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Background: Systematic treatment with intravenous acyclovir is usually given when varicella zoster virus (VZV) DNA is isolated in cerebrospinal fluid (CSF), indicating central nervous system (CNS) involvement. Our study aimed to describe therapeutic management and acute kidney injury (AKI) occurrence during acyclovir treatment of VZV infection with CNS involvement. Methods: Multicentre, retrospective study including all patients from 2010 to 2022 with VZV DNA in CSF. Patient management and outcomes were compared according to clinical presentation and indications for intravenous acyclovir: i) definite (encephalitis, myelitis or stroke, peripheral nervous system (PNS) with ≥ 2 roots, herpes zoster ≥ 3 dermatomes, immunosuppression), ii) questionable (1 or 2 dermatomes) or iii) no indication (other situations). Results: 154 patients were included (median age 66 (interquartile range 43–77), 87 (56%) males); 60 (39%) had encephalitis, myelitis or stroke, 35 (23%) had PNS involvement, 37 (24%) had isolated meningitis, 14 (9%) had isolated cutaneous presentation, and 8 (5%) had other presentations. Overall, 128 (83%) received intravenous acyclovir for more than 72 h. AKI occurred in 57 (37%) patients. Finally, 42 (27%) and 25 (16%) patients had respectively no or a questionable indication for intravenous acyclovir, while 29 (69%) and 23 (92%) of them received it for more than 72 h, with AKI in 13 (35%) and 13 (52%) patients, respectively. In-hospital mortality was 12% (n = 18), and no deaths were reported in isolated meningitis. Conclusions: Intravenous acyclovir is widely prescribed when VZV DNA is isolated in CSF, regardless of the clinical presentation, with a high rate of AKI. Further studies are needed to better define the value of intravenous acyclovir in isolated VZV meningitis. [ABSTRACT FROM AUTHOR]

Background We aimed to evaluate the cardiac adverse events (AEs) in hospitalized patients with coronavirus disease 2019 (COVID-19) who received remdesivir plus standard of care (SoC) compared with SoC alone (control), as an association was noted in some cohort studies and disproportionality analyses of safety databases. Methods This post hoc safety analysis is based on data from the multicenter, randomized, open-label, controlled DisCoVeRy trial in hospitalized patients with COVID-19. Any first AE that occurred between randomization and day 29 in the modified intention-to-treat (mITT) population randomized to either remdesivir or control group was considered. Analysis was performed using Kaplan-Meier survival curves, and Kaplan-Meier estimates were calculated for event rates. Results Cardiac AEs were reported in 46 (11.2%) of 410 and 48 (11.3%) of 423 patients in the mITT population (n = 833) enrolled in the remdesivir and control groups, respectively. The difference between both groups was not significant (hazard ratio [HR], 1.0; 95% confidence interval [CI],.7–1.5; P =.98), even when serious and nonserious cardiac AEs were evaluated separately. The majority of reports in both groups were of arrhythmic nature (remdesivir, 84.8%; control, 83.3%) and were associated with a favorable outcome. There was no significant difference between the two groups in the occurrence of cardiac AE subclasses, including arrhythmic events (HR, 1.1; 95% CI,.7–1.7; P =.68). Conclusions Remdesivir treatment was not associated with an increased risk of cardiac AEs compared with control in patients hospitalized with moderate or severe COVID-19. These results are consistent with other randomized, controlled trials and meta-analyses. Clinical Trials Registration. NCT 04315948; EudraCT 2020-000936-23. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is one of the main causes of healthcare-associated infection in Europe that increases patient morbidity and mortality. Multi-resistant pathogens are a major public health issue in burn centers. Mortality increases when the initial antibiotic treatment is inappropriate, especially if the patient is infected with P. aeruginosa strains that are resistant to many antibiotics. Phage therapy is an emerging option to treat severe P. aeruginosa infections. It involves using natural viruses called bacteriophages, which have the ability to infect, replicate, and, theoretically, destroy the P. aeruginosa population in an infected patient. We report here the case of a severely burned patient who experienced relapsing ventilator-associated pneumonia associated with skin graft infection and bacteremia due to extensively drug-resistant P. aeruginosa. The patient was successfully treated with personalized nebulized and intravenous phage therapy in combination with immunostimulation (interferon-γ) and last-resort antimicrobial therapy (imipenem-relebactam). [ABSTRACT FROM AUTHOR]

