Efficacy and safety of anakinra in adults presenting deteriorating respiratory symptoms from COVID-19: A randomized controlled trial.

OBJECTIVE: We aimed to investigate whether anakinra, an interleukin-1receptor inhibitor, could improve outcome in moderate COVID-19 patients. METHODS: In this controlled, open-label trial, we enrolled adults with COVID-19 requiring oxygen. We randomly assigned patients to receive intravenous anakinra plus optimized standard of care (oSOC) vs. oSOC alone. The primary outcome was treatment success at day 14 defined as patient alive and not requiring mechanical ventilation or extracorporeal membrane oxygenation. RESULTS: Between 27th April and 6th October 2020, we enrolled 71 patients (240 patients planned to been enrolled): 37 were assigned to the anakinra group and 34 to oSOC group. The study ended prematurely by recommendation of the data and safety monitoring board due to safety concerns. On day 14, the proportion of treatment success was significantly lower in the anakinra group 70% (n = 26) vs. 91% (n = 31) in the oSOC group: risk difference-21 percentage points (95% CI, -39 to -2), odds ratio 0.23 (95% CI, 0.06 to 0.91), p = 0.027. After a 28-day follow-up, 9 patients in the anakinra group and 3 in the oSOC group had died. Overall survival at day 28 was 75% (95% CI, 62% to 91%) in the anakinra group versus 91% (95% CI, 82% to 100%) (p = 0.06) in the oSOC group. Serious adverse events occurred in 19 (51%) patients in the anakinra group and 18 (53%) in the oSOC group (p = 0·89). CONCLUSION: This trial did not show efficacy of anakinra in patients with COVID-19. Furthermore, contrary to our hypothesis, we found that anakinra was inferior to oSOC in patients with moderate COVID-19 pneumonia.

Relationship between serotypes, disease characteristics and 30-day mortality in adults with invasive pneumococcal disease.

PURPOSE: Invasive pneumococcal disease (IPD) is responsible for substantial mortality and morbidity worldwide. We aimed to identify host and bacterial factors associated with 30-day mortality in 18-year-old patients hospitalized with IPD in France from 2013 to 2015. METHODS: This study analyzed data collected from consecutives IPD cases included in two parallel multi-center cohort studies: COMBAT study (280 patients with pneumococcal community-acquired bacterial meningitis) and SIIP study (491 patients with non-meningitis IPD). Factors associated with 30-day mortality were identified using logistic regression. RESULTS: Among the 771 enrolled patients (median age 66 years, IQR [52.0-79.7]), 592/767 (77.2%) had at least one chronic disease. Patients with meningitis were younger (60.2 vs 70.9 years; p < 0.001) and had fewer chronic diseases than those with non-meningitis IPD (73.3% vs 79.4%; p = 0.05). Non-vaccine serotypes were more frequent in meningitis patients than in those with other IPD (36.1% vs 23.1%; p < 0.001). The overall 30-day mortality was 16.7% and patients with concurrent meningitis and extra-cerebral IPD had the highest 30-day mortality rate (26.5%). On multivariate analyses, older age, history of malignant solid tumor, meningeal IPD and serotypes previously identified with high mortality potential were independently associated with 30-day mortality. Of the serotypes with high mortality potential, 80% were included in licensed (PCV13 or PPV23) vaccines. CONCLUSION: We observed an effect of both host factors and pneumococcal serotypes on 30-day mortality in IPD. This highlights the need for a focused strategy to vaccinate at-risk patients. CLINICAL TRIAL: ClinicalTrial. Gov identification number: NCT01730690.

Factors associated with unfavorable outcome in a multicenter audit of 100 infective endocarditis.

