Etiology of Clinical Community-Acquired Pneumonia in Swedish Children Aged 1-59 Months with High Pneumococcal Vaccine Coverage-The TREND Study

(1) Immunization with pneumococcal conjugate vaccines has decreased the burden of community-acquired pneumonia (CAP) in children and likely led to a shift in CAP etiology. (2) The Trial of Respiratory infections in children for ENhanced Diagnostics (TREND) enrolled children 1-59 months with clinical CAP according to the World Health Organization (WHO) criteria at Sachs' Children and Youth Hospital, Stockholm, Sweden. Children with rhonchi and indrawing underwent "bronchodilator challenge". C-reactive protein and nasopharyngeal PCR detecting 20 respiratory pathogens, were collected from all children. Etiology was defined according to an a priori defined algorithm based on microbiological, biochemical, and radiological findings. (3) Of 327 enrolled children, 107 (32%) required hospitalization; 91 (28%) received antibiotic treatment; 77 (24%) had a chest X-ray performed; and 60 (18%) responded to bronchodilator challenge. 243 (74%) episodes were classified as viral, 11 (3%) as mixed viral-bacterial, five (2%) as bacterial, two (0.6%) as atypical bacterial and 66 (20%) as undetermined etiology. After exclusion of children responding to bronchodilator challenge, the proportion of bacterial and mixed viral-bacterial etiology was 1% and 4%, respectively. (4) The novel TREND etiology algorithm classified the majority of clinical CAP episodes as of viral etiology, whereas bacterial etiology was uncommon. Defining CAP in children <5 years is challenging, and the WHO definition of clinical CAP is not suitable for use in children immunized with pneumococcal conjugate vaccines

VACCELERATE Site Network: Real-time definition of clinical study capacity in Europe

Background: The inconsistent European vaccine trial landscape rendered the continent of limited interest for vaccine developers. The VACCELERATE consortium created a network of capable clinical trial sites throughout Europe. VACCELERATE identifies and provides access to state-of-the-art vaccine trial sites to accelerate clinical development of vaccines. Methods: Login details for the VACCELERATE Site Network (vaccelerate.eu/site-network/) questionnaire can be obtained after sending an email to. Interested sites provide basic information, such as contact details, affiliation with infectious disease networks, main area of expertise, previous vaccine trial experience, site infrastructure and preferred vaccine trial settings. In addition, sites can recommend other clinical researchers for registration in the network. If directly requested by a sponsor or sponsor representative, the VACCELERATE Site Network pre-selects vaccine trial sites and shares basic study characteristics provided by the sponsor. Interested sites provide feedback with short surveys and feasibility questionnaires developed by VACCELERATE and are connected with the sponsor to initiate the site selection process. Results: As of April 2023, 481 sites from 39 European countries have registered in the VACCELERATE Site Network. Of these, 137 (28.5 %) sites have previous experience conducting phase I trials, 259 (53.8 %) with phase II, 340 (70.7 %) with phase III, and 205 (42.6 %) with phase IV trials, respectively. Infectious diseases were reported as main area of expertise by 274 sites (57.0 %), followed by any kind of immunosuppression by 141 (29.3 %) sites. Numbers are super additive as sites may report clinical trial experience in several indications. Two hundred and thirty-one (47.0 %) sites have the expertise and capacity to enrol paediatric populations and 391 (79.6 %) adult populations. Since its launch in October 2020, the VACCELERATE Site Network has been used 21 times for academic and industry trials, mostly interventional studies, focusing on different pathogens such as fungi, monkeypox virus, Orthomyxoviridae/influenza viruses, SARS-CoV-2, or Streptococcus pneumoniae/pneumococcus. Conclusions: The VACCELERATE Site Network enables a constantly updated Europe-wide mapping of experienced clinical sites interested in executing vaccine trials. The network is already in use as a rapid-turnaround single contact point for the identification of vaccine trials sites in Europe.The VACCELERATE Site Network has received funding from the European Union’s Horizon 2020 research and innovation pro gramme (grant agreement No 101037867) and the German Federal Ministry of Education and Research (Bundesministerium für Bil dung und Forschung [BMBF]) (grant agreement No BMBF01KX2040).S

Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19

SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. Here, we systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in unexposed individuals, exposed family members, and individuals with acute or convalescent COVID-19. Acute-phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent-phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative exposed family members and convalescent individuals with a history of asymptomatic and mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits broadly directed and functionally replete memory T cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19

