs, variably described between studies as hospitalisation, antimicrobial and microbiology costs. Total hospitalisation cost was reduced in 1 study and unchanged in 2 studies. CONCLUSION Whilst MEP implementation reduces acyclovir usage in patients evaluated for ME, the benefits in terms of antibiotic use, and length of stay are variable and likely depend on the study population, implementation strategy and standard of care testing available in each institution.
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Affiliation(s)
- Nastaran Rafiei
- Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Australia; Caboolture Hospital, Queensland, Australia.
| | - Shradha Subedi
- Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Australia; Sunshine Coast University Hospital and Health Service, Queensland, Australia; Pathology Queensland, Queensland, Australia
| | - Patrick Na Harris
- Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Australia; Pathology Queensland, Queensland, Australia
| | - David L Paterson
- Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Australia; National University of Singapore, Singapore
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Phillips K, Nirantharakumar K, Wakerley BR, Crowe FL. Trends in the prevalence and pharmacological management of migraine during pregnancy in the UK, 2000-2018. J Neurol Neurosurg Psychiatry 2024; 95:938-946. [PMID: 38569874 PMCID: PMC11420713 DOI: 10.1136/jnnp-2024-333530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Accepted: 03/19/2024] [Indexed: 04/05/2024]
Abstract
BACKGROUND Migraine is common in women of reproductive age. This study aimed to (1) describe the prevalence of migraine in pregnant women in the UK, (2) identify drugs commonly prescribed for migraine during pregnancy and (3) identify characteristics associated with being prescribed medication for migraine during pregnancy. METHODS The Clinical Practice Research Datalink pregnancy register, a database of pregnancy episodes identified in anonymised primary care health records, was used.Crude and age-standardised prevalence of migraine during pregnancy and the proportion of women with migraine prescribed drugs used for migraine management were calculated for each year between 2000 and 2018.Logistic regression was used to describe the relationship between patient characteristics and being prescribed migraine medication during pregnancy. RESULTS 1 377 053 pregnancies were included, of which 187 328 were in women with a history of migraine. The age-adjusted prevalence increased from 11.4% in 2000 to 17.2% in 2018. There was an increase in the rates of prescription for numerous medications for the management of migraine.Older women (adjusted OR (aOR) 1.41 (1.20 to 1.66)), women of black (aOR 1.40 (1.32 to 1.48)) and South Asian ethnicity (aOR 1.48 (1.38 to 1.59)), those living in the most deprived areas (aOR 1.60 (1.54 to 1.66)), women who were obese (aOR 1.39 (1.35 to 1.43)), smokers (aOR 1.15 (1.12 to 1.18)) and those with comorbid conditions were more likely to receive a prescription during pregnancy. CONCLUSIONS Rates of recorded migraine have increased over the past two decades as well as rates of prescribing in women with migraine. Higher prescribing rates are seen in certain groups, which has the potential to exacerbate health inequalities.
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Affiliation(s)
- Katherine Phillips
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Krishnarajah Nirantharakumar
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
- Midlands Health Data Research UK, University of Birmingham, Birmingham, UK
| | - Benjamin R Wakerley
- Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
- Department of Neurology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Francesca L Crowe
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
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Milburn J, Suresh R, Doyle R, Jarvis JN. The diagnosis of central nervous system infections in resource-limited settings and the use of novel and molecular diagnostic platforms to improve diagnosis. Expert Rev Mol Diagn 2024; 24:219-230. [PMID: 38369939 DOI: 10.1080/14737159.2024.2317414] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Accepted: 02/07/2024] [Indexed: 02/20/2024]
Abstract
INTRODUCTION Central nervous system infections (CNSI) disproportionately affect individuals in low-resource settings where diagnosis is challenging; large proportions of patients never receive a confirmed microbiological diagnosis resulting in inadequate management and high mortality. The epidemiology of CNSI varies globally and conventional diagnostics deployed in resource-limited settings have significant limitations, with an urgent need for improved diagnostic strategies. AREAS COVERED This review describes molecular platforms and other novel diagnostics used in the diagnosis of CNSI that are applicable to resource-limited settings. An extensive literature search of Medline and PubMed was performed. The emphasis is on investigations targeting infections of relevance to resource-limited settings either due to variation in regional CNSI epidemiology or due to increased prevalence in patients with immunosuppression. This includes commercially available multiplex PCR platforms, mycobacterial PCR platforms, and rapid diagnostics tests. To offer a framework for the optimal implementation in clinical settings, existing evidence highlighting the advantages and limitations of available platforms is reviewed. EXPERT OPINION The implementation of molecular platforms and other novel diagnostics has the potential to transform CNSI diagnosis in resource-limited settings, with several examples of successful rollout of novel diagnostics such as Xpert MTB/RIF Ultra and cryptococcal antigen testing.
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Affiliation(s)
- James Milburn
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana
- Department of Clinical Research, Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
| | - Rachita Suresh
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana
| | - Ronan Doyle
- Department of Clinical Research, Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
| | - Joseph N Jarvis
- Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana
- Department of Clinical Research, Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
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Ivaska L, Herberg J, Sadarangani M. Distinguishing community-acquired bacterial and viral meningitis: Microbes and biomarkers. J Infect 2024; 88:106111. [PMID: 38307149 DOI: 10.1016/j.jinf.2024.01.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 01/16/2024] [Accepted: 01/22/2024] [Indexed: 02/04/2024]
Abstract
Diagnostic tools to differentiate between community-acquired bacterial and viral meningitis are essential to target the potentially lifesaving antibiotic treatment to those at greatest risk and concurrently spare patients with viral meningitis from the disadvantages of antibiotics. In addition, excluding bacterial meningitis and thus decreasing antibiotic consumption would be important to help reduce antimicrobial resistance and healthcare expenses. The available diagnostic laboratory tests for differentiating bacterial and viral meningitis can be divided microbiological pathogen-focussed methods and biomarkers of the host response. Bacterial culture-independent microbiological methods, such as highly multiplexed nucleic acid amplification tests, are rapidly making their way into the clinical practice. At the same time, more conventional host protein biomarkers, such as procalcitonin and C-reactive protein, are supplemented by newer proteomic and transcriptomic signatures. This review aims to summarise the current state and the recent advances in diagnostic methods to differentiate bacterial from viral meningitis.
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Affiliation(s)
- Lauri Ivaska
- Department of Paediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Savitehtaankatu 5, 20521 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Kiinanmyllynkatu 10, 20520 Turku, Finland.
| | - Jethro Herberg
- Section of Paediatric Infectious Disease, Faculty of Medicine, Imperial College London, Norfolk Place, London, United Kingdom.
