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.

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.

Novel Penicillin-Based Sulfone-Siderophore Conjugates for Restoring β-Lactam Antibiotic Efficacy.

Membrane permeability is a natural defense barrier that contributes to increased bacterial drug resistance, particularly for Gram-negative pathogens. As such, accurate delivery of the antibacterial agent to the target has become a growing research area in the infectious diseases field as a means of improving drug efficacy. Although the efficient transport of siderophore-antibiotic conjugates into the cytosol still remains challenging, great success has been achieved in the delivery of β-lactam antibiotics into the periplasmic space via bacterial iron uptake pathways.

Epidemiology, resistance genomics and susceptibility of species: results from the 2020 Spanish nationwide surveillance study.

BackgroundAs increasing antibiotic resistance in poses a global healthcare challenge, understanding its evolution is crucial for effective control strategies.AimWe aimed to evaluate the epidemiology, antimicrobial susceptibility and main resistance mechanisms of spp. in Spain in 2020, and to explore temporal trends of .

In vitro development of imipenem/relebactam resistance in KPC-producing Klebsiella pneumoniae involves multiple mutations including OmpK36 disruption and KPC modification.

Objectives: In order to inform and anticipate potential strategies aimed at combating KPC-producing Klebsiella pneumoniae infections, we analysed imipenem/relebactam and ceftazidime/avibactam single-step mutant frequencies, resistance development trajectories, differentially selected resistance mechanisms and their associated fitness cost using four representative high-risk K. pneumoniae clones.

Methods: Mutant frequencies and mutant preventive concentrations were determined using agar plates containing incremental concentrations of β-lactam/β-lactamase inhibitor.

Interplay between OXA-10 β-Lactamase Production and Low Outer-Membrane Permeability in Carbapenem Resistance in Enterobacterales.

The OXA-10 class D β-lactamase has been reported to contribute to carbapenem resistance in non-fermenting Gram-negative bacilli; however, its contribution to carbapenem resistance in Enterobacterales is unknown. In this work, minimum inhibitory concentrations (MICs), whole genome sequencing (WGS), cloning experiments, kinetic assays, molecular modelling studies, and biochemical assays for carbapenemase detection were performed to determine the impact of OXA-10 production on carbapenem resistance in two XDR clinical isolates of with the carbapenem resistance phenotype (ertapenem resistance). WGS identified the two clinical isolates as belonging to ST57 in close genomic proximity to each other.

Direct Detection of Carbapenemase-Producing Klebsiella pneumoniae by MALDI-TOF Analysis of Full Spectra Applying Machine Learning.

MALDI-TOF MS is considered to be an important tool for the future development of rapid microbiological techniques. We propose the application of MALDI-TOF MS as a dual technique for the identification of bacteria and the detection of resistance, with no extra hands-on procedures. We have developed a machine learning approach that uses the random forest algorithm for the direct prediction of carbapenemase-producing Klebsiella pneumoniae (CPK) isolates, based on the spectra of complete cells.

Antimicrobial Activity of Cefiderocol against the Carbapenemase-Producing Enterobacter cloacae Complex and Characterization of Reduced Susceptibility Associated with Metallo-β-Lactamase VIM-1.

Emergence of cefiderocol resistance among carbapenemase-producing Enterobacterales, particularly those in the Enterobacter cloacae complex (ECC), is becoming of alarming concern; however, the mechanistic basis of this phenomenon remains poorly understood. We describe the acquisition of VIM-1-mediated reduced cefiderocol susceptibility (MICs 0.5 to 4 mg/L) in a collection of 54 carbapenemase-producing isolates belonging to the ECC.

Simultaneous and divergent evolution of resistance to cephalosporin/β-lactamase inhibitor combinations and imipenem/relebactam following ceftazidime/avibactam treatment of MDR Pseudomonas aeruginosa infections.

Objectives: To describe and characterize the emergence of resistance to ceftolozane/tazobactam, ceftazidime/avibactam and imipenem/relebactam in a patient receiving ceftazidime/avibactam treatment for an MDR Pseudomonas aeruginosa CNS infection.

Methods: One baseline (PA1) and two post-exposure (PA2 and PA3) isolates obtained before and during treatment of a nosocomial P. aeruginosa meningoventriculitis were evaluated.

