scholarly journals Multicenter Evaluation of BioFire FilmArray Meningitis/Encephalitis Panel for Detection of Bacteria, Viruses, and Yeast in Cerebrospinal Fluid Specimens

2016 ◽  
Vol 54 (9) ◽  
pp. 2251-2261 ◽  
Author(s):  
Amy L. Leber ◽  
Kathy Everhart ◽  
Joan-Miquel Balada-Llasat ◽  
Jillian Cullison ◽  
Judy Daly ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
False Negative ◽  
Human Herpesvirus ◽  
Rapid Test ◽  
Complete Analysis ◽  
Specific Test ◽  
Content Type ◽  
Herpesvirus Type ◽  
Varicella Zoster

Rapid diagnosis and treatment of infectious meningitis and encephalitis are critical to minimize morbidity and mortality. Comprehensive testing of cerebrospinal fluid (CSF) often includes Gram stain, culture, antigen detection, and molecular methods, paired with chemical and cellular analyses. These methods may lack sensitivity or specificity, can take several days, and require significant volume for complete analysis. The FilmArray Meningitis/Encephalitis (ME) Panel is a multiplexedin vitrodiagnostic test for the simultaneous, rapid (∼1-h) detection of 14 pathogens directly from CSF specimens:Escherichia coliK1,Haemophilus influenzae,Listeria monocytogenes,Neisseria meningitidis,Streptococcus pneumoniae,Streptococcus agalactiae, cytomegalovirus, enterovirus, herpes simplex virus 1 and 2, human herpesvirus 6, human parechovirus, varicella-zoster virus, andCryptococcus neoformans/Cryptococcus gattii. We describe a multicenter evaluation of 1,560 prospectively collected CSF specimens with performance compared to culture (bacterial analytes) and PCR (all other analytes). The FilmArray ME Panel demonstrated a sensitivity or positive percentage of agreement of 100% for 9 of 14 analytes. Enterovirus and human herpesvirus type 6 had agreements of 95.7% and 85.7%, andL. monocytogenesandN. meningitidiswere not observed in the study. ForS. agalactiae, there was a single false-positive and false-negative result each, for a sensitivity and specificity of 0 and 99.9%, respectively. The specificity or negative percentage of agreement was 99.2% or greater for all other analytes. The FilmArray ME Panel is a sensitive and specific test to aid in diagnosis of ME. With use of this comprehensive and rapid test, improved patient outcomes and antimicrobial stewardship are anticipated.

scholarly journals In Vitro Activity and Mechanism of Action of Methylenecyclopropane Analogs of Nucleosides against Herpesvirus Replication

2005 ◽  
Vol 49 (3) ◽  
pp. 1039-1045 ◽  
Author(s):  
Earl R. Kern ◽  
Nicole L. Kushner ◽  
Caroll B. Hartline ◽  
Stephanie L. Williams-Aziz ◽  
Emma A. Harden ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Human Herpesvirus ◽  
Murine Cytomegalovirus ◽  
Enzyme Linked Immunosorbent Assay ◽  
Herpesvirus Type ◽  
Varicella Zoster ◽  
Barr Virus ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT We have reported previously that methylenecyclopropane analogs of nucleosides have excellent activity against certain members of the herpesvirus family. A second generation, the 2,2-bis-hydroxymethyl derivatives, were synthesized, and 18 compounds were tested for activity in vitro against herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), human and murine cytomegalovirus (HCMV and MCMV), varicella-zoster virus (VZV), and Epstein-Barr virus (EBV). Selected analogs were also evaluated against human herpesvirus type 6 (HHV-6) and HHV-8. None of the 18 compounds had activity against HSV-1 or HSV-2, but four were active against VZV by plaque reduction (PR) assay at 50% effective concentration (EC50) levels of ≤50 μM. Six of the 18 compounds were active against HCMV by cytopathic effect or PR assays with EC50s of 0.5 to 44 μM, and all were active against MCMV by PR (0.3 to 54 μM). Four of the compounds were active against EBV by enzyme-linked immunosorbent assay (<0.3 to 4.4 μM). Four compounds with CMV activity were also active against HHV-6A and HHV-6B (0.7 to 28 μM), and three compounds were active against HHV-8 (5.5 to 16 μM). One of these, ZSM-I-62, had particularly good activity against CMV, HHV-6, and HHV-8, with EC50s of 0.7 to 8 μM. Toxicity was evaluated in adherent and nonadherent cells, and minimal cytotoxicity was observed. Mechanism of action studies with HCMV suggested that these compounds are phosphorylated by the ppUL97 phosphotransferase and are potent inhibitors of viral DNA synthesis. These results indicate that at least one of these compounds may have potential for use in treating CMV and other herpesvirus infections in humans.