| | - Manish Sadarangani
- Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada; Vaccine Evaluation Center, BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
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Sunnerhagen T, Widén J, Handhal S, Özkaya Şahin G. A retrospective observational study of 1000 consecutive patients tested with the FilmArray® Meningitis/Encephalitis panel: clinical diagnosis at discharge and microbiological findings. Sci Rep 2024; 14:4015. [PMID: 38369552 PMCID: PMC10874959 DOI: 10.1038/s41598-024-54621-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2023] [Accepted: 02/14/2024] [Indexed: 02/20/2024] Open
Abstract
FilmArray® Meningitis/Encephalitis panel (FAME-p) is used to diagnose central nervous system (CNS) infections. In this study, we investigated performance of FAME-p compared to comparator assays (CA), and for the first time, clinical diagnosis at discharge (CDD). 1000 consecutive patients with a cerebrospinal fluid (CSF) sample analyzed with FAME-p were identified. As CA, culture, polymerase chain reaction and cryptococcal antigen test were used. Medical records of patients were obtained. A CDD of CNS infection was made in 139 of 1000 CSF samples. FAME-p was positive in 66 samples with 44 viral and 22 bacterial agents. Thirteen FAME-p findings were not confirmed by CA, with four discrepant results remaining after comparison with the CDD. Positive percentage agreement (PPA) calculated against CA was 100%. Negative percentage agreement (NPA) calculated against CA was 94.4-99.8% for Haemophilus influenzae, Listeria monocytogenes, Streptococcus agalactiae, S. pneumoniae and varicella-zoster virus (VZV). NPA calculated against CDD was higher (compared to CA) for L. monocytogenes, S. agalactiae and VZV (100%), and lower for Escherichia coli, enterovirus and herpes simplex virus 2 (50-83.3%). NPA of FAME-p for human herpes virus 6 was difficult to interpret. Eighty-four cases received diagnosis of CNS-infection despite negative FAME-p. The four most common non-infectious etiologies were primary headache disorders, cranial nerve palsies, neuroinflammatory disorders and seizure. Although FAME-p shows good performance in diagnosis of CNS infections, result of FAME-p should be interpreted carefully. Considering infectious diseases not covered by FAME-p as well as non-infectious differential diagnoses is important in this context.
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Affiliation(s)
- Torgny Sunnerhagen
- Clinical Microbiology, Infection Prevention and Control, Office for Medical Services, Region Skåne, Lund, Sweden.
- Division of Infection Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
| | - Johan Widén
- Division of Infection Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden
- Clinic of Infectious Diseases, Skåne University Hospital, Lund, Sweden
| | - Sahar Handhal
- Clinical Microbiology, Infection Prevention and Control, Office for Medical Services, Region Skåne, Lund, Sweden
| | - Gülşen Özkaya Şahin
- Clinical Microbiology, Infection Prevention and Control, Office for Medical Services, Region Skåne, Lund, Sweden
- Division of Medical Microbiology, Department of Laboratory Medicine Lund, Medical Faculty, Lund University, Lund, Sweden
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Ota K, Fujiwara S, Ishii J, Yoshimura H, Kohara N, Kawamoto M. [Efficacy of FilmArray ® ME panel for the rapid diagnosis of meningitis and encephalitis]. Rinsho Shinkeigaku 2023; 63:528-531. [PMID: 37518019 DOI: 10.5692/clinicalneurol.cn-001840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/01/2023]
Abstract
Microbial tests are essential for appropriate management for acute meningitis and encephalitis, but it often takes several days to identify the results of culture tests or PCR. BioFire FilmArray® meningitis/encephalitis panel (ME panel) is a rapid multiplex PCR assay that targets 14 bacteria, viruses, and yeast in 1 hour. In this single-center retrospective study, we reviewed adult patients who underwent ME panel test in parallel with conventional microbial tests from January to August 2021. Eighteen of 70 patients (26%) tested positive by ME panel, of which 8 patients (11%) were helpful in altering treatment strategy. Fifty-two patients (74%) could stop empirical treatment such as acyclovir or antibiotics due to negative results on ME panel. All results of ME panel were same as traditional assays. Use of ME panel can contribute to early diagnosis and treatment.
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Affiliation(s)
- Kazuma Ota
- Department of Neurology, Kobe City Medical Center General Hospital
| | - Satoru Fujiwara
- Department of Neurology, Kobe City Medical Center General Hospital
| | - Junko Ishii
- Department of Neurology, Kobe City Medical Center General Hospital
| | - Hajime Yoshimura
- Department of Neurology, Kobe City Medical Center General Hospital
| | - Nobuo Kohara
- Department of Neurology, Kobe City Medical Center General Hospital
| | - Michi Kawamoto
- Department of Neurology, Kobe City Medical Center General Hospital
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Debbagh F, Harrar S, Babokh F, Lamrani Hanchi A, Soraa N. The Contribution of Multiplex Polymerase Chain Reaction in the Diagnosis of Central Nervous System Infections in Intensive Care Units. Cureus 2023; 15:e35338. [PMID: 36851943 PMCID: PMC9963464 DOI: 10.7759/cureus.35338] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/22/2023] [Indexed: 02/25/2023] Open
Abstract
Introduction The aim of this study was to evaluate the contribution and limits of BioFire® FilmArray® meningitis/encephalitis panel (FA MEP) polymerase chain reaction (PCR) (bioMérieux, Marcy-l'Étoile, France) (product references: LLC RFIT-ASY-0118) coupled with bacterial and fungal culture in the diagnosis of central nervous system infections (CNSIs). Methods This was a retrospective observational study including all patients (adults and children) hospitalized in the intensive care units (ICUs) of a Moroccan university hospital, who benefited from multiplex PCR on a cerebrospinal fluid (CSF) sample. Results A total of 112 PCRs were performed, with a positivity rate of 18%. Bacterial etiology was the most frequent (70%), represented mainly by Streptococcus pneumoniae (45%), followed by viruses (25%), with four isolates of Herpes simplex virus (HSV) 1. On 94 samples, there was an agreement between the culture and PCR results. Their discordance was found in 18 cases, including 16 suspected CNSIs recovered only by PCR and two diagnoses confirmed only by bacterial culture. Conclusion This study revealed the significant impact of multiplex PCR on the early and targeted diagnostic and therapeutic management of infectious meningitis and meningoencephalitis in intensive care unit patients.
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Affiliation(s)
- Fayrouz Debbagh
- Microbiology Laboratory, Faculty of Medicine and Pharmacy, Mohammed VI University Hospital of Marrakech, Cadi Ayyad University, Marrakech, MAR.,Biochemistry-Toxicology Laboratory, Avicenna Military Hospital, Marrakech, MAR
| | - Sara Harrar
- Microbiology Department, Arrazi Hospital, Mohammed VI University Hospital of Marrakech, Marrakech, MAR
| | - Fatima Babokh
- Biology Department/Parasitology and Mycology Laboratory, Faculty of Medicine and Pharmacy, Mohammed VI University Hospital of Marrakech, Cadi Ayyad University, Marrakech, MAR
| | - Asma Lamrani Hanchi
- Microbiology Department, Arrazi Hospital, Mohammed VI University Hospital of Marrakech, Marrakech, MAR
| | - Nabila Soraa
- Microbiology Laboratory, Arrazi Hospital, Mohammed VI University Hospital of Marrakech, Marrakech, MAR
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Yadav D, Singh O, Juneja D, Goel A, Kataria S, Beniwal A. Role of cerebrospinal fluid lactate in diagnosing meningitis in critically ill patients. World J Crit Care Med 2023; 12:1-9. [PMID: 36683964 PMCID: PMC9846869 DOI: 10.5492/wjccm.v12.i1.1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 11/30/2022] [Accepted: 12/23/2022] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Meningitis is a life-threatening clinical condition associated with high mortality and morbidity. Early diagnosis and specific treatment may improve outcomes. Lack of specific clinical signs or tests make the diagnosis challenging. AIM To assess the efficacy of cerebrospinal fluid (CSF) lactate in diagnosing meningitis in critically ill patients. METHODS A prospective, observational cohort study was carried out in a neuro-medical intensive care unit (ICU) over a 22 mo period. Adult patients, with suspected meningitis admitted in ICU, were serially recruited. Patients who refused consent, those with peripheral sensorineural deficit, or with any contraindication to lumber puncture were excluded. CSF cytology, bio-chemistry, lactates, culture and polymerase chain reaction based meningo-encephalitis panel were evaluated. Patients were divided in two groups based on clinical diagnosis of meningitis. The efficacy of CSF lactate in diagnosing meningitis was evaluated and compared with other tests. RESULTS Seventy-one patients were included and 23 were diagnosed with meningitis. The mean values of CSF total leucocyte count (TLC), proteins and lactates were significantly higher in meningitis group. There was a significant correlation of CSF lactate levels with CSF cultures and meningo-encephalitis panel. CSF lactate (> 2.72 mmol/L) showed good accuracy in diagnosing meningitis with an area under the curve of 0.81 (95% confidence interval: 0.69-0.93), sensitivity of 82.6%, and specificity 72.9%. These values were comparable to those of CSF TLC and protein. Twelve patients with bacterial meningitis had significantly higher CSF lactate (8.9 ± 4.7 mmol/L) than those with non-bacterial meningitis (4.2 ± 3.8 mmol/L), P = 0.006. CONCLUSION CSF lactate may be used to aid in our diagnosis of meningitis in ICU patients. CSF lactate (> 2.72 mmol/L) showed good accuracy, sensitivity, and specificity in diagnosing meningitis and may also help to differentiate between bacterial and non-bacterial meningitis.
