In Vitro Susceptibility to Imipenem/Relebactam and Comparators in a Multicentre Collection of Complex Isolates.

Infections caused by non-tuberculous mycobacteria (NTM), including complex (MABc), are increasing globally and are notoriously difficult to treat due to the intrinsic resistance of these bacteria to many common antibiotics. The aims of this study were to demonstrate the in vitro activity of imipenem/relebactam against MABc clinical isolates and to determine any in vitro synergism between imipenem/relebactam and other antimicrobials. A nationwide collection of 175 MABc clinical respiratory isolates obtained from 24 hospitals in Spain (August 2022-April 2023) was studied.

Broad spectrum of β-lactamase coverage and potent antimicrobial activity of xeruborbactam in combination with meropenem against carbapenemase-producing Enterobacterales, including strains resistant to new β-lactam/β-lactamase inhibitor combinations.

Xeruborbactam is a broad-spectrum boronate-type β-lactamase inhibitor. We aimed to evaluate its activity in combination with meropenem and compare it with other β-lactam/β-lactamase inhibitor combinations against Enterobacterales. The following isolates were screened: (i) an isogenic collection of 94 isolates producing β-lactamases under wild-type and low-permeability conditions, (ii) 300 genetically diverse clinical Enterobacterales isolates producing the three main carbapenemase types (KPC-like, OXA-48-like, and metallo-β-lactamases), and (iii) two collections of isolates producing mechanisms of resistance to β-lactam/β-lactamase inhibitor combinations, such as KPC variants or PBP3 insertions combined with metallo-β-lactamases (MBLs).

Nanopore full length 16S rRNA gene sequencing increases species resolution in bacterial biomarker discovery.

Discovery of disease-related bacterial biomarkers could be a useful approach for early prevention or diagnosis of various afflictions, such as colorectal cancer. This typically involves analyzing small regions of the 16S rRNA gene (e.g.

Engineering and Evaluation of a Live-Attenuated Vaccine Candidate with Enhanced Type 1 Fimbriae Expression to Optimize Protection Against Typhimurium.

Typhimurium is a major zoonotic pathogen, in which type 1 fimbriae play a crucial role in intestinal colonization and immune modulation. This study aimed to improve the protective immunity of a previously developed growth-deficient strain-a double auxotroph for D-glutamate and D-alanine-by engineering the inducible expression of type 1 fimbriae. : P-driven expression of the operon was achieved by λ-Red mutagenesis.

Functional and structural analyses of amino acid sequence variation in PDC β-lactamase reveal different mechanistic pathways toward cefiderocol resistance in .

A wide variety of clinically observed amino acid alterations in the chromosomal β-lactamase AmpC (-derived cephalosporinase [PDC]) are associated with increased resistance to cefepime, ceftolozane/tazobactam, or ceftazidime/avibactam, but their impact on cefiderocol resistance is unclear. We took advantage of a previously engineered collection of wild-type (PAO1) and iron uptake-deficient (PAO Δ) isolates producing 19 distinct PDC variants with substitutions in key catalytic regions. While most variants had moderate effects on cefiderocol minimum inhibitory concentrations compared to PDC-1, the E219K (Ω-loop) and L293P (helix H10) variants significantly affected cefiderocol activity.

The novel polymyxin analogue SPR206 exhibits higher activity than colistin against both colistin-susceptible and colistin-resistant strains of .

Colistin resistance is increasing globally and complicates treatments of infections. The next-generation polymyxin SPR206 shows potent activity against multidrug-resistant Gram-negative pathogens with low toxicity. SPR206 exhibited higher activity against colistin-susceptible and colistin-resistant strains (MIC/MIC = 0.

Effectiveness of oral step-down therapy and early oral switch for bloodstream infections caused by Enterobacterales: A post hoc emulation trial of the SIMPLIFY trial.

Objectives: We investigated the effectiveness of early oral switch for treating Enterobacterales bloodstream infection (BSI) by performing a post hoc emulation trial of the SIMPLIFY trial.

