Efficacy of high doses of intravenous fosfomycin for treatment of urinary tract infection caused by KPC carbapenemase-producing Klebsiella pneumoniae. An observational study.

Objectives: To evaluate the efficacy of high-dose intravenous fosfomycin for the treatment of urinary tract infections (UTI) caused by KPC carbapenemase-producing Klebsiella pneumoniae (KPC-Kp). A secondary objective was to evaluate the impact of the results of fosfomycin susceptibility testing on prognosis.

Methods: This is an observational and retrospective study.

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.

Real-World Experience of Imipenem-Relebactam Treatment as Salvage Therapy in Difficult-to-Treat Pseudomonas aeruginosa Infections (IMRECOR Study).

Introduction: Difficult-to-treat-resistant (DTR) infections caused by Pseudomonas aeruginosa represent a global public health threat, prioritizing the search and development of new antibiotics for this microorganism.

Methods: We present the real-life experience of the compassionate use of imipenem/cilastatin/relebactam in a descriptive study involving 14 patients with DTR-P. aeruginosa infection and limited treatment options.

Porin expression in clinical isolates of Klebsiella pneumoniae: a comparison of SDS-PAGE and MALDI-TOF/MS and limitations of whole genome sequencing analysis.

Background: The permeability of the outer membrane barrier modulates the susceptibility of microorganisms to antimicrobial agents. Loss or structural alterations of porins contribute to decreased antibiotic concentration of multiple antimicrobial agents. Precise definition of porin profiles is of critical importance to understand the role of porins in antimicrobial resistance.

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.

Long-Term Clinical and Ecological Impact of an Antimicrobial Stewardship Program on the Incidence of Carbapenem-Resistant Infections in a High-Endemic Hospital.

Carbapenem-resistant (CR-Kp) is currently a serious global concern. Antimicrobial stewardship programs (ASPs) are one of the key strategies to overcome this resistance. However, evidence about the long-term clinical and ecological impacts of ASPs is scarce.

Genetic background of aminoglycoside-modifying enzymes in various genetic lineages of clinical aminoglycosides-resistant E. coli and K. pneumoniae isolates in Tunisia.

Aims: This study was conducted to evaluate the in vitro activity of clinically relevant aminoglycosides and to determine the prevalence of genes encoding aminoglycoside modifying enzymes (AMEs) and 16S ribosomal RNA (rRNA) methyltransferases among aminoglycoside-resistant E. coli (n = 61) and K. pneumoniae (n = 44) clinical isolates.

Probing Quantum Efficiency: Exploring System Hardness in Electronic Ground State Energy Estimation.

We consider the question of how correlated the system hardness is between classical algorithms of electronic structure theory in ground state estimation and quantum algorithms. To define the system hardness for classical algorithms, we employ empirical criterion based on the deviation of electronic energies produced by coupled cluster and configuration interaction methods from the exact ones along multiple bonds dissociation in a set of molecular systems. For quantum algorithms, we have selected the Variational Quantum Eigensolver (VQE) and Quantum Phase Estimation (QPE) methods.

Synthesis of Novel Triazine-Based Chalcones and 8,9-dihydro-7-pyrimido[4,5-][1,4]diazepines as Potential Leads in the Search of Anticancer, Antibacterial and Antifungal Agents.

This study presents the synthesis of four series of novel hybrid chalcones ()- and ()- and six series of 1,3,5-triazine-based pyrimido[4,5-][1,4]diazepines (-)- and the evaluation of their anticancer, antibacterial, antifungal, and cytotoxic properties. Chalcones ,, ,, ,-, - and the pyrimido[4,5-][1,4]diazepines ,, , ,,-, ,,- exhibited outstanding anticancer activity against a panel of 60 cancer cell lines with GI values between 0.01 and 100 μM and LC values in the range of 4.

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.

Corrigendum: CARB-ES-19 multicenter study of carbapenemase-producing and from all Spanish provinces reveals interregional spread of high-risk clones such as ST307/OXA-48 and ST512/KPC-3.

[This corrects the article DOI: 10.3389/fmicb.2022.

Heteroresistance to colistin in wild-type isolates from clinical origin.