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Affiliation(s)
- Devraj Yadav
- Institute of Critical Care Medicine, Max Super Speciality Hospital, Saket, New Delhi 110017, India
| | - Omender Singh
- Institute of Critical Care Medicine, Max Super Speciality Hospital, Saket, New Delhi 110017, India
| | - Deven Juneja
- Institute of Critical Care Medicine, Max Super Speciality Hospital, Saket, New Delhi 110017, India
| | - Amit Goel
- Institute of Critical Care Medicine, Max Super Speciality Hospital, Saket, New Delhi 110017, India
| | - Sahil Kataria
- Institute of Critical Care Medicine, Max Super Speciality Hospital, Saket, New Delhi 110017, India
| | - Anisha Beniwal
- Institute of Critical Care Medicine, Max Super Speciality Hospital, Saket, New Delhi 110017, India
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Dahan S, Azrad M, Abozaid S, Glikman D, Zayyad H, Zaidman-Shimshovitz A, Peretz A. Assessing the impact of a positive Biofire® FilmArray® Meningitis/Encephalitis Panel result on clinical management and outcomes. Diagn Microbiol Infect Dis 2022; 104:115769. [DOI: 10.1016/j.diagmicrobio.2022.115769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 07/03/2022] [Accepted: 07/12/2022] [Indexed: 11/03/2022]
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Trujillo-Gómez J, Tsokani S, Arango-Ferreira C, Atehortúa-Muñoz S, Jimenez-Villegas MJ, Serrano-Tabares C, Veroniki AA, Florez ID. Biofire FilmArray Meningitis/Encephalitis panel for the aetiological diagnosis of central nervous system infections: A systematic review and diagnostic test accuracy meta-analysis. EClinicalMedicine 2022; 44:101275. [PMID: 35198914 PMCID: PMC8851290 DOI: 10.1016/j.eclinm.2022.101275] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 12/30/2021] [Accepted: 01/07/2022] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND The FilmArray Meningitis/Encephalitis(FA/ME) panel brings benefits in clinical practice, but its diagnostic test accuracy (DTA) remains unclear. We aimed to determine the DTA of FA/ME for the aetiological diagnostic in patients with suspected central nervous system(CNS) infection. METHODS We performed a systematic review with DTA meta-analysis (PROSPERO: CRD42020139285). We searched Embase, Medline (Ovid), and Web of Science from inception until September 1st, 2021. We assessed the study-level risk of bias with the QUADAS-2 tool and applied the GRADE approach to assess the certainty of the synthesised evidence. We included studies that simultaneously measured the reference test (CSF/blood culture for bacteria, and specific polymerase chain reaction for viruses) and the FA/ME in patients with suspected CNS infection. We performed random-effects bivariate meta-analysis models of combined sensitivity and specificity using CSF/blood cultures(reference test 1) and a final diagnosis adjudication based on clinical/laboratory criteria (reference test 2). FINDINGS We included 19 studies (11,351 participants). For all bacteria with reference test 1 (16 studies/6183 patients) sensitivity was estimated at 89·5% (95%CI 81·1-94·4), and specificity at 97·4% (95%CI 94-98·9). With reference test 2 (15 studies/5,524 patients), sensitivity was estimated at 92·1%(95%CI 86·8-95·3) and specificity at 99.2(95%CI 98·3-99·6) For herpes simplex virus-2(HSV-2), enteroviruses, and Varicella-Zoster virus (VZV), we obtained sensitivities between 75·5 and 93·8%, and specificities above 99% (reference test 1). Certainty of the evidence was low. INTERPRETATION FA/ME may have acceptable-to-high sensitivities and high specificities for identifying bacteria, especially for S.pneumoniae, and viruses, especially for HSV-2, and enteroviruses. Sensitivities for L.monocytogenes, H.influenzae, E.coli, and HSV-1 were suboptimal. FUNDING None.
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Affiliation(s)
- Juliana Trujillo-Gómez
- Department of Paediatrics, Universidad de Antioquia, Calle 67 No. 53-108, Medellín, Antioquia 050001, Colombia
- Hospital San Vicente Fundacion, Calle 64 # 51D - 154, Medellín 050010, Colombia
- Hospital General de Medellín, Carrera 48 # 32-102, Medellín 0500515, Colombia
| | - Sofia Tsokani
- Department of Primary Education, School of Education, University of Ioannina, PO Box: 1186, Ioannina 45110, Greece
| | - Catalina Arango-Ferreira
- Department of Paediatrics, Universidad de Antioquia, Calle 67 No. 53-108, Medellín, Antioquia 050001, Colombia
- Hospital San Vicente Fundacion, Calle 64 # 51D - 154, Medellín 050010, Colombia
| | | | - Maria José Jimenez-Villegas
- Department of Paediatrics, Universidad de Antioquia, Calle 67 No. 53-108, Medellín, Antioquia 050001, Colombia
- Hospital San Vicente Fundacion, Calle 64 # 51D - 154, Medellín 050010, Colombia
| | - Carolina Serrano-Tabares
- Department of Paediatrics, Universidad de Antioquia, Calle 67 No. 53-108, Medellín, Antioquia 050001, Colombia
- Clínica Universitaria Bolivariana, Carrera 72A # 78b -50, Medellín 050015, Colombia
| | - Areti-Angeliki Veroniki
- St. Michael's Hospital, Li Ka Shing Knowledge Institute, 8 Shuter St, Toronto, ON M5B 1A6, Canada
| | - Ivan D. Florez
- Department of Paediatrics, Universidad de Antioquia, Calle 67 No. 53-108, Medellín, Antioquia 050001, Colombia
- School of Rehabilitation Science, McMaster University, 1400 Main St. W. Hamilton, Hamilton, ON L8S 1C7, Canada
- Paediatric Intensive Care Unit, Clínica Las Americas AUNA, Dg. 75B ##2A-80/140, Medellin, Colombia
- Corresponding author at: Department of Paediatrics, Universidad de Antioquia, Calle 67 No. 53-108, Medellín, Antioquia 050001, Colombia.
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Dumkow LE, Worden LJ, Rao SN. Syndromic diagnostic testing: a new way to approach patient care in the treatment of infectious diseases. J Antimicrob Chemother 2021; 76:iii4-iii11. [PMID: 34555157 PMCID: PMC8460095 DOI: 10.1093/jac/dkab245] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Advanced microbiology technologies such as multiplex molecular assays (i.e. syndromic diagnostic tests) are a novel approach to the rapid diagnosis of common infectious diseases. As the global burden of antimicrobial resistance continues to rise, the judicious use of antimicrobials is of utmost importance. Syndromic panels are now being recognized in some clinical practice guidelines as a 'game-changer' in the diagnosis of infectious diseases. These syndromic panels, if implemented thoughtfully and interpreted carefully, have the potential to improve patient outcomes through improved clinical decision making, optimized laboratory workflow, and enhanced antimicrobial stewardship. This paper reviews the potential benefits of and considerations regarding various infectious diseases syndromic panels, and highlights how to maximize impact through collaboration between clinical microbiology laboratory and antimicrobial stewardship programmes.
