An Antibiotic Stewardship Program in Pancreatic Surgery.

Importance: Antimicrobial stewardship (AMS) programs optimize antibiotic use and mitigate antimicrobial resistance. The literature on the efficacy of AMS programs in pancreatic surgery is limited.

Objective: To investigate the association of a multifaceted AMS intervention targeting surgical antibiotic prophylaxis (SAP) with the rate of surgical site infections (SSIs) following pancreatic surgery.

Exploring the anticancer properties of indenyl and allyl palladates through their interaction with nucleic acids.

In this work, we analyse the mechanistic features of the interaction of indenyl (1-Ind) and allyl (2-All) palladates with nucleic acids (NAs) such as DNA (natural, poly(dA)-poly(dT) and poly(dG)-poly(dC)), RNA (in double and triple helices) and non-canonical structures of DNA (G-quadruplex and i-motif). Spectrophotometric titrations under different temperature and salt content conditions, viscosimetric experiments, fluorescent intercalator displacement (FID) tests together with theoretical Density Functional Theory (DFT)/Docking calculations are used to enlighten the complicated features of the interaction. The binding occurs in the grooves of the polynucleotides and is dominated by the geometrical features of the NA.

Evaluation of QuickMIC system for rapid antimicrobial susceptibility testing of Gram-negative pathogens from positive blood cultures, including strains producing extended-spectrum β-lactamases and carbapenemases.

The accuracy and turnaround time (TAT) of the QuickMIC system (QMIC) for rapid antimicrobial susceptibility testing (AST) of Gram-negative pathogens from positive blood cultures were evaluated, in comparison with a standard-of-care workflow based on culture and AST with broth microdilution. Essential agreement (EA) and bias were evaluated according to the ISO 20776-2:2021, category agreement (CA), categorical overestimation (CO), and underestimation (CU) rates were evaluated according to the European Committee on Antimicrobial Susceptibility Testing(EUCAST) breakpoints, and major discrepancy (MD) and very major discrepancy (VMD) rates were evaluated according to the Food and Drug Administration (FDA) guidelines and breakpoints. QMIC yielded evaluable data for 103/118 blood cultures (87.

Next-generation diagnostics of bloodstream infections enabled by rapid whole-genome sequencing of bacterial cells purified from blood cultures.

Background: Blood culture (BC) remains the cornerstone for diagnosis of bloodstream infections (BSI), but the long turn-around time (TAT) hampers timely selection of appropriate chemotherapy. Novel molecular approaches have been developed to provide faster results but are also affected by limitations. We developed a analytical workflow named LC-WGS (Whole-Genome Sequencing of Liquid Colony) for rapid whole-genome sequencing-based diagnosis of BSI, evaluating its accuracy performance over standard of care (SoC) diagnostic procedures.

Evaluation of the Vitek® Reveal™ system for rapid antimicrobial susceptibility testing of Gram-negative pathogens, including ESBL, CRE and CRAB, from positive blood cultures.

Blood culture (BC) remains the reference diagnostic tool for bloodstream infections but is hampered by long turn-around time (TAT). This study evaluated the Vitek® Reveal™ (VR) system for rapid antimicrobial susceptibility testing (AST) with 72 cases of monomicrobial BCs (55 Enterobacterales, 12 Pseudomonas aeruginosa and 5 Acinetobacter baumannii), including isolates producing carbapenemases and/or extended-spectrum β-lactamases. VR returned AST results with a mean TAT of 5.

Evaluation of Quantamatrix dRAST system for rapid antimicrobial susceptibility testing of bacterial isolates from positive blood cultures, in comparison with commercial Micronaut broth microdilution system.

Antimicrobial susceptibility testing (AST) from blood culture (BC) may take several days, limiting the eventual impact on antimicrobial stewardship. Hence, rapid AST systems represent a valuable support in shorting the time-to-response. In this work, the Quantamatrix dRAST system (dRAST) was evaluated for rapid AST on 100 monomicrobial BCs (50 Gram-negatives and 50 Gram-positives), including several isolates with clinically relevant resistance mechanisms.

Evaluation of two commercial broth microdilution systems for dalbavancin susceptibility testing of methicillin-resistant Staphylococcus aureus and other resistant Gram-positive cocci.

Objectives: This study aims to evaluate two commercial broth microdilution (BMD) systems, E1-185-100 (Merlin) and FDANDPF (ThermoFisher), for dalbavancin susceptibility testing in comparison with reference BMD assay.

Methods: Study collection was composed of 200 non-replicate multidrug-resistant Gram-positive cocci of clinical origin, including 180 methicillin-resistant Staphylococcus aureus, 10 vancomycin-resistant enterococci, seven linezolid-resistant Staphylococcus epidermidis, and three methicillin-resistant coagulase-negative staphylococci. S.

Evaluation of the Liquid Colony™ Produced by the FAST System for Shortening the Time of Bacterial Identification and Phenotypic Antimicrobial Susceptibility Testing and Detection of Resistance Mechanisms from Positive Blood Cultures.

Background: the aim of this study was to evaluate the performance of the Liquid Colony™ (LC) generated directly from positive blood cultures (PBCs) by the FAST System (Qvella, Richmond Hill, ON, Canada) for rapid identification (ID) and antimicrobial susceptibility testing (AST) compared with the standard of care (SOC) workflow.

