Effect of intravenous clarithromycin in patients with sepsis, respiratory and multiple organ dysfunction syndrome: a randomized clinical trial.

BACKGROUND: Clarithromycin may act as immune-regulating treatment in sepsis and acute respiratory dysfunction syndrome. However, clinical evidence remains inconclusive. We aimed to evaluate whether clarithromycin improves 28-day mortality among patients with sepsis, respiratory and multiple organ dysfunction syndrome. METHODS: We conducted a multicenter, randomized, clinical trial in patients with sepsis. Participants with ratio of partial oxygen pressure to fraction of inspired oxygen less than 200 and more than 3 SOFA points from systems other than the respiratory function were enrolled between December 2017 and September 2019. Patients were randomized to receive 1 gr of clarithromycin or placebo intravenously once daily for 4 consecutive days. The primary endpoint was 28-day all-cause mortality. Secondary outcomes were 90-day mortality; sepsis response (defined as at least 25% decrease in SOFA score by day 7); sepsis recurrence; and differences in peripheral blood cell populations and leukocyte transcriptomics. RESULTS: Fifty-five patients were allocated to each arm. By day 28, 27 (49.1%) patients in the clarithromycin and 25 (45.5%) in the placebo group died (risk difference 3.6% [95% confidence interval (CI) - 15.7 to 22.7]; P = 0.703, adjusted OR 1.03 [95%CI 0.35-3.06]; P = 0.959). There were no statistical differences in 90-day mortality and sepsis response. Clarithromycin was associated with lower incidence of sepsis recurrence (OR 0.21 [95%CI 0.06-0.68]; P = 0.012); significant increase in monocyte HLA-DR expression; expansion of non-classical monocytes; and upregulation of genes involved in cholesterol homeostasis. Serious and non-serious adverse events were equally distributed. CONCLUSIONS: Clarithromycin did not reduce mortality among patients with sepsis with respiratory and multiple organ dysfunction. Clarithromycin was associated with lower sepsis recurrence, possibly through a mechanism of immune restoration. Clinical trial registration clinicaltrials.gov identifier NCT03345992 registered 17 November 2017; EudraCT 2017-001056-55.

Burnout syndrome and its association with anxiety and fear of medical errors among intensive care unit physicians: A cross-sectional study.

Burnout is a work-specific syndrome with high incidence among intensive care unit personnel. Although several risk factors have been proposed, data regarding the association of anxiety and burnout among intensive care unit physicians are scarce. The aim of this study is to investigate the incidence of burnout and its association with state and trait anxiety and other sociodemographic, behavioural and occupational-related parameters, among intensivists. A population of intensive care physicians was evaluated using the self-completed Maslach Burnout Inventory and the State-Trait Anxiety Inventory Form Y, and data regarding sociodemographic and occupational-related variables were also recorded. From the 98 intensive care physicians addressed, 80 returned fully completed questionnaires; 26.9% of them presented with high emotional exhaustion, 37.5% with high depersonalisation and 41.5% with low personal accomplishment scores. Trait anxiety, fear of having committed a medical error and self-reporting difficulty when having to act accurately were independently associated with high burnout. In conclusion, burnout is common among intensivists and is associated with specific behavioural characteristics and personality traits, but not with work-related factors.