In-vitro activity of the novel β-lactam/β-lactamase inhibitor combinations and cefiderocol against carbapenem-resistant Pseudomonas spp. clinical isolates collected in Switzerland in 2022.

To evaluate the in-vitro activity of the novel commercially-available drugs, including meropenem-vaborbactam (MEV), ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), imipenem-relebactam (IPR) as well as cefiderocol (FDC), against carbapenem-resistant Pseudomonas spp. (CRP) isolates. All CRP isolates collected at the Swiss National Reference Laboratory (NARA) over the year 2022 (n = 170) have been included.

Early reduction in gut microbiota diversity in critically ill patients is associated with mortality.

Background: Critical illness is associated with an altered gut microbiota, yet its association with poor outcomes remains unclear. This study evaluates the early gut microbiota diversity changes in intensive care unit patients and its association with mortality. Additionally, it explores fecal pH as a potential biomarker for these changes.

In-vitro activity of newly-developed β-lactamase inhibitors avibactam, relebactam and vaborbactam in combination with anti-pseudomonal β-lactam antibiotics against AmpC-overproducing clinical Pseudomonas aeruginosa isolates.

Purpose: Overproduction of the intrinsic chromosomally-encoded AmpC β-lactamase is one of the main mechanisms responsible for broad-spectrum β-lactam resistance in Pseudomonas aeruginosa. Our study aimed to evaluate the in-vitro activity of anti-pseudomonal β-lactam molecules associated with the recently-developed and commercially-available β-lactamase inhibitors, namely avibactam, relebactam and vaborbactam, against P. aeruginosa isolates overproducing their AmpC.

Relative inhibitory activities of newly developed diazabicyclooctanes, boronic acid derivatives, and penicillin-based sulfone β-lactamase inhibitors against broad-spectrum AmpC β-lactamases.

The relative inhibitory activities of diazabicyclooctanes (avibactam, relebactam, zidebactam, nacubactam, durlobactam), boronic acid derivatives (vaborbactam, taniborbactam, xeruborbactam), and penicillin-based sulfone derivative enmetazobactam were evaluated against several intrinsic and acquired class C β-lactamases. By contrast to vaborbactam and enmetazobactam, taniborbactam, xeruborbactam, and all diazabicyclooctanes demonstrated effective activities against most AmpC enzymes. Notably, durlobactam exhibited the most pronounced inhibitory effect.

Impact of intensive prone position therapy on outcomes in intubated patients with ARDS related to COVID-19.

Background: Previous retrospective research has shown that maintaining prone positioning (PP) for an average of 40 h is associated with an increase of survival rates in intubated patients with COVID-19-related acute respiratory distress syndrome (ARDS). This study aims to determine whether a cumulative PP duration of more than 32 h during the first 2 days of intensive care unit (ICU) admission is associated with increased survival compared to a cumulative PP duration of 32 h or less.

Methods: This study is an ancillary analysis from a previous large international observational study involving intubated patients placed in PP in the first 48 h of ICU admission in 149 ICUs across France, Belgium and Switzerland.

Impact of extended-spectrum chromosomal AmpC (ESAC) of on susceptibility to cefiderocol.

Unlabelled: The impact of chromosomally encoded wild-type or extended-spectrum (ESAC) AmpC β-lactamases of on susceptibility to ceftazidime, cefepime, and cefiderocol was evaluated in different genetic backgrounds, including wild-type, PBP3-modified, and porin-deficient strains. Recombinant strains possessing the different backgrounds and producing variable ESACs were evaluated. Although ESAC enzymes conferred resistance to ceftazidime and decreased susceptibility to cefepime as expected, we showed here that cefiderocol was also a substrate of ESAC enzymes.

Relative inhibitory activities of the broad-spectrum β-lactamase inhibitor xeruborbactam in comparison with taniborbactam against metallo-β-lactamases produced in and .

Xeruborbactam is a newly developed β-lactamase inhibitor designed for metallo-β-lactamases (MBLs). This study assessed the relative inhibitory properties of this novel inhibitor in comparison with another MBL inhibitor, namely taniborbactam (TAN), against a wide range of acquired MBL produced either in or . As observed with taniborbactam, the combination of xeruborbactam (XER) with β-lactams, namely, ceftazidime, cefepime and meropenem, led to significantly decreased MIC values for a wide range of B1-type MBL-producing , including most recombinant strains producing NDM, VIM, IMP, GIM-1, and DIM-1 enzymes.

Effect of modification of penicillin-binding protein 3 on susceptibility to ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam, aztreonam-avibactam, cefepime-taniborbactam, and cefiderocol of strains producing broad-spectrum β-lactamases.

The impact of penicillin-binding protein 3 (PBP3) modifications that may be identified in was evaluated with respect to susceptibility to β-lactam/β-lactamase inhibitor combinations including ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam, aztreonam-avibactam, cefepime-taniborbactam, and to cefiderocol. A large series of recombinant strains producing broad-spectrum β-lactamases was evaluated. While imipenem-relebactam showed a similar activity regardless of the PBP3 background, susceptibility to other molecules tested was affected at various levels.

