Effect of Combination of Point-of-Care C-Reactive Protein Testing and General Practitioner Education and Long-Term Effect of Education on Reducing Antibiotic Prescribing for Children Presenting with Acute Infections in General Practice in Latvia: A Randomized Controlled Intervention Study.

BACKGROUND: Antibiotics are often overprescribed in children in general practice. We investigated whether the availability of C-reactive protein point-of-care testing (CRP POCT) in daily practice and general practitioner (GP) education reduces antibiotic prescribing for children with acute infections and whether GP education has a long-term effect on antibiotic prescribing. METHODS: This was a randomized controlled intervention study with randomization at the GP practice level. Eligible patients were children aged 1 month to 17 years presenting to general practice with an acute infection. INTERVENTIONS: In the first study period, one GP group received combined interventions (CRP POCT was provided for daily use in combination with a live educational session), while the second GP group continued usual care. During the second study period, the GP groups were switched. During this period, the long-term education effect was evaluated in the GP group, which had previously received both interventions: the CRP POCT was no longer available in their practices in accordance with the study protocol, but education could have a lasting effect. PRIMARY OUTCOME: Antibiotic prescribing at index consultation. RESULTS: GP with combined intervention enrolled 1784 patients, GP with usual care enrolled 886 patients, and GP with long-term education effect enrolled 647 patients. Most of the patients had upper (76.8%) and lower (18.8%) respiratory infections. In total, 29.3% of the study patients received antibiotic prescriptions. Adjusted binary logistic regression analysis showed no differences for the primary outcome between GPs with usual care and GPs with combined intervention (aOR 0.89 (0.74-1.07), p = 0.20), but significantly lower antibiotic prescribing was observed for GPs with long-term education in comparison with GPs with usual care (aOR 0.75 (0.59-0.96), p = 0.02); however, after multilevel analyses, any differences in the antibiotic prescription between intervention groups became non-significant. GPs widely used CRP POCT when it was available in practice (for 69.1% of patients in the combined intervention group), but rarely measured CRP in the laboratory in the usual care group (8.8% (n = 78)) or long-term education group (14.8% (n = 98)). The majority of the tested patients had low CRP levels (below 20 mg/L); despite this, up to 35.4% of them received antibiotic prescriptions. CONCLUSIONS: Our results show that the availability of CRP POCT and educational training for GPs together did not reduce antibiotic prescribing, and one-time education did not have a long-term effect on antibiotic prescribing.

Mapping the evidence about the natural history of acute infections commonly seen in primary care and managed with antibiotics: a scoping review.

BACKGROUND: Knowing the natural history of acute infections in primary care, defined as the course of a disease over time in the absence of specific therapy or treatment, can inform clinicians' and patients' expectations about illness recovery, but this evidence is fragmented across the literature. This scoping review aimed to map existing research and research gaps relevant to the natural history of acute infections. METHODS: We searched MEDLINE, Embase and CENTRAL using a 2-phase hierarchical search approach. In Phase A, we focused on identifying systematic reviews synthesising natural history data for eligible infections (acute respiratory, urinary, and skin and soft tissue) and systematic reviews of treatment effectiveness (of RCTs with placebo or no treatment arm, or cohort studies). For infections without existing reviews, in Phase B, we searched for primary studies (placebo-controlled RCTs or cohort studies). Two reviewers independently screened and extracted the data (study characteristics, outcome data - e.g., symptom duration, proportion with resolution at various time points). RESULTS: We identified 40 systematic reviews, reporting on 45 infections, most commonly (90%) respiratory tract infections. Six (15%) of these aimed to synthesise natural history information. Most reviews reported the proportion of participants with symptom resolution at various time point/s, with 58% providing data on mean symptom duration. Recovery data show the spontaneous resolution of some infections in some people. We found no eligible studies for cellulitis, ecthyma, carbuncle, and erysipelas. CONCLUSIONS: Our review has shown that natural history evidence exists for many common acute infections. It can be utilised by clinicians in implementing patient-centred antibiotic stewardship strategies in primary care. Future research should focus on generating natural history evidence for skin and soft tissue infections and urinary tract infections.

Implementation of a program for treatment of acute infections in nursing homes without hospital transfer.

