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Background: De-escalation of empirical antimicrobial therapy, a key component of antibiotic stewardship, is considered difficult in ICUs with high rates of antimicrobial resistance., Objectives: To assess the feasibility and the impact of antimicrobial de-escalation in ICUs with high rates of antimicrobial resistance., Methods: Multicentre, prospective, observational study in septic patients with documented infections. Patients in whom de-escalation was applied were compared with patients without de-escalation by the use of a propensity score matching by SOFA score on the day of de-escalation initiation., Results: A total of 262 patients (mean age 62.2 ± 15.1 years) were included. Antibiotic-resistant pathogens comprised 62.9%, classified as MDR (12.5%), extensively drug-resistant (49%) and pandrug-resistant (1.2%). In 97 (37%) patients de-escalation was judged not feasible in view of the antibiotic susceptibility results. Of the remaining 165 patients, judged as patients with de-escalation possibility, de-escalation was applied in 60 (22.9%). These were matched to an equal number of patients without de-escalation. In this subset of 120 patients, de-escalation compared with no de-escalation was associated with lower all-cause 28 day mortality (13.3% versus 36.7%, OR 0.27, 95% CI 0.11-0.66, P = 0.006); ICU and hospital mortality were also lower. De-escalation was associated with a subsequent collateral decrease in the SOFA score. Cox multivariate regression analysis revealed de-escalation as a significant factor for 28 day survival (HR 0.31, 95% CI 0.14-0.70, P = 0.005)., Conclusions: In ICUs with high levels of antimicrobial resistance, feasibility of antimicrobial de-escalation was limited because of the multi-resistant pathogens isolated. However, when de-escalation was feasible and applied, it was associated with lower mortality., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Bronchospasm is a known side effect of the administration of beta-blockers to asthmatics. The purpose of this study was to investigate the frequency of bronchospasm caused by the administration of relatively low doses (2.5-7.5 mg) of pindolol, a beta-blocker with intrinsic sympathetic activity (ISA) to asthmatics, the severity of the bronchospasm and its reversibility and the probable correlations of bronchial asthma (BA) characteristics (severity, duration, allergy and airway hyperreactivity) with existing or nonexisting bronchospasm. Seventeen asthmatic patients: 10 men and 7 women, with a mean age of 44 +/- 10 years, participated in this study. The duration and severity of BA, the presence of allergy determined by skin tests and the bronchial hyperreactivity to methacholine inhalation challenge were observed on the first day of study. On the following days, the respiratory function parameters forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), and the pulse rate were measured before and 30, 60 and 90 min after the administration of placebo and pindolol. Then salbutamol was administered by a dosimetric aerosol (DA) at the usual dosage (200 micrograms) and the change in FEV1 was observed at 60 min; thereafter 40 micrograms of ipratropium bromide (IB) were administered by DA and FEV1 was measured after 60 min. Pindolol was administered gradually by mouth (2.5 mg every 30 min), the maximal total dose being 7.5 mg. Administration of pindolol caused a significant fall of FEV1 of 12 +/- 11% compared to placebo. A significant total decrease of FEV1 (greater than or equal to 20% of baseline) was observed in 9 patients.(ABSTRACT TRUNCATED AT 250 WORDS)