Latent class analysis-based subgroups and response to corticosteroids in hospitalised community-acquired pneumonia patients: a validation study

Latent class analysis (LCA), a statistical method to identify "hidden” subgroups within a population, has identified clinically distinct subgroups with treatment implications in acute respiratory distress syndrome and COVID-19 [1–3]. We recently showed that LCA could also identify two clinically distinct subgroups in community-acquired pneumonia (CAP) [4]. In patients with community-acquired pneumonia, LCA can identify robust prognostic subgroups based on clinical and inflammatory parameters. Yet, these subgroups have not proven robust in predicting response to adjunctive dexamethasone treatment.https://bit.ly/3O5eaxz

Overweight and obesity are not associated with worse clinical outcomes in COVID-19 patients treated with fixed-dose 6 mg dexamethasone.

OBJECTIVE: A fixed 6 mg dexamethasone dose for 10 days is the standard treatment for all hospitalised COVID-19 patients who require supplemental oxygen. Yet, the pharmacokinetic properties of dexamethasone can lead to diminishing systemic dexamethasone exposure with increasing body mass index (BMI). The present study examines whether this translates to overweight and obesity being associated with worse clinical outcomes, defined as ICU admission or in hospital death, in COVID-19 patients treated with fixed-dose dexamethasone. METHODS: We conducted a single centre retrospective cohort study in COVID-19 patients who were admitted to a non-ICU ward and were treated with dexamethasone (6 mg once daily for a maximum of ten days) between June 2020 and January 2021. Univariable and multivariable logistic regression analyses were conducted to assess the association between BMI-categories and an unfavourable clinical course (ICU admission and/or in hospital death). Analyses were adjusted for age, comorbidities, inflammatory status, and oxygen requirement at admission. For reference, similar analyses were repeated in a cohort of patients hospitalised before dexamethasone was introduced (March 2020 through May 2020). RESULTS: In patients treated with dexamethasone (n = 385) an unfavourable clinical course was most prevalent in patients with normal weight (BMI < 25) compared to patients with overweight (BMI 25-30) and patients with obesity (BMI ≥ 30) with percentages of 33, 26 and 21% respectively. In multivariable analyses, there was no association between BMI-category and an unfavourable clinical course (respectively with aORs of 0.81 (0.43-1.53) and 0.61 (0.30-1.27) with normal weight as reference). In the reference cohort (n = 249) the opposite was observed with an unfavourable clinical course being most prevalent in patients with overweight (39% vs 28%; aOR 2.17 (0.99-4.76)). In both cohorts, CRP level at admission was higher and lymphocyte count was lower in patients with normal weight compared to patients with obesity. CONCLUSIONS: Overweight and obesity are not associated with an unfavourable clinical course in COVID-19 patients admitted to a non-ICU ward and treated with 6 mg dexamethasone once daily.

The dynamics in applied COVID-19 pharmacotherapy and the influence of national guidance in The Netherlands: a quantitative and qualitative study.

OBJECTIVE: At the beginning of the COVID-19 pandemic in the Netherlands, the Dutch Working Party on Antibiotic Policy constructed an advisory document about off-label drug treatment options that was regularly updated with new scientific findings. The aim of this study is to describe the dynamics in applied COVID-19 pharmacotherapy during the first 100 days of the pandemic and to assess how the national advisory document influenced local hospital policies. METHODS: A multicentre observational cohort study was conducted in six hospitals in the Netherlands. Patients with confirmed COVID-19 admitted between 27 February and 7 June 2020 were studied. Drug prescription data were collected and percentages of patients receiving a specific treatment were calculated. These percentages were plotted together with release dates of the national advisory document. Semi-structured in-depth interviews with hospital pharmacists and infectious diseases specialists were conducted to gain insight into the development and implementation of pharmacotherapy treatment protocols in hospitals. RESULTS: Data from 1511 patients (60% men, mean age 66 years) were analysed. From mid-March (hydroxy)chloroquine was being prescribed in all six hospitals to approximately 70% of patients at admission. Frequencies of other off-label treatments were below 2%. In the week of 6 April 2020, the first hospital discontinued prescribing (hydroxy)chloroquine and the last hospital discontinued in the week of 4 May 2020 (total range -19 to +10 days after the national advisory document advised against its use (1 May 2020)). All interviewees (n=6) stated that the hospitals based their policies mainly on the national advisory document but also assessed scientific literature themselves. Order panels were constructed to support prescribing. CONCLUSION: Dutch hospitals opted en masse for (hydroxy)chloroquine as COVID-19 therapy at the start of the pandemic, although the time until the therapy was no longer prescribed differed by several weeks. The fact that hospitals defined pharmacotherapy regimens based on their own assessment of the scientific literature besides the national advisory document can explain this variation.

Recommendations for antibacterial therapy in adults with COVID-19 - an evidence based guideline.

SCOPE: The Dutch Working Party on Antibiotic Policy constituted a multidisciplinary expert committee to provide evidence-based recommendation for the use of antibacterial therapy in hospitalized adults with a respiratory infection and suspected or proven 2019 Coronavirus disease (COVID-19). METHODS: We performed a literature search to answer four key questions. The committee graded the evidence and developed recommendations by using Grading of Recommendations Assessment, Development, and Evaluation methodology. QUESTIONS ADDRESSED BY THE GUIDELINE AND RECOMMENDATIONS: We assessed evidence on the risk of bacterial infections in hospitalized COVID-19 patients, the associated bacterial pathogens, how to diagnose bacterial infections and how to treat bacterial infections. Bacterial co-infection upon admission was reported in 3.5% of COVID-19 patients, while bacterial secondary infections during hospitalization occurred up to 15%. No or very low quality evidence was found to answer the other key clinical questions. Although the evidence base on bacterial infections in COVID-19 is currently limited, available evidence supports restrictive antibiotic use from an antibiotic stewardship perspective, especially upon admission. To support restrictive antibiotic use, maximum efforts should be undertaken to obtain sputum and blood culture samples as well as pneumococcal urinary antigen testing. We suggest to stop antibiotics in patients who started antibiotic treatment upon admission when representative cultures as well as urinary antigen tests show no signs of involvement of bacterial pathogens after 48 hours. For patients with secondary bacterial respiratory infection we recommend to follow other guideline recommendations on antibacterial treatment for patients with hospital-acquired and ventilator-associated pneumonia. An antibiotic treatment duration of five days in patients with COVID-19 and suspected bacterial respiratory infection is recommended upon improvement of signs, symptoms and inflammatory markers. Larger, prospective studies about the epidemiology of bacterial infections in COVID-19 are urgently needed to confirm our conclusions and ultimately prevent unnecessary antibiotic use during the COVID-19 pandemic.