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Affiliation(s)
- Lisa E Dumkow
- Mercy Health Saint Mary's Hospital, Grand Rapids, MI, USA
| | - Lacy J Worden
- Mercy Health Saint Mary's Hospital, Grand Rapids, MI, USA
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Rapid diagnostic testing for antimicrobial stewardship: Utility in Asia Pacific. Infect Control Hosp Epidemiol 2021; 42:864-868. [PMID: 34128462 DOI: 10.1017/ice.2021.149] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Rapid diagnostic testing (RDT) can provide prompt, accurate identification of infectious organisms and be a key component of antimicrobial stewardship (AMS) programs. However, their use is less widespread in Asia Pacific than western countries. Cost can be prohibitive, particularly in less resource-replete settings. A selective approach is required, possibly focusing on the initiation of antimicrobials, for differentiating bacterial versus viral infections and identifying locally relevant tropical diseases. Across Asia Pacific, more data are needed on RDT use within AMS, focusing on the impact on antimicrobial usage, patient morbidity and mortality, and cost effectiveness. Moreover, in the absence of formal guidelines, regional consensus statements to guide clinical practice are warranted. These will provide a regionally relevant definition for RDT; greater consensus on its role in managing infections; advice on implementation and overcoming barriers; and guidance on optimizing human resource capacity. By addressing these issues, the outcomes of AMS programs should improve.
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Park SE, Lim TJ, Nam SO, Chang CL, Byun SY, Ko A, Kong J, Cho JW, Yeon GM, Lee YJ. Clinical utility of the FilmArray meningitis/encephalitis panel in children at a tertiary center in South Korea. Brain Dev 2021; 43:234-243. [PMID: 32893079 DOI: 10.1016/j.braindev.2020.08.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Revised: 07/25/2020] [Accepted: 08/16/2020] [Indexed: 11/27/2022]
Abstract
BACKGROUND We retrospectively evaluated the pathogens in the cerebrospinal fluid (CSF) of pediatric meningitis/encephalitis (M/E) by FilmArray meningitis/encephalitis panel (FA-MEP), and the characteristics of children showing positive and negative FA-MEP results. METHOD FA-MEP along with conventional tests (bacterial/viral cultures, and polymerase chain reaction tests) was performed in children who presented symptoms of M/E. Clinical and laboratory data were reviewed to evaluate the characteristics of children with pathogens detected by FA-MEP. RESULTS The CSF specimens from 110 pediatric M/E patients were enrolled. Mean age of the patients was 5.9 ± 5.2 years. Overall positive rate of FA-MEP was 46.4% (51/110). The pathogens detected in the patients were enterovirus (23/51, 45.1%), parechovirus (10/51, 19.6%), S. pneumoniae (7/51, 13.7%), human herpesvirus type 6 (6/51, 11.8%), S. agalactiae (3/51, 5.9%), herpes simplex virus type 2 (1/51, 2.0%), and E. coli (1/51, 2.0%). Aseptic meningitis (OR, 3.24, 95% CI, 1.18-12.73) and a duration of <2 days from onset of symptoms to CSF test (OR, 3.56, 95% CI, 0.1-0.91) significantly contributed to detection of pathogens by the FA-MEP. Among the 14 children who were administered empiric antibiotics before the CSF test, the detection rate was significantly higher in the FA-MEP than in the conventional test (28.6 vs. 0.0%, p = 0.031). CONCLUSIONS FA-MEP had a higher detection rate in children with M/E compared with conventional tests, particularly aseptic meningitis, and in case of shorter duration of time-to-test. This test was more effective than the conventional test in pediatric M/E patients that had been administered empiric antibiotics.
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Affiliation(s)
- Su Eun Park
- Department of Pediatrics, Pusan National University Children's Hospital, Pusan National University School of Medicine, Yangsan, South Korea; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea
| | - Taek Jin Lim
- Department of Pediatrics, Pusan National University Children's Hospital, Pusan National University School of Medicine, Yangsan, South Korea; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea
| | - Sang Ook Nam
- Department of Pediatrics, Pusan National University Children's Hospital, Pusan National University School of Medicine, Yangsan, South Korea; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea
| | - Chulhun L Chang
- Department of Laboratory Medicine, Pusan National University Yangsan Hospital, Yangsan, South Korea
| | - Shin Yun Byun
- Department of Pediatrics, Pusan National University Children's Hospital, Pusan National University School of Medicine, Yangsan, South Korea; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea
| | - Ara Ko
- Department of Pediatrics, Pusan National University Children's Hospital, Pusan National University School of Medicine, Yangsan, South Korea; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea
| | - JuHyun Kong
- Department of Pediatrics, Pusan National University Children's Hospital, Pusan National University School of Medicine, Yangsan, South Korea; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea
| | - Jae Wook Cho
- Department of Neurology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, South Korea
| | - Gyu Min Yeon
- Department of Pediatrics, Kosin University Gospel Hospital, Kosin University, Busan, South Korea
| | - Yun-Jin Lee
- Department of Pediatrics, Pusan National University Children's Hospital, Pusan National University School of Medicine, Yangsan, South Korea; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea.
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Firouzi M, Sherkatolabbasieh H, Shafizadeh S. Clinical Signs, Prevention and Treatment of Viral Infections in Infants. Infect Disord Drug Targets 2021; 22:e160921190908. [PMID: 33511936 DOI: 10.2174/1871526521666210129145317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Revised: 07/22/2020] [Accepted: 11/23/2020] [Indexed: 11/22/2022]
Abstract
Certain infectious diseases are common in infants than any other age groups and are associated with morbidities in childhood and adulthood, and even mortality in severe cases. Environment, epidemic and maternal immunity are the main causes of these infections. Early diagnosis using molecular methods and treatment is therefore important to prevent future complications. Vaccines are recommended during infancy and childhood to prevent these infections. This review highlights some of the most commonly reported viral infections in children, their clinical signs, prevention and treatment.
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Affiliation(s)
- Majid Firouzi
- Department of Pediatrics, Faculty of Medicine, Lorestan University of Medical Sciences, Khoramabad. Iran
| | | | - Shiva Shafizadeh
- Department of Internal Medicine, Lorestan University of Medical Sciences, Khoramabad. Iran
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Utilization, Yield, and Accuracy of the FilmArray Meningitis/Encephalitis Panel with Diagnostic Stewardship and Testing Algorithm. J Clin Microbiol 2020; 58:JCM.00311-20. [PMID: 32493787 DOI: 10.1128/jcm.00311-20] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Accepted: 05/28/2020] [Indexed: 01/08/2023] Open
Abstract
The impact of diagnostic stewardship and testing algorithms on the utilization and performance of the FilmArray meningitis/encephalitis (ME) panel has received limited investigation. We performed a retrospective single-center cohort study assessing all individuals with suspected ME between February 2017 and April 2019 for whom the ME panel was ordered. Testing was restricted to patients with cerebrospinal fluid (CSF) pleocytosis. Positive ME panel results were confirmed before reporting through correlation with direct staining (Gram and calcofluor white) and CSF cryptococcal antigen or by repeat ME panel testing. Outcomes included the ME panel test utilization rate, negative predictive value of nonpleocytic CSF samples, test yield and false-positivity rate, and time to appropriate deescalation of acyclovir. Restricting testing to pleocytic CSF samples reduced ME panel utilization by 42.7% (263 versus 459 tests performed) and increased the test yield by 61.8% (18.6% versus 11.5% positivity rate; P < 0.01) with the application of criteria. The negative predictive values of a normal CSF white blood cell (WBC) count for ME panel targets were 100% (195/195) for nonviral targets and 98.0% (192/196) overall. All pathogens detected in nonpleocytic CSF samples were herpesviruses. The application of a selective testing algorithm based on repeat testing of nonviral targets avoided 75% (3/4) of false-positive results without generating false-negative results. The introduction of the ME panel reduced the duration of acyclovir treatment from an average of 66 h (standard deviation [SD], 43 h) to 46 h (SD, 36 h) (P = 0.03). The implementation of the ME panel with restriction criteria and a selective testing algorithm for nonviral targets optimizes its utilization, yield, and accuracy.
