- Volume 74, Issue 2, 2025

Metagenomics is increasingly used for diagnosis in hospital settings. It is useful particularly in cases of unknown aetiology, where novel or difficult-to-diagnose pathogens are suspected, and/or following unexplained disease outbreaks. In this paper, we present three use cases that draw on existing reports: one involving a patient in intensive care with encephalitis of unknown aetiology; a second case with likely infection with drug-resistant Klebsiella pneumoniae and an incidental finding of unknown relevance; and a third case situated in an unexplained outbreak of acute hepatitis in children, with severe outcomes due to co-infection. We examine each case in turn, highlighting ethical questions arising in relation to clinical issues including: disclosure to patients of untreatable disease, cost-effectiveness, the value of resistance testing, sensitivity and specificity, uncertain or unexpected findings, patient consent and data sharing. We conclude by proposing recommendations for further research and developing particular pieces of guidance to improve clinical uses of metagenomics for diagnosis.

RNA interference regulates gene expression by selectively silencing target genes through the introduction of small RNA molecules, such as microRNA, small interfering RNA and short hairpin RNA. These molecules offer significant therapeutic potential for diverse human ailments like cancer, viral infections and neurodegenerative disorders. Whilst non-viral vectors like nanoparticles have been extensively explored for delivering these RNAs, viral vectors, with superior specificity and delivery efficiency, remain less studied. This review examines current viral vectors for small RNA delivery, focusing on design strategies and characteristics. It compares the advantages and drawbacks of each vector, aiding readers in selecting the optimal one for small RNA delivery.

Introduction. Urinary tract infections (UTIs) are associated with a high burden of morbidity, mortality and cost. Pseudomonas aeruginosa employs a myriad of virulence factors, including biofilm formation and motility mechanisms, to cause infections including persistent UTIs. P. aeruginosa is highly resistant to antibiotics, and the World Health Organization has identified it as a pathogen for which novel antimicrobials are urgently required.

Gap statement. Genotypic and phenotypic characterization of P. aeruginosa from UTIs is underreported. In addition, the rise of antimicrobial resistance (AMR) is a cause for concern, particularly in many countries where surveillance is severely lacking.

Aim. To identify genotypic and phenotypic characteristics of P. aeruginosa UTI isolates sourced from the UK and the state of Kuwait, with an emphasis on genotypic diversity and AMR.

Methods. Twenty-three P. aeruginosa UTI isolates were sourced from the UK and Kuwait. To establish the phenotypes of UK isolates, growth analysis, biofilm formation assays, motility assays and antibiotic disc diffusion assays were performed. Whole-genome sequencing, antimicrobial susceptibility assays and in silico detection of AMR-associated genes were conducted on both sets of isolates.

Results. In terms of their phenotypic characteristics and genomic composition, the UTI isolates varied. Multiple resistance genes are associated with resistance to various classes of antibiotics, such as aminoglycosides, fluoroquinolones and β-lactams, particularly in isolates from Kuwait. Extreme antibiotic resistance was detected in the isolates obtained from Kuwait, indicating that the country may be an antibiotic resistance hotspot.

Conclusion. This study highlights that isolates from UTIs are diverse and can display extremely high resistance. Surveillance in countries such as Kuwait is currently limited, and this study suggests the need for greater surveillance.

Introduction. Carbapenems are usually employed as first-line antimicrobials against bacteria harbouring extended-spectrum beta-lactamases (ESBLs). These enzymes confer resistance often to multiple classes of antimicrobials.

Hypothesis/Gap Statement. This indiscriminate use of carbapenems and the inevitable development of carbapenem resistance have prompted the need for carbapenem-sparing strategies.

Methodology. The non-carbapenem antimicrobial susceptibility patterns of 60 ESBL-producing Enterobacterales (ESBL-PE) isolates responsible for bloodstream infections, in 2022–2023 inclusive, processed at our institution were reviewed.

Results. The non-carbapenem antimicrobial susceptibility patterns of 60 ESBL-PE isolates from bloodstream infections during the study period were determined. Escherichia coli was the most common species isolated (87%, n=52), with the majority of cases (73.3%, n=44) originating from a presumed urinary source. Temocillin (TMC), mecillinam (MEC), cefiderocol (FDC), amikacin and fosfomycin (FOS) displayed excellent activity against all ESBL-PE isolates tested, with susceptibility rates of≥85%. Ciprofloxacin and amoxicillin–clavulanic acid were the least efficacious agents, with susceptibility rates≤20%.

Conclusions. TMC, MEC, FDC and FOS offer promising alternatives to carbapenems, demonstrating efficacy against ESBL-PE. The use of these agents not only broadens the therapeutic arsenal against ESBL-PE but also mitigates the potential for escalating carbapenem resistance, especially in regions where the incidence of carbapenem resistance is increasing.