Methods: Anonymized PBCs were processed in parallel by the FAST System and FAST PBC Prep cartridge (35 min runtime) and SOC. ID was performed by MALDI-ToF mass spectrometry (Bruker, Billerica, MA, USA).

Performance evaluation of the UMIC® Cefiderocol to determine MIC in Gram-negative bacteria.

Background: Cefiderocol is a catechol-substituted cephalosporin with potent in vitro activity against carbapenem-resistant (CR) Gram-negative bacteria (GNB). Cefiderocol susceptibility testing is complex because iron concentrations need to be taken into consideration. Here, we assessed the clinical performance of Bruker's UMIC® Cefiderocol and corresponding iron-depleted CAMHB to determine MIC by broth microdilution (BMD) for clinically relevant GNB.

Up-regulation of resident chromosomal fosB gene expression: a novel mechanism of acquired fosfomycin resistance in MRSA.

Objectives: This study investigated fosfomycin susceptibility and mechanisms of resistance in a collection of 99 Staphylococcus aureus isolated from cases of hospital-acquired pneumonia, previously collected from a multicentre survey carried out in Italy.

Methods: Fosfomycin susceptibility was tested by reference agar dilution. Bioinformatic and gene expression analysis, mutant selection experiments and WGS were executed to characterize fosfomycin resistance mechanisms.

Editorial: Special Issue "Molecular Epidemiology of Antimicrobial Resistance".

Antimicrobial resistance and multidrug-resistant organisms currently constitute a severe public health problem [...

Treatment and diagnosis of severe KPC-producing infections: a perspective on what has changed over last decades.

Antimicrobial resistance is a global health threat. Among Gram-negative bacteria, resistance to carbapenems, a class of β-lactam antibiotics, is usually a proxy for difficult-to-treat resistance, since carbapenem-resistant organisms are often resistant to many classes of antibiotics. Carbapenem resistance in the Gram-negative pathogen is mostly due to the production of carbapenemases, enzymes able to hydrolyze carbapenems, and carbapenemase (KPC)-type enzymes are overall the most prevalent carbapenemases in .

Deciphering variable resistance to novel carbapenem-based β-lactamase inhibitor combinations in a multi-clonal outbreak caused by Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae resistant to ceftazidime/avibactam.

Objectives: Carbapenemase-producing Enterobacterales represent a major cause of difficult-to-treat infections world-wide. Novel β-lactam/β-lactamase inhibitor combinations, including ceftazidime/avibactam (CZA), meropenem/vaborbactam (MVB), and imipenem/relebactam (IMR), represented a break-through in the treatment of some carbapenemase-producing Enterobacterales infections. However, acquired resistance to these agents has been reported in Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales.

Nosocomial outbreak by NDM-1-producing highly resistant to cefiderocol, Florence, Italy, August 2021 to June 2022.

A nosocomial outbreak by cefiderocol (FDC)-resistant NDM-1-producing (NDM-Kp) occurred in a large tertiary care hospital from August 2021-June 2022 in Florence, Italy, an area where NDM-Kp strains have become endemic. Retrospective analysis of NDM-Kp from cases observed in January 2021-June 2022 revealed that 21/52 were FDC-resistant. The outbreak was mostly sustained by clonal expansion of a mutant with inactivated siderophore receptor gene, which exhibited high-level resistance to FDC (MIC ≥ 32 mg/L) and spread independently of FDC exposure.

Recurrent emergence of carbapenem resistance mediated by an inhibitory mRNA secondary structure.

Outer membrane porins in Gram-negative bacteria facilitate antibiotic influx. In , modifications in the porin OmpK36 are implicated in increasing resistance to carbapenems. An analysis of large genome collections, encompassing major healthcare-associated clones, revealed the recurrent emergence of a synonymous cytosine-to-thymine transition at position 25 (25c > t) in We show that the 25c > t transition increases carbapenem resistance through depletion of OmpK36 from the outer membrane.

Effectiveness of a Multifaced Antibiotic Stewardship Program: A Pre-Post Study in Seven Italian ICUs.

Multidrug resistance has become a serious threat for health, particularly in hospital-acquired infections. To improve patients’ safety and outcomes while maintaining the efficacy of antimicrobials, complex interventions are needed involving infection control and appropriate pharmacological treatments in antibiotic stewardship programs. We conducted a multicenter pre-post study to assess the impact of a stewardship program in seven Italian intensive care units (ICUs).

Clinical and microbiological features of ceftolozane/tazobactam-resistant Pseudomonas aeruginosa isolates in a university hospital in central Italy.

Objectives: Ceftolozane/tazobactam (C/T) is a novel cephalosporin and β-lactamase inhibitor combination with great activity against Pseudomonas aeruginosa. To assess P. aeruginosa susceptibility to C/T, a surveillance study was conducted from October 2018 to March 2019 at the University Hospital 'Ospedali Riuniti' in Ancona, Italy.

Widespread emergence of OmpK36 loop 3 insertions among multidrug-resistant clones of Klebsiella pneumoniae.

Mutations in outer membrane porins act in synergy with carbapenemase enzymes to increase carbapenem resistance in the important nosocomial pathogen, Klebsiella pneumoniae (KP). A key example is a di-amino acid insertion, Glycine-Aspartate (GD), in the extracellular loop 3 (L3) region of OmpK36 which constricts the pore and restricts entry of carbapenems into the bacterial cell. Here we combined genomic and experimental approaches to characterise the diversity, spread and impact of different L3 insertion types in OmpK36.