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Abstract
Meningitis and encephalitis (ME) are important causes of morbidity and mortality worldwide. Patients suspected of having ME are often hospitalized and started on empiric antimicrobial treatment, because of the potential adverse consequences of delaying the diagnosis or treatment. Multiplexed polymerase chain reaction panels are one of several rapid diagnostic technologies that have the potential to overcome some of the limitations of conventional diagnostic methods for ME. The BioFire FilmArray Meningitis/Encephalitis Panel was the first Food and Drug Administration-cleared multiplex polymerase chain reaction for the evaluation of cerebrospinal fluid samples, able to identify 14 organisms in a single test reaction. This newer rapid diagnostic tool has an overall high sensitivity and specificity for the diagnosis of ME with a fast turnaround time and has the potential to improve resource utilization for patients presenting with suspicion of ME. However, further research is needed to determine its optimal use in the evaluation of patients with suspected ME.
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Impact of the Film Array Meningitis/Encephalitis panel in adults with meningitis and encephalitis in Colombia. Epidemiol Infect 2020; 148:e173. [PMID: 32713368 PMCID: PMC7439290 DOI: 10.1017/s0950268820001648] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
The Biofire® Film Array Meningitis Encephalitis (FAME) panel can rapidly diagnose common aetiologies but its impact in Colombia is unknown. A retrospective study of adults with CNS infections in one tertiary hospital in Colombia. The cohort was divided into two time periods: before and after the implementation of the Biofire® FAME panel in May 2016. A total of 98 patients were enrolled, 52 and 46 were enrolled in the Standard of Care (SOC) group and in the FAME group, respectively. The most common comorbidity was human immunodeficiency virus infection (47.4%). The median time to a change in therapy was significantly shorter in the FAME group than in the SOC group (3 vs. 137.3 h, P < 0.001). This difference was driven by the timing to appropriate therapy (2.1 vs. 195 h, P < 0.001) by identifying viral aetiologies. Overall outcomes and length of stay were no different between both groups (P > 0.2). The FAME panel detected six aetiologies that had negative cultures but missed identifying one patient with Cryptococcus neoformans. The introduction of the Biofire FAME panel in Colombia has facilitated the identification of viral pathogens and has significantly reduced the time to the adjustment of empirical antimicrobial therapy.
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Posnakoglou L, Siahanidou T, Syriopoulou V, Michos A. Impact of cerebrospinal fluid syndromic testing in the management of children with suspected central nervous system infection. Eur J Clin Microbiol Infect Dis 2020; 39:2379-2386. [PMID: 32683594 DOI: 10.1007/s10096-020-03986-6] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Accepted: 07/06/2020] [Indexed: 12/14/2022]
Abstract
The aim of the study was to evaluate the impact of the use of BioFire® FilmArray® meningitis/encephalitis(FA-ME) panel which enables rapid automated CSF testing for 14 common viral, bacterial, and yeast pathogens that cause CNS infections, in the management of children with suspected CNS infection. A prospective cohort study was performed on children admitted to a tertiary pediatric hospital, over a period of 1 year, with possible CNS infection and CSF pleocytosis (> 15 cells/mm3). Children were randomized 1:1, either to use FA-ME or separate molecular CSF microbiological tests according to usual pediatric practice in the hospital. Length of hospital stay, duration of antimicrobials, and total cost of hospitalization were compared between groups. A total of 142 children were included in the study (71 cases). A pathogen was detected in 37/71(52.1%) children with the use of FA-ME and in 16/71(22.5%) in the control group (P value < 0.001). In aseptic meningitis cases a virus was detected in 27/61(44.2%) and in 11/66(16.7%) controls (P value < 0.001). Median (IQR) length of stay in cases and controls with aseptic meningitis was 5(4-8) and 8(6-10) days, respectively (P value < 0. 001). The median (IQR) duration of antimicrobials in cases and controls was 4(2-5.7) and 7(5-10) days, respectively (P value < 0.001). The hospitalization cost was calculated in cases and controls 1042€ (932-1372) and 1522€ (1302-1742), respectively (P value < 0.001). The use of FA-ME was able to reduce significantly the use of antimicrobials, the hospitalization days, and the total cost comparing to the control group in children with suspected CNS infection.
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Affiliation(s)
- Lamprini Posnakoglou
- First Department of Pediatrics, Infectious Diseases and Chemotherapy Research Laboratory, National and Kapodistrian University of Athens, "Aghia Sophia" Children's Hospital, Thivon and Papadiamantopoulou, Goudi, 11527, Athens, Greece
| | - Tania Siahanidou
- First Department of Pediatrics, Infectious Diseases and Chemotherapy Research Laboratory, National and Kapodistrian University of Athens, "Aghia Sophia" Children's Hospital, Thivon and Papadiamantopoulou, Goudi, 11527, Athens, Greece
| | - Vasiliki Syriopoulou
- First Department of Pediatrics, Infectious Diseases and Chemotherapy Research Laboratory, National and Kapodistrian University of Athens, "Aghia Sophia" Children's Hospital, Thivon and Papadiamantopoulou, Goudi, 11527, Athens, Greece
| | - Athanasios Michos
- First Department of Pediatrics, Infectious Diseases and Chemotherapy Research Laboratory, National and Kapodistrian University of Athens, "Aghia Sophia" Children's Hospital, Thivon and Papadiamantopoulou, Goudi, 11527, Athens, Greece.
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Pfefferle S, Christner M, Aepfelbacher M, Lütgehetmann M, Rohde H. Implementation of the FilmArray ME panel in laboratory routine using a simple sample selection strategy for diagnosis of meningitis and encephalitis. BMC Infect Dis 2020; 20:170. [PMID: 32087681 PMCID: PMC7036261 DOI: 10.1186/s12879-020-4904-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Accepted: 02/18/2020] [Indexed: 12/13/2022] Open
Abstract
Background Infectious meningitis is a serious disease and patient outcome relies on fast and reliable diagnostics. A syndromic panel testing approach like the FilmArray ME can accelerate diagnosis and therefore decrease the time to pathogen specific therapy. Yet, its clinical utility is controversial, mainly because of a remaining uncertainty in correct interpretation of results, limited data on its performance on clinical specimens and its relatively high costs. The aim of this study was to analyze clinical performance of the assay in a real life setting at a tertiary university hospital using a pragmatic and simple sample selection strategy to reduce the overall cost burden. Methods Over a period of 18 months we received 4623 CSF samples (2338 hospitalizations, 1601 individuals). FilmArray ME analysis was restricted to CSF-samples with a high pretest probability of infectious meningitis, e.g. positive Gram-stain, samples in which leukocytes and/or bacteria were evident or urgent suspicion of infection was communicated by clinicians. N = 171 samples matched to our risk criteria and were subjected to FilmArray ME analysis. Those samples were also analyzed by reference methods: culture only (n = 45), PCR only (n = 20) or both methods (n = 106). Results 56/171 (32.75%) were FilmArray ME positive. Bacterial pathogens were detected in 30/56 (53.57%), viral pathogens were detected in 27/56 (48.21%) and yeast DNA was detected in 1/56 (1.79%) of positive samples. Double detection occurred in 2/56 samples. In 52/56 (92.86%) FilmArray ME positive samples, results could be confirmed by the reference assays (sensitivity = 96.30%, specificity =96.58%). Conclusion The FilmArray ME assay is a fast and reliable diagnostic tool for the management of infectious meningitis and can easily be implemented in routine diagnostic workflows. However, correlation of test results and underlying clinical symptoms requires experienced users and the awareness of potentially false negative or false positive results. Moreover, considering the need for antimicrobial susceptibility testing, the use of molecular tests as a stand-alone diagnostic cannot be recommended.
