Background Septic shock remains a major cause of death that can be complicated by a long-term impairment in immune function defining immunosuppression induced by sepsis (IS). Among Treg cells, the tumor necrosis factor receptor 2 positive (TNFR2 pos) Treg cell subset endorses significant immunosuppressive functions in human tumors and in a sepsis mouse model but have not been investigated during septic shock in humans. Methods We prospectively enrolled patients with septic shock hospitalized in Intensive Care Unit (ICU). We performed immunophenotyping and functional tests of CD4+T cells, Treg cells and TNFR2 posTregcells, on blood samples collected at 1, 4 and 7 days after admission in ICU. Results We investigated 10 patients with septic shock and compared to 10 healthy controls. Although the proportions of circulating Tregcells and TNFR2 posTregcells subsets were not increased, their CTLA-4 expression and suppressive functions in vitro were increased at 4 days of septic shock. Also, PBMC from healthy donors cultured with serum from septic shock patients had increased CTLA4 expression in TNFR2 pos Treg cells compared to TNFR2 neg Treg cells. Conclusion In patients with septic shock, CTLA-4 expression and suppressive function were increased in circulating TNFR2 posTreg cells. We identify TNFR2 posTreg cells as a potential attractive target for therapeutic intervention.

Objectives Brain abscess is one of the most serious diseases of the CNS and is associated with high morbidity and mortality. With regard to the lack of data supporting an optimal therapeutic strategy, this study aimed to explore the prognostic factors of brain abscess, putting emphasis on the impact of therapeutic decisions. Methods We retrospectively included patients hospitalized for brain abscess during a period of 13 years. Comorbidities (Charlson scale), clinical presentation, microbiology culture, radiological features and therapeutic management were collected. Glasgow Outcome Scale (GOS) at 3 months and length of hospital stay were, respectively, the main and the secondary outcomes. Logistic regression was used to determine factors associated with outcome independently. Results Initial Glasgow Coma Scale (GCS) ≤14 and comorbidities (Charlson scale ≥2) were associated with poor neurological outcome while oral antibiotic switch was associated with better neurological outcome. Oral switch did not appear to be associated with an unfavourable evolution in the subset of patients without initial neurological severity (GCS >14) on admission. Duration of IV regimen and time to oral switch were associated with the length of inpatient stay. Conclusions This study confirms the role of GCS and comorbidities as prognostic factors and presents reassuring data regarding the safety of oral switch for the antibiotic treatment of brain abscesses. Oral switch could prevent catheter-induced iatrogenic complications and allow a higher quality of life for patients.

Objectives Monitoring the appropriateness of antibiotic prescriptions with indicators based on reimbursement data is required to guide antibiotic stewardship (AMS) interventions in nursing homes (NHs). Quantity metrics (QMs) monitor the volume of prescriptions while proxy indicators (PIs) reflect the appropriateness of antibiotic use. Our objectives were: (i) to provide a relevant consensual set of indicators to be used in French NHs; and (ii) to assess the feasibility of their implementation at the national and local scale. Methods Nine French professional organizations implicated in AMS in NHs were asked to nominate at least one member to create a national expert panel of 20 physicians. Twenty-one recently published QMs and 11 PIs were assessed by the expert panel. Indicators were evaluated using a RAND-modified Delphi procedure comprising two online surveys and a videoconference meeting. Indicators were kept in the final list if >70% of stakeholders validated their relevance for estimating the volume (QMs) and appropriateness (PIs) of prescriptions. Results Of the 21 QM indicators submitted to the panel, 14 were selected, describing the consumption of antibiotics overall (n = 3), broad-spectrum (n = 6) and second-line antibiotics (n = 2). The three remaining QMs evaluated the route of administration (n = 1) and urine culture prescriptions (n = 2). Ten PIs (six modified, two rejected, one new) were selected to assess the appropriateness of prescriptions for urinary tract infections (n = 2), seasonal variations in prescriptions (n = 2), repeated prescriptions of fluoroquinolones (n = 1), cephalosporins’ route of administration (n = 1), duration of treatment (n = 1), rate of second-line antibiotics (n = 1), co-prescriptions with non-steroidal anti-inflammatory drugs (n = 1), and flu vaccine coverage (n = 1). The panel was in favour of using these indicators for regional and facility level AMS programmes (91%), feedback to NH prescribers (82%), benchmarking by health authorities (55%) and public reporting at the facility level (9%). Conclusions This consensual list of indicators, covering a wide range of frequent clinical situations, may be used as part of the French national AMS strategy for monitoring antibiotic prescriptions in NHs at the national and local levels. Regional AMS networks might manage this selected list to guide personalized action plans with concrete objectives of reducing the quantity and improving the quality of antibiotic prescriptions.

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