The DENOVA score efficiently identifies patients with monomicrobial Enterococcus faecalis bacteremia where echocardiography is not necessary

Objectives: Enterococcal bacteremia can be complicated by infective endocarditis (IE) and when suspected, transesophageal echocardiography (TEE) should be performed. The previously published NOVA score can identify patients with enterococcal bacteremia at risk for IE and we aimed to improve the score. Methods: Factors associated with IE were studied retrospectively in a population-based cohort of patients with monomicrobial Enterococcus faecalis bacteremia (MEFsB). Factors associated with IE in multivariable analysis were included in a new score system which was compared to the NOVA score and validated in a cohort of patients with MEFsB from another region. Results: Among 397 episodes of MEFsB, 44 episodes with IE were compared to those without IE. Long Duration of symptoms (≥ 7 days) and Embolization were associated with IE in the multivariate analysis and hence were added to the NOVA variables (Number of positive cultures, Origin of infection unknown, Valve disease, and Auscultation of murmur) to generate a novel score; DENOVA. The area under the curve in ROC analyses was higher for DENOVA (0.95) compared to NOVA (0.91) (p = 0.001). With a cutoff at ≥ 3 positive variables the DENOVA score has a sensitivity of 100% and specificity of 83% which is superior to the NOVA score (specificity 29%). The DENOVA score was applied to the validation cohort (26 IE episodes and 256 non-IE episodes) and the resulting sensitivity was 100% and the specificity was 85% compared to 35% for NOVA. Conclusions: The DENOVA score is a useful tool to identify patients with MEFsB where TEE is not needed

The accuracy of fully-automated algorithms for the surveillance of central venous catheter-related bloodstream infection in hospitalised patients

Abstract Background Continuous surveillance for healthcare-associated infections such as central venous catheter-related bloodstream infections (CVC-BSI) is crucial for prevention. However, traditional surveillance methods are resource-intensive and prone to bias. This study aimed to develop and validate fully-automated surveillance algorithms for CVC-BSI. Methods Two algorithms were developed using electronic health record data from 1000 admissions with a positive blood culture (BCx) at Karolinska University Hospital from 2017: (1) Combining microbiological findings in BCx and CVC cultures with BSI symptoms; (2) Only using microbiological findings. These algorithms were validated in 5170 potential CVC-BSI-episodes from all admissions in 2018–2019, and results extrapolated to all potential CVC-BSI-episodes within this period (n = 181,354). The reference standard was manual record review according to ECDC’s definition of microbiologically confirmed CVC-BSI (CRI3-CVC). Results In the potential CVC-BSI-episodes, 51 fulfilled ECDC’s definition and the algorithms identified 47 and 49 episodes as CVC-BSI, respectively. Both algorithms performed well in assessing CVC-BSI. Overall, algorithm 2 performed slightly better with in the total period a sensitivity of 0.880 (95%-CI 0.783–0.959), specificity of 1.000 (95%-CI 0.999–1.000), PPV of 0.918 (95%-CI 0.833–0.981) and NPV of 1.000 (95%-CI 0.999–1.000). Incidence according to the reference and algorithm 2 was 0.33 and 0.31 per 1000 in-patient hospital-days, respectively. Conclusions Both fully-automated surveillance algorithms for CVC-BSI performed well and could effectively replace manual surveillance. The simpler algorithm, using only microbiology data, is suitable when BCx testing adheres to recommendations, otherwise the algorithm using symptom data might be required. Further validation in other settings is necessary to assess the algorithms’ generalisability

External validation of semi-automated surveillance algorithms for deep surgical site infections after colorectal surgery in an independent country

Abstract Background Automated surveillance methods that re-use electronic health record data are considered an attractive alternative to traditional manual surveillance. However, surveillance algorithms need to be thoroughly validated before being implemented in a clinical setting. With semi-automated surveillance patients are classified as low or high probability of having developed infection, and only high probability patients subsequently undergo manual record review. The aim of this study was to externally validate two existing semi-automated surveillance algorithms for deep SSI after colorectal surgery, developed on Spanish and Dutch data, in a Swedish setting. Methods The algorithms were validated in 225 randomly selected surgeries from Karolinska University Hospital from the period January 1, 2015 until August 31, 2020. Both algorithms were based on (re)admission and discharge data, mortality, reoperations, radiology orders, and antibiotic prescriptions, while one additionally used microbiology cultures. SSI was based on ECDC definitions. Sensitivity, specificity, positive predictive value, negative predictive value, and workload reduction were assessed compared to manual surveillance. Results Both algorithms performed well, yet the algorithm not relying on microbiological culture data had highest sensitivity (97.6, 95%CI: 87.4–99.6), which was comparable to previously published results. The latter algorithm aligned best with clinical practice and would lead to 57% records less to review. Conclusions The results highlight the importance of thorough validation before implementation in other clinical settings than in which algorithms were originally developed: the algorithm excluding microbiology cultures had highest sensitivity in this new setting and has the potential to support large-scale semi-automated surveillance of SSI after colorectal surgery

Study Population Characteristics and Risk Factors for Colonization with ESBL-Producing Bacteria.

