A randomized placebo-controlled trial of convalescent plasma for adults hospitalized with COVID-19 pneumonia

Passive immunotherapy with convalescent plasma may be the only available agent during the early phases of a pandemic. Here, we report safety and efficacy of high-titer convalescent plasma for COVID-19 pneumonia. Double-blinded randomized multicenter placebo-controlled trial of adult patients hospitalized with COVID-19 pneumonia. The intervention was COVID-19 convalescent plasma and placebo was saline allocated 2:1. The primary outcome was clinical status 14 days after the intervention evaluated on a clinical ordinal scale. The trial was registered at ClinicalTrials.Gov, NCT04345289, 14/04/2020. The CCAP-2 trial was terminated prematurely due to futility. Of 147 patients randomized, we included 144 patients in the modified intention-to-treat population. The ordinal clinical status 14 days post-intervention was comparable between treatment groups (odds ratio (OR) 1.41, 95% confidence interval (CI) 0.72–2.09). Results were consistent when evaluating clinical progression on an individual level 14 days after intervention (OR 1.09; 95% CI 0.46–1.73). No significant differences in length of hospital stay, admission to ICU, frequency of severe adverse events or all-cause mortality during follow-up were found between the intervention and the placebo group. Infusion of convalescent plasma did not influence clinical progression, survival or length of hospitalization in patients with COVID-19 pneumonia

Blood neutrophil to lymphocyte ratio is associated with 90-day mortality and 60-day readmission in Gram negative bacteremia: a multi-center cohort study

Abstract Introduction The Neutrophil-Lymphocyte Ratio (NLR) in blood has demonstrated its capability to predict bacteremia in emergency departments, and its association with mortality has been established in patients with sepsis in intensive care units. However, its potential concerning mortality and readmission in patients with Gram-negative bacteremia (GNB) is unexplored. Methods This retrospective cohort study included patients with GNB between 2018 and 2022 from six hospitals in the Capital Region of Denmark. Patients who were immunosuppressed or had missing NLR values on the day of blood culture were excluded. Logistic regression models were used to analyze the association between NLR levels and 90-day all-cause mortality, while the logit link interpretation of the cumulative incidence function was used to assess the association between NLR levels and 60-day readmission. Associations were quantified as odds ratios (OR) with corresponding 95% confidence intervals (CI). Results The study included 1763 patients with a median age was 76.8 years and 51.3% were female. The median NLR was 17.3 and 15.8% of patients had a quick sequential organ failure assessment score of two or three. Urinary tract infection (UTI) was the most frequent focus and Escherichia coli the most frequent pathogen. Statistically significant differences in median NLR were found by age group and pathogen, and for patients with or without hypertension, liver disease, chronic obstructive pulmonary disease, dementia, and alcohol abuse. 378 patients (21.4%) died before 90 days. 526 (29.8%) patients were readmitted to the hospital within 60 days. For each doubling of the NLR, the OR for all-cause 90-day mortality was 1.15 (95% CI, 1.04–1.27) and 1.12 (95% CI, 1.02–1.24) for 60-day readmission. Analysis of subgroups did not show statistically significant differences between groups in relation to the association between NLR and mortality. The discriminatory ability of NLR for mortality was limited and comparable to blood neutrophil or lymphocyte count, producing receiver operating characteristic curves with an area under the curve of 0.59 (95% CI, 0.56–0.63), 0.60 (95% CI, 0.56–0.65) and 0.53 (95% CI, 0.49–0.56), respectively. Conclusion Blood neutrophil-lymphocyte ratio was associated with 90-day all-cause mortality and 60-day readmission in patients with GNB. However, the ratio has limited ability in predicting mortality or readmission

Short course antibiotic treatment of Gram-negative bacteraemia (GNB5): a study protocol for a randomised controlled trial

Introduction Prolonged use of antibiotics is closely related to antibiotic-associated infections, antimicrobial resistance and adverse drug events. The optimal duration of antibiotic treatment for Gram-negative bacteremia (GNB) with a urinary tract source of infection is poorly defined.Methods and analysis Investigator-initiated multicentre, non-blinded, non-inferiority randomised controlled trial with two parallel treatment arms. One arm will receive shortened antibiotic treatment of 5 days and the other arm will receive antibiotic treatment of 7 days or longer. Randomisation will occur in equal proportion (1:1) no later than day 5 of effective antibiotic treatment as determined by antibiogram. Immunosuppressed patients and those with GNB due to non-fermenting bacilli (Acinetobacter spp, Pseudomonas spp), Brucella spp, Fusobacterium spp or polymicrobial growth are ineligible.The primary endpoint is 90-day survival without clinical or microbiological failure to treatment. Secondary endpoints include all-cause mortality, total duration of antibiotic treatment, hospital readmission and Clostridioides difficile infection. Interim safety analysis will be performed after the recruitment of every 100 patients. Given an event rate of 12%, a non-inferiority margin of 10%, and 90% power, the required sample size to determine non-inferiority is 380 patients. Analyses will be performed on both intention-to-treat and per-protocol populations.Ethics and dissemination The study is approved by the Danish Regional Committee on Health Research (H-19085920) and the Danish Medicines Agency (2019-003282-17). The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.Trial registration number ClinicalTrials.Gov:NCT04291768