Impact of Cerebrospinal Fluid Multiplex Assay on Diagnosis and Outcomes of Central Nervous System Infections in Children

O'Brien, Matthew P; Francis, Joshua; Marr, Ian; Baird, Robert W.

doi:10.1097/inf.0000000000001936

Cited by 27 publications

(36 citation statements)

References 13 publications

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“…Moreover, SAA has been widely used to diagnose pediatric infectious diseases because it is a simple and rapid detection method, requiring only 40 L of ngertip blood. It has been previously reported that occasionally, SAA was not signi cantly increased in some types of acute in ammation (e.g., viral CNS infection) in which children may experience life-threatening events or severe sequela (5)(6)(7)(8)(9)(10)(11).Therefore, a retrospective case review was performed in this study to analyze the differences in SAA between two high risk pediatric diseases: viral CNS infection and KD (12-24).…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: A Comparison of SAA Levels in Children With Viral CNS Infection and Kawasaki’s Disease

Yang

Huo

2020

Preprint

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Background: The purpose of this study was to analyze the epidemiological differences of SAA in children with viral central nervous system (CNS) infection and Kawasaki’s Disease(KD). The former is viral invasion of central nervous system, whereas the latter is a viral systemic vasculitis. Differences in the SAA concentration in the blood and the proportion of high level SAA cases reflected the influence of the blood-cerebrospinal fluid barrier (BCB) on the concentration of peripheral blood infection markers.Methods: The SAA data comprised 226 consecutive cases of children, including 112 cases of viral CNS infection and 114 cases of KD. Differences in the proportion and concentration of SAA in the cases of the two groups were verified with a Kruskal-Wallis H-test and the chi-square test.Results: The concentration of SAA differed between children with KD and viral CNS infection, and the high level SAA proportion was lower in children with viral CNS infection compared to that in the KD group.Conclusions: The observed differences may be due to the sequestration effect, as the blood-cerebrospinal fluid barrier (BCB) can compartmentalize the pathogens at the site of disease. Therefore, other organs are unable to be stimulated to release additional SAA.

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Section: Introductionmentioning

confidence: 99%

WITHDRAWN: A Comparison of SAA Levels in Children With Viral CNS Infection and Kawasaki’s Disease

Yang

Huo

2020

Preprint

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“…Another study recently published, evaluated the impact of the FA ME Panel on antibiotic therapy in children with confirmed CNS infection by comparing antibiotic usage before and after its introduction. However, only patients with a discharge diagnosis of meningitis or encephalitis were included [32]. In contrast to that study, our study includes all patients with suspected CNS infection and also analyzes the usage of antiviral agents.…”

Section: Discussionmentioning

confidence: 99%

Comparison of antibiotic and acyclovir usage before and after the implementation of an on-site FilmArray meningitis/encephalitis panel in an academic tertiary pediatric hospital: a retrospective observational study

et al. 2020

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Background: Prompt initiation of empiric therapy is common practice in case of suspected meningitis or encephalitis. However, in children the most common pathogens are viruses that usually do not require and are not covered by the applied anti-infective treatment. Novel multiplex PCR (mPCR) panels provide rapid on-site diagnostic testing for a variety of pathogens. This study compared empiric antibiotic and acyclovir usage before and after the introduction of an on-site FilmArray Meningitis/Encephalitis Panel (FA ME Panel). Methods: We retrospectively compared data for empiric antibiotic and acyclovir usage between pediatric patients with suspected central nervous system (CNS) infection receiving mPCR testing and a matched historical control group. Patients were matched by age and suspected CNS infection. We included all patients for whom empiric antibiotics and/or acyclovir were prescribed. Results: Each study group consisted of 46 patients with 29 (63.0%) infants and 17 (37.0%) older children. A viral pathogen was diagnosed in 5/46 (10.9%) patients in the control group (all enteroviruses) and in 14/46 (30.4%) patients in the mPCR group (enterovirus n = 9; human herpesvirus 6 (HHV-6) n = 5), (p = 0.038)). Length of Therapy (LoT) and Days of Therapy (DoT) for antibiotics were significantly lower for infants (4.0 vs. 3.0, p = 0.038 and 8.0 vs. 6.0, p = 0.015, respectively). Acyclovir therapy was significantly shorter for both, infants and older children (3.0 vs. 1.0 day, p < 0.001 for both age groups). Conclusion: The findings of our study suggest that the introduction of a FA ME Panel into clinical routine procedures is associated with a significantly reduced LoT and DoT of empiric anti-infective treatment in children with suspected meningoencephalitis. The largest effect was observed in infants.

