Guidelines recommend macrolides and fluoroquinolones in patients hospitalized with community-acquired pneumonia (CAP), but their use has been associated with cardiac events. We quantified associations between macrolide and fluoroquinolone use and cardiac events in patients hospitalized with CAP in non-ICU wards. This was a post-hoc analysis of a cluster-randomized trial as a cohort study; including patients with a working diagnosis of CAP admitted to non-ICU wards without a cardiac event on admission. We calculated cause-specific hazard ratio’s (HR’s) for effects of time-dependent macrolide and fluoroquinolone exposure as compared to beta-lactam monotherapy on cardiac events, defined as new or worsening heart failure, arrhythmia, or myocardial ischemia during hospitalization. Cardiac events occurred in 146 (6.9%) of 2107 patients, including heart failure (n = 101, 4.8%), arrhythmia (n = 53, 2.5%), and myocardial ischemia (n = 14, 0.7%). These occurred in 11 of 207 (5.3%), 18 of 250 (7.2%), and 31 of 277 (11.2%) patients exposed to azithromycin, clarithromycin, and erythromycin for at least one day, and in 9 of 234 (3.8%), 5 of 194 (2.6%), and 23 of 566 (4.1%) exposed to ciprofloxacin, levofloxacin, and moxifloxacin, respectively. HR’s for erythromycin, compared to beta-lactam monotherapy, on any cardiac event and heart failure were 1.60 (95% CI 1.09;2.36) and 1.89 (95% CI 1.22;2.91), respectively. HR’s for levofloxacin and moxifloxacin, compared to beta-lactam monotherapy, on any cardiac event were 0.40 (95% CI 0.18;0.87)and 0.56 (95% CI 0.36;0.87), respectively. Findings remained consistent after adjustment for confounders and/or in a sensitivity analysis of radiologically confirmed CAP (n = 1604, 76.1%). Among patients with CAP hospitalized to non-ICU wards, erythromycin use was associated with a 68% increased risk of hospital-acquired cardiac events, mainly heart failure. Levofloxacin and moxifloxacin were associated with a lower risk of heart failure. Although our study does not fully exclude confounding bias, findings remained largely unchanged in crude, adjusted, and sensitivity analyses. These findings may caution the use of erythromycin as empirical therapy in these patients. The original trial was retrospectively registered under ClinicalTrials.gov Identifier NCT01660204 on August 8th, 2012.

Purpose: Sepsis is a leading cause of morbidity and mortality globally. The lack of specific prognostic markers necessitates tools for early risk identification in patients with suspected infections in emergency department (ED). This study evaluates the prognostic accuracy of various Early Warning Scores (EWS)—MEWS, NEWS, NEWS-2, and qSOFA—for in-hospital mortality, 30-day mortality, and ICU admission, considering the site of infection. Methods: A retrospective analysis was conducted using data from the Acutelines cohort, which included data collected from patients admitted to the University Medical Centre Groningen ED between September 2020 and July 2023. Patients were included if they had an ICD-10 code for infection. EWS were calculated using clinical data within 8 h post-admission. Predictive performance was assessed using AUC-ROC, calibration by the Hosmer-Lemeshow test and calibration curves, and operative characteristics like sensitivity and specificity. Results: A total of 1661 patients were analyzed, with infections distributed as follows: lower respiratory tract (32.9%), urinary tract (30.7%), abdominal (12.5%), skin and soft tissue (9.5%), and others (8.2%). The overall in-hospital mortality was 6.7%, and ICU admission was 7.1%. The highest AUC-ROC for in-hospital mortality prediction was observed with NEWS and NEWS-2 in abdominal infections (0.86), while the lowest was for qSOFA in skin and soft tissue infections (0.57). Predictive performance varied by infection site. Conclusions: The study highlights the variability in EWS performance based on infection site, emphasizing the need to consider the source of infection in EWS development for sepsis prognosis. Tailored or hybrid models may enhance predictive accuracy, balancing simplicity and specificity.

Galactomannan (GM) testing of bronchoalveolar lavage (BAL) fluid samples has become an essential tool to diagnose invasive pulmonary aspergillosis (IPA) and is part of diagnostic guidelines. Enzyme-linked immunosorbent assays (ELISAs) (enzyme immunoassays [EIAs]) are commonly used, but they have a long turnaround time. In this study, we evaluated the performance of an automated chemiluminescence immunoassay (CLIA) with BAL fluid samples.

