Multidrug-resistant Gram-negative clinical isolates with reduced susceptibility/resistance to cefiderocol: which are the best present and future therapeutic alternatives?

PURPOSE: To evaluate the different present and future therapeutic ß-lactam/ß-lactamase inhibitor (BL/BLI) alternatives, namely aztreonam-avibactam, imipenem-relebactam, meropenem-vaborbactam, cefepime-zidebactam, cefepime-taniborbactam, meropenem-nacubactam, and sulbactam-durlobactam against clinical isolates showing reduced susceptibility or resistance to cefiderocol in Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa. METHODS: MIC values of aztreonam, aztreonam-avibactam, cefepime, cefepime-taniborbactam, cefepime-zidebactam, imipenem, imipenem-relebactam, meropenem, meropenem-vaborbactam, meropenem-nacubactam, sulbactam-durlobactam, and cefiderocol combined with a BLI were determined for 67, 9, and 11 clinical Enterobacterales, P. aeruginosa or A. baumannii isolates, respectively, showing MIC values of cefiderocol being ≥1 mg/L. If unavailable, the respective ß-lactam breakpoints according to EUCAST were used for BL/BLI combinations. RESULTS: For Enterobacterales, the susceptibility rates for aztreonam, cefepime, imipenem, and meropenem were 7.5%, 0%, 10.4%, and 10.4%, respectively, while they were much higher for cefepime-zidebactam (91%), cefiderocol-zidebactam (91%), meropenem-nacubactam (71.6%), cefiderocol-nacubactam (74.6%), and cefiderocol-taniborbactam (76.1%), as expected. For P. aeruginosa isolates, the higher susceptibility rates were observed for imipenem-relebactam, cefiderocol-zidebactam, and meropenem-vaborbactam (56% for all combinations). For A. baumannii isolates, lower susceptibility rates were observed with commercially or under development BL/BLI combos; however, a high susceptibility rate (70%) was found for sulbactam-durlobactam and when cefiderocol was associated to some BLIs. CONCLUSIONS: Zidebactam- and nacubactam-containing combinations showed a significant in vitro activity against multidrug-resistant Enterobacterales clinical isolates with reduced susceptibility to cefiderocol. On the other hand, imipenem-relebactam and meropenem-vaborbactam showed the highest susceptibility rates against P. aeruginosa isolates. Finally, sulbactam-durlobactam and cefiderocol combined with a BLI were the only effective options against A. baumannii tested isolates.

Association of Trace Element Levels with Outcomes in Critically Ill COVID-19 Patients.

The primary objective of this study was to compare the plasma levels of copper, selenium, and zinc between critically ill COVID-19 patients and less severe COVID-19 patients. The secondary objective was to investigate the association of these trace element levels with adverse outcomes, including the duration of mechanical ventilation, occurrence of septic shock, and mortality in critically ill COVID-19 patients. All COVID-19 patients admitted to the ICU of the Geneva University Hospitals between 9 March 2020 and 19 May 2020 were included in the study. Plasma levels of copper, selenium and zinc were measured on admission to the ICU and compared with levels measured in COVID-19 patients hospitalized on the ward and in non-hospitalized COVID-19 patients. To analyze the association of trace elements with clinical outcomes, multivariate linear and logistic regressions were performed. Patients in the ICU had significantly lower levels of selenium and zinc and higher levels of copper compared to COVID-19 patients hospitalized on the ward and in non-hospitalized COVID-19 patients. In ICU patients, lower zinc levels tended to be associated with more septic shock and increased mortality compared to those with higher zinc levels (p = 0.07 for both). Having lower copper or selenium levels was associated with a longer time under mechanical ventilation (p = 0.01 and 0.04, respectively). These associations remained significant in multivariate analyses (p = 0.03 for copper and p = 0.04 for selenium). These data support the need for interventional studies to assess the potential benefit of zinc, copper and selenium supplementation in severe COVID-19 patients.

The Effect of Positive Therapeutic Communication on Pain (POPAIN) and Anxiety During Arterial Blood Gas Standardized Procedures in the Emergency Department Compared to Traditional Communication: Protocol for a Monocentric Randomized Controlled Trial.