Methods: We conducted a post hoc analysis of a randomized controlled trial. We specified the target trial characteristics selecting patients who achieved clinical stability on day 5.

Rapid prediction of carbapenemases in by imipenem/relebactam and MALDI-TOF MS.

is a major nosocomial pathogen commonly involved in multidrug-resistant (MDR) infections that are very difficult to treat. Imipenem/relebactam is a new carbapenem/β-lactamase inhibitor combination with robust activity against . However, resistance is increasingly reported, and rapid detection is, therefore, crucial so that appropriate treatments can be prescribed.

Anti-inflammatory and antimicrobial efficacy of coconut oil for periodontal pathogens: a triple-blind randomized clinical trial.

Objectives: To evaluate the effect of coconut oil on the oral bacteriome and inflammatory response in patients with periodontitis by integrating next-generation sequencing analyses of pathogenic bacterial shifts and quantification of inflammatory markers, thereby assessing its potential as a natural adjunct to standard nonsurgical periodontal therapy.

Materials And Methods: A triple-blind clinical trial was conducted with 30 participants diagnosed with periodontitis, randomized into 3 groups: (1) coconut oil, (2) chlorhexidine and (3) placebo. Saliva and gingival crevicular fluid (GCF) samples were collected before treatment, one month after treatment, and one month post-non-surgical periodontal therapy.

Vaccine Development: Lessons, Challenges, and Future Innovations.

is an opportunistic pathogen with a multidrug-resistant profile that has become a critical threat to global public health. It is one of the main causes of severe nosocomial infections, including ventilator-associated pneumonia, chronic infections in patients with cystic fibrosis, and bloodstream infections in immunosuppressed individuals. Development of vaccines against is a major challenge owing to the high capacity of this bacterium to form biofilms, its wide arsenal of virulence factors (including secretion systems, lipopolysaccharides, and outer membrane proteins), and its ability to evade the host immune system.

Advancements in the fight against globally distributed OXA-48 carbapenemase: evaluating the new generation of carbapenemase inhibitors.

Carbapenemase OXA-48 and its variants pose a serious threat to the development of effective treatments for bacterial infections. OXA-48-producing Enterobacterales are the most prevalent carbapenemase-producing bacteria in large parts of the world. Although these bacteria exhibit low-level carbapenem resistance , the infections they cause are challenging to treat with conventional therapies, owing to their spread and complex detection in clinical settings.

Unravelling the mechanisms causing murepavadin resistance in : lipopolysaccharide alterations and its consequences.

Introduction: Murepavadin is an antimicrobial peptide (AMP) in clinical development that selectively targets LptD and whose resistance profile remains unknown. We aimed to explore genomic modifications and consequences underlying murepavadin and/or colistin susceptibility.

Methods: To define genomic mechanisms underlying resistance, we performed two approaches: 1) a genome-wide association study (GWAS) in a clinical collection (n=496), considering >0.

Analysis of high-molecular-weight proteins using MALDI-TOF MS and machine learning for the differentiation of clinically relevant Clostridioides difficile ribotypes.

Purpose: Clostridioides difficile is the main cause of antibiotic related diarrhea and some ribotypes (RT), such as RT027, RT181 or RT078, are considered high risk clones. A fast and reliable approach for C. difficile ribotyping is needed for a correct clinical approach.

Activity and resistance mechanisms of the third generation tetracyclines tigecycline, eravacycline and omadacycline against nationwide Spanish collections of carbapenemase-producing Enterobacterales and Acinetobacter baumannii.

Introduction: The rise in multidrug-resistant bacteria challenges clinical microbiology. Tigecycline, eravacycline, and omadacycline show promise against carbapenem-resistant Enterobacterales and Acinetobacter baumannii. This study evaluates their activity and resistance mechanisms.

Multicenter evaluation of Fourier transform infrared (FTIR) spectroscopy as a first-line typing tool for carbapenemase-producing in clinical settings.

