Genomic virulence markers are associated with severe outcomes in patients with Pseudomonas aeruginosa bloodstream infection.

Background: Pseudomonas aeruginosa (PA) bloodstream infection (BSI) is a common healthcare-associated complication linked to antimicrobial resistance and high mortality. Ongoing clinical trials are exploring novel anti-virulence agents, yet studies on how bacterial virulence affects PA infection outcomes is conflicting and data from real-world clinical populations is limited.

Methods: We studied a multicentre cohort of 773 adult patients with PA BSI consecutively collected during 7-years from sites in Europe and Australia.

GPT-4-based AI agents-the new expert system for detection of antimicrobial resistance mechanisms?

Unlabelled: The European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommends two steps for detecting beta-lactamases in Gram-negative bacteria. Screening for potential extended-spectrum beta-lactamase (ESBL), plasmid-mediated AmpC beta-lactamase, or carbapenemase production is confirmed. We aimed to validate generative pre-trained transformer (GPT)-4 and GPT-agent for pre-classification of disk diffusion to indicate potential beta-lactamases.

Pandrug-resistant Klebsiella pneumoniae isolated from Ukrainian war victims are hypervirulent.

Objectives: Carbapenem- and colistin-resistant Klebsiella pneumoniae were isolated from war victims treated in hospitals in Ukraine. The question was whether these pandrug-resistant K. pneumoniae are pathogenic and capable of causing disease in a broader context.

Resistance to aztreonam-avibactam among clinical isolates of Escherichia coli is primarily mediated by altered penicillin-binding protein 3 and impermeability.

This study was conducted to investigate decreased susceptibility (minimum inhibitory concentrations [MICs] 0.25-4 mg/L) and resistance (MICs > 4 mg/L) to aztreonam-avibactam (ATM-AVI). Contemporary non-replicate clinical isolates of carbapenemase-producing Escherichia coli (CP-EC) (n=90) and ESBL-producing E.

Amoxicillin-Clavulanate Breakpoints Against Enterobacterales: Rationale for Revision by the Clinical and Laboratory Standards Institute.

Amoxicillin-clavulanate (AMC) is among the most frequently prescribed antibiotics globally. It has broad antibacterial activity against gram-positive, gram-negative, and anaerobic bacteria and has been used to treat infections caused by a broad range of pathogens. AMC breakpoints against Enterobacterales were initially set in the 1980s.

A decade of neonatal sepsis in Stockholm, Sweden: Gram-positive pathogens were four times as common as Gram-negatives.

Purpose: To assess Gram-positive bacterial (GPB) bloodstream infection (BSI) in neonates, covering incidence, morbidity, mortality, antimicrobial resistance patterns and biomarkers in Region Stockholm, Sweden between 2006 and 2016.

Methods: A population-based retrospective epidemiological study including infants with GPB-BSI, admitted to the neonatal units at Karolinska University Hospital (KUH). Data were collected from patient records, the Swedish Neonatal Quality Register, the microbiological laboratory at KUH and the Swedish Public Health Agency.

Quality, availability and suitability of antimicrobial stewardship guidance: a multinational qualitative study.

Background: Antimicrobial stewardship (AMS) programmes are established across the world to treat infections efficiently, prioritize patient safety, and reduce the emergence of antimicrobial resistance. One of the core elements of AMS programmes is guidance to support and direct physicians in making efficient, safe and optimal decisions when prescribing antibiotics. To optimize and tailor AMS, we need a better understanding of prescribing physicians' experience with AMS guidance.

Effect of tebipenem pivoxil hydrobromide on the normal gut microbiota of a healthy adult population in Sweden: a randomised controlled trial.

Background: Antimicrobials cause perturbations in the composition and diversity of the host microbiome. We aimed to compare gut microbiome perturbations caused by oral tebipenem pivoxil hydrobromide (a novel carbapenem) and by amoxicillin-clavulanic acid (an orally administered β-lactam-β-lactam inhibitor combination widely used in clinical practice).

Methods: We did a phase 1, single-centre, randomised, parallel-group, active-control trial to evaluate the effect of tebipenem pivoxil hydrobromide on the human gut microbiota.

