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Key Points: Question: Is there a difference in mortality between continuous and intermittent infusions of β-lactam antibiotics in critically ill patients with sepsis? Findings: In this randomized clinical trial that included 7031 adult patients with sepsis, there was not a statistically significant difference in the proportion of patients who died within 90 days who received continuous (24.9%) compared with intermittent (26.8%) β-lactam antibiotic infusions (odds ratio, 0.91). Meaning: In critically ill patients with sepsis, continuous vs intermittent β-lactam antibiotic infusions did not significantly reduce 90-day mortality in the primary analysis. Importance: Whether β-lactam antibiotics administered by continuous compared with intermittent infusion reduces the risk of death in patients with sepsis is uncertain. Objective: To evaluate whether continuous vs intermittent infusion of a β-lactam antibiotic (piperacillin-tazobactam or meropenem) results in decreased all-cause mortality at 90 days in critically ill patients with sepsis. Design, Setting, and Participants: An international, open-label, randomized clinical trial conducted in 104 intensive care units (ICUs) in Australia, Belgium, France, Malaysia, New Zealand, Sweden, and the United Kingdom. Recruitment occurred from March 26, 2018, to January 11, 2023, with follow-up completed on April 12, 2023. Participants were critically ill adults (≥18 years) treated with piperacillin-tazobactam or meropenem for sepsis. Intervention: Eligible patients were randomized to receive an equivalent 24-hour dose of a β-lactam antibiotic by either continuous (n = 3498) or intermittent (n = 3533) infusion for a clinician-determined duration of treatment or until ICU discharge, whichever occurred first. Main Outcomes and Measures: The primary outcome was all-cause mortality within 90 days after randomization. Secondary outcomes were clinical cure up to 14 days after randomization; new acquisition, colonization, or infection with a multiresistant organism or Clostridioides difficile infection up to 14 days after randomization; ICU mortality; and in-hospital mortality. Results: Among 7202 randomized participants, 7031 (mean [SD] age, 59 [16] years; 2423 women [35%]) met consent requirements for inclusion in the primary analysis (97.6%). Within 90 days, 864 of 3474 patients (24.9%) assigned to receive continuous infusion had died compared with 939 of 3507 (26.8%) assigned intermittent infusion (absolute difference, −1.9% [95% CI, −4.9% to 1.1%]; odds ratio, 0.91 [95% CI, 0.81 to 1.01]; P =.08). Clinical cure was higher in the continuous vs intermittent infusion group (1930/3467 [55.7%] and 1744/3491 [50.0%], respectively; absolute difference, 5.7% [95% CI, 2.4% to 9.1%]). Other secondary outcomes were not statistically different. Conclusions and Relevance: The observed difference in 90-day mortality between continuous vs intermittent infusions of β-lactam antibiotics did not meet statistical significance in the primary analysis. However, the confidence interval around the effect estimate includes the possibility of both no important effect and a clinically important benefit in the use of continuous infusions in this group of patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03213990 This clinical trial compares the efficacy of continuous vs intermittent infusion of a β-lactam antibiotic (piperacillin-tazobactam or meropenem) in decreasing all-cause mortality at 90 days in critically ill patients with sepsis. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to explore attitudes and decision-making by pregnant women regarding antidepressant and anxiolytic use during pregnancy.Method: An observational study at an outer metropolitan hospital in Brisbane, Queensland. Pregnant women presenting for their first antenatal clinic visit were invited to complete a questionnaire. Participants were asked about current or previous antidepressant/anxiolytic use, influences on drug decision-making and the adequacy of information received. Perceptions were measured on a 7-point Likert scale.Results: A total of 503 pregnant women were surveyed. The background prevalence of anxiety and depression was 30.0% (151), with 9.3% (47) respondents using antidepressant or anxiolytic medications during the current pregnancy. Of these 47 women, 68% ceased these medications during or while trying to become pregnant, most commonly due to potential side effects to the baby (16), health professional advice (8) and symptomatology that was under control (7). While the effect was modest, decision-making was most strongly influenced by general practitioners, family and the internet.Conclusions: Most women cease antidepressant/anxiolytic medication before and during pregnancy for reasons other than stability of condition. This study reveals an unmet need for accessible reliable information to guide pregnant women and their care providers. [ABSTRACT FROM AUTHOR]

Background: Infection with multidrug‐resistant (MDR) Gram‐negative organisms leads to poorer outcomes in the critically ill burn patient. The aim of this study was to identify the risk factors for MDR Gram‐negative pathogen infection in critically ill burn patients admitted to a major tertiary referral intensive care unit (ICU) in Australia. Methods: A retrospective case–control study of all adult burn patients admitted over a 7‐year period was conducted. Twenty‐one cases that cultured an MDR Gram‐negative organism were matched with 21 controls of similar age, gender, burn size and ICU stay. Multivariable conditional logistic regression was used to individually assess risk factors after adjusting for Acute Burn Severity Index. Adjusted odds ratios (ORs) were reported. P‐values < 0.25 were considered as potentially important risk factors. Results: Factors increasing the risk of MDR Gram‐negative infection included superficial partial thickness burn size (OR: 1.08; 95% confidence interval (CI): 1.01–1.16; P‐value: 0.034), prior meropenem exposure (OR: 10.39; 95% CI: 0.96–112.00; P‐value: 0.054), Gram‐negative colonization on admission (OR: 9.23; 95% CI: 0.65–130.15; P‐value: 0.10) and escharotomy (OR: 2.66; 95% CI: 0.52–13.65; P‐value: 0.24). For cases, mean age was 41 (SD: 13) years, mean total body surface area burned was 47% (SD: 18) and mean days in ICU until MDR specimen collection was 17 (SD: 10) days. Conclusion: Prior meropenem exposure, Gram‐negative colonization on admission, escharotomy and superficial partial thickness burn size may be potentially important factors for increasing the risk of MDR Gram‐negative infection in the critically ill burn patient. [ABSTRACT FROM AUTHOR]

Context: Severe sepsis or septic shock. Aims: The aim of this study is to examine the effect of a fluid challenge on the B-type natriuretic peptide (BNP) and the hemodynamic state. Settings and Design: This observational study was conducted in an intensivist-led academic, mixed medical-surgical Intensive Care Unit. Subjects and Methods: Focused transthoracic echocardiogram, plasma BNP, and hemodynamic measurements were recorded at baseline and following a 500 ml fluid challenge in thirty patients. Independent predictors of the percentage (%) change in stroke volume (SV) were sought. Next, these independent predictors were assessed for a relationship with the percentage change in BNP. Statistical Analysis Used: Multiple linear regressions, Wilcoxon rank-sum test, f-test, and Pearson's correlation were used. Data analysis was carried out using SAS. The 5% significance level was used. Results: Using a multiple regression models, the percentage increase in SV was independently predicted by the percentage increase in mean arterial pressure, left ventricular end-diastolic volume/dimension (LVEDV/LVEDd), ejection fraction, and a decrease in Acute Physiology and Chronic Health Evaluation II score (P < 0.0001). Preload, measured using LVEDV1 (before the fluid challenge) was significantly larger in the fluid nonresponders (%SV increase <15%) vs. the responders (%SV increase ≥15%). Finally, the percentage change in BNP was positively correlated with left ventricular size at end diastole LVEDd, r = 0.4, P < 0.035). Conclusions: An increase in BNP soon after a fluid challenge may have some predictive utility of a large LVEDd, which in turn can be used to independently predict the SV response to a fluid challenge. [ABSTRACT FROM AUTHOR]