scholarly journals Novel Biomarkers Differentiating Viral from Bacterial Infection in Febrile Children: Future Perspectives for Management in Clinical Praxis

Children ◽  
2021 ◽  
Vol 8 (11) ◽  
pp. 1070
Author(s):  
Samuel Rhedin ◽  
Kristina Elfving ◽  
Anna Berggren
Keyword(s):  
Bacterial Infections ◽  
Expression Profiles ◽  
Protein A ◽  
Gene Expression Profiles ◽  
Diagnostic Tools ◽  
Reactive Protein ◽  
Asymptomatic Children ◽  
Novel Biomarkers ◽  
Tract Infections ◽  
Viral Respiratory

Differentiating viral from bacterial infections in febrile children is challenging and often leads to an unnecessary use of antibiotics. There is a great need for more accurate diagnostic tools. New molecular methods have improved the particular diagnostics of viral respiratory tract infections, but defining etiology can still be challenging, as certain viruses are frequently detected in asymptomatic children. For the detection of bacterial infections, time consuming cultures with limited sensitivity are still the gold standard. As a response to infection, the immune system elicits a cascade of events, which aims to eliminate the invading pathogen. Recent studies have focused on these host–pathogen interactions to identify pathogen-specific biomarkers (gene expression profiles), or “pathogen signatures”, as potential future diagnostic tools. Other studies have assessed combinations of traditional bacterial and viral biomarkers (C-reactive protein, interleukins, myxovirus resistance protein A, procalcitonin, tumor necrosis factor-related apoptosis-inducing ligand) to establish etiology. In this review we discuss the performance of such novel diagnostics and their potential role in clinical praxis. In conclusion, there are several promising novel biomarkers in the pipeline, but well-designed randomized controlled trials are needed to evaluate the safety of using these novel biomarkers to guide clinical decisions.

#54: Sensitivity and Specificity of Procalcitonin vs C Reactive Protein in Identifying Pediatric Bacterial infections

2021 ◽  
Vol 10 (Supplement_2) ◽  
pp. S16-S16
Author(s):  
Sara Kim ◽  
Avni Bhatt ◽  
Silvana Carr ◽  
Frances Saccoccio ◽  
Judy Lew
Keyword(s):  
Urinary Tract ◽  
Sensitivity And Specificity ◽  
Urinary Tract Infections ◽  
Bacterial Infections ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Culture Positivity ◽  
Serious Bacterial Infections ◽  
Tract Infections ◽  
Culture Positive

Abstract Background Procalcitonin (PCT) and c-reactive protein (CRP) have been utilized in children to assess risk for serious bacterial infections. However, there have been different cut-offs reported for PCT and CRP, which yield different sensitivity and specificity. This study aims to compare the sensitivity and specificity of PCT and CRP in detecting serious bacterial infections (SBIs), specifically urinary tract infections, bacteremia and meningitis. Methods In this retrospective, single center cohort study from January 2018 to June 2019, we analyzed children with a fever greater than 38C with both PCT and CRP value within 24 hours of admission. Each patient had a blood, urine and/or cerebrospinal fluid culture collected within 48 hours of admission. No antibiotics were administered from the admitting hospital prior to collection of the PCT or CRP. Our gold standard was a positive culture obtained from blood, cerebrospinal fluid, or urine. The statistical analysis included categorical variables as percentages and compared them using the Fisher exact test. The optimal cutoff values for PCT or CRP were based on ROC curve analysis and Youden Index. Sensitivity and specificity analysis were based on literature review cut offs and ROC curves cut offs. Results Among 202 children, we had 45 culture positive patients (11 urinary tract infections, 4 meningitis, and 32 bacteremia). The patients with culture positivity had higher PCT levels (7.9 ng/mL vs 2.5 ng/mL, P=0.0111), CRP levels (110.9 mg/L vs 49.6 mg/L, P<0.0001) and temperature (39.2C vs 39C, P<0.0052). The area under the curve (AUC) comparing culture positivity vs negativity for all culture types was 0.72 (p<0.0001) for PCT and 0.66 (p=0.001) for CRP. In Figure 1, the AUC for culture positive bacteremia was 0.68 (p=0.0011) for PCT and 0.70 (p=0.0003). The AUC for culture positive urinary tract infections (UTI) only was 0.86 (p=0.0001) for PCT and 0.70 (p=0.3607). For the cut-off value for PCT at 0.5 ng/mL, the sensitivity and specificity was 64% (95% confidence interval [CI] 0.5–0.77) and 70% (95% CI 0.62–0.77) respectively in identifying children with bacterial infection. For the cut-off value for CRP at 20 mg/L, the sensitivity and specificity was 67% (95% CI 0.52–0.79) and 52% (95% CI 0.44–0.59) respectively in identifying children with bacterial infection. Conclusion In this study, PCT and CRP are nearly equivalent classifiers for detecting SBIs as a group and bacteremia, but PCT is statistically better for urinary tract infections; however, the clinical utility is unknown.