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Affiliation(s)
- Susanne Pfefferle
- Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
| | - Martin Christner
- Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
| | - Martin Aepfelbacher
- Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
| | - Marc Lütgehetmann
- Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
| | - Holger Rohde
- Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
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Säll O, Thulin Hedberg S, Neander M, Tiwari S, Dornon L, Bom R, Lagerqvist N, Sundqvist M, Mölling P. Etiology of Central Nervous System Infections in a Rural Area of Nepal Using Molecular Approaches. Am J Trop Med Hyg 2020; 101:253-259. [PMID: 31162021 PMCID: PMC6609203 DOI: 10.4269/ajtmh.18-0434] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
The etiology of infections of the central nervous system (CNS) in Nepal often remains unrecognized because of underdeveloped laboratory facilities. The aim of this study was to investigate the etiology of CNS infections in a rural area of Nepal using molecular methods. From November 2014 to February 2016, cerebrospinal fluid (CSF) was collected from 176 consecutive patients presenting at United Mission Hospital in Tansen, Nepal, with symptoms of possible CNS infection. After the CSF samples were stored and transported frozen, polymerase chain reaction (PCR) was performed in Sweden, targeting a total of 26 pathogens using the FilmArray® ME panel (BioFire, bioMerieux, Salt Lake City, UT), the MeningoFinder® 2SMART (PathoFinder, Maastricht, The Netherlands), and an in-house PCR test for dengue virus (DENV), Japanese encephalitis virus (JEV), and Nipah virus (NiV). The etiology could be determined in 23%. The bacteria detected were Haemophilus influenzae (n = 5), Streptococcus pneumoniae (n = 4), and Neisseria meningitidis (n = 1). The most common virus was enterovirus detected in eight samples, all during the monsoon season. Other viruses detected were cytomegalovirus (n = 6), varicella zoster virus (n = 5), Epstein–Barr virus (n = 3), herpes simplex virus (HSV) type 1 (HSV-1) (n = 3), HSV-2 (n = 3), human herpes virus (HHV) type 6 (HHV-6) (n = 3), and HHV-7 (n = 2). Cryptococcus neoformans/gatti was found in four samples. None of the samples were positive for DENV, JEV, or NiV. Of the patients, 67% had been exposed to antibiotics before lumbar puncture. In conclusion, the etiology could not be found in 77% of the samples, indicating that the commercial PCR panels used are not suitable in this setting. Future studies on the etiology of CNS infections in Nepal could include metagenomic techniques.
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Affiliation(s)
- Olof Säll
- Department of Infectious Diseases, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Sara Thulin Hedberg
- Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Marita Neander
- Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | | | | | - Rabin Bom
- United Mission Hospital Tansen, Tansen, Nepal
| | | | - Martin Sundqvist
- Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Paula Mölling
- Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
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Van TT, Kim TH, Butler-Wu SM. Evaluation of the Biofire FilmArray meningitis/encephalitis assay for the detection of Cryptococcus neoformans/gattii. Clin Microbiol Infect 2020; 26:1375-1379. [PMID: 31972318 DOI: 10.1016/j.cmi.2020.01.007] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 01/06/2020] [Accepted: 01/07/2020] [Indexed: 01/09/2023]
Abstract
OBJECTIVES Cryptococcal meningitis (CM) remains an important cause of morbidity and mortality among immunocompromised patients. Laboratory diagnostics for CM includes antigen detection, staining and culture. Data on the performance of the Biofire® FilmArray® meningitis/encephalitis (ME) panel for detecting Cryptococcus neoformans/gattii is limited, with several reports describing false negativity for this target. METHODS A retrospective analysis of 1384 physician-ordered ME panel tests ordered between January 2017 to October 2018 was performed. ME panel results were compared to cerebrospinal fluid (CSF) cryptococcal antigen (CrAg) and CSF culture testing and clinical significance of cryptococcal detection was determined. RESULTS There were 34 patients positive for cryptococcal detection by either ME panel, CSF CrAg or CSF culture in 2.7% of CSF specimens tested (38/1384). Of the 34 patients positive for cryptococcal detection, 85.3% were human immunodeficiency virus positive (29/34). The ME panel detected 32/38 (84.2%) cryptococcal-positive specimens, culture detected 28/38 (73.7%) and CSF CrAg was positive in 37/38 specimens (97.4%). The ME panel had a sensitivity and specificity of 96.4% (95% CI 81.7-99.9%) and 99.6% (95% CI 99.2-99.9%) compared with culture, and 83.8% (95% CI 68.0-93.8%) and 99.9% (95% CI 99.6-100.0%) compared to CSF CrAg testing, respectively. CrAg titres were lower among ME panel-negative, culture-negative specimens compared with ME panel-positive, culture-negative specimens (reciprocal median end-point titres of 128 ± 60 vs. 1920 ± 1730, p 0.04). All five CrAg-positive, ME panel- and culture-negative specimens were obtained from previously treated CM patients. DISCUSSION The ME panel had high correlation with CSF culture and a somewhat lower correlation with CSF CrAg testing. The potential utility of using negative ME panel test results to predict culture sterility among patients undergoing treatment for CM warrants further study.
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Affiliation(s)
- T T Van
- Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA, USA; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - T H Kim
- Department of Pathology and Laboratory Medicine, Keck School of Medicine of USC, Los Angeles, CA, USA
| | - S M Butler-Wu
- Department of Pathology and Laboratory Medicine, Keck School of Medicine of USC, Los Angeles, CA, USA.
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Au CC, Hon KL, Leung AKC, Torres AR. Childhood Infectious Encephalitis: An Overview of Clinical Features, Investigations, Treatment, and Recent Patents. RECENT PATENTS ON INFLAMMATION & ALLERGY DRUG DISCOVERY 2020; 14:156-165. [PMID: 33238854 DOI: 10.2174/1872213x14999201124195724] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Revised: 10/14/2020] [Accepted: 10/19/2020] [Indexed: 06/11/2023]
Abstract
BACKGROUND Infectious encephalitis is a serious and challenging condition to manage. This overview summarizes the current literature regarding the etiology, clinical manifestations, diagnosis, management, and recent patents of acute childhood infectious encephalitis. METHODS We used PubMed Clinical Queries as a search engine and used keywords of "encephalitis" AND "childhood" Patents were searched using the key term "encephalitis" in google.patents.- com and patentsonline.com. RESULTS Viral encephalitis is the most common cause of acute infectious encephalitis in children. In young children, the clinical manifestations can be non-specific. Provision of empiric antimicrobial therapy until a specific infectious organism has been identified, which in most cases includes acyclovir, is the cornerstone of therapy. Advanced investigation tools, including nucleic acid-based test panel and metagenomic next-generation sequencing, improve the diagnostic yield of identifying an infectious organism. Supportive therapy includes adequate airway and oxygenation, fluid and electrolyte balance, cerebral perfusion pressure support, and seizure control. Recent patents are related to the diagnosis, treatment, and prevention of acute infectious encephalitis. CONCLUSION Viral encephalitis is the most common cause of acute infectious encephalitis in children and is associated with significant morbidity. Recent advances in understanding the genetic basis and immunological correlation of infectious encephalitis may improve treatment. Third-tier diagnostic tests may be incorporated into clinical practice. Treatment is targeted at the infectious process but remains mostly supportive. However, specific antimicrobial agents and vaccines development is ongoing.
