Phenotypic Differentiation Within the ' Aminoglycoside Resistance Gene Family Suggests a Novel Subtype IV of Contemporary Clinical Relevance.

Background: Whole genome sequencing of clinical bacterial isolates holds promise in predicting their susceptibility to antibiotic therapy, based on a detailed understanding of the phenotypic manifestation of genotypic variation. The ' aminoglycoside acetyltransferase gene family is the most abundant aminoglycoside resistance determinant encountered in clinical practice. A variety of AAC(6') isozymes have been described, suggesting a phenotypic distinction between subtype I, conferring resistance to amikacin (AMK), and subtype II, conferring resistance to gentamicin (GEN) instead.

Model-informed drug development for antimicrobials: translational pharmacokinetic-pharmacodynamic modelling of apramycin to facilitate prediction of efficacious dose in complicated urinary tract infections.

Objectives: The use of mouse models of complicated urinary tract infection (cUTI) has usually been limited to a single timepoint assessment of bacterial burden. Based on longitudinal in vitro and in vivo data, we developed a pharmacokinetic-pharmacodynamic (PKPD) model to assess the efficacy of apramycin, a broad-spectrum aminoglycoside antibiotic, in mouse models of cUTI.

Methods: Two Escherichia coli strains were studied (EN591 and ATCC 700336).

Target Attainment and Population Pharmacokinetics of Cefazolin in Patients with Invasive Infections: A Prospective Cohort Study.

This study aimed to determine cefazolin target attainment in patients with invasive () infections and to develop a population pharmacokinetic (PK) model. Adult patients with invasive infections treated with cefazolin bolus infusions were included. Unbound and total trough and mid-dose cefazolin concentrations were measured, and strain-specific MICs were determined.

Synthesis and antibacterial action of 3',6'-disubstituted spectinomycins.

Spectinomycin is an aminocyclitol antibiotic with a unique ribosomal binding site. Prior synthetic modifications of spectinomycin have enhanced potency and antibacterial spectrum through addition at the 6'-position to produce trospectomycin and to the 3'-position to produce spectinamides and aminomethyl spectinomycins. This study focused on the design, synthesis, and evaluation of three 3',6'-disubstituted spectinomycin analogs: trospectinamide, N-benzyl linked aminomethyl, and N-ethylene linked aminomethyl trospectomycins.

Type IV-A3 CRISPR-Cas systems drive inter-plasmid conflicts by acquiring spacers in trans.

Plasmid-encoded type IV-A CRISPR-Cas systems lack an acquisition module, feature a DinG helicase instead of a nuclease, and form ribonucleoprotein complexes of unknown biological functions. Type IV-A3 systems are carried by conjugative plasmids that often harbor antibiotic-resistance genes and their CRISPR array contents suggest a role in mediating inter-plasmid conflicts, but this function remains unexplored. Here, we demonstrate that a plasmid-encoded type IV-A3 system co-opts the type I-E adaptation machinery from its host, Klebsiella pneumoniae (K.

Diphtheria in a Swiss Asylum Seeker Reception Centre: Outbreak Investigation and Evaluation of Testing and Vaccination Strategies.

To describe a suspected diphtheria outbreak in a Swiss asylum seeker reception centre, and to analyse its management response regarding testing and vaccination. We retrospectively analysed clinical, microbiology, and case management data of all asylum seekers tested for between 28th August and 31st December 2022 while residing at the centre. Results are reported descriptively.

Utilization of a Meningitis/Encephalitis PCR panel at the University Hospital Basel - a retrospective study to develop a diagnostic decision rule.

Background: The Biofire FilmArray Meningitis/Encephalitis (ME) PCR panel covers 14 viral, bacterial, and fungal pathogens and has been implemented in many institutions worldwide. Post-marketing studies indicate a reduced sensitivity and overutilization underscoring the need for a more targeted usage. The aim of our study is to describe the utilization of the ME panel and to develop a diagnostic-stewardship based decision rule.

Apramycin efficacy against carbapenem- and aminoglycoside-resistant Escherichia coli and Klebsiella pneumoniae in murine bloodstream infection models.

Background: The aminoglycoside apramycin has been proposed as a drug candidate for the treatment of critical Gram-negative systemic infections. However, the potential of apramycin in the treatment of drug-resistant bloodstream infections (BSIs) has not yet been assessed.

Methods: The resistance gene annotations of 40 888 blood-culture isolates were analysed.

Rapid detection of plasmid-mediated AmpC-producers by eazyplex® SuperBug AmpC assay compared to whole-genome sequencing.

Current methods for plasmid-mediated AmpC β-lactamase (pAmpC) detection in routine microbiological laboratories are based on various phenotypic tests. Eazyplex®SuperBug AmpC assay is a molecular assay based on isothermal amplification for rapid detection of the most common pAmpC types from bacterial culture: CMY-2 group, DHA, ACC and MOX. Our aim was to evaluate the diagnostic performance of this assay.

In vitro susceptibility of Neisseria gonorrhoeae to netilmicin and etimicin in comparison to gentamicin and other aminoglycosides.