Monitoring both serum amyloid protein A and C-reactive protein as inflammatory markers in infectious diseases

1993 ◽  
Vol 39 (2) ◽  
pp. 293-297 ◽  
Author(s):  
T Nakayama ◽  
S Sonoda ◽  
T Urano ◽  
T Yamada ◽  
M Okada
Keyword(s):  
Inflammatory Markers ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Protein A ◽  
Acute Stage ◽  
Serum Amyloid ◽  
Amyloid Protein ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
The Mean

Abstract We examined serum amyloid protein A (SAA) and C-reactive protein (CRP) as inflammatory markers of viral and bacterial infections. Both acute-phase reactants increased in the acute stage and thereafter decreased in the convalescent stage. In viral infections, the mean serum concentrations of SAA during the acute stage were 141 mg/L in infections with adenovirus, 77 mg/L with measles virus, 63 mg/L with influenza virus, 55 mg/L with parainfluenza virus, 31 mg/L with respiratory syncytial virus, and 31 mg/L in aseptic meningitis. The mean serum concentration of CRP was 19 mg/L for adenovirus infection and < 7 mg/L in all other viral infections. The SAA concentrations were 5- to 11-fold greater than the CRP concentrations. Both the SAA and the CRP concentrations were higher in bacterial infections than in viral infections. Changes in the concentrations of serum SAA paralleled those in serum CRP in bacterial infection; during the course of viral infection, however, serum SAA tended to disappear more quickly than CRP did. SAA appears to be a clinically useful marker of inflammation in acute viral infections, with or without significant changes in the CRP concentration.

scholarly journals In Vivo mRNA Profiling of Uropathogenic Escherichia coli from Diverse Phylogroups Reveals Common and Group-Specific Gene Expression Profiles

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
Piotr Bielecki ◽  
Uthayakumar Muthukumarasamy ◽  
Denitsa Eckweiler ◽  
Agata Bielecka ◽  
Sarah Pohl ◽  
...  
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Specific Gene ◽  
Content Type ◽  
E Coli ◽  
Human Host ◽  
Tract Infections

ABSTRACTmRNA profiling of pathogens during the course of human infections gives detailed information on the expression levels of relevant genes that drive pathogenicity and adaptation and at the same time allows for the delineation of phylogenetic relatedness of pathogens that cause specific diseases. In this study, we used mRNA sequencing to acquire information on the expression ofEscherichia colipathogenicity genes during urinary tract infections (UTI) in humans and to assign the UTI-associatedE. coliisolates to different phylogenetic groups. Whereas thein vivogene expression profiles of the majority of genes were conserved among 21E. colistrains in the urine of elderly patients suffering from an acute UTI, the specific gene expression profiles of the flexible genomes was diverse and reflected phylogenetic relationships. Furthermore, genes transcribedin vivorelative to laboratory media included well-described virulence factors, small regulatory RNAs, as well as genes not previously linked to bacterial virulence. Knowledge on relevant transcriptional responses that drive pathogenicity and adaptation of isolates to the human host might lead to the introduction of a virulence typing strategy into clinical microbiology, potentially facilitating management and prevention of the disease.IMPORTANCEUrinary tract infections (UTI) are very common; at least half of all women experience UTI, most of which are caused by pathogenicEscherichia colistrains. In this study, we applied massive parallel cDNA sequencing (RNA-seq) to provide unbiased, deep, and accurate insight into the nature and the dimension of the uropathogenicE. coligene expression profile during an acute UTI within the human host. This work was undertaken to identify key players in physiological adaptation processes and, hence, potential targets for new infection prevention and therapy interventions specifically aimed at sabotaging bacterial adaptation to the human host.