Background: Nursing care residents have high hospitalization rates. To address this, we established a unique virtual geriatric unit that has developed a program aimed at providing support to nursing homes. Aims: We aimed to evaluate effectiveness of in-house intravenous antibiotic treatment in nursing hospitals after the implementation of the specially designed training program. Methods: A cohort study of nursing home residents to evaluate a training program for providers, designed to increase awareness and give practical tools for in-house treatment of acute infections. Data obtained included types of infections, antibiotics used, hospital transfer, and length of treatment. Primary outcomes were in-house recovery, hospitalization and mortality. Univariate analysis and multivariable logistic regression analysis to assess association between different factors and recovery. Results: A total of 890 cases of acute infections were treated with intravenous antibiotics across 10 nursing homes over a total of 4,436 days. Of these cases, 34.8% were aged 90 years or older. Acute pneumonia was the most prevalent infection accounted for 354 cases (40.6%), followed by urinary tract infections (35.7%), and fever of presumed bacterial infection (17.1%). The mean duration of intravenous antibiotic treatment was 5.09 ± 3.86 days. Of the total cases, 800 (91.8%) recovered, 62 (7.1%) required hospitalization and nine (1.0%) resulted in mortality. There was no significant difference observed in recovery rates across different types of infections. Discussion: Appling a simple yet unique intervention program has led to more "in-house" residents receiving treatment, with positive clinical results. Conclusion: Treating in-house nursing home residents with acute infections resulted in high recovery rates. Special education programs and collaboration between healthcare organizations can improve treatment outcomes and decrease the burden on the healthcare system.

Siglec-1, an easy and contributory inflammation marker in rheumatology.

Objectives: Inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are poorly informative about interferon (IFN)-related disorders. In these conditions, the measure of the interferon score (IS), obtained by measuring the expression of IFN-stimulated genes, has been proposed. Flow cytometry-based assays measuring sialic-acid-binding Ig-like lectin 1 (Siglec-1) expression could be a more practical tool for evaluating IFN-inflammation. The study compared Siglec-1 measures with IS and other inflammatory indexes. We compared Siglec-1 measures with IS and other inflammatory indexes in real-world paediatric rheumatology experience. Methods: We recruited patients with immuno-rheumatological conditions, acute infectious illness and patients undergoing orthopaedic surgery as controls. Siglec-1 expression was measured in all samples, and IS, ESR and CRP were also recorded if available. Results: Overall, 98 subjects were enrolled in the study, with a total of 104 measures of Siglec-1. Compared with IS, Siglec-1 expression showed good accuracy (86.0%), specificity (72.7%) and sensitivity (85.7%). The measure of the percentage of Siglec-1-positive cells performed best at low levels of IFN-inflammation, while the measure of mean fluorescence intensity performed best at higher levels. Ex vivo studies on IFN-stimulated monocytes confirmed this behaviour. There was no link between Siglec-1 expression and either ESR or CRP, and positive Siglec-1 results were found even when ESR and CRP were normal. A high Siglec-1 expression was also recorded in subjects with acute infections. Conclusion: Siglec-1 measurement by flow cytometry is an easy tool to detect IFN-related inflammation, even in subjects with normal results of common inflammation indexes.

Vitamin D and immune system.

The active metabolite of vitamin D 1,25(OH)2D is well known for its role in regulating calcium-phosphate homeostasis of the human body. However, the immunomodulating activity of 1,25(OH)2D has been known for many years. There are numerous reports correlating low vitamin D levels in blood serum with the onset of autoimmune diseases and with the severe course of acute infections. In this chapter, we address the role of 1,25(OH)2D in these diseases, and we discuss the possible mechanisms of action of 1,25(OH)2D in immune cells.

Skin Lesions with Loss of Tissue and Cutaneous-Onset Sepsis: The Skin Infection-Sepsis Relationship.

Infectious and inflammatory dermatoses featuring skin lesions with loss of tissue expose skin layers to microbial invasions, disrupt the normal skin microbiome, and potentially lead to sepsis. However, literature data on the incidence of cutaneous-onset sepsis are scarce. This retrospective observational study assessed hospital admissions for primary skin lesions without bacterial infections and sepsis during 2020-2022 in the largest emergency hospital in NE Romania. Of 509 patients, 441 had infected lesions, 78 had sepsis caused by venous ulcers from microbial eczema cellulitis, superinfected bullous dermatoses, erysipelas, and erythroderma. Cultured samples revealed S. aureus, P. aeruginosa, and E. coli; and K. pneumoniae and S. ß-hemolytic associated with sepsis, even if this was rarer. Clinical manifestations included ulcerations, erosions, fissures, excoriations, bullae, vesicles, pruritus, tumefaction, edema, fever, chills, pain, adenopathy, and mildly altered mental status. Underlying chronic heart failure, atrial fibrillation, anemia, and type-1 diabetes mellitus were comorbidities associated with infection and sepsis. Significant associations and risk factors, including their combined effects, are discussed to draw attention to the need for further research and adequate management to prevent sepsis in adult patients of any age presenting with infected skin lesions (especially cellulitis) and comorbidities (especially type 1 diabetes mellitus and anemia).