Molecular characteristics, fitness, and virulence of high-risk and non-high-risk clones of carbapenemase-producing .

Extensively drug-resistant (XDR) inflict a notable burden on healthcare worldwide. Of specific concern are strains producing carbapenem-hydrolyzing enzymes, as the therapeutic options for these strains are still very limited. Specific sequence types of have been noted for their epidemic occurrence globally, but the mechanisms behind the success of specific clones remain unclear.

Treatment, outcomes and characterization of pathogens in urinary tract infections caused by ESBL-producing Enterobacterales: a prospective multicentre study.

Objectives: Treatment options for urinary tract infections (UTIs) caused by ESBL-producing Enterobacterales are limited. Moreover, evidence to support therapeutic decisions is lacking. This study assessed current treatment strategies and patient and pathogen characteristics in relation to clinical and microbiological outcomes.

Pseudomonasaeruginosa antimicrobial susceptibility profiles, resistance mechanisms and international clonal lineages: update from ESGARS-ESCMID/ISARPAE Group.

Scope: Pseudomonas aeruginosa, a ubiquitous opportunistic pathogen considered one of the paradigms of antimicrobial resistance, is among the main causes of hospital-acquired and chronic infections associated with significant morbidity and mortality. This growing threat results from the extraordinary capacity of P. aeruginosa to develop antimicrobial resistance through chromosomal mutations, the increasing prevalence of transferable resistance determinants (such as the carbapenemases and the extended-spectrum β-lactamases), and the global expansion of epidemic lineages.

Antimicrobial susceptibilities and genomic characteristics of methicillin-resistant Staphylococcus aureus resistant to mupirocin in Stockholm, Sweden.

The aim of this study was to investigate antimicrobial susceptibilities and genomic characteristics of mupirocin-resistant MRSA isolates in Stockholm, Sweden. In total, 44 non-duplicate mupirocin-resistant MRSA isolates detected in Stockholm during 2010-2022 were investigated. Antimicrobial susceptibility testing was performed using broth microdilution method and further tested for high-level mupirocin-resistance (MuH) and rifampicin by Etest®.

Swedish multicentre study of target attainments with β-lactams in the ICU: which MIC parameter should be used?

Background: Therapeutic drug monitoring (TDM) has been suggested to optimize antimicrobial target attainment, typically using 100%T>MIC, in β-lactam treatment in the ICU. The MIC parameter used in this equation is mostly the worst case scenario MIC (MICWCS)-the highest MIC the empirical treatment should cover. However, the impact of the MIC parameter used in pharmacokinetic/pharmacodynamic calculations has been poorly investigated.

The activity of carbapenems alone and in combination with β-lactamase inhibitors against difficult-to-treat mycobacteria; and complex: A systematic review.

Difficult-to-treat mycobacterial infections are increasing globally. There is an urgent need of new treatment alternatives for multidrug-resistant Mycobacterium tuberculosis (MTB), as well as nontuberculous mycobacteria such as the Mycobacterium abscessus complex (MABC) and Mycobacterium avium complex (MAC). Recently, new carbapenems and combinations of carbapenems with β-lactamase inhibitors have become available, but activity data in vitro against mycobacteria are so far scarce.

Performance of automated antimicrobial susceptibility testing for the detection of antimicrobial resistance in gram-negative bacteria: a NordicAST study.

Automated testing of antimicrobial susceptibility is common in clinical microbiology laboratories but their ability to detect low-level resistance has been questioned. This Nordic multicentre study aimed to evaluate the performance of commercially available automated AST systems. A phenotypically well-characterised collection of gram-negative bacilli (Escherichia coli (n = 7), Klebsiella pneumoniae (n = 6) and Pseudomonas aeruginosa (n = 7)) with and without resistance mechanisms was examined by Danish (n = 1), Finnish (n = 6), Norwegian (n = 16) and Swedish (n = 5) laboratories.

Therapeutic-oligonucleotides activated by nucleases (TOUCAN): A nanocarrier system for the specific delivery of clinical nucleoside analogues.