Waning antibody responses after COVID-19 vaccination combined with the emergence of the SARS-CoV-2 Omicron lineage led to reduced vaccine effectiveness. As a countermeasure, bivalent mRNA-based booster vaccines encoding the ancestral spike protein in combination with that of Omicron BA.1 or BA.5 were introduced. Since then, different BA.2-descendent lineages have become dominant, such as XBB.1.5, JN.1, or EG.5.1. Here, we report post-hoc analyses of data from the SWITCH-ON study, assessing how different COVID-19 priming regimens affect the immunogenicity of bivalent booster vaccinations and breakthrough infections (NCT05471440). BA.1 and BA.5 bivalent vaccines boosted neutralizing antibodies and T-cells up to 3 months after boost; however, cross-neutralization of XBB.1.5 was poor. Interestingly, different combinations of prime-boost regimens induced divergent responses: participants primed with Ad26.COV2.S developed lower binding antibody levels after bivalent boost while neutralization and T-cell responses were similar to mRNA-based primed participants. In contrast, the breadth of neutralization was higher in mRNA-primed and bivalent BA.5 boosted participants. Combined, our data further support the current use of monovalent vaccines based on circulating strains when vaccinating risk groups, as recently recommended by the WHO. We emphasize the importance of the continuous assessment of immune responses targeting circulating variants to guide future COVID-19 vaccination policies.

Introduction: The aim of this study was to determine the efficacy of early tocilizumab treatment for hospitalized patients with COVID-19 disease. Methods: Open-label randomized phase II clinical trial investigating tocilizumab in patients with proven COVID-19 admitted to the general ward and in need of supplemental oxygen. The primary endpoint of the study was 30-day mortality with a prespecified 2-sided significance level of α = 0.10. A post-hoc analysis was performed for a combined endpoint of mechanical ventilation or death at 30 days. Secondary objectives included comparing the duration of hospital stay, ICU admittance and duration of ICU stay and the duration of mechanical ventilation. Results: A total of 354 patients (67% men; median age 66 years) were enrolled of whom 88% received dexamethasone. Thirty-day mortality was 19% (95% CI 14%-26%) in the standard arm versus 12% (95% CI: 8%-18%) in the tocilizumab arm, hazard ratio (HR) = 0.62 (90% CI 0.39–0.98; p = 0.086). 17% of patients were admitted to the ICU in each arm (p = 0.89). The median stay in the ICU was 14 days (IQR 9–28) in the standard arm versus 9 days (IQR 5–14) in the tocilizumab arm (p = 0.014). Mechanical ventilation or death at thirty days was 31% (95% CI 24%-38%) in the standard arm versus 21% (95% CI 16%-28%) in the tocilizumab arm, HR = 0.65 (95% CI 0.42–0.98; p = 0.042). Conclusions: This randomized phase II study supports efficacy for tocilizumab when given early in the disease course in hospitalized patients who need oxygen support, especially when concomitantly treated with dexamethasone. Trial registration: https://www.trialregister.nl/trial/8504.

Purpose: Sepsis has a high incidence and a poor prognosis. Early recognition is important to facilitate timely initiation of adequate care. Sepsis screening tools, such as the (quick) Sequential Organ Failure Assessment ((q)SOFA) and National Early Warning Score (NEWS), could help recognize sepsis. These tools have been validated in a general immunocompetent population, while their performance in immunocompromised patients, who are particularly at risk of sepsis development, remains unknown. Methods: This study is a post hoc analysis of a prospective observational study performed at the emergency department. Inclusion criteria were age ≥ 18 years with a suspected infection, while ≥ two qSOFA and/or SOFA criteria were used to classify patients as having suspected sepsis. The primary outcome was in-hospital mortality. Results: 1516 patients, of which 40.5% used one or more immunosuppressives, were included. NEWS had a higher prognostic accuracy as compared to qSOFA for predicting poor outcome among immunocompromised sepsis patients. Of all tested immunosuppressives, high-dose glucocorticoid therapy was associated with a threefold increased risk of both in-hospital and 28-day mortality. Conclusion: In contrast to NEWS, qSOFA underestimates the risk of adverse outcome in patients using high-dose glucocorticoids. As a clinical consequence, to adequately assess the severity of illness among immunocompromised patients, health care professionals should best use the NEWS.