Purpose: Single doses of gentamicin have demonstrated clinical efficacy in the treatment of urogenital gonorrhea, but lower cure rates for oropharyngeal and anorectal gonorrhea. Formulations selectively enriched in specific gentamicin C congeners have been proposed as a less toxic alternative to gentamicin, potentially permitting higher dosing to result in increased plasma exposures at the extragenital sites of infection. The purpose of the present study was to compare the antibacterial activity of individual gentamicin C congeners against Neisseria gonorrhoeae to that of other aminoglycoside antibiotics.

Experimental Determination of the p Values of Clinically Relevant Aminoglycoside Antibiotics: Toward Establishing p-Activity Relationships.

Investigating the relationship between individual p values and the efficacy of aminoglycosides is essential for the development of more effective and targeted therapies. In this work, we measured the p values for individual amino groups of the six clinically relevant aminoglycoside antibiotics gentamicin, tobramycin, amikacin, arbekacin, plazomicin, and apramycin using N-H heteronuclear multiple-bond correlation and H NMR experiments. For arbekacin and plazomicin, the p values are reported for the first time.

Phage Paride can kill dormant, antibiotic-tolerant cells of Pseudomonas aeruginosa by direct lytic replication.

Bacteriophages are ubiquitous viral predators that have primarily been studied using fast-growing laboratory cultures of their bacterial hosts. However, microbial life in nature is mostly in a slow- or non-growing, dormant state. Here, we show that diverse phages can infect deep-dormant bacteria and suspend their replication until the host resuscitates ("hibernation").

Cefepime versus carbapenems for treatment of AmpC beta-lactamase-producing Enterobacterales bloodstream infections.

Purpose: Cefepime is recommended for treating infections caused by AmpC beta-lactamase-producing Enterobacterales (AmpC-PE), though supporting evidence is limited. Therefore, this study compared outcomes associated with cefepime versus carbapenem therapy for bloodstream infections (BSIs) caused by AmpC-PE after phenotypic exclusion of ESBL-co-producing isolates.

Methods: This retrospective cohort study compared definite cefepime versus carbapenem treatment for AmpC-PE BSI in hospitalized patients of the University Hospital Basel, Switzerland, between 01/2015 and 07/2020.

Whole genomes from bacteria collected at diagnostic units around the world 2020.

The Two Weeks in the World research project has resulted in a dataset of 3087 clinically relevant bacterial genomes with pertaining metadata, collected from 59 diagnostic units in 35 countries around the world during 2020. A relational database is available with metadata and summary data from selected bioinformatic analysis, such as species prediction and identification of acquired resistance genes.

A systematic outbreak investigation of SARS-CoV-2 transmission clusters in a tertiary academic care center.

Background: We sought to decipher transmission pathways in healthcare-associated infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within our hospital by epidemiological work-up and complementary whole genome sequencing (WGS). We report the findings of the four largest epidemiologic clusters of SARS-CoV-2 transmission occurring during the second wave of the pandemic from 11/2020 to 12/2020.

Methods: At the University Hospital Basel, Switzerland, systematic outbreak investigation is initiated at detection of any nosocomial case of SARS-CoV-2 infection, as confirmed by polymerase chain reaction, occurring more than five days after admission.

Automatic Discrimination of Species within the Enterobacter cloacae Complex Using Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry and Supervised Algorithms.

The Enterobacter cloacae complex (ECC) encompasses heterogeneous clusters of species that have been associated with nosocomial outbreaks. These species may have different acquired antimicrobial resistance and virulence mechanisms, and their identification is challenging. This study aims to develop predictive models based on matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) profiles and machine learning for species-level identification.

PorinPredict: Identification of OprD Loss from WGS Data for Improved Genotype-Phenotype Predictions of P. aeruginosa Carbapenem Resistance.

The increasing integration of genomics into routine clinical diagnostics requires reliable computational tools to identify determinants of antimicrobial resistance (AMR) from whole-genome sequencing data. Here, we developed PorinPredict, a bioinformatic tool that predicts defects of the Pseudomonas aeruginosa outer membrane porin OprD, which are strongly associated with reduced carbapenem susceptibility. PorinPredict relies on a database of intact OprD variants and reports inactivating mutations in the coding or promoter region.

Nosocomial outbreak of vancomycin-resistant (VRE) ST796, Switzerland, 2017 to 2020.

A large clonal outbreak caused by vancomycin-resistant (VRE) affected the Bern University Hospital group from the end of December 2017 until July 2020. We describe the characteristics of the outbreak and the bundle of infection prevention and control (IPC) measures implemented. The outbreak was first recognised when two concomitant cases of VRE bloodstream infection were identified on the oncology ward.

Aerococcus urinae - significance of detection in the paediatric urinary tract: a case series.

Aerococcus urinae (A. urinae) is primarily recognized as a common pathogen in the geriatric population, causing urinary tract infection (UTI), sepsis, and endocarditis, predominantly in female patients. In the paediatric population, only a few case reports exist suggesting A.

Swiss public health measures associated with reduced SARS-CoV-2 transmission using genome data.

Genome sequences from evolving infectious pathogens allow quantification of case introductions and local transmission dynamics. We sequenced 11,357 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from Switzerland in 2020-the sixth largest effort globally. Using a representative subset of these data, we estimated viral introductions to Switzerland and their persistence over the course of 2020.