The RNA-seq approach to discriminate gene expression profiles in response to Beauveria bassiana and Micrococcus luteus microbial pathogens on Actias selene (Lepidoptera: Saturniidae)

Zootaxa ◽  
2019 ◽  
Vol 4591 (1) ◽  
pp. 1
Author(s):  
DAN LIANG ◽  
PEI WANG ◽  
LINGLING WU ◽  
XIAOLI JIANG ◽  
GUOQING WEI ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Beauveria Bassiana ◽  
Bacterial Infections ◽  
Micrococcus Luteus ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Differentially Expressed ◽  
Microbial Pathogens ◽  
Pcr Analysis ◽  
Immune Mechanism

Actias selene (Hübner) is an important silk-spinning moth. Like other moths, it has innate immunity but no acquired immunity. However, there are few studies on immune-related genes of A. selene. Here, differential expression RNAseq experiment was employed to examine the genes related to different metabolic pathways and to explore the immune mechanism of the A. selene post Beauveria bassiana (Bb) and Micrococcus luteus (ML) stimuli. A total of 64,372,921 clean reads were obtained and 39,057 differentially expressed genes (DEGs) were identified. In the Bb vs. PBS group (PBS as the control), 9,092 genes were up-regulated and 4,438 genes were down-regulated; in the ML vs. PBS group, 5,903 genes were up-regulated and 5,175 genes were down-regulated. The KEGG (Kyoto Encyclopedia of Genes and Genomes) and GO (Gene Ontology) analyses of DEGs confirmed that many DEGs were associated with "Metabolism pathway", "cellular process", "cell" and "catalytic activity". Among them, 194 and 149 differentially expressed genes were related to immunity in the Bb vs. PBS group and ML vs. PBS group, respectively. We verified the reliability of the data with reverse transcription quantitative real-time PCR analysis of randomly selected genes. Furthermore, the phylogenetic tree results showed that HSP90, PGRP and MyD88 genes of A. selene were most closely related to Antheraea pernyi (Guérin-Méneville). These results will provide an overview of the molecular mechanism of A. selene resistance to fungal and bacterial infections as well as an evolutionary aspect of these genes. Moreover, the interrelated trophic mechanisms among different groups of organisms are vital to explore, thus this study will lay a foundation for further studies on the innate immune mechanism of saturniid moths, and provide important theoretical basis for studying the relationship between A. selene and other species.

scholarly journals Discovery and Validation of Novel Biomarkers for Detection of Epithelial Ovarian Cancer

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 713 ◽  
Author(s):  
Kulbe ◽  
Otto ◽  
Darb-Esfahani ◽  
Lammert ◽  
Abobaker ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Biomarker Discovery ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Pelvic Mass ◽  
Aurora Kinase ◽  
Malignant Tumours ◽  
Novel Biomarkers