Nucleoside analogues have been in clinical use since 1960s and they are still used as the first therapeutic option for several cancers and viral infections, due to their high therapeutic efficacy. However, their wide clinical acceptance has been limited due to their high toxicity and severe side effects to patients. Herein, we report on a nanocarrier system that delivers nucleosides analogues in a target-specific manner, making nucleoside-based therapeutics safer and with the possibility to be used in other human conditions.

Recurrent bacteremia with Enterococcus faecalis, the clinical findings predicting endocarditis, and genomic characterization of the isolates: a retrospective cohort study.

Multiple episodes of Enterococcus faecalis bacteremia (EfsB) may indicate a relapse and be due to an undiagnosed infective endocarditis (IE). The aims were to study the clinical presentation of patients with EfsB with focus on the risk of recurrent infection and IE, identify potential improvements of the management, and to investigate whether E. faecalis isolates from different episodes in the same patient were identical.

Antimicrobial susceptibility testing of Bacteroides species by disk diffusion: The NordicAST Bacteroides study.

Objectives: Antimicrobial susceptibility testing (AST) of anaerobic bacteria has until recently been done by MIC methods. We have carried out a multi-centre evaluation of the newly validated EUCAST disk diffusion method for AST of Bacteroides spp.

Methods: A panel of 30 Bacteroides strains was assembled based on reference agar dilution MICs, resistance gene detection and quantification of cfiA carbapenemase gene expression.

Agreement between rapid antigen detection test and culture for group A streptococcus in patients recently treated for pharyngotonsillitis - a prospective observational study in primary care.

Objective: The aim was to compare rapid antigen detection test (RADT) and throat culture for group A streptococci (GAS) among patients recently treated with penicillin V for GAS pharyngotonsillitis.

Design And Setting: The study was a secondary analysis within a randomized controlled trial comparing 5 versus 10 days of penicillin V for GAS pharyngotonsillitis. Patients were recruited at 17 primary health care centres in Sweden.

Strain-level bacterial typing directly from patient samples using optical DNA mapping.

Background: Identification of pathogens is crucial to efficiently treat and prevent bacterial infections. However, existing diagnostic techniques are slow or have a too low resolution for well-informed clinical decisions.

Methods: In this study, we have developed an optical DNA mapping-based method for strain-level bacterial typing and simultaneous plasmid characterisation.

Effects of penicillin V on the faecal microbiota in patients with pharyngotonsillitis-an observational study.

Background: The intestinal microbiota functions as a reservoir of antibiotic resistance.

Objectives: To evaluate penicillin V (phenoxymethylpenicillin) effects on the faecal microbiota with focus on beta-lactam resistance.

Methods: We included 31 primary care patients with group A streptococcal pharyngotonsillitis treated with penicillin V for 5 (800 mg × 4) or 10 days (1000 mg × 3).

Towards clinical breakpoints for non-tuberculous mycobacteria - Determination of epidemiological cut off values for the Mycobacterium avium complex and Mycobacterium abscessus using broth microdilution.

Objective: For non-tuberculous mycobacteria (NTM), minimum inhibitory concentration (MIC) distributions of wild-type isolates have not been systematically evaluated despite their importance for establishing antimicrobial susceptibility testing (AST) breakpoints.

Methods: We gathered MIC distributions for drugs used against the Mycobacterium avium complex (MAC) and Mycobacterium abscessus (MAB) obtained by commercial broth microdilution (SLOMYCOI and RAPMYCOI) from 12 laboratories. Epidemiological cut-off values (ECOFFs) and tentative ECOFFs (TECOFFs) were determined by EUCAST methodology including quality control (QC) strains.

Network-based multi-omics integration reveals metabolic at-risk profile within treated HIV-infection.

Multiomics technologies improve the biological understanding of health status in people living with HIV on antiretroviral therapy (PWH). Still, a systematic and in-depth characterization of metabolic risk profile during successful long-term treatment is lacking. Here, we used multi-omics (plasma lipidomic, metabolomic, and fecal 16 S microbiome) data-driven stratification and characterization to identify the metabolic at-risk profile within PWH.