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Affiliation(s)
- Cheuk C Au
- Department of Paediatrics and Adolescent Medicine, The Hong Kong Children's Hospital, Kowloon Bay, Kowloon, Hong Kong
| | - Kam L Hon
- Department of Paediatrics and Adolescent Medicine, The Hong Kong Children's Hospital, Kowloon Bay, Kowloon, Hong Kong
| | - Alexander K C Leung
- Department of Pediatrics, The University of Calgary and The Alberta Children's Hospital, Calgary, Alberta, Canada
| | - Alcy R Torres
- Department of Pediatrics, Division of Pediatric Neurology, Pediatric Traumatic Brain Injury Program, Associate Professor of Pediatrics and Neurology, Boston University, School of Medicine, Boston, MA, United States
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Vetter P, Schibler M, Herrmann JL, Boutolleau D. Diagnostic challenges of central nervous system infection: extensive multiplex panels versus stepwise guided approach. Clin Microbiol Infect 2019; 26:706-712. [PMID: 31899336 DOI: 10.1016/j.cmi.2019.12.013] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 12/20/2019] [Accepted: 12/22/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Cerebrospinal fluid (CSF) testing is a key component for the diagnosis of central nervous system (CNS) infections. Current meningitis and encephalitis management guidelines agree on the need for CSF molecular testing in combination with other direct and indirect biological testing, both in CSF and blood. Multiplex molecular tests have been developed to reduce turnaround times and facilitate the diagnostic approach. OBJECTIVES We aim to discuss the role of multiplex molecular panels in the management of CNS infections. SOURCES The MEDLINE database and the grey literature have been searched for relevant articles. CONTENT New molecular multiplex panels are being developed to simultaneously detect a large array of neuropathogens in CSF. Although one of these assays has been US Food and Drug Administration-approved, extensive analytical and clinical validation is still missing, and suboptimal performance related issues have been raised. Its use has been associated with decreased costs, reduced length of hospital stay and reduced antiviral therapy administration in retrospective, industry-sponsored studies. The pros and cons of this multiplex syndromic approach are discussed in this narrative review. IMPLICATIONS Molecular multiplex CNS infection diagnosis panels have been developed and present several attractive features, including ease of use and low turnaround time. However, suboptimal analytical performances render these tests difficult to use without additional confirmatory tests. Such panels are not comprehensive nor adapted to all situations, depending on the epidemiological or clinical context. Overall, available data in the literature currently do not support the use of a multiplex PCR panel in clinical routine as a 'stand-alone' molecular assay. Except in restricted laboratory capacity settings where such easy-to-use multiplex panels offer the diagnostic means that would otherwise not be available, the stepwise testing approach remains a more rational option. Serological testing both in blood and CSF should not be neglected, but it represents essential complementary tools regarding some neuropathogens.
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Affiliation(s)
- P Vetter
- Laboratory of Virology, Geneva University Hospitals, Geneva, Switzerland; Infectious Diseases Division, Geneva University Hospitals, Geneva, Switzerland.
| | - M Schibler
- Laboratory of Virology, Geneva University Hospitals, Geneva, Switzerland; Infectious Diseases Division, Geneva University Hospitals, Geneva, Switzerland
| | - J L Herrmann
- 2I, UVSQ, INSERM, Université Paris Saclay, Versailles France; AP-HP, GHU Paris Saclay, Hôpital Raymond Poincaré, Garches, France
| | - D Boutolleau
- Sorbonne Université, INSERM, Institut Pierre Louis D'Epidémiologie et de Santé Publique (iPLESP), Paris, France; AP-HP, GHU AP-HP. Sorbonne Université, Hôpitaux Universitaires Pitié-Salpêtrière - Charles Foix, Virology Department, National Reference Center for Herpesviruses (associate Laboratory), Paris, France
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Nakagawa S, Inoue S, Kryukov K, Yamagishi J, Ohno A, Hayashida K, Nakazwe R, Kalumbi M, Mwenya D, Asami N, Sugimoto C, Mutengo MM, Imanishi T. Rapid sequencing-based diagnosis of infectious bacterial species from meningitis patients in Zambia. Clin Transl Immunology 2019; 8:e01087. [PMID: 31709051 PMCID: PMC6831930 DOI: 10.1002/cti2.1087] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Revised: 10/05/2019] [Accepted: 10/10/2019] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES We have developed a portable system for the rapid determination of bacterial composition for the diagnosis of infectious diseases. Our system comprises of a nanopore technology-based sequencer, MinION, and two laptop computers. To examine the accuracy and time efficiency of our system, we provided a proof-of-concept for the detection of the causative bacteria of 11 meningitis patients in Zambia. METHODS We extracted DNA from cerebrospinal fluid samples of each patient and amplified the 16S rRNA gene regions. The sequencing library was prepared, and the sequenced reads were simultaneously processed for bacterial composition determination using the minimap2 software and the representative prokaryote genomes. RESULTS The sequencing results of four of the six culture-positive samples were consistent with those of conventional culture-based methods. The dominant bacterial species in each of these samples were identified from the sequencing data within only 3 min. Although the major bacterial species were also detected from the other two culture-positive samples and five culture-negative samples, their presence could not be confirmed. Moreover, as a whole, although the number of sequencing reads obtained within a short sequencing run was small, there was no change in the major bacterial species over time with prolonged sequencing. In addition, the processing time strongly correlated with the number of sequencing reads used for the analysis. CONCLUSION Our results suggest that time-effective analysis could be achieved by determining the number of sequencing reads required for the rapid diagnosis of infectious bacterial species depending on the complexity of bacterial species in a sample.