1<p>Mid-upper arm circumference at time of enrolment examined on children ≥6 months of age.</p>2<p>Test for linear trend.</p>3<p>Child breastfed at time of enrolment.</p>4<p>Bedsharing with another child <5 years of age.</p>5<p>Number of children <5 years of age living in the same household.</p>6<p>Antibiotic treatment initiated prior to presentation at emergency ward.</p>7<p>Reported antibiotic usage during the month prior to study enrolment (excluding antibiotic usage for current disease).</p>8<p>Child hospitalized ≥1 day during the month prior to enrolment.</p

Carriage Prevalence of ESBL-Producing <i>E. coli</i> and <i>K. pneumoniae</i> According to Age.

<p>Full legend: The ESBL carriage prevalence did not vary depending on age. Absolute numbers are presented within bars.</p

Minimal Spanning Tree of <i>K. pneumoniae</i> Isolates in Fecal Carriage in Children in Guinea-Bissau.

<p>Full legend: The tree maps the relatedness of <i>K. pneumoniae</i> isolates. Isolates ≥93% related in DiversiLab analysis are grouped in a pie where each slice represents one isolate in the cluster. Each cluster was assigned a Roman numeral. Red indicates resistance to gentamicin, ciprofloxacin and trimethoprim-sulfamethoxazole, which at the time of the study were all easily available antibiotics except cephalosporin to treat gram-negative bacterial infections in Guinea-Bissau. Green indicates susceptibility to at least one of the mentioned agents.</p

Peripheral Oxygen Saturation Facilitates Assessment of Respiratory Dysfunction in the Sequential Organ Failure Assessment Score with Implications for the Sepsis-3 Criteria

OBJECTIVES: Sequential Organ Failure Assessment score is the basis of the Sepsis-3 criteria and requires arterial blood gas analysis to assess respiratory function. Peripheral oxygen saturation is a noninvasive alternative but is not included in neither Sequential Organ Failure Assessment score nor Sepsis-3. We aimed to assess the association between worst peripheral oxygen saturation during onset of suspected infection and mortality. DESIGN: Cohort study of hospital admissions from a main cohort and emergency department visits from four external validation cohorts between year 2011 and 2018. Data were collected from electronic health records and prospectively by study investigators. SETTING: Eight academic and community hospitals in Sweden and Canada. PATIENTS: Adult patients with suspected infection episodes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main cohort included 19,396 episodes (median age, 67.0 [53.0-77.0]; 9,007 [46.4%] women; 1,044 [5.4%] died). The validation cohorts included 10,586 episodes (range of median age, 61.0-76.0; women 42.1-50.2%; mortality 2.3-13.3%). Peripheral oxygen saturation levels 96-95% were not significantly associated with increased mortality in the main or pooled validation cohorts. At peripheral oxygen saturation 94%, the adjusted odds ratio of death was 1.56 (95% CI, 1.10-2.23) in the main cohort and 1.36 (95% CI, 1.00-1.85) in the pooled validation cohorts and increased gradually below this level. Respiratory assessment using peripheral oxygen saturation 94-91% and less than 91% to generate 1 and 2 Sequential Organ Failure Assessment points, respectively, improved the discrimination of the Sequential Organ Failure Assessment score from area under the receiver operating characteristics 0.75 (95% CI, 0.74-0.77) to 0.78 (95% CI, 0.77-0.80; p < 0.001). Peripheral oxygen saturation/Fio2ratio had slightly better predictive performance compared with peripheral oxygen saturation alone, but the clinical impact was minor. CONCLUSIONS: These findings provide evidence for assessing respiratory function with peripheral oxygen saturation in the Sequential Organ Failure Assessment score and the Sepsis-3 criteria. Our data support using peripheral oxygen saturation thresholds 94% and 90% to get 1 and 2 Sequential Organ Failure Assessment respiratory points, respectively. This has important implications primarily for emergency practice, rapid response teams, surveillance, research, and resource-limited settings