How symptoms of simple acute infections affect the SSS-8 and SSD-12 as screening instruments for somatic symptom disorder in the primary care setting.

Objective: Somatic symptom disorder (SSD) is one of the most common reasons for consultations in primary care, in addition to simple acute infections. Questionnaire-based screening instruments to identify patients at high risk of SSD are thus of great clinical relevance. Although screening instruments are frequently used, it is currently unclear to what extent they are influenced by the concurrent presence of simple acute infections. Therefore, this study aimed to investigate how symptoms of simple acute infections affect the two established questionnaires as screening instruments for somatic symptom disorder in the primary care setting. Methods: In our cross-sectional, multicenter design, a total of 1,000 patients in primary care practices were screened using the two most established SSD screening questionnaires, the 8-item Somatic Symptom Scale (SSS-8) and the 12-item Somatic Symptom Disorder-B Criteria Scale (SSD-12), followed by clinical assessment by the primary care physician. Results: A total of 140 patients with a simple acute infection (acute infection group, AIG) and 219 patients with chronic somatic symptoms (somatic symptom group, SSG) were included. The patients in the SSG showed higher total SSS-8 and SSD-12 scores than the patients in the AIG; however, the SSS-8 was more susceptible to changes triggered by symptoms of a simple acute infection than the SSD-12. Conclusion: These results suggest that the SSD-12 is less susceptible to symptoms of a simple acute infection. Its total score and corresponding cutoff value provide a more specific and thus less susceptible screening tool for identifying SSD in primary care.

Local Gentamicin Fixation with Sprayed Fibrin-An In Vivo Animal Study Reveals New Options to Treat Soft Tissue Infections.

For acute and chronic soft tissue infections, radical surgical debridement is required and is considered the gold standard, along with its immediate systemic antibiotic therapy. Treatment with local antibiotics and/or antibiotic-containing materials is commonly used as an additional tool in clinical practice. Spraying with fibrin and antibiotics is a newer technique that has been studied for some antibiotics. However, for gentamicin, data are not yet available on absorption, optimal application, antibiotic fate at the site and transfer of antibiotic into the blood. In an animal study involving 29 Sprague Dawley rats, 116 back wounds were sprayed with gentamicin using either gentamicin alone or one of two possible spray combinations of gentamicin and fibrin. Simultaneous application of gentamicin and fibrin via a spray system to soft tissue wounds resulted in significant antibiotic concentration over a long period of time. The technique is easy and cost-effective. The systemic crossover was significantly minimized in our study, which may have led to fewer side effects in patients. These results could lead to an improvement in local antibiotic therapy.

Pseudomonas aeruginosa: Infections, Animal Modeling, and Therapeutics.

Pseudomonas aeruginosa is an important Gram-negative opportunistic pathogen which causes many severe acute and chronic infections with high morbidity, and mortality rates as high as 40%. What makes P. aeruginosa a particularly challenging pathogen is its high intrinsic and acquired resistance to many of the available antibiotics. In this review, we review the important acute and chronic infections caused by this pathogen. We next discuss various animal models which have been developed to evaluate P. aeruginosa pathogenesis and assess therapeutics against this pathogen. Next, we review current treatments (antibiotics and vaccines) and provide an overview of their efficacies and their limitations. Finally, we highlight exciting literature on novel antibiotic-free strategies to control P. aeruginosa infections.

Phytochemistry, Pharmacology and Molecular Mechanisms of Herbal Bioactive Compounds for Sickness Behaviour.