Detection of epithelial ovarian cancer (EOC) poses a critical medical challenge. However, novel biomarkers for diagnosis remain to be discovered. Therefore, innovative approaches are of the utmost importance for patient outcome. Here, we present a concept for blood-based biomarker discovery, investigating both epithelial and specifically stromal compartments, which have been neglected in search for novel candidates. We queried gene expression profiles of EOC including microdissected epithelium and adjacent stroma from benign and malignant tumours. Genes significantly differentially expressed within either the epithelial or the stromal compartments were retrieved. The expression of genes whose products are secreted yet absent in the blood of healthy donors were validated in tissue and blood from patients with pelvic mass by NanoString analysis. Results were confirmed by the comprehensive gene expression database, CSIOVDB (Ovarian cancer database of Cancer Science Institute Singapore). The top 25% of candidate genes were explored for their biomarker potential, and twelve were able to discriminate between benign and malignant tumours on transcript levels (p < 0.05). Among them T-cell differentiation protein myelin and lymphocyte (MAL), aurora kinase A (AURKA), stroma-derived candidates versican (VCAN), and syndecan-3 (SDC), which performed significantly better than the recently reported biomarker fibroblast growth factor 18 (FGF18) to discern malignant from benign conditions. Furthermore, elevated MAL and AURKA expression levels correlated significantly with a poor prognosis. We identified promising novel candidates and found the stroma of EOC to be a suitable compartment for biomarker discovery.

scholarly journals Development of a Novel Plasmid-Free Thymidine Producer by Reprogramming Nucleotide Metabolic Pathways

2015 ◽  
Vol 81 (22) ◽  
pp. 7708-7719 ◽  
Author(s):  
Jin-Sook Kim ◽  
Min-Kyung Jeong ◽  
Bong-Seong Koo ◽  
Hyeon-Cheol Lee
Keyword(s):  
Dna Microarrays ◽  
Expression Profiles ◽  
Protein A ◽  
Gene Expression Profiles ◽  
Nucleotide Metabolism ◽  
Redox Stress ◽  
Content Type ◽  
E Coli ◽  
Positive Effects ◽  
Fed Batch Fermentation

ABSTRACTA novel thymidine-producing strain ofEscherichia coliwas prepared by genome recombineering. Eleven genes were deleted by replacement with an expression cassette, and 7 genes were integrated into the genome. The resulting strain,E. coliHLT013, showed a high thymidine yield with a low deoxyuridine content. DNA microarrays were then used to compare the gene expression profiles of HLT013 and its isogenic parent strain. Based on microarray analysis, thepyrbiosynthesis genes and 10 additional genes were selected and then expressed in HLT013 to find reasonable candidates for enhancing thymidine yield. Among these, phage shock protein A (PspA) showed positive effects on thymidine production by diminishing redox stress. Thus, we integratedpspAinto the HLT013 genome, resulting inE. colistrain HLT026, which produced 13.2 g/liter thymidine for 120 h with fed-batch fermentation. Here, we also provide a basis for new testable hypotheses regarding the enhancement of thymidine productivity and the attainment of a more complete understanding of nucleotide metabolism in bacteria.

scholarly journals C-reactive protein and procalcitonin for antimicrobial stewardship in COVID-19

Infection ◽  
2021 ◽  
Author(s):  
Isabell Pink ◽  
David Raupach ◽  
Jan Fuge ◽  
Ralf-Peter Vonberg ◽  
Marius M. Hoeper ◽  
...  
Keyword(s):  
Antibiotic Therapy ◽  
Bacterial Infection ◽  
Bacterial Infections ◽  
Roc Analysis ◽  
Secondary Infection ◽  
C Reactive Protein ◽  
Laboratory Findings ◽  
Secondary Bacterial Infection ◽  
Reactive Protein ◽  
Tract Infections