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Affiliation(s)
- So Nakagawa
- Department of Molecular Life ScienceTokai University School of MedicineIseharaJapan
- Micro/Nano Technology CenterTokai UniversityHiratsukaJapan
| | - Shigeaki Inoue
- Department of Emergency and Critical Care MedicineTokai University School of MedicineIseharaJapan
- Department of Disaster and Emergency MedicineKobe University Graduate School of MedicineKobeJapan
| | - Kirill Kryukov
- Department of Molecular Life ScienceTokai University School of MedicineIseharaJapan
| | - Junya Yamagishi
- Research Center for Zoonosis ControlHokkaido UniversitySapporoJapan
- Global Station for Zoonosis ControlGI‐CoREHokkaido UniversitySapporoJapan
| | - Ayumu Ohno
- Department of Molecular Life ScienceTokai University School of MedicineIseharaJapan
| | - Kyoko Hayashida
- Research Center for Zoonosis ControlHokkaido UniversitySapporoJapan
| | - Ruth Nakazwe
- Department of Pathology and MicrobiologyUniversity Teaching HospitalLusakaZambia
| | - Mox Kalumbi
- Department of Pathology and MicrobiologyUniversity Teaching HospitalLusakaZambia
- Institute of Basic and Biomedical SciencesLevy Mwanawasa Medical UniversityLusakaZambia
| | - Darlington Mwenya
- Department of Pathology and MicrobiologyUniversity Teaching HospitalLusakaZambia
| | - Nana Asami
- Department of Molecular Life ScienceTokai University School of MedicineIseharaJapan
| | - Chihiro Sugimoto
- Research Center for Zoonosis ControlHokkaido UniversitySapporoJapan
- Global Station for Zoonosis ControlGI‐CoREHokkaido UniversitySapporoJapan
| | - Mable M Mutengo
- Department of Pathology and MicrobiologyUniversity Teaching HospitalLusakaZambia
- Institute of Basic and Biomedical SciencesLevy Mwanawasa Medical UniversityLusakaZambia
| | - Tadashi Imanishi
- Department of Molecular Life ScienceTokai University School of MedicineIseharaJapan
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Boudet A, Pantel A, Carles MJ, Boclé H, Charachon S, Enault C, Stéphan R, Cadot L, Lavigne JP, Marchandin H. A review of a 13-month period of FilmArray Meningitis/Encephalitis panel implementation as a first-line diagnosis tool at a university hospital. PLoS One 2019; 14:e0223887. [PMID: 31647847 PMCID: PMC6812749 DOI: 10.1371/journal.pone.0223887] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Accepted: 09/21/2019] [Indexed: 12/21/2022] Open
Abstract
Early diagnosis and treatment of meningitis and encephalitis is essential for reducing both their morbidity and mortality. The FilmArray® Meningitis/Encephalitis (FA-M/E) panel is a recently available molecular tool allowing the simultaneous detection of 14 pathogens in about one hour. We evaluated its routine use over a 13-month period at Nîmes University Hospital, France. Cerebrospinal fluid (CSF) specimens were prospectively analyzed, independently of cell count; results were retrospectively analyzed and positive results compared to clinical and microbiological data. Among the 708 patients included (734 CSF samples), 89 (12.6%) had a positive FA-M/E panel, 71 (80%) for a viral pathogen and 18 (20%) for a bacterial pathogen. Enterovirus and HHV-6 were the main detected pathogens. Mean time-to-results was 1h46mn. Four non-clinically relevant results were detected (3 HHV-6 and 1 Haemophilus influenzae) on the basis of inconsistent clinical and/or biological data, and/or after visualization of melting curves. No CSF pleocytosis was observed in 11% of the patients with a positive FA-M/E panel. For the 18 patients with a positive FA-M/E panel for a bacterial pathogen, five (28%) had CSF samples showing a positive Gram stain allowing an early diagnosis of bacterial infection and 67% had CSF displaying a positive culture. Altogether the panel detected 5 cases of bacterial M/E (29%) not diagnosed by culture. Despite undeniable advantages, mainly ease of use, quick result availability, and an extremely low rate of invalid results, measures should be implemented to limit false-positive results due to contamination and a careful interpretation based on the overall data for each patient is required.
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Affiliation(s)
- Agathe Boudet
- U1047, INSERM, Montpellier University, Department of Microbiology, Nîmes University Hospital, Nîmes, France
| | - Alix Pantel
- U1047, INSERM, Montpellier University, Department of Microbiology, Nîmes University Hospital, Nîmes, France
| | | | - Hélène Boclé
- U1047, INSERM, Montpellier University, Department of Infectious Diseases, Nîmes University Hospital, Nîmes, France
| | - Sylvie Charachon
- Department of Microbiology, Nîmes University Hospital, Nîmes, France
| | - Cécilia Enault
- Department of Microbiology, Nîmes University Hospital, Nîmes, France
| | - Robin Stéphan
- U1047, INSERM, Montpellier University, Department of Microbiology, Nîmes University Hospital, Nîmes, France
| | - Lucile Cadot
- Laboratory of Medical Biology, Alès General Hospital, Alès, France
| | - Jean-Philippe Lavigne
- U1047, INSERM, Montpellier University, Department of Microbiology, Nîmes University Hospital, Nîmes, France
| | - Hélène Marchandin
- HydroSciences Montpellier, CNRS, IRD, Montpellier University, Department of Microbiology, Nimes University Hospital, Nîmes, France
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Visseaux B, Armand-Lefèvre L. Approche syndromique multiplexe en réanimation. MEDECINE INTENSIVE REANIMATION 2019. [DOI: 10.3166/rea-2019-0109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Le développement récent des nouveaux tests de diagnostic rapide par PCR multiplexe à visée syndromique, capables de détecter plusieurs dizaines de pathogènes en quelques heures, a entraîné un changement de paradigme en microbiologie et en pratique clinique. Plusieurs d’entre eux, comme les panels pour détecter les germes en cause dans les bactériémies, les infections respiratoires hautes ou basses et les méningoencéphalites, sont déjà disponibles et peuvent apporter une aide dans le diagnostic des infections chez les patients de réanimation. Bien que ces nouvelles techniques présentent des avantages évidents pour le dénombrement de micro-organismes et parfois pour la détection simultanée de gènes de résistance, pour les délais d’exécution et de rendus de résultats, elles présentent cependant certains défis, comme l’évaluation de leurs performances réelles, leur coût très élevé, le choix des stratégies d’utilisation et l’interprétation clinicobiologique des résultats. Dans cet article, nous avons passé en revue les différents tests qui peuvent ou pourront aider les réanimateurs dans leur pratique quotidienne, relevé leurs limites et leur impact bénéfique potentiel sur le soin des patients.
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Lee SH, Chen SY, Chien JY, Lee TF, Chen JM, Hsueh PR. Usefulness of the FilmArray meningitis/encephalitis (M/E) panel for the diagnosis of infectious meningitis and encephalitis in Taiwan. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2019; 52:760-768. [PMID: 31085115 DOI: 10.1016/j.jmii.2019.04.005] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 04/24/2019] [Accepted: 04/24/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND/PURPOSE Early recognition of causative pathogens is critical for the appropriate management of central nervous system infection and improved outcomes. The BioFire® FilmArray® Meningitis/Encephalitis Panel (BioFire® ME Panel, BioFire Diagnostics) is the first U.S. Food and Drug Administration (FDA)-approved multiplex PCR assay that allows the rapid detection of 14 pathogens, including bacteria (n = 6), viruses (n = 7), and fungi (n = 1), from cerebrospinal fluid (CSF). The performance of the panel is expected to be dependent on the epidemiology of M/E in different geographical regions. METHODS In this preliminary study, we used the BioFire® ME Panel in 42 subjects who presented to the emergency department with symptoms of M/E in our hospital. The results were compared to conventional culture, antigen detection, PCR, and various laboratory findings. RESULTS The panel detected six positive samples, of which five were viral and one bacterial. We observed an overall agreement rate of 88% between the BioFire® ME Panel results and the conventional methods. There were no false-positive findings, but five discordant results were observed for enterovirus, herpes simplex virus type 1, Escherichia coli, and Cryptococcus species. CONCLUSIONS The BioFire® ME Panel performed equivalently to the traditional PCR methods for virus detection, and better than bacterial cultures. This revolutionary system represents a paradigm shift in the diagnosis of M/E and may aid in the rapid identification of community-acquired M/E. However, the usefulness of this tool is limited in regions with a high prevalence of infectious M/E caused by microorganisms not included in the panel.
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Affiliation(s)
- Sze Hwei Lee
- Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Shey-Ying Chen
- Department of Emergency Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jung-Yien Chien
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Tai-Fen Lee
- Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jong-Min Chen
- Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Pediatrics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Po-Ren Hsueh
- Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
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