Multidrug resistant (or antimicrobial-resistant) pathogens - alternatives to new antibiotics?

For the last few decades, multidrug resistance has become an increasing concern for both Gram-positive and Gram-negative bacteria. The number of new molecules has dramatically decreased and antibiotic resistance is now a priority in the international community. Facing this new threat, a large number of new as well as "old" solutions are now being discussed in the medical community to propose an alternative to antibiotic treatments. A first option is to potentiate the effect of existing molecules through combinations to circumvent the individual molecule resistance. The second option is to neutralise either the infectious agent itself or its by-products using specific antibodies. A third option is to use the pathogen signaling mechanism and inhibit the production of virulence factor through quorum sensing inhibition. A fourth pathway would be to interact with the patient's microbiota using either probiotics or faecal transplantation to modulate the innate immune response and improve response to the infectious challenge, but also to act directly against colonisation by resistant bacteria by replacing the flora with susceptible strains. The last option is to target the bacteria using phage therapy. Phages are natural viruses that specifically infect target bacteria independently of any antibiotic-susceptibility profile. In this review, we will discuss each of these options and provide the scientific rationale and the available clinical data. In the majority of cases, these treatments represent an interesting approach but not the ultimate solution to multiresistance. Well-performed clinical trials are still missing and the major priority remains to promote good use and appropriate stewardship of antibiotics to decrease resistance

Clostridioides difficile Infection, Still a Long Way to Go.

Clostridioides difficile is an increasingly common pathogen both within and outside the hospital and is responsible for a large clinical spectrum from asymptomatic carriage to complicated infection associated with a high mortality. While diagnostic methods have considerably progressed over the years, the optimal diagnostic algorithm is still debated and there is no single diagnostic test that can be used as a standalone test. More importantly, the heterogeneity in diagnostic practices between centers along with the lack of robust surveillance systems in all countries and an important degree of underdiagnosis due to lack of clinical suspicion in the community, hinder a more accurate evaluation of the burden of disease. Our improved understanding of the physiopathology of CDI has allowed some significant progress in the treatment of CDI, including a broader use of fidaxomicine, the use of fecal microbiota transplantation for multiples recurrences and newer approaches including antibodies, vaccines and new molecules, already developed or in the pipeline. However, the management of CDI recurrences and severe infections remain challenging and the main question remains: how to best target these often expensive treatments to the right population. In this review we discuss current diagnostic approaches, treatment and potential prevention strategies, with a special focus on recent advances in the field as well as areas of uncertainty and unmet needs and how to address them

Core genome multilocus sequence typing of Clostridioides difficile to investigate transmission in the hospital setting.

Traditional epidemiological investigations of healthcare-associated Clostridioides difficile infection (HA-CDI) are often insufficient. This study aimed to evaluate a procedure that includes secondary isolation and genomic typing of single toxigenic colonies using core genome multilocus sequence typing (cgMLST) for the investigation of C. difficile transmission. We analyzed retrospectively all toxigenic C. difficile-positive stool samples stored at the Lausanne University Hospital over 6 consecutive months. All isolates were initially typed and classified using a modified double-locus sequence typing (DLST) method. Genome comparison of isolates with the same DLST and clustering were subsequently performed using cgMLST. The electronic administrative records of patients with CDI were investigated for spatiotemporal epidemiological links supporting hospital transmission. A comparative descriptive analysis between genomic and epidemiological data was then performed. From January to June 2021, 86 C. difficile isolates were recovered from thawed samples of 71 patients. Thirteen different DLST types were shared by > 1 patient, and 13 were observed in single patients. A genomic cluster was defined as a set of isolates from different patients with ≤ 3 locus differences, determined by cgMLST. Seven genomic clusters were identified, among which plausible epidemiological links were identified in only 4/7 clusters. Among clusters determined by cgMLST analysis, roughly 40% included unexplained HA-CDI acquisitions, which may be explained by unidentified epidemiological links, asymptomatic colonization, and/or shared common community reservoirs. The use of DLST, followed by whole genome sequencing analysis, is a promising and cost-effective stepwise approach for the investigation of CDI transmission in the hospital setting

Predictors of Mortality of Streptococcal Bacteremia and the Role of Infectious Diseases Consultation: A Retrospective Cohort Study.

Streptococcal bacteremia is associated with high mortality. Thia study aims to identify predictors of mortality among patients with streptococcal bacteremia. This retrospective study was conducted at the Lausanne University Hospital, Switzerland, and included episodes of streptococcal bacteremia among adult patients from 2015 to 2023. During the study period, 861 episodes of streptococcal bacteremia were included. The majority of episodes were categorized in the Mitis group (348 episodes; 40%), followed by the Pyogenic group (215; 25%). Endocarditis was the most common source of bacteremia (164; 19%). The overall 14-day mortality rate was 8% (65 episodes). The results from the Cox multivariable regression model showed that a Charlson comorbidity index >4 (P .001; hazard ratio [HR], 2.87; confidence interval [CI]: 1.58-5.22), Streptococcus pyogenes (P = .011; HR, 2.54;CI: 1.24-5.21), sepsis (P < .001; HR, 7.48; CI: 3.86-14.47), lower respiratory tract infection (P = .002; HR, 2.62; CI: 1.42-4.81), and absence of source control interventions within 48 hours despite being warranted (P = .002; HR, 2.62; CI: 1.43-4.80) were associated with 14-day mortality. Conversely, interventions performed within 48 hours of bacteremia onset, such as infectious diseases consultation (P < .001; HR, 0.29; CI: .17-.48) and appropriate antimicrobial treatment (P < .001; HR, .28; CI: .14-.57), were associated with improved outcome. Our findings underscore the pivotal role of infectious diseases consultation in guiding antimicrobial treatment and recommending source control interventions for patients with streptococcal bacteremia

Frequencies and Damping rates of a 2D Deformed Trapped Bose gas above the Critical Temperature

We derive the equation of motion for the velocity fluctuations of a 2D deformed trapped Bose gas above the critical temperature in the hydrodynamical regime. From this equation, we calculate the eigenfrequencies for a few low-lying excitation modes. Using the method of averages, we derive a dispersion relation in a deformed trap that interpolates between the collisionless and hydrodynamic regimes. We make use of this dispersion relation to calculate the frequencies and the damping rates for monopole and quadrupole mode in both the regimes. We also discuss the time evolution of the wave packet width of a Bose gas in a time dependent as well as time independent trap.Comment: 13 pages, latex fil

Dissipative dynamics of vortex arrays in trapped Bose-condensed gases: neutron stars physics on μ\muK scale

We develop a theory of dissipative dynamics of large vortex arrays in trapped Bose-condensed gases. We show that in a static trap the interaction of the vortex array with thermal excitations leads to a non-exponential decay of the vortex structure, and the characteristic lifetime depends on the initial density of vortices. Drawing an analogy with physics of pulsar glitches, we propose an experiment which employs the heating of the thermal cloud in the course of the decay of the vortex array as a tool for a non-destructive study of the vortex dynamics.Comment: 4 pages, revtex; revised versio

Finite-temperature simulations of the scissors mode in Bose-Einstein condensed gases

The dynamics of a trapped Bose-condensed gas at finite temperatures is described by a generalized Gross-Pitaevskii equation for the condensate order parameter and a semi-classical kinetic equation for the thermal cloud, solved using $N$-body simulations. The two components are coupled by mean fields as well as collisional processes that transfer atoms between the two. We use this scheme to investigate scissors modes in anisotropic traps as a function of temperature. Frequency shifts and damping rates of the condensate mode are extracted, and are found to be in good agreement with recent experiments.Comment: 4 pages, 3 figure