Other specific DSP article suggested by Editorial Board
Risk factors for immunological sensitization to Mycobacterium tuberculosis and progression to incident TB disease among HIV-uninfected adults in a high burden setting
Authors: Humphrey Mulenga
Abstract
Background: Identifying risk factors for Mtb sensitization (defined as IGRA-positive) and progression to TB disease is critical to guide targeted prevention strategies.
Methods: We analyzed data from a prospective cohort of adults (18–60 years) without HIV, enrolled at five high-incidence South African sites. Participants underwent testing for Mtb sensitization and microbiologically-confirmed TB at baseline, and during 15 months follow-up. Multivariable logistic and Cox regression models were used to assess factors associated with Mtb sensitization and TB progression. Sampling weights were applied to reflect the screened population.
Results: Among 2,912 participants with valid IGRA results, 63.4% (n=1895) were Mtb-sensitized. Prevalent TB was detected in 1.81% (62/1895) of Mtb-sensitized versus 0.62% (12/1017) of Mtb-unsensitized individuals (p=0.01). During follow-up of participants without prevalent TB, 2.01% (48/1833) Mtb-sensitized and 0.53% (8/1005) Mtb-unsensitized individuals developed TB (p=0.01). Factors associated with Mtb sensitization included increasing age (adjusted-odds-ratio; aOR=1.02 , 95%CI 1.01–1.03), male sex (aOR=1.34, 95%CI 1.08–1.67), smoking (aOR=1.31, 95%CI 1.05–1.64), prior TB (aOR=2.20, 95%CI 1.40–3.47), and TB contact history (aOR=1.40, 95%CI 1.08–1.83). Risk factors for progression to TB were Mtb sensitization (adjusted-hazard-ratio; aHR=3.05, 95%CI 1.14–8.18), smoking history (aHR=2.34, 95%CI 1.03–5.31), and lower body-mass index (aHR=0.89, 95%CI 0.82–0.97).
Conclusion: Mtb-sensitized individuals had a three-fold higher risk of prevalent TB and progressing to TB compared to Mtb-unsensitized individuals. In high-prevalence settings, identifying individuals at greatest risk—such as those recently infected, with a history of smoking, or low BMI—could help refine TB prevention efforts and reduce community-level transmission.”
Other specific DSP article suggested by Editorial Board
Plasma biomarkers of immunothrombosis are independently associated with death in patients with COVID-19 on ECMO
Authors: Andrew P Platt
Abstract
Background: Critical illness in COVID-19 may require support with Extracorporeal Membrane Oxygenation (ECMO). As immunothrombosis contributes to pathogenesis of critical illness we quantified immunothrombotic markers in patients with COVID-19 on ECMO and evaluated the predictive capacity of these markers for death.
Methods: We performed a retrospective analysis of 74 consecutive patients with COVID-19 on ECMO at a single academic medical center between March 2020 and February 2021. SARS-CoV-2 nucleocapsid RNA and 16 immunothrombotic biomarkers were longitudinally quantified. Biomarker trajectories were assessed with univariate and multivariate models and used to predict death and decannulation across multiple models.
Results: Male sex, smoking status, high serum bilirubin level, and low partial pressure of oxygen in arterial blood to the fraction of inspired oxygen (P/F) ratio were associated with an increased risk of death. Plasma levels of 10 immunothrombotic markers were significantly elevated in fatal cases. Elevated IL-8 and von Willebrand factor (VWF) were associated with an increased hazard of death and elevated angiopoietin-2, IL-1β, IL-6, IL-8, IL-18, ICAM, p-selectin, syndecan-1, and VWF were associated with a decreased hazard for decannulation when adjusting for sex, smoking status, and time to cannulation. Predictive models incorporating biomarkers were superior to demographics alone and equivalent to models including clinical information.
Conclusions : We found increased immunothrombotic markers, male sex, and history of smoking were risk factors in patients with COVID-19 on ECMO who died as compared to those who were decannulated. These findings are important for understanding the pathogenesis of severe COVID-19 and prognostication.”
Other specific DSP article suggested by Editorial Board
Variable Staphylothrombin Activity in Staphylococcus aureus Bloodstream Infections
Authors: Gregory L Damhorst
Abstract
Background: Although manipulation of host hemostasis is a central mechanism in Staphylococcus aureus virulence, clinically relevant phenotypes of S aureus coagulase activity and the variability thereof in the context of bloodstream infections are unknown.
Methods: We created a high-throughput staphylothrombin activity and growth fitness assay to characterize fibrin formation and S aureus replication by adding bacterial culture supernatant to human blood plasma. Supernatant is rich in bacterial proteins, including coagulases secreted during growth, but it contains relatively few viable cells. As a result, staphylothrombin activity driven by secreted coagulases can initially be observed and a contribution from bacterial replication can also be captured.
