Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency.

Antibiotic-resistant bacteria threaten life worldwide. Although new antibiotics are scarce, the use of bacteriophages, viruses that infect bacteria, is rarely proposed as a means of offsetting this shortage. Doubt also remains widespread about the efficacy of phage therapy despite recent encouraging results. Using a bioluminescent Pseudomonas aeruginosa strain, we monitored and quantified the efficacy of a bacteriophage treatment in mice during acute lung infection. Bacteriophage treatment not only was effective in saving animals from lethal infection, but also was able to prevent lung infection when given 24 h before bacterial infection, thereby extending the potential use of bacteriophages as therapeutic agents to combat bacterial lung infection.

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Background Integrase strand transfer inhibitors (INSTIs) are increasingly used in patients living with HIV due to their safety, effectiveness and high genetic barrier. However, an association with weight gain has recently been suggested and several cases of diabetes mellitus have been reported with raltegravir and dolutegravir. The long-time metabolic impact of these recent molecules remains unclear. Objectives To assess if an INSTI as a third agent is statistically associated with new-onset diabetes mellitus compared with an NNRTI or a PI. Patients and methods Patients undergoing first-line combined ART (cART) without diabetes at baseline were retrospectively included from the Dat’AIDS French cohort study (ClinicalTrials.gov NCT02898987). Incident diabetes mellitus was defined as a notification of new diabetes in the medical history, a glycated haemoglobin (HbA1c) level superior to 7.5% or the start of a diabetes therapy following the initiation of ART. Results From 2009 to 2017, 19 462 patients were included, among which 265 cases of diabetes mellitus occurred. Multivariate and survival analyses did not highlight an increase in new-onset diabetes in patients undergoing cART with an INSTI as a third agent compared with an NNRTI or a PI. BMI >30 kg/m2, age >37 years old (in survival analysis), black race or Hispanic ethnicity, arterial hypertension and AIDS were associated with a higher proportion of incident diabetes. Conclusions INSTIs were not statistically associated with new-onset diabetes. However, clinicians should remain aware of this possible metabolic comorbidity, particularly in patients with a high BMI and older patients.

on behalf of the COCO-OLD Study group. Writing committee, Methodology and statistics, Centres (alphabetically), 14-Day survival among older adults with severe SARS-Cov2 infection treated with corticosteroid: a cohort study, Clinical Microbiology and Infection,

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Objective To assess the effectiveness of corticosteroids on outcomes of patients with COVID-19 pneumonia requiring oxygen without mechanical ventilation. Methods We used routine care data from 51 hospitals in France and Luxembourg to assess the effectiveness of corticosteroids at 0.8 mg/kg/day eq. prednisone (CTC group) versus standard of care (no-CTC group) among adults 18 to 80 years old with confirmed COVID-19 pneumonia requiring oxygen without mechanical ventilation. The primary outcome was intubation or death by day 28. In our main analysis, characteristics of patients at baseline (i.e., time when patients met all inclusion criteria) were balanced by using propensity-score inverse probability of treatment weighting. Results Among the 891 patients included in the analysis, 203 were assigned to the CTC group. Use of corticosteroids was not significantly associated with risk of intubation or death by day 28 (weighted hazard ratio [wHR] 0.92, 95% CI 0.61 to 1.39) or cumulative death rate (wHR 1.03, 95% CI 0.54 to 1.98). However, use of corticosteroids was associated with reduced risk of intubation or death by day 28 in the prespecified subgroups of patients requiring oxygen ≥ 3 L/min (wHR 0.50, 95% CI 0.30 to 0.85) or C-reactive protein level ≥ 100 mg/L (wHR 0.44, 95%CI 0.23 to 0.85). Number of hyperglycaemia events was higher for patients with than without corticosteroids, but number of infections was similar. Conclusions We found no association between the use of corticosteroids and intubation or death in the broad population of patients 18 to 80 years old with COVID-19 hospitalized in non-intensive care unit settings. However, the treatment was associated with reduced risk of intubation or death for patients with ≥ 3 L/min oxygen or C-reactive protein level ≥ 100 mg/L at baseline. Further research need to confirm the right timing of corticosteroids for patients with COVID-19 requiring oxygen only.

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