BACKGROUND: In the emergency department (ED), medical procedures, such as arterial blood gas (ABG) testing, can cause pain and high stress levels. However, ABG testing is a routine procedure assessing the severity of the patient's condition. To reduce the pain of ABG, several methods have been investigated without significant difference in pain perception. Communication, a key element of care, has shown a significant effect on pain perception. A positive communication strategy, including positive, kind, or reassuring words, can reduce pain perception, while negative words can raise this perception, causing discomfort, known as the "nocebo effect." Although some studies have compared the impact of verbal attitudes, particularly in anesthesia and mainly with staff already trained in hypnosis, to the best of our knowledge, none have investigated the effect of communication in the emergency setting, where patients may be more suggestible to the words used. OBJECTIVE: In this study, we will investigate the effect of positive therapeutic communication on pain, anxiety, discomfort, and global satisfaction in patients requiring ABG compared to nocebo and neutral communication. METHODS: A single-center, double-blind randomized controlled trial (RCT) with 3 parallel arms will be conducted with 249 patients requiring ABG during their ED visit. Patients will be randomly assigned to 1 of 3 groups before receiving ABG: positive communication group, negative communication (nocebo) group, or neutral communication (neutral) group. The communication and the words used by the physicians during hygiene preparation, artery location, and puncture will be imposed in each group. The study will be proposed to each patient corresponding to the inclusion criteria. The physicians will not be trained in hypnosis or in positive therapeutic communication. The procedure will be recorded with audio recorders to test its quality. Intention-to-treat analysis will be performed. The primary endpoint is the onset of pain. The secondary outcomes are patient comfort, patient anxiety, and global satisfaction of the patient with the communication strategy used. RESULTS: On average, 2000 ABG procedures are performed each year in the EDs of hospitals. In this study, 249 patients are expected to be included. With a projected positive response rate of 80%, we intend to include 25 (10%) patients per month. The inclusion period began in April 2023 and will run until July 2024. We hope to publish the results of the study during the fall of 2024. CONCLUSIONS: To the best of our knowledge, this study is the first RCT assessing the use of positive communication on pain and anxiety in patients undergoing the ABG procedure in the ED. A reduction in pain, discomfort, and anxiety is expected when using positive communication. If the results are positive, this could be useful to the medical community and encourage clinicians to monitor their communication during care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05434169; https://clinicaltrials.gov/ct2/show/NCT05434169. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/42043.

Impact of nutritional therapy during the first wave of the COVID-19 pandemic in intensive care patients: A retrospective observational study.

BACKGROUND & AIMS: The COVID-19 pandemic has caused major organizational challenges to healthcare systems concerning staff, material and bed availability. Nutrition was not a priority in the intensive care unit (ICU) at the beginning of the pandemic with the need for simplified protocols. We aimed to assess the impact of a simplified nutritional protocol for critically ill COVID-19 patients during the pandemic first wave. METHODS: We included all patients with SARS-CoV-2 infections, admitted to the ICU of the Geneva University Hospitals for at least 4 days from March 9 to May 19, 2020. Data on the route and solution of nutritional therapy, prescribed and received volume, calorie and protein intake, amount of insulin, propofol and glucose administered were collected daily during the entire ICU stay. We compared nutritional outcomes between patients admitted to the ICU before and after implementing the simplified nutritional protocol using unpaired t-test. RESULTS: Out of 119 patients, 48 were hospitalized in the ICU before, 47 across and 24 after the implementation of the nutritional protocol. The mean age was 63.2 (±12.7) years and 76% were men without significant difference between before and after group. The nutritional protocol implementation led to an increase in caloric intake (1070 vs. 1357 kcal/day, p = 0.018) and in the percentage of days within 80-100% of the energy target (11 vs. 20%, p = 0.021). The protein debt decreased significantly from 48 g/day to 37 g/day (p = 0.015). No significant difference in the percentage of days within the protein target (80-100%) was observed. CONCLUSIONS: Calorie and protein coverage improved after the implementation of the simplified nutritional protocol in critically ill COVID-19 patients. Further studies are needed to assess the impact of such an approach on patients' clinical outcomes.