Cross-Protection against Acute Lung Infection in Mice by a D-Glutamate Auxotrophic Vaccine Candidate.

is regarded as a threatening bacterial pathogen causing invasive pneumonia in healthcare settings and in the community. The continuous emergence of multidrug resistant strains is narrowing the treatment options for these infections. The development of an effective vaccine is, therefore, a global priority.

Activity of aztreonam in combination with novel β-lactamase inhibitors against metallo-β-lactamase-producing Enterobacterales from Spain.

Metallo-β-lactamase (MBL)-producing Enterobacterales are of particular concern because they are widely disseminated and difficult to treat, being resistant to almost all β-lactam antibiotics. Aztreonam is not hydrolysed by MBLs but is labile to serine β-lactamases (SBLs), which are usually co-produced by MBL-producing Enterobacterales. This study investigated the activity of aztreonam in combination with novel β-lactamase inhibitors (BLIs) against a national multi-centre study collection of strains co-producing MBLs and SBLs.

Activity of cefiderocol, imipenem/relebactam, cefepime/taniborbactam and cefepime/zidebactam against ceftolozane/tazobactam- and ceftazidime/avibactam-resistant Pseudomonas aeruginosa.

Objectives: To evaluate the activity of cefiderocol, imipenem/relebactam, cefepime/taniborbactam and cefepime/zidebactam against a clinical and laboratory collection of ceftolozane/tazobactam- and ceftazidime/avibactam-resistant Pseudomonas aeruginosa β-lactamase mutants.

Methods: The activity of cefiderocol, imipenem/relebactam, cefepime/taniborbactam, cefepime/zidebactam and comparators was evaluated against a collection of 30 molecularly characterized ceftolozane/tazobactam- and/or ceftazidime/avibactam-resistant P. aeruginosa isolates from patients previously treated with cephalosporins.

Antimicrobial Diterpene Alkaloids from an Sponge Collected in the Yucatán Peninsula.

Three new diterpene alkaloids, (+)-8-epiagelasine T (), (+)-10-epiagelasine B (), and (+)-12-hydroxyagelasidine C (), along with three known compounds, (+)--agelasine F (), (+)-agelasine B (), and (+)-agelasidine C (), were isolated from the sponge , collected on the coasts of the Yucatán Peninsula (Mexico). Their chemical structures were elucidated by 1D and 2D NMR spectroscopy, HRESIMS techniques, and a comparison with literature data. Although the synthesis of (+)--agelasine F () has been previously reported, this is the first time that it was isolated as a natural product.

Carbapenem Resistance in Acinetobacter nosocomialis and Acinetobacter junii Conferred by Acquisition of and Genetic Characterization of the Transmission Mechanism between Acinetobacter Genomic Species.

Carbapenem resistance is increasing among Gram-negative bacteria, including the genus Acinetobacter. This study aimed to characterize, for the first time, the development of carbapenem resistance in clinical isolates of Acinetobacter junii and Acinetobacter nosocomialis conferred by the acquisition of a plasmid-borne gene and also to characterize the dissemination of this gene between species of Acinetobacter. Carbapenem-resistant A.

Selection of AmpC β-Lactamase Variants and Metallo-β-Lactamases Leading to Ceftolozane/Tazobactam and Ceftazidime/Avibactam Resistance during Treatment of MDR/XDR Pseudomonas aeruginosa Infections.

Infections caused by ceftolozane-tazobactam and ceftazidime-avibactam-resistant P. aeruginosa infections are an emerging concern. We aimed to analyze the underlying ceftolozane-tazobactam and ceftazidime-avibactam resistance mechanisms in all multidrug-resistant or extensively drug-resistant (MDR/XDR) P.

Emergence of 16S rRNA methyltransferases among carbapenemase-producing Enterobacterales in Spain studied by whole-genome sequencing.

The emergence of 16S rRNA methyltransferases (RMTs) in Gram-negative pathogens bearing other clinically relevant resistance mechanisms, such as carbapenemase-producing Enterobacterales (CPE), is becoming an alarming concern. We investigated the prevalence, antimicrobial susceptibility, resistance mechanisms, molecular epidemiology and genetic support of RMTs in CPE isolates from Spain. This study included a collection of 468 CPE isolates recovered during 2018 from 32 participating Spanish hospitals.