The host's response to acute infections or tissue injury is a sophisticated and coordinated adaptive modification called sickness behaviour. Many herbs have been studied for their ability to protect animals against experimentally induced sickness behaviour. However, there is a lack of knowledge and experimental evidence on the use of herbal bioactive compounds (HBACs) in the management of sick behaviour. The goal of this review is to provide a concise summary of the protective benefits and putative mechanisms of action of phytochemicals on the reduction of lipopolysaccharide (LPS)-induced sickness behaviour. Relevant studies were gathered from the search engines Scopus, ScienceDirect, PubMed, Google Scholar, and other scientific databases (between 2000 and to date). The keywords used for the search included "Lipopolysaccharide" OR "LPS" OR "Sickness behaviour" OR "Sickness" AND "Bioactive compounds" OR "Herbal medicine" OR "Herbal drug" OR "Natural products" OR "Isolated compounds". A total of 41 published articles that represented data on the effect of HBACs in LPS-induced sickness behaviour were reviewed and summarised systemically. There were 33 studies that were conducted in mice and 8 studies in rats. A total of 34 HBACs have had their effects against LPS-induced changes in behaviour and biochemistry investigated. In this review, we examined 34 herbal bioactive components that have been tested in animal models to see if they can fight LPS-induced sickness behaviour. Future research should concentrate on the efficacy, safety, and dosage needed to protect against illness behaviour in humans, because there is a critical shortage of data in this area.

Information about the natural history of acute infections commonly seen in primary care: a systematic review of clinical practice guidelines.

BACKGROUND: Many of the acute infections that are seen in primary care and sometimes managed with antibiotics are self-resolving and antibiotics may be unnecessary. Information about the natural history of these infections underpins antibiotic stewardship strategies such as delayed prescribing and shared decision making, yet whether it's reported in guidelines is unknown. We examined, in clinical guidelines, the reporting of natural history information and relevant antibiotic stewardship strategies for acute infections commonly seen in primary care. METHODS: A systematic review of national and international guidelines (2010 onwards), available electronically, for managing acute infections (respiratory, urinary, or skin and soft tissue). We searched MEDLINE, CINAHL, EMBASE, TRIP, and GIN databases and websites of 22 guideline-publishing organisations. RESULTS: We identified 82 guidelines, covering 114 eligible infections. Natural history information was reported in 49 (59.8%) of the guidelines and 66 (57.9%) of the reported conditions, most commonly for respiratory tract infections. Quantitative information about the expected infection duration was provided for 63.5% (n = 42) of the infections. Delayed antibiotic prescribing strategy was recommended for 34.2% (n = 39) of them and shared decision making for 21% (n = 24). CONCLUSIONS: Just over half of the guidelines for acute infections that are commonly managed in primary care and sometimes with antibiotics contained natural history information. As many of these infections spontaneously improve, this is a missed opportunity to disseminate this information to clinicians, promote antibiotic stewardship, and facilitate conversations with patients and informed decision making. Systematic review registration CRD42021247048.

Impact of educational training and C-reactive protein point-of-care testing on antibiotic prescribing in rural and urban family physician practices in Latvia: a randomised controlled intervention study.

BACKGROUND: Although self-limiting viral infections are predominant, children with acute infections are often prescribed antibiotics by family physicians. The aim of the study is to evaluate the impact of two interventions, namely C-reactive protein point-of-care testing and educational training, on antibiotic prescribing by family physicians. METHODS: This randomised controlled intervention study included acutely ill children consulted by 80 family physicians from urban and rural practices in Latvia. The family physicians were divided into two groups of 40. The family physicians in the intervention group received both interventions, i.e. C-reactive protein point-of-care testing and educational training, whereas the family physicians in the control group continued to dispense their standard care. The primary outcome measure was the antibiotic prescribing at the index consultation (delayed or immediate prescription) in both study groups. The secondary outcome was CRP testing per study group. Patient- and family physician- related predictors of antibiotic prescribing were analysed as associated independent variables. Practice location effect on the outcomes was specially addressed, similar to other scientific literature. RESULTS: In total, 2039 children with acute infections were enrolled in the study. The most common infections observed were upper and lower respiratory tract infections. Overall, 29.8% (n = 607) of the study population received antibiotic prescription. Our binary logistic regression analysis did not find a statistically significant association between antibiotic prescriptions and the implemented interventions. In the control group of family physicians, a rural location was associated with more frequent antibiotic prescribing and minimal use of CRP testing of venous blood samples. However, in the intervention group of family physicians, a rural location was associated with a higher level of C-reactive protein point-of-care testing. Furthermore, in rural areas, a significant reduction in antibiotic prescribing was observed in the intervention group compared with the control group (29.0% (n = 118) and 37.8% (n = 128), respectively, p = 0.01). CONCLUSION: Our results show that the availabilty of C-reactive protein point-of-care testing and educational training for family physicians did not reduce antibiotic prescribing. Nevertheless, our data indicate that regional variations in antibiotic-prescribing habits exist and the implemented interventions had an effect on family physicians practices in rural areas.