Background: The antiviral efficacy of Evusheld (AZD7442) in patients hospitalized for SARS-CoV-2 is unknown., Methods: We analysed the evolution of both the nasopharyngeal viral load and the serum neutralization activity against the variant of infection in 199 hospitalized patients (109 treated with Evusheld, 90 treated with placebo) infected with the SARS-CoV-2 virus and included in the randomized, double-blind, trial DisCoVeRy (NCT04315948). Using a mechanistic mathematical model, we reconstructed the trajectories of viral kinetics and how they are modulated by the increase in serum neutralization activity during Evusheld treatment., Results: Our model identified that the neutralization activity was associated with viral kinetics. Reflecting the variant-dependent neutralization activity of Evusheld, the antiviral activity of Evusheld was larger in patients infected with pre-Omicron or Omicron BA.2 variants than in patients infected with Omicron BA.1 variant. More specifically, the model predicted that Evusheld reduced the median time to viral clearance compared with placebo-treated patients by more than 5 days in patients infected by pre-Omicron (median: 5.9; 80% PI: 2.1-13.6) or Omicron BA.2 (median: 5.4; 80% PI: 2.0-12.4), respectively. The effect was more modest in patients infected by the Omicron BA.1 variant, reducing the median time to viral clearance by 2 days (median: 2.2; 80% PI: 0.4-8.9)., Conclusions: Hospitalized patients treated with Evusheld had a shorter median time to SARS-CoV-2 viral clearance. As Evusheld antiviral activity is mediated by the level of neutralization activity, its impact on viral clearance varies largely according to the variant of infection., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

This retrospective study aimed to compare the mortality and burden of respiratory syncytial virus (RSV group), SARS-CoV-2 (COVID-19 group), non-H1N1 (Seasonal influenza group) and H1N1 influenza (H1N1 group) in adult patients admitted to intensive care unit (ICU) with respiratory failure. A total of 807 patients were included. Mortality was compared between the four following groups: RSV, COVID-19, seasonal influenza, and H1N1 groups. Patients in the RSV group had significantly more comorbidities than the other patients. At admission, patients in the COVID-19 group were significantly less severe than the others according to the simplified acute physiology score-2 (SAPS-II) and sepsis-related organ failure assessment (SOFA) scores. Using competing risk regression, COVID-19 (sHR = 1.61; 95% CI 1.10; 2.36) and H1N1 (sHR = 1.87; 95% CI 1.20; 2.93) were associated with a statistically significant higher mortality while seasonal influenza was not (sHR = 0.93; 95% CI 0.65; 1.31), when compared to RSV. Despite occurring in more severe patients, RSV and seasonal influenza group appear to be associated with a more favorable outcome than COVID-19 and H1N1 groups., (© 2024. The Author(s).)

BackgroundData on infectious encephalitis in immunodeficient (ID) individuals are scarce. This population may present with atypical clinical symptoms, be infected by uncommon pathogens and develop poor outcomes.AimWe aimed to describe the epidemiology of infectious encephalitis among HIV-negative ID patients.MethodsPatients from the ENCEIF (Etude Nationale de Cohorte des Encéphalites Infectieuses en France) prospective cohort meeting criteria for infectious encephalitis between January 2016 and December 2019 were included. We compared clinical presentation, magnetic resonance imaging (MRI) results, biological results, infection causes and outcome of ID patients with immunocompetent (IC) patients using Pearson's chi-squared test and Student's t-test. We carried out logistic regression to assess the role of immunodeficiency as risk factor for poor outcome.ResultsID patients (n = 58) were older (mean 72 vs 59 years), had higher prevalence of diabetes (26% vs 12%), pre-existing neurological disorders (12% vs 5%) and higher case-fatality rate (23.6% vs 5.6%) compared to IC patients (n = 436). Varicella zoster virus was the primary cause of encephalitis in ID patients (this aetiology was more frequent in ID (25.9%) than in IC patients (11.5%)), with herpes simplex virus second (22.4% in ID patients vs 27.3% in IC patients). Immunodeficiency was an independent risk factor for death or major sequelae (odds ratio: 3.41, 95%CI: 1.70-6.85).ConclusionsVaricella zoster virus is the most frequent cause of infectious encephalitis in ID patients. Immunodeficiency is a major risk factor for poor outcome. ID encephalitis patients should benefit from stringent investigation of cause and early empiric treatment.