scholarly journals Evaluation of CARBA PAcE, a novel rapid test for detection of carbapenemase-producing Enterobacterales

2020 ◽  
Author(s):  
Janko Sattler ◽  
Anne Brunke ◽  
Axel Hamprecht
Keyword(s):  
False Negative ◽  
Rapid Test ◽  
Content Type ◽  
Columbia Blood Agar ◽  
Fast Detection ◽  
The Poor ◽  
Colorimetric Test ◽  
Mueller Hinton ◽  
Mueller Hinton Agar ◽  
Moderate Sensitivity

Introduction. Carbapenemase-producing Enterobacterales (CPE) are an increasing threat to global health. Fast detection is crucial for patient management and outbreak control. Hypothesis/Gap statement. Recently, a new commercial colorimetric test, CARBA PAcE, was released that has not yet been scientifically evaluated. Aim. Our goals were to evaluate the performance of CARBA PAcE using a large variety of different CPE. Methodology. CARBA PAcE was challenged with 107 molecularly characterized CPE and 53 non-CPE controls. Isolates were grown on Mueller-Hinton agar (MHA); in the case of a false-negative result, isolates were additionally inoculated on Columbia blood agar (CBA) and CARBA PAcE was repeated. The test was performed according to the manufacturer’s protocol. Results. CARBA PAcE showed an overall sensitivity and specificity of 72 % [confidence interval (CI) 62–80 %] and 91 % (CI 79–97 %), respectively, when isolates were grown on MHA. With growth on CBA, detection improved (especially of metallo-β-lactamases), resulting in an extrapolated sensitivity of 89 % (CI 81–94 %) for all carbapenemases and 96 % (CI 89–99 %) for the four major carbapenemases (NDM, OXA-48-like, KPC, VIM). Conclusion. CARBA PAcE is a simple and very rapid test for the detection of CPE which performs well for the major carbapenemases when isolates are grown on CBA. Laboratories should be aware of the limitations of this assay, such as moderate sensitivity when isolates are grown on more challenging agars such as MHA and the poor detection of some rare carbapenemases (e.g. IMI, OXA-58).

Kutapressin Inhibits In Vitro Infection of Human Herpesvirus Type 6

1994 ◽  
Vol 18 (Supplement_1) ◽  
pp. S113-S113
Author(s):  
D. V. Ablashi ◽  
Z. Berneman ◽  
C. Lawyer ◽  
A. Komaroff
Keyword(s):  
Human Herpesvirus ◽  
Herpesvirus Type ◽  
Human Herpesvirus Type

scholarly journals Updating Molecular Diagnostics for Detecting Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus Isolates in Blood Culture Bottles

2019 ◽  
Vol 57 (11) ◽  
Author(s):  
Fred C. Tenover ◽  
Isabella A. Tickler ◽  
Victoria M. Le ◽  
Scott Dewell ◽  
Rodrigo E. Mendes ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Blood Culture ◽  
False Negative ◽  
The United States ◽  
Molecular Diagnostic ◽  
Methicillin Resistant ◽  
Content Type ◽  
Target Nucleic Acid ◽  
Antimicrobial Resistance Genes