Local Fixation of Colistin With Fibrin Spray: An in vivo Animal Study for the Therapy of Skin and Soft Tissue Infections.

Objective: Skin and soft tissue infections (SSTI) are a commonly known entity of diseases associated with difficult treatment procedures. The current gold standard when there is a rapidly progressing infection of soft tissues with a risk of sepsis is radical surgical debridement accompanied by systemic antibiotic therapy. In clinical settings, local antibiotics alone or formulated within carrier material are commonly used alongside this therapy regimen. One possibility of local antibiotic application is the fixation of colistin with fibrin glue spray. It is not yet sufficiently researched how the local antibiotic concentrations remain as high as possible over time. Methods: We conducted an animal study including 29 male Wistar rats inducing sterile back sores reaching the muscle fascia. We sprayed only colistin, simultaneously or consecutively, with fibrin glue in different groups in order to measure the tissue concentration of the antibiotic applied locally. Results: After liquid chromatography and quadrupole mass spectrometry analysis, it could be demonstrated that in comparison to the colistin group, tissue concentrations of colistin stayed significantly higher in the wound tissue when it was fixed with fibrin glue. This was observed in both groups, the simultaneous as well as in the consecutively fibrin glue sprayed groups after colistin application. Conclusion: The fixation of colistin with the fibrin-glue-spray technique as a carrier for local antibiotic therapy is an easy and inexpensive method and shows promising potential for the treatment of SSTI.

Oregano Oil and Harmless Blue Light to Synergistically Inactivate Multidrug-Resistant Pseudomonas aeruginosa.

Blue light (BL) at 405 nm and oregano essential oil (OEO) have shown bactericidal activity by its own. Here, we demonstrated that the two synergistically killed multidrug-resistant (MDR) Pseudomonas aeruginosa (Pa). Pa ATCC19660 and HS0065 planktonic cells and mature biofilms were reduced by more than 7 log10 after treatment by BL combined with OEO, in sharp contrast to no significant bacterial reduction with the monotreatment. The duo also sufficiently eliminated acute or biofilm-associated infection of open burn wounds in murine without incurring any harmful events in the skin. The synergic bactericide was attributed mainly to the ability of OEO to magnify cytotoxic reactive oxygen species (ROS) production initiated by BL that excited endogenous tetrapyrrole macrocycles in bacteria while completely sparing the surrounding tissues from the phototoxic action. OEO ingredient analysis in combination with microbial assays identified carvacrol and its isomer thymol to be the major phytochemicals that cooperated with BL executing synergic killing. The finding argues persuasively for valuable references of carvacrol and thymol in assessing and standardizing the bactericidal potential of various OEO products.

Impact of the 2014 CDC HIV testing guidelines on detection of acute HIV infections.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) issued updated guidelines for HIV testing in 2014. These guidelines recommend screening using an HIV-1/2 antigen/antibody (Ag/Ab) test and create the ability to identify algorithm-defined acute HIV infections (AHI). The guidelines also recommend laboratory confirmation of preliminary positive point of care (POC) rapid HIV test results and specimens from high-risk individuals who test POC rapid negative. The Florida Public Health Laboratory (FPHL) switched from an antibody-only algorithm to the CDC recommended algorithm April 16, 2012. OBJECTIVES: To analyze the FPHL HIV testing data and evaluate the impact of the CDC recommended algorithm on the identification of AHI, time to result and inconclusive HIV reports. STUDY DESIGN: FPHL HIV test data, for the period January 1, 2010 through December 31, 2019, was reviewed to determine the number of AHI cases identified, the number of indeterminate HIV results and the time from specimen receipt to result for tests in the antibody-only and CDC recommended algorithms. In addition, POC rapid results were compared to laboratory-based results for AHI cases for which rapid test results were available. RESULTS: There was no difference in time to result between the antibody-only and CDC recommended algorithms for HIV negative specimens. The time to result for HIV-1 positive specimens decreased from an average of 5 days with the antibody-only algorithm to an average of 1 day with the CDC recommended algorithm. The average number of indeterminate results per month decreased from 6.25 per month with the antibody-only algorithm to an average of 2.5 per month using the CDC recommended algorithm. Despite HIV seropositivity decreasing by 0.5% during the study period (2012 = 3.1% [3,892/124,394]: 2019 = 2.6% [2,456/95,525]), AHI cases increased annually from a total of 4 in 2012 to over 50 in 2019 and cases were identified in 30 of 67 Florida counties. The increase in identification of AHIs is credited to educational efforts with healthcare providers to encourage further testing on individuals with risk factors for HIV and a recent POC HIV-1/2 rapid negative test result. CONCLUSIONS: Data indicates that performing HIV testing according to the CDC recommended algorithm decreased time to result for HIV positive results, reduced the number of indeterminate results and identified algorithm-defined AHI. In addition, laboratory-based testing is warranted for high-risk individuals who test negative by POC rapid testing.