Abstract Purpose Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) has spread around the world. Differentiation between pure viral COVID-19 pneumonia and secondary infection can be challenging. In patients with elevated C-reactive protein (CRP) on admission physicians often decide to prescribe antibiotic therapy. However, overuse of anti-infective therapy in the pandemic should be avoided to prevent increasing antimicrobial resistance. Procalcitonin (PCT) and CRP have proven useful in other lower respiratory tract infections and might help to differentiate between pure viral or secondary infection. Methods We performed a retrospective study of patients admitted with COVID-19 between 6th March and 30th October 2020. Patient background, clinical course, laboratory findings with focus on PCT and CRP levels and microbiology results were evaluated. Patients with and without secondary bacterial infection in relation to PCT and CRP were compared. Using receiver operating characteristic (ROC) analysis, the best discriminating cut-off value of PCT and CRP with the corresponding sensitivity and specificity was calculated. Results Out of 99 inpatients (52 ICU, 47 Non-ICU) with COVID-19, 32 (32%) presented with secondary bacterial infection during hospitalization. Patients with secondary bacterial infection had higher PCT (0.4 versus 0.1 ng/mL; p = 0.016) and CRP (131 versus 73 mg/L; p = 0.001) levels at admission and during the hospital stay (2.9 versus 0.1 ng/mL; p < 0.001 resp. 293 versus 94 mg/L; p < 0.001). The majority of patients on general ward had no secondary bacterial infection (93%). More than half of patients admitted to the ICU developed secondary bacterial infection (56%). ROC analysis of highest PCT resp. CRP and secondary infection yielded AUCs of 0.88 (p < 0.001) resp. 0.86 (p < 0.001) for the entire cohort. With a PCT cut-off value at 0.55 ng/mL, the sensitivity was 91% with a specificity of 81%; a CRP cut-off value at 172 mg/L yielded a sensitivity of 81% with a specificity of 76%. Conclusion PCT and CRP measurement on admission and during the course of the disease in patients with COVID-19 may be helpful in identifying secondary bacterial infections and guiding the use of antibiotic therapy.

scholarly journals Virulence and Antibiotic Resistance of Acinetobacter baumannii among Urinary Tract Infections

2020 ◽  
Author(s):  
Hussein O.M. Al-Dahmoshi ◽  
Noor S.K. Al-Khafaji ◽  
Farah T. Al-Alaq
Keyword(s):  
Antibiotic Resistance ◽  
Urinary Tract ◽  
Acinetobacter Baumannii ◽  
Urinary Tract Infections ◽  
Bacterial Infections ◽  
Iron Acquisition ◽  
Protein A ◽  
Community Acquired Pneumonia ◽  
Tract Infections ◽  
Hospital Acquired

Acinetobacter baumannii is one of the opportunistic bacteria firstly related with the hospital acquired infection influencing primarily to weakening the patient in the ICU. It is sometimes transferred to the patient by transient colonization of hands of the workers of healthcare, and persistence on eco-surfaces. Acinetobacter baumannii inhalation aerosolized through endo-tracheal suctioning of the ventilated patient is widespread among ventilator-related pneumonia (VAP). It is infections mainly associated with ventilator-related pneumonia (VAP), community Acquired Pneumonia (CAP), invasive bacterial infections (IBIs) and UTI (urinary tract infection). It is one of the prominent uropathogens problematic with antibiotic resistance especially carbapenem resistant Acinetobacter baumannii (CRAB). Their colonization of urinary tract and establishment of infection may attributed mainly to set of virulence factors like: Acinetobactin-assisted iron acquisition system, Bap (biofilm-related protein), phospholipase D, Ata (Acinetobacter trimeric autotransporter), chaperone-usher type pilus (Csu), OmpA (outer membrane protein A), and Plasminogen-binding protein (CipA). The common drugs used for treatment Acinetobacter baumannii infections involve polymyxins, glycylcyclines, tetracyclines, mono-bactams, fluoroquinolones, aminoglycosides, antipseudomonal carbapenems, antipseudomonal cephalosporins, and sulbactam. The rates of MDR isolation or also comprehensively the resistant Acinetobacter baumannii are significantly increased and so the combination of two or more (colistin, tigecycline, or colistin-rifampicin combination therapy) drugs is sometimes used to treat infections of MDR-AB. As a conclusion the Acinetobacter baumannii engagement in urinary tract infections attributed mainly to their adhesins, invasins and intrinsic antibiotic resistance.

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