ABSTRACT Molecular diagnostic tests can be used to provide rapid identification of staphylococcal species in blood culture bottles to help improve antimicrobial stewardship. However, alterations in the target nucleic acid sequences of the microorganisms or their antimicrobial resistance genes can lead to false-negative results. We determined the whole-genome sequences of 4 blood culture isolates of Staphylococcus aureus and 2 control organisms to understand the genetic basis of genotype-phenotype discrepancies when using the Xpert MRSA/SA BC test (in vitro diagnostic medical device [IVD]). Three methicillin-resistant S. aureus (MRSA) isolates each had a different insertion of a genetic element in the staphylococcal cassette chromosome (SCCmec)-orfX junction region that led to a misclassification as methicillin-susceptible S. aureus (MSSA). One strain contained a deletion in spa, which produced a false S. aureus-negative result. A control strain of S. aureus that harbored an SCCmec element but no mecA (an empty cassette) was correctly called MSSA by the Xpert test. The second control contained an SCCM1 insertion. The updated Xpert MRSA/SA BC test successfully detected both spa and SCCmec variants of MRSA and correctly identified empty-cassette strains of S. aureus as MSSA. Among a sample of 252 MSSA isolates from the United States and Europe, 3.9% contained empty SCCmec cassettes, 1.6% carried SCCM1, <1% had spa deletions, and <1% contained SCCmec variants other than those with SCCM1. These data suggest that genetic variations that may interfere with Xpert MRSA/SA BC test results remain rare. Results for all the isolates were correct when tested with the updated assay.

scholarly journals Amphipathic DNA Polymers Exhibit Antiherpetic Activity In Vitro and In Vivo

2008 ◽  
Vol 52 (8) ◽  
pp. 2727-2733 ◽  
Author(s):  
David I. Bernstein ◽  
Nathalie Goyette ◽  
Rhonda Cardin ◽  
Earl R. Kern ◽  
Guy Boivin ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Broad Spectrum ◽  
Parent Compound ◽  
Human Herpesvirus ◽  
Varicella Zoster ◽  
Barr Virus ◽  
Simplex Virus ◽  
Acid Stable

ABSTRACT Phosphorothioated oligonucleotides have a sequence-independent antiviral activity as amphipathic polymers (APs). The activity of these agents against herpesvirus infections in vitro and in vivo was investigated. The previously established sequence-independent, phosphorothioation-dependent antiviral activity of APs was confirmed in vitro by showing that a variety of equivalently sized homo- and heteropolymeric AP sequences were similarly active against herpes simplex virus type 1 (HSV-1) infection in vitro compared to the 40mer degenerate parent compound (REP 9), while the absence of phosphorothioation resulted in the loss of antiviral activity. In addition, REP 9 demonstrated in vitro activity against a broad spectrum of other herpesviruses: HSV-2 (50% effective concentration [EC50], 0.02 to 0.06 μM), human cytomegalovirus (EC50, 0.02 to 0.13 μM), varicella zoster virus (EC50, <0.02 μM), Epstein-Barr virus (EC50, 14.7 μM) and human herpesvirus types 6A/B (EC50, 2.9 to 10.2 μM). The murine microbicide model of genital HSV-2 was then used to evaluate in vivo activity. REP 9 (275 mg/ml) protected 75% of animals from disease and infection when provided 5 or 30 min prior to vaginal challenge. When an acid-stable analog (REP 9C) was used, 75% of mice were protected when treated with 240 mg/ml 5 min prior to infection (P < 0.001), while a lower dose (100 mg/ml) protected 100% of the mice (P < 0.001). The acid stable REP 9C formulation also provided protection at 30 min (83%, P < 0.001) and 60 min (50%, P = 0.07) against disease. These observations suggest that APs may have microbicidal activity and potential as broad-spectrum antiherpetic agents and represent a novel class of agents that should be studied further.

scholarly journals Recombination of Globally Circulating Varicella-Zoster Virus

2015 ◽  
Vol 89 (14) ◽  
pp. 7133-7146 ◽  
Author(s):  
Peter Norberg ◽  
Daniel P. Depledge ◽  
Samit Kundu ◽  
Claire Atkinson ◽  
Julianne Brown ◽  
...  
Keyword(s):  
Varicella Zoster Virus ◽  
Genetic Recombination ◽  
Human Herpesvirus ◽  
Infectious Laryngotracheitis Virus ◽  
Live Attenuated Vaccine ◽  
Herpes Simplex Viruses ◽  
Varicella Zoster ◽  
Laryngotracheitis Virus

