Background: We introduce a relatively new difficult-to-treat resistance (DTR) category to specialists. It significantly influences the predictability of morbidity and mortality in patients with invasive infections caused by DTR strains. Therefore, surveillance of DTR is an important tool of antimicrobial stewardship (AMS) and widely contributes to cooperation between microbiologists and clinicians. We also report the prevalence of strains meeting the criteria for the category in a teaching hospital.
Methods: This retrospective cohort single center study included invasive isolates of gram-negative rods from patients hospitalized in the General University Hospital in Prague in 2009-2013 and in 2017-2021.
Results: From a total of 1 732 (920 and 812, respectively) unique strains of gram-negative rods isolated from blood cultures in both periods, 6.6 % were carbapenem-resistant in 2009-2013 and 6.0 % in 2017-2021; 3.7 % were identified as DTR in both periods. Most of the DTR strains were A. baumannii (23.1 % and 45.0 %, respectively) and P. aeruginosa (22.2 % and 15.3 %, respectively). We identified no carbapenem-resistant E. coli and therefore no DTR E. coli.
Conclusion: Infections caused by bacterial strains with a DTR phenotype are grave complications and are tricky to manage. The prevalence of severe infections caused by these strains was relatively low in the studied facility. Antibiotics with anti-DTR effects should be considered the last resort, so it is very important to comply with AMS rules and examine the susceptibility of these agents.
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Proc Natl Acad Sci U S A
January 2025
Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139.
Protein language models (PLMs) have demonstrated impressive success in modeling proteins. However, general-purpose "foundational" PLMs have limited performance in modeling antibodies due to the latter's hypervariable regions, which do not conform to the evolutionary conservation principles that such models rely on. In this study, we propose a transfer learning framework called Antibody Mutagenesis-Augmented Processing (AbMAP), which fine-tunes foundational models for antibody-sequence inputs by supervising on antibody structure and binding specificity examples.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital, Aachen 52074, Germany.
Postnatal establishment of enteric metabolic, host-microbial and immune homeostasis is the result of precisely timed and tightly regulated developmental and adaptive processes. Here, we show that infection with the invasive enteropathogen Typhimurium results in accelerated maturation of the neonatal epithelium with premature appearance of antimicrobial, metabolic, developmental, and regenerative features of the adult tissue. Using conditional Myd88-deficient mice, we identify the critical contribution of immune cell-derived mediators.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Plant Pathology, College of Plant Protection, China Agricultural University, Beijing 100193, China.
Host plants and various fungicides inhibit plant pathogens by inducing the release of excessive reactive oxygen species (ROS) and causing DNA damage, either directly or indirectly leading to cell death. The mechanisms by which the oomycete manages ROS stress resulting from plant immune responses and fungicides remains unclear. This study elucidates the role of histone acetylation in ROS-induced DNA damage responses (DDR) to adapt to stress.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Division of Livestock Infectious Diseases, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.
Historically considered to be nonenveloped, hepatitis E virus (HEV), an important zoonotic pathogen, has recently been discovered to egress from infected cells as quasi-enveloped virions. These quasi-enveloped virions circulating in the blood are resistant to neutralizing antibodies, thereby facilitating the stealthy spread of infection. Despite abundant evidence of the essential role of the HEV-encoded ORF3 protein in quasi-enveloped virus formation, the underlying mechanism remains unclear.
View Article and Find Full Text PDFOtol Neurotol
February 2025
Department of ORL-Head & Neck Surgery and Audiology, Odense University Hospital, Odense C, Denmark.
Objective: To investigate the association between postoperative antibiotic prophylaxis and the risk of infections leading to implant explantation or hospitalization, with a follow-up of up to 12 years.
Study Design: Retrospective cohort study.
Setting: Tertiary medical institution.
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