Long-term olfactory enrichment promotes non-olfactory cognition, noradrenergic plasticity and remodeling of brain functional connectivity in older mice.

Brain functional and structural changes lead to cognitive decline during aging, but a high level of cognitive stimulation during life can improve cognitive performances in the older adults, forming the cognitive reserve. Noradrenaline has been proposed as a molecular link between environmental stimulation and constitution of the cognitive reserve. Taking advantage of the ability of olfactory stimulation to activate noradrenergic neurons of the locus coeruleus, we used repeated olfactory enrichment sessions over the mouse lifespan to enable the cognitive reserve buildup.

Reduced susceptibility to aztreonam-avibactam conferred by acquired AmpC-type β-lactamases in PBP3-modified Escherichia coli.

Purpose: Carbapenemase-producing Enterobacterales are a growing threat, and very few therapeutic options remain active against those multidrug resistant bacteria. Aztreonam is the molecule of choice against metallo-beta-lactamases (MBL) producers since it is not hydrolyzed by those enzymes, but the co-production of acquired plasmidic cephalosporinases or extended-spectrum β-lactamases leading to aztreonam resistance may reduce the efficacy of this molecule. Hence, the development of the aztreonam-avibactam (AZA) combination provides an interesting therapeutic alternative since avibactam inhibits the activity of both cephalosporinases and extended-spectrum β-lactamases.

Pulmonary embolism impacts clinical outcomes of intubated patients with acute respiratory distress syndrome related to COVID-19.

Background: Pulmonary embolism (PE) in critically ill patients with acute respiratory distress syndrome (ARDS) caused by COVID-19 is a major complication which might impact survival. We aimed to determine the prevalence of PE and assess its impact of PE on clinical outcomes in intubated patients with ARDS due to COVID-19.

Methods: All intubated patients with ARDS due to COVID-19 admitted to the intensive care unit (ICU) of Geneva University Hospitals between March 9, 2020, and May 31, 2022, were included.

Structural basis of metallo-β-lactamase resistance to taniborbactam.

The design of inhibitors against metallo-β-lactamases (MBLs), the largest family of carbapenemases, has been a strategic goal in designing novel antimicrobial therapies. In this regard, the development of bicyclic boronates, such as taniborbactam (TAN) and xeruborbactam, is a major achievement that may help in overcoming the threat of MBL-producing and carbapenem-resistant Gram-negative pathogens. Of concern, a recent report has shown that New Delhi MBL-9 (NDM-9) escapes the inhibitory action of TAN by a single amino acid substitution with respect to New Delhi MBL-1 (NDM-1), the most widely disseminated MBL.

Relative inhibitory activities of the broad-spectrum β-lactamase inhibitor taniborbactam against metallo-β-lactamases.

Taniborbactam (TAN) is a novel broad-spectrum β-lactamase inhibitor with significant activity against subclass B1 metallo-β-lactamases (MBLs). Here, we showed that TAN exhibited an overall excellent activity against B1 MBLs including most NDM- and VIM-like as well as SPM-1, GIM-1, and DIM-1 enzymes, but not against SIM-1. Noteworthy, VIM-1-like enzymes (particularly VIM-83) were less inhibited by TAN than VIM-2-like.

Impact of acquired broad-spectrum β-lactamases on susceptibility to oral penems/carbapenems (tebipenem, sulopenem, and faropenem) alone or in combination with avibactam and taniborbactam β-lactamase inhibitors in .

The impact of β-lactamases on susceptibility to oral penems/carbapenems (tebipenem, sulopenem, and faropenem) and other carbapenem molecules was evaluated in , alone and in combination with avibactam or taniborbactam β-lactamase inhibitors. Tebipenem and sulopenem exhibited a similar spectrum of activity compared to the intravenous carbapenems and displayed lower MIC values than ceftibuten-avibactam against producing extended-spectrum β-lactamases or AmpC enzymes. Combined with taniborbactam, tebipenem and sulopenem exhibited low MIC values against almost all tested recombinant , including metallo-β-lactamase producers.

No waiting lying in a corridor: a quality improvement initiative in an emergency department.

Background: Overcrowding in the emergency department (ED) is a global problem and a source of morbidity and mortality and exhaustion for the teams. Despite multiple strategies proposed to overcome overcrowding, the accumulation of patients lying in bed awaiting treatment or hospitalisation is often inevitable and a major obstacle to quality of care. We initiated a quality improvement project with the objective of zero patients lying in bed awaiting care/referral outside a care area.

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.

Ophthalmic complications during the dengue epidemic in Reunion Island in 2020: a case series and review of the literature.

Introduction: Dengue is an arboviral disease transmitted by the dengue virus, whose vectors are Aedes aegypti and Aedes albopictus. The acute phase with its cohort of well-known symptoms is usually spontaneously favorable. Since 2020 in Reunion Island, a new symptom has appeared: the ocular damage of dengue fever, which has already been described in South Asia and South-East Asia.