Latvian Primary Care Management of Children with Acute Infections: Antibiotic-Prescribing Habits and Diagnostic Process Prior to Treatment.

Background and Objectives: Primary care physicians frequently prescribe antibiotics for acutely ill children, even though they usually have self-limiting diseases of viral etiology. The aim of this research was to evaluate the routine antibiotic-prescribing habits of primary care in Latvia, in response to children presenting with infections. Materials and Methods: This cross-sectional study included acutely ill children who consulted eighty family physicians (FP) in Latvia, between November 2019 and May 2020. The data regarding patient demographics, diagnoses treated with antibiotics, the choice of antibiotics and the use of diagnostic tests were collected. Results: The study population comprised 2383 patients aged between one month and 17 years, presenting an acute infection episode, who had a face-to-face consultation with an FP. Overall, 29.2% of these patients received an antibiotic prescription. The diagnoses most often treated with antibiotics were otitis (45.8% of all antibiotic prescriptions), acute bronchitis (25.0%) and the common cold (14.8%). The most commonly prescribed antibiotics were amoxicillin (55.9% of prescriptions), amoxicillin/clavulanate (18.1%) and clarithromycin (11.8%). Diagnostic tests were carried out for 59.6% of children presenting with acute infections and preceded 66.4% of antibiotic prescriptions. Conclusion: Our data revealed that a high level of antibiotic prescribing for self-limiting viral infections in children continues to occur. The underuse of narrow-spectrum antibiotics and suboptimal use of diagnostic tests before treatment decision-making were also identified. To achieve a more rational use of antibiotics in primary care for children with a fever, professionals and parents need to be better educated on this subject, and diagnostic tests should be used more extensively, including the implementation of daily point-of-care testing.

The Optimization and Biological Significance of a 29-Host-Immune-mRNA Panel for the Diagnosis of Acute Infections and Sepsis.

In response to the unmet need for timely accurate diagnosis and prognosis of acute infections and sepsis, host-immune-response-based tests are being developed to help clinicians make more informed decisions including prescribing antimicrobials, ordering additional diagnostics, and assigning level of care. One such test (InSep™, Inflammatix, Inc.) uses a 29-mRNA panel to determine the likelihood of bacterial infection, the separate likelihood of viral infection, and the risk of physiologic decompensation (severity of illness). The test, being implemented in a rapid point-of-care platform with a turnaround time of 30 min, enables accurate and rapid diagnostic use at the point of impact. In this report, we provide details on how the 29-biomarker signature was chosen and optimized, together with its molecular, immunological, and medical significance to better understand the pathophysiological relevance of altered gene expression in disease. We synthesize key results obtained from gene-level functional annotations, geneset-level enrichment analysis, pathway-level analysis, and gene-network-level upstream regulator analysis. Emerging findings are summarized as hallmarks on immune cell interaction, inflammatory mediators, cellular metabolism and homeostasis, immune receptors, intracellular signaling and antiviral response; and converging themes on neutrophil degranulation and activation involved in immune response, interferon, and other signaling pathways.

VB10, a new blood biomarker for differential diagnosis and recovery monitoring of acute viral and bacterial infections.