We aimed to identify factors associated with unfavorable outcome in patients treated for infective endocarditis (IE), with a focus on departure from European guidelines. We conducted a retrospective audit of all adult patients treated for endocarditis during a 1-year period across a regional network of nine care centers in the south-east of France. Medical records were reviewed regarding patient and infection characteristics, antibiotic therapy, outcome, and compliance to the European Society of Cardiology guidelines. Antibiotic treatment appropriateness was evaluated regarding molecule, dosage, and duration, according to guidelines. Primary endpoint was the assessment of factors associated with unfavorable outcome, defined as in-hospital mortality or IE relapse at 1-year follow-up. Secondary endpoints were intensive care admission, iatrogenic events, and nosocomial infections that occurred during hospital stay. One hundred patients were included. Median age was 71 years old. Twenty-two patients died and IE relapse occurred in two patients, representing 24 patients with unfavorable outcome. Overall, antibiotic treatment was deemed appropriate in 28 cases. Thirty-three patients required intensive care, 34 iatrogenic events were found, including 19 acute kidney injuries, and 13 nosocomial infections occurred during care. Using a logistic regression, factors associated with unfavorable outcome were admission in the intensive care unit (adjusted odd ratio 7.26 [1.8-29.28]; p = 0.005), new-onset nosocomial infection (adjusted odd ratio 8.83 [1.42-54.6]; p = 0.019), and age > 71 years old (adjusted odd ratio 11.2 [2.76-46.17]; p < 0.001). Departure from guidelines was frequent but not related to unfavorable outcome in our study. Only intensive care, age, and nosocomial infections were associated with mortality and relapse. Iatrogenic events were numerous, with no impact on outcome.

Staphylococcus lugdunensis: a neglected pathogen of infections involving fracture-fixation devices.

PURPOSE: Cases of fracture-fixation device infection involving Staphylococcus lugdunensis are not frequent. The clinical characteristics and the choice of treatment strategies of these infections are not obviously known to date. METHODS: We performed a review of fracture-fixation device infection involving S. lugdunensis managed by our centres. RESULTS: Among the 38 cases of fracture-fixation device infection involving S. lugdunensis, 53% were located in the tibia. Most of our cases (87%) were chronic infections. Purulent discharge, which occurred in 79% of cases, was the most frequent clinical symptom, followed by pain in 63%, local inflammation in 55%, and fever in 37%. Bacteremia and severe sepsis occurred in 10% and 18% of cases, respectively. Four cases (10%) were treated exclusively with antimicrobial treatment alone. Thirty-four cases (89%) were treated with a combination of surgery with antimicrobial therapy including surgical debridement, antibiotics and osteosynthesis device retention in six cases (16%), and osteosynthesis device removal in 27 cases (71%). The mean length of antibiotic treatment was 119 days. The relapse rate was high that was not related to selection of resistant strains. Polymicrobial infection had no impact on clinical outcome. A combination of surgery with antimicrobial therapy was identified as a significant prognostic factor associated with remission (p = 0.042). CONCLUSIONS: S. lugdunensis is probably involved in more infections than has been reported. Using appropriate microbiological methods laboratories should routinely identify the species of all coagulase-negative Staphylococci isolates involved in fracture-fixation device infection to better achieve the treatment strategies of fracture-fixation device infection involving S. lugdunensis.

Early bacterial and inflammatory responses to antibiotic therapy in a model of polymicrobial peritonitis in rats.

OBJECTIVE: To assess the consequences of different more or less selective treatments on the microbiological and inflammatory responses within the peritoneum. METHODS: The early effects of various antibiotic regimens were evaluated in a model of polymicrobial peritonitis with specifically prepared organisms. Six regimens (amoxycillin plus gentamicin, pefloxacin, ornidazole, pefloxacin plus ornidazole, imipenem and imipenem plus gentamicin) were evaluated at 24 h and 3 days in a non-fatal model of peritonitis in rats achieved by implantation of a capsule containing Escherichia coli, Bacteroides fragilis and Enterococcus faecalis. RESULTS: Therapies that disregarded several organisms were associated with persistence of the strains and an increased peritoneal inflammatory response within the peritoneum. In contrast, therapies active against Enterobacteriaceae and anaerobes were associated with decreases of all the inoculated organisms and a smaller inflammatory response. CONCLUSION: Therapies that disregarded the microorganisms implicated in peritoneal infection are associated with delayed bacterial eradication. The persistence of these organisms within the peritoneal fluid might be involved in prolonged peritoneal inflammation. Although it disregards enterococci, the standard therapy, represented by therapy against Enterobacteriaceae and anaerobes, demonstrates satisfactory effects towards all the inoculated organisms. This apparent contradiction could be related to mechanisms of bacterial synergy.