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“…Also, one study tested with the ME panel used only frozen specimens that were previously positive with routine testing methods [22]. In total, eight studies reported on a mixed population (adult and paediatric patients) or did not determine the age of the study population [3,16,17,19e22,25], and five studies reported exclusively on paediatric patients [4,15,18,23,24]. The studies included patients with infections caused by a variety of analytes (bacterial, viral, C. neoformans/gattii) found on the panel.…”

Section: Study Characteristicsmentioning

confidence: 99%

Diagnostic test accuracy of the BioFire® FilmArray® meningitis/encephalitis panel: a systematic review and meta-analysis

Tansarli

Chapin

2020

Clinical Microbiology and Infection

157

120

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Background: The FilmArray® meningitis/encephalitis (ME) panel is a multiplex PCR assay which can detect the most commonly identified pathogens in central nervous system infections. It significantly decreases the time to diagnosis of ME and data has yielded several positive outcomes. However, in part, reports of both false positive and false negative detections have resulted in concerns about adoption. Objectives: The aim was to evaluate the ME panel in a diagnostic test accuracy review. Data sources: The PubMed and EMBASE databases were systematically searched through May 2019. Study eligibility criteria: Eligible studies were those providing sensitivity and specificity data for the ME panel compared with a reference standard. Studies providing details on false positive and false negative results of the panel as well as further investigation (adjudication) of the discordant results between the panel and comparator assays were included and assessed separately. Participants: Patients with suspected ME for whom a panel was ordered were included. Methods: The ME panel was compared to reference standard methods for diagnosing communityacquired ME. We performed a meta-analysis and calculated the summary sensitivity and specificity of the ME panel. Moreover, we evaluated the false positive and false negative results of the panel. Results: Thirteen studies (3764 patients) were included in the review and 8 of them (3059 patients) were pooled in a meta-analysis. The summary estimates of sensitivity and specificity with 95% confidence intervals (CI) was 90% (95% CI 86e93%) and 97% (95% CI 94e99%), respectively. When we looked specifically at studies that assessed further the false positive and false negative results, false positive detections were 11.4% and 4% before and after adjudication, respectively. The highest proportion of false positive was observed for Streptococcus pneumoniae followed by Streptococcus agalactiae. False negative isolates were 2.2% and 1.5% before and after adjudication, respectively. Herpes simplex virus 1 and 2, enterovirus and Cryptococcus neoformans/gattii had the highest proportions of false negative determinations. False negative C. neoformans/gattii were mostly patients with positive antigen titres, on treatment or cleared disease. Conclusions: The currently available literature suggests that the ME panel has high diagnostic accuracy. However, the decision for implementation should be individualized based on the needs of the patient population, the capabilities of the laboratory, and the knowledge of the healthcare providers that will utilize the test.

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Impact of Cerebrospinal Fluid Multiplex Assay on Diagnosis and Outcomes of Central Nervous System Infections in Children

Abstract: The multiplex assay is a useful adjunct diagnostic tool enabling prompt organism identification and reducing antibiotic treatment and hospitalization duration. The assay would be of most value to hospitals that do not have access to an onsite molecular laboratory.

Cited by 27 publications

References 13 publications

WITHDRAWN: A Comparison of SAA Levels in Children With Viral CNS Infection and Kawasaki’s Disease

WITHDRAWN: A Comparison of SAA Levels in Children With Viral CNS Infection and Kawasaki’s Disease

Comparison of antibiotic and acyclovir usage before and after the implementation of an on-site FilmArray meningitis/encephalitis panel in an academic tertiary pediatric hospital: a retrospective observational study

Diagnostic test accuracy of the BioFire® FilmArray® meningitis/encephalitis panel: a systematic review and meta-analysis

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