BACKGROUND: Precise differential diagnosis between acute viral and bacterial infections is important to enable appropriate therapy, avoid unnecessary antibiotic prescriptions and optimize the use of hospital resources. A systems view of host response to infections provides opportunities for discovering sensitive and robust molecular diagnostics. METHODS: We combine blood transcriptomes from six independent datasets (n = 756) with a knowledge-based human protein-protein interaction network, identifies subnetworks capturing host response to each infection class, and derives common response cores separately for viral and bacterial infections. We subject the subnetworks to a series of computational filters to identify a parsimonious gene panel and a standalone diagnostic score that can be applied to individual samples. We rigorously validate the panel and the diagnostic score in a wide range of publicly available datasets and in a newly developed Bangalore-Viral Bacterial (BL-VB) cohort. FINDING: We discover a 10-gene blood-based biomarker panel (Panel-VB) that demonstrates high predictive performance to distinguish viral from bacterial infections, with a weighted mean AUROC of 0.97 (95% CI: 0.96-0.99) in eleven independent datasets (n = 898). We devise a new stand-alone patient-wise score (VB10) based on the panel, which shows high diagnostic accuracy with a weighted mean AUROC of 0.94 (95% CI 0.91-0.98) in 2996 patient samples from 56 public datasets from 19 different countries. Further, we evaluate VB10 in a newly generated South Indian (BL-VB, n = 56) cohort and find 97% accuracy in the confirmed cases of viral and bacterial infections. We find that VB10 is (a) capable of accurately identifying the infection class in culture-negative indeterminate cases, (b) reflects recovery status, and (c) is applicable across different age groups, covering a wide spectrum of acute bacterial and viral infections, including uncharacterized pathogens. We tested our VB10 score on publicly available COVID-19 data and find that our score detected viral infection in patient samples. INTERPRETATION: Our results point to the promise of VB10 as a diagnostic test for precise diagnosis of acute infections and monitoring recovery status. We expect that it will provide clinical decision support for antibiotic prescriptions and thereby aid in antibiotic stewardship efforts. FUNDING: Grand Challenges India, Biotechnology Industry Research Assistance Council (BIRAC), Department of Biotechnology, Govt. of India.

Clinical, biological and bacteriological characteristics of osteoarticular infections in infants less than 12 months of age.

Aim: This retrospective study's objective was to evaluate osteoarticular infection in infants less than 12 months of age, with a particular focus on biological features and bacteriological etiology. Material & methods: We retrospectively reviewed the medical records of every infant younger than 12 months old admitted in our institution for a suspected osteoarticular infection between January 1980 and December 2016. Results: Sixty-nine patients records were reviewed, including eight neonates, 16 infants from 1 to 5 months old, and 45 from 6 to 12 months old. Conclusion: Neonates and infants aged from 6 to 12 months old were more exposed to infections. Staphylococcus aureus remained the main pathogen in children <6 months, whereas Kingella kingae has become the most frequently isolated microorganism in infants aged from 6 to 12 months old.

A Multi-mRNA Host-Response Molecular Blood Test for the Diagnosis and Prognosis of Acute Infections and Sepsis: Proceedings from a Clinical Advisory Panel.

Current diagnostics are insufficient for diagnosis and prognosis of acute infections and sepsis. Clinical decisions including prescription and timing of antibiotics, ordering of additional diagnostics and level-of-care decisions rely on understanding etiology and implications of a clinical presentation. Host mRNA signatures can differentiate infectious from noninfectious etiologies, bacterial from viral infections, and predict 30-day mortality. The 29-host-mRNA blood-based InSepTM test (Inflammatix, Burlingame, CA, formerly known as HostDxTM Sepsis) combines machine learning algorithms with a rapid point-of-care platform with less than 30 min turnaround time to enable rapid diagnosis of acute infections and sepsis, as well as prediction of disease severity. A scientific advisory panel including emergency medicine, infectious disease, intensive care and clinical pathology physicians discussed technical and clinical requirements in preparation of successful introduction of InSep into the market. Topics included intended use; patient populations of greatest need; patient journey and sample flow in the emergency department (ED) and beyond; clinical and biomarker-based decision algorithms; performance characteristics for clinical utility; assay and instrument requirements; and result readouts. The panel identified clear demand for a solution like InSep, requirements regarding test performance and interpretability, and a need for focused medical education due to the innovative but complex nature of the result readout. Innovative diagnostic solutions such as the InSep test could improve management of patients with suspected acute infections and sepsis in the ED, thereby lessening the overall burden of these conditions on patients and the healthcare system.