Results: Some S aureus isolates showed slow or absent staphylothrombin activity in a subset of plasma specimens despite robust and rapid fibrin polymerization in other plasmas, suggesting that a host-pathogen match or mismatch determines the observed phenotype. Characterization of S aureus transposon mutant behavior, host plasma coagulation factors, pharmacologic direct thrombin inhibition, and across-host patterns provides clues to complex determinants of coagulase-mediated virulence.
Conclusions: Observations of variable staphylothrombin phenotypes may have implications for novel therapeutic approaches and clinical risk stratification in S aureus bloodstream infections.”
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A Double Blind, Randomized Trial of Oral Chlorhexidine Gluconate for Treatment of Oral Staphylococcus aureus Colonization in Healthy Children
DOI: 10.1093/ofid/ofag072
Authors: Lucia Liu
Abstract
Background:
Staphylococcus aureus is the most common cause of skin and soft tissue infection (SSTI). Nasal S. aureus colonization may precede SSTI and decolonization may decrease SSTI risk. However, many S. aureus colonized persons are oropharyngeally colonized, sometimes without concomitant nasopharyngeal colonization. However, there are few data on oropharyngeal S. aureus decolonization, especially in children.
Methods: We performed a prospective, double-blind, randomized controlled clinical trial of twice daily 0.12% chlorhexidine gluconate (CHG) gargle versus a placebo for 7 days in healthy children oropharyngeally colonized with S. aureus. At each study visit (Day 1, 8, 29), throat and nares cultures were performed. All S. aureus isolates underwent spa typing.
Results: We screened 189 children, 120 (63%) of whom had S. aureus oropharyngeal colonization; of these 67 (56%) were randomized. Median participant age was 11 years (mean 11.7) and 27 (40%) were female. In the intention to treat population, oropharyngeal colonization at Day 8 was 45% (15/33) and 79% (27/34) in the CHG and placebo groups, respectively (P=0.004), and 61% (20/33) vs. 85% (29/34) at Day 29 (P=0.03). Among children who were oropharyngeally decolonized at Day 8 but positive for S. aureus at Day 29, 8/12 (66%) exhibited a new spa type compared to baseline.
Conclusions: We found that a 7-day 0.12% chlorhexidine gluconate mouthwash regimen significantly reduced S. aureus oropharyngeal colonization compared to placebo. This difference persisted at Day 29, suggesting that CHG mouthwash may be a promising adjunctive decolonization agent that may decrease the high SSTI recurrence risk in children.
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Other specific DSP article suggested by Editorial Board
ESCMID Clinical Guidelines on the Evaluation and Management of a Reported Antibiotic Allergy.
Authors: Joean O et al
Abstract
Scope: Antibiotic allergies remain one of the most frequently documented drug allergies in clinical records. It is well established that only a small proportion – estimated at 5-10% – represents true immune-mediated hypersensitivity. Mislabelling can contribute to the development of antimicrobial resistance (AMR) via prescription of suboptimal antimicrobial therapy (i.e. unnecessary avoidance of first-line antibiotics), increased use of broad-spectrum agents, and complications such as drug toxicity. This guideline, developed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), provides evidence-based recommendations for the clinical evaluation and management of patients with reported antibiotic allergies. It is aimed at non-allergist clinicians and seeks to harmonise practice across healthcare settings in Europe and beyond. Methods: The guideline was developed by a multidisciplinary panel of 16 experts in infectious diseases, allergy, pharmacy, paediatrics and clinical microbiology, following a modified GRADE-ADOLOPMENT process. Systematic searches were conducted in PubMed and the Trip Database (2015-2023) to identify relevant guidelines, complemented by an additional systematic search for primary studies (2021-2024). The included guidelines were assessed using the AGREE Global Rating Scale. Four existing guidelines, from 2022 and 2023, met methodological quality criteria and were included. Key questions were identified and prioritised by the panel, and relevant data were extracted using piloted Evidence to Decision (EtD) framework sheets. The panel developed recommendations by adopting, adapting or formulating new recommendations, through an iterative work-up and consensus process. All recommendations were finalised through panel discussion and formal voting, with consensus defined as agreement by ≥80% of members. Recommendations: The guideline recommends a structured clinical assessment to evaluate a reported antibiotic allergy, taking into consideration the characteristics of the index reaction. Where the clinical history suggests a very low or low likelihood of true allergy, direct delabelling or performing a controlled drug challenge test is appropriate. By supporting allergy evaluation and prudent prescribing practices, the recommendations aim to improve individual patient outcomes and reinforce antimicrobial stewardship goals.