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PurposeIndividualising drug dosing using model-informed precision dosing (MIPD) of beta-lactam antibiotics and ciprofloxacin has been proposed as an alternative to standard dosing to optimise antibiotic efficacy in critically ill patients. However, randomised clinical trials (RCT) on clinical outcomes have been lacking.MethodsThis multicentre RCT, including patients admitted to the intensive care unit (ICU) who were treated with antibiotics, was conducted in eight hospitals in the Netherlands. Patients were randomised to MIPD with dose and interval adjustments based on monitoring serum drug levels (therapeutic drug monitoring) combined with pharmacometric modelling of beta-lactam antibiotics and ciprofloxacin. The primary outcome was ICU length of stay (LOS). Secondary outcomes were ICU mortality, hospital mortality, 28-day mortality, 6-month mortality, delta sequential organ failure assessment (SOFA) score, adverse events and target attainment.ResultsIn total, 388 (MIPD n = 189; standard dosing n = 199) patients were analysed (median age 64 [IQR 55–71]). We found no significant differences in ICU LOS between MIPD compared to standard dosing (10 MIPD vs 8 standard dosing; IRR = 1.16; 95% CI 0.96–1.41; p = 0.13). There was no significant difference in target attainment before intervention at day 1 (T1) (55.6% MIPD vs 60.9% standard dosing; p = 0.24) or at day 3 (T3) (59.5% vs 60.4%; p = 0.84). There were no significant differences in other secondary outcomes.ConclusionsWe could not show a beneficial effect of MIPD of beta-lactam antibiotics and ciprofloxacin on ICU LOS in critically ill patients. Our data highlight the need to identify other approaches to dose optimisation.

Background: Critically ill COVID-19 patients have proven to be at risk for developing invasive fungal infections. However, the incidence and impact of possible/probable COVID-19-associated pulmonary aspergillosis (CAPA) in severe COVID-19 patients varies between cohorts. We aimed to assess the incidence, risk factors, and clinical outcome of invasive pulmonary aspergillosis in a regional cohort of COVID-19 intensive care patients. Methods: We performed a regional, multicentre, retrospective cohort study in the intensive care units (ICUs) in North Brabant, The Netherlands. We included adult patients with rt-PCR-confirmed SARS-CoV-2 infection (COVID-19), requiring mechanical ventilation for acute respiratory distress syndrome. Demographics, clinical course, biomarker value, and treatment outcomes were compared between the groups with possible/probable CAPA from the main study centre and the regional centres, and without signs of CAPA from the main study centre as controls. The primary aim was to assess the regional impact of possible/probable CAPA in COVID-19 ICU patients, measured as all-cause mortality at 30 days after ICU admission. Secondary outcomes were risk factors for developing CAPA, based on underlying host factors and to identify the value of the mycological arguments for the diagnosing of CAPA. Results: Between 1 March and 30 April 2020, we included 123 patients with severe COVID-19: 29 patients (30.9%) in the main ICU with possible/probable CAPA, and 65 (69.1%) with no signs of CAPA; 29 patients in the regional ICUs with signs of CAPA. Patients’ characteristics and risk factors did not differ for CAPA and non-CAPA patients. Patients with COPD and/or chronic steroid medication developed CAPA more frequently, although this was not statistically significant. CAPA patients were admitted to the ICU earlier, had lower PF-ratios, and more often required renal replacement therapy. All-cause 30-day mortality was significantly higher in mechanically ventilated COVID-19 patients with possible/probable CAPA 39.7% (23/58) compared to patients without evidence for CAPA 16.9% (11/65) (OR 3.2 [95% CI 1.4–7.4] p = 0.005). Conclusion: The high incidence of possible and probable CAPA in critically ill COVID-19 patients is alarming. The increase in 30-day mortality in CAPA highlights the need for active surveillance and management strategies in critically ill COVID-19 patients.

Ischemic heart disease is a major cause of out-of-hospital cardiac arrest. The role of immediate coronary angiography (CAG) and percutaneous coronary intervention (PCI) after restoration of spontaneous circulation following cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) remains debated. We hypothesize that immediate CAG and PCI, if indicated, will improve 90-day survival in post–cardiac arrest patients without signs of STEMI. In a prospective, multicenter, randomized controlled clinical trial, 552 post–cardiac arrest patients with restoration of spontaneous circulation and without signs of STEMI will be randomized in a 1:1 fashion to immediate CAG and PCI (within 2 hours) versus initial deferral with CAG and PCI after neurological recovery. The primary end point of the study is 90-day survival. The secondary end points will include 90-day survival with good cerebral performance or minor/moderate disability, myocardial injury, duration of inotropic support, occurrence of acute kidney injury, need for renal replacement therapy, time to targeted temperature control, neurological status at intensive care unit discharge, markers of shock, recurrence of ventricular tachycardia, duration of mechanical ventilation, and reasons for discontinuation of treatment. The COACT trial is a multicenter, randomized, controlled clinical study that will evaluate the effect of an immediate invasive coronary strategy in post–cardiac arrest patients without STEMI on 90-day survival.

Background: Central-line–associated bloodstream infections (CLABSIs) are serious complications of modern health care, leading to increased morbidity, mortality, and costs. Since 2012, a multimodal insertion and care bundle for central venous catheters (CVCs) has been implemented in the intensive care unit (ICU) of the Amphia Hospital Breda, The Netherlands. The implementation of this bundle was associated with sustainable low CLABSI rates (1 per 1,000 CVC days). There was no surveillance of CLABSI in the other departments of the hospital. Objectives: We implemented semiautomated surveillance for CLABSI in non-ICU inpatients. Methods: A single-center, retrospective study was conducted in a 1,370-bed teaching hospital in The Netherlands between January 2017 and December 2018. All hospitalized patients (aged ≥18 years) in non-ICU wards, with a CVC inserted, were screened for CLABSI. CLABSIs were diagnosed using the definitions of the national nosocomial surveillance network PREZIES, excluding infections already present on admission and secondary bloodstream infection. CLABSI rates were calculated as cases per 1,000 CVC days with 95% CIs. Results: In 2017, 14 CLABSI were reported during 4,656 CVC days (3.0 per 1,000 CVC days; 95% CI, 1.8–5.1). In 2018, 13 CLABSIs were reported during 4,995 catheter days (2.6 per 1,000 CVC days; 95% CI, 1.5–4.5). The mean duration of CVC days prior to CLABSI in 2017 and 2018 were 20 days (range, 4–28) and 14 days (range, 4–25), respectively. Most CLABSI events occurred in patients admitted to the hematology ward (13 of 27, 48.1%). Of those, 11 of 13 (84,6%) were patients with an acute myeloid leukemia (AML) and severe mucositis due to the intensive chemotherapy at the time of CLABSI. The remaining cases occurred in patients of 4 different surgical departments. Coagulase-negative staphylococci were the most common organisms recovered (25 of 27, 92.6%). Conclusions: To our knowledge, this is the first report of CLABSI-rates in non-ICU wards in the Netherlands. The CLABSI rates were higher in non-ICU wards compared to the ICU of our hospital. This difference was mainly because of the high CLABSI rate in the patients with AML. Funding: None Disclosures: None