ABSTRACTVaricella-zoster virus (VZV) is a human herpesvirus, which during primary infection typically causes varicella (chicken pox) and establishes lifelong latency in sensory and autonomic ganglia. Later in life, the virus may reactivate to cause herpes zoster (HZ; also known as shingles). To prevent these diseases, a live-attenuated heterogeneous vaccine preparation, vOka, is used routinely in many countries worldwide. Recent studies of another alphaherpesvirus, infectious laryngotracheitis virus, demonstrate that live-attenuated vaccine strains can recombinein vivo, creating virulent progeny. These findings raised concerns about using attenuated herpesvirus vaccines under conditions that favor recombination. To investigate whether VZV may undergo recombination, which is a prerequisite for VZV vaccination to create such conditions, we here analyzed 115 complete VZV genomes. Our results demonstrate that recombination occurs frequently for VZV. It thus seems that VZV is fully capable of recombination if given the opportunity, which may have important implications for continued VZV vaccination. Although no interclade vaccine-wild-type recombinant strains were found, intraclade recombinants were frequently detected in clade 2, which harbors the vaccine strains, suggesting that the vaccine strains have already been involved in recombination events, eitherin vivoorin vitroduring passages in cell culture. Finally, previous partial and complete genomic studies have described strains that do not cluster phylogenetically to any of the five established clades. The additional VZV strains sequenced here, in combination with those previously published, have enabled us to formally define a novel sixth VZV clade.IMPORTANCEAlthough genetic recombination has been demonstrated to frequently occur for other human alphaherpesviruses, herpes simplex viruses 1 and 2, only a few ancient and isolated recent recombination events have hitherto been demonstrated for VZV. In the present study, we demonstrate that VZV also frequently undergoes genetic recombination, including strains belonging to the clade containing the vOKA strain.

Improved tumor-specific immunotoxins in the treatment of CNS and leptomeningeal neoplasia

1989 ◽  
Vol 70 (2) ◽  
pp. 240-248 ◽  
Author(s):  
Virginia G. Johnson ◽  
Charles Wrobel ◽  
Debra Wilson ◽  
John Zovickian ◽  
Larry Greenfield ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Cell Lines ◽  
Human Tumor ◽  
Therapeutic Window ◽  
Human Tumor Cells ◽  
Tumor Patients ◽  
General Applicability ◽  
Content Type ◽  
Normal Humans

✓ A novel antibody-toxin conjugate has been developed for use in cancer therapy. This report demonstrates that this new reagent selectively kills glioblastoma- and medulloblastoma-derived cell lines, medulloblastoma cells in primary culture, and cell lines derived from tumors commonly metastatic to the cerebrospinal fluid (CSF). Efficient killing of human tumor cells occurred at concentrations between 3.9 × 10−13 M and 1.1 × 10−10 M, whereas guinea pigs and rhesus monkeys tolerated intrathecal levels of 2 × 10−9 M. Cerebrospinal fluid from normal humans and from brain-tumor patients does not inhibit the in vitro efficacy of this reagent. The wide therapeutic window, extreme potency, and general applicability of this antibody-toxin conjugate against CSF-borne primary or metastatic tumors warrants clinical trials.

Cerebrospinal fluid cytology after subarachnoid hemorrhage

1979 ◽  
Vol 51 (3) ◽  
pp. 352-354 ◽  
Author(s):  
Umeo Ito ◽  
Yutaka Inaba
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
False Negative ◽  
Content Type ◽  
Cerebrospinal Fluid Cytology ◽  
Csf Cells ◽  
Fine Print ◽  
Fluid Cytology

✓ A method is described which has been found capable of detecting subarachnoid hemorrhage (SAH) up to 15 to 17 weeks after its occurrence. The episode of SAH was confirmed by bloody and/or xanthochromic cerebrospinal fluid (CSF) at the time of SAH onset. In this study, 47 samples of lumbar CSF from diagnostically confirmed SAH patients were used. The CSF cells were collected onto slides and stained with May-Gruenwald-Giemsa or Perl's reagent. Iron-positive cells were detected at 1 week, increased by 4 to 6 weeks to 8.5% of total nucleated cells, and decreased to 1% by 15 to 17 weeks. All 27 samples obtained at 2 to 9 weeks after SAH showed iron-positive cells. No iron-positive cells (false-negative samples) were noted in 25% (one of four) of samples obtained during the first week, and in 33% (one of three) of samples obtained 10 to 12 weeks and 15 to 17 weeks after SAH. Of the total samples (37) obtained within 17 weeks after SAH, 8.1% (three of 37) were false negative. No iron-positive cells were detected in samples obtained later than 21 weeks after the SAH episode (10 samples).

Sign in / Sign up

Export Citation Format

Share Document