Colistin is one of the last remaining therapeutic options for dealing with Enterobacteriaceae. Unfortunately, heteroresistance to colistin is also rapidly increasing. We described the prevalence of colistin heteroresistance in a variety of wild-type strains of and the evolution of these strains with colistin heteroresistance to a resistant phenotype after colistin exposure and withdrawal.

Untargeted metagenomic sequencing identifies Toscana virus in patients with idiopathic meningitis, southern Spain, 2015 to 2019.

BackgroundVarious pathogens, including bacteria, fungi, parasites, and viruses can lead to meningitis. Among viruses causing meningitis, Toscana virus (TOSV), a phlebovirus, is transmitted through sandfly bites. TOSV infection may be suspected if patients with enterovirus- and herpesvirus-negative aseptic (non-bacterial) meningitis recall recent insect bites.

antibiotic susceptibility profiles, genomic epidemiology and resistance mechanisms: a nation-wide five-year time lapse analysis.

Background: healthcare-associated infections are one of the top antimicrobial resistance threats world-wide. In order to analyze the current trends, we performed a Spanish nation-wide high-resolution analysis of the susceptibility profiles, the genomic epidemiology and the resistome of over a five-year time lapse.

Methods: A total of 3.

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.

Heteroresistance to Colistin in Clinical Isolates of Producing OXA-48.

Heteroresistance to colistin can be defined as the presence of resistant subpopulations in an isolate that is susceptible to this antibiotic. Colistin resistance in Gram-negative bacteria is more frequently related to chromosomal mutations and insertions. This work aimed to study heteroresistance in nine clinical isolates of producing OXA-48 and to describe genomic changes in mutants with acquired resistance in vitro.

Real-life use of cefiderocol for salvage therapy of severe infections due to carbapenem-resistant Gram-negative bacteria.

Treatment of infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) is challenging and new active antibiotics are needed urgently. This study describes the efficacy and safety of cefiderocol in a retrospective series of 13 patients with severe CR-GNB infection and limited treatment options. Pseudomonas aeruginosa was the predominant CR-GNB (n=8), followed by Burkholderia cepacia (n=3), Sthenotrophomona maltophilia (n=1) and KPC-producing Klebsiella pneumoniae (n=1).

Efficacy of ceftazidime-avibactam in solid organ transplant recipients with bloodstream infections caused by carbapenemase-producing Klebsiella pneumoniae.

We aimed to compare the efficacy of ceftazidime-avibactam (CAZ-AVI) versus the best available therapy (BAT) in solid organ transplant (SOT) recipients with bloodstream infection caused by carbapenemase-producing Klebsiella pneumoniae (CPKP-BSI). A retrospective (2016-2021) observational cohort study was performed in 14 INCREMENT-SOT centers (ClinicalTrials.gov identifier: NCT02852902; Impact of Specific Antimicrobials and MIC Values on the Outcome of Bloodstream Infections Due to ESBL- or Carbapenemase-producing Enterobacterales in Solid Organ Transplantation: an Observational Multinational Study).

Proteomic Study of the Interactions between Phages and the Bacterial Host .

Phages and bacteria have acquired resistance mechanisms for protection. In this context, the aims of the present study were to analyze the proteins isolated from 21 novel lytic phages of Klebsiella pneumoniae in search of defense mechanisms against bacteria and also to determine the infective capacity of the phages. A proteomic study was also conducted to investigate the defense mechanisms of two clinical isolates of K.

Outcomes of octogenarians and nonagenarians with Pseudomonas aeruginosa bacteremia: a multicenter retrospective study.

Background: P. aeruginosa bacteremia is a common and severe infection carrying high mortality in older adults. We aimed to evaluate outcomes of P.

Executive summary of the consensus document of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) on the diagnosis and antimicrobial treatment of infections due to carbapenem-resistant Gram-negative bacteria.

Infections caused by multidrug resistant Gram-negative bacteria are becoming a worldwide problem due to their increasing incidence and associated high mortality. Carbapenem-resistant bacteria such as Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii are the most important in clinical practice. The objective of these guidelines is to update the recommendations for the diagnosis and treatment of infections caused by these multidrug resistant bacteria.