Early use of infection control methods is critical for preventing the spread of antimicrobial resistance. Whole-genome sequencing (WGS) is considered the gold standard for investigating outbreaks; however, the turnaround time is usually too long for clinical decision-making and the method is also costly. The aim of this study was to evaluate the performance of Fourier transform infrared (FTIR) and artificial intelligence tools as a first-line typing tool for typing carbapenemase-producing (CPK) in the hospital setting.

Mutant prevention concentrations, resistance evolution dynamics, and mechanisms of resistance to imipenem and imipenem/relebactam in carbapenem-susceptible isolates showing ceftazidime/avibactam resistance.

carbapenemase (KPC) variants selected during ceftazidime/avibactam treatment usually develop susceptibility to carbapenems and carbapenem/β-lactamase inhibitors, such as imipenem and imipenem/relebactam. We analyzed imipenem and imipenem/relebactam single-step mutant frequencies, resistance development trajectories and differentially selected resistance mechanisms using two representative isolates that had developed ceftazidime/avibactam resistance during therapy (ST512/KPC-31 and ST258/KPC-35). Mutant frequencies and mutant prevention concentrations were measured in Mueller-Hinton agar plates containing incremental concentrations of imipenem or imipenem/relebactam.

emergence of resistance to ceftazidime/avibactam through modification of chromosomal AmpC β-lactamase in .

We describe the emergence of resistance to ceftazidime/avibactam via modification of AmpC in a clinical isolate during therapy with this combination. Paired ceftazidime/avibactam-susceptible/resistant isolates were obtained before and during ceftazidime/avibactam treatment. Whole genome sequencing revealed a differential mutation in AmpC (R148W) in the ceftazidime/avibactam-resistant isolate.

Impact of transferable β-lactamases and intrinsic AmpC amino acid substitutions on the activity of cefiderocol against wild-type and iron uptake-deficient mutants of Pseudomonas aeruginosa.

Objectives: We aimed to analyse the interplay between impaired iron uptake and β-lactamases on cefiderocol resistance in Pseudomonas aeruginosa.

Methods: Thirty-one transferable β-lactamases and 16 intrinsic P. aeruginosa AmpC (PDC) variants were cloned and expressed in wild-type (PAO1) and iron uptake-deficient (PAO ΔpiuC) P.

Native and non-native freshwater bivalves in the bioremediation of bacterial pollution caused by the disposal of sewage.

Treated sewage contains a large diversity of pathogens that can be transmitted to the environment and, directly or indirectly, infect humans through water use (i.e., consumption, bathing, or irrigation).

Impact of chromosomally encoded resistance mechanisms and transferable β-lactamases on the activity of cefiderocol and innovative β-lactam/β-lactamase inhibitor combinations against Pseudomonas aeruginosa.

Objectives: We aimed to compare the stability of the newly developed β-lactams (cefiderocol) and β-lactam/β-lactamase inhibitor combinations (ceftazidime/avibactam, ceftolozane/tazobactam, aztreonam/avibactam, cefepime/taniborbactam, cefepime/zidebactam, imipenem/relebactam, meropenem/vaborbactam, meropenem/nacubactam and meropenem/xeruborbactam) against the most clinically relevant mechanisms of mutational and transferable β-lactam resistance in Pseudomonas aeruginosa.

Methods: We screened a collection of 61 P. aeruginosa PAO1 derivatives.

Rapid and Simple Morphological Assay for Determination of Susceptibility/Resistance to Combined Ciprofloxacin and Ampicillin, Independently, in .

Current antibiograms cannot discern the particular effect of a specific antibiotic when the bacteria are incubated with a mixture of antibiotics. To prove that this task is achievable, strains were treated with ciprofloxacin for 45 min, immobilized on a slide and stained with SYBR Gold. In susceptible strains, the nucleoid relative surface started to decrease near the MIC, being progressively condensed as the dose increased.