Clinical Microbiology and Infection最新文献

Background: Rapid advances in microbiome science have sparked clinical and commercial enthusiasm for interventions, yet translation into practice risks outpacing both mechanistic understanding and the infrastructure required for safe adoption.

Objectives: To outline a coordinated research, clinical, social, and policy agenda for advancing safe, effective, and equitable microbiome-based interventions.

Sources: We convened an interdisciplinary Royal Society-funded expert workshop (Leeds, UK, October 2024) with international leaders in microbiome science, clinical trials, regulation, and social science. Thematic analysis of workshop discussions and written contributions identified priority domains for translation.

Content: Three intersecting priorities emerged: scientific credibility, practical viability, and stakeholder engagement. Scientific credibility demands investment in multiomic and strain-level characterisation of host-microbiome interactions on a large scale, benchmarking of clinical and microbiological endpoints, and harmonisation of trial conduct and reporting. Clinical adoption requires fit-for-purpose regulation, diversified investment to address funding bottlenecks, and coordinated capacity building. Meaningful stakeholder engagement with clinicians, patients, policymakers, and the public is essential to foster confidence, develop clinically relevant research questions, and ensure equitable implementation of any new technology.

Implications: To realise the clinical impact of microbiome interventions, sustained collaboration across disciplines is essential. This Review offers a translational roadmap and actionable priorities to accelerate safe, effective, and equitable microbiome-based interventions - ensuring the field fulfils its clinical potential and delivers real-world impact.

Objectives: Metagenomic next-generation sequencing (mNGS) is a promising tool for diagnosing central nervous system (CNS) infections. However, the low-biomass nature of cerebrospinal fluid (CSF) increases susceptibility to contamination and host-background interference, potentially compromising accuracy. This study aimed to evaluate CSF mNGS performance across multiple laboratories and to identify key factors influencing detection accuracy.

Methods: A reference panel of fifteen CSF samples was designed to evaluate CSF mNGS performance across laboratories, including three replicate samples, five serial concentration-gradient samples, three anti-interference samples with added human serum albumin or increased host nucleic acids, and three simulated clinical case samples, along with one negative sample. A total of 127 laboratories participated, which apply mNGS in clinical diagnostics or research. Each laboratory used independently developed mNGS workflow, which varied in experimental procedures, bioinformatic pipelines, and positive detection thresholds. Accuracy, repeatability, sensitivity, and anti-interference capability were systematically evaluated, and sources of erroneous results and methodological factors influencing accuracy were analyzed.

Results: Overall performance across 127 laboratories was favorable (average F1-score 0.98, reflecting overall accuracy by balancing sensitivity and specificity). Most false-positive results (83.43%) were due to experimental contamination, while false negatives were mainly attributed to RNA viruses (57.14%). Methodological factors significantly affected detection, with impact varying by microbial type. Generally, pelleting impaired the detection of all microbes. Notably, microbial enrichment through DNase treatment and Kraken2 improved detection accuracy for DNA viruses, bacteria, fungi and atypical pathogens, but had little effect on RNA viruses.

Conclusions: This large-scale study underscores the need for improved contamination controls, optimized RNA virus detection, and enhancement of key wet-lab procedures to strengthen CSF mNGS reliability. These findings provide actionable insights to refine mNGS workflows and advance its clinical utility for diagnosing CNS infections.

Background: Antibiotics are essential for treating and preventing bacterial infections, yet inappropriate use drives the development of antimicrobial resistance (AMR), posing a major global health challenge. Antimicrobial stewardship (AMS) aims to optimise antibiotic use, making the definition and measurement of "appropriate" prescribing critical.

Objectives: The primary objective was to identify indicators used to measure appropriateness of antibiotic prescribing in high-income countries. The secondary objective was to describe levels of inappropriate prescribing in high-income countries (HICs). MethodsA rapid systematic review (PROSPERO registration no: CRD42024628584) was conducted using Embase, Medline and Cochrane databases. Eligible peer-reviewed studies published from 2014 to January 2025 reported indicators for measuring appropriateness of antibiotic prescribing in HICs. Each article was independently reviewed for inclusion, extracted, and assessed for risk of bias by one reviewer, with 10% verified at each stage.

Results: This rapid review identified 103 unique indicators from 165 studies: 58 patient-specific/prescription related (PSPR) indicators from 128 studies and 45 proxy indicators from 38 studies. The most frequent PSPR indicator was compliance with guidelines (95/128, 74.2%). This was followed by indicators related to appropriate duration (70/128, 54.7%) and appropriate dose (60/128, 46.9%). The most common proxy indicator was rate of prescribing by indication (22/38, 58%) followed by correct choice of antibiotic according to indication (14/38, 36.8%). Indicators were applied across diverse settings, populations, and types of infection. Among studies describing PSPR indicators, 103/128 gave quantifiable outcomes for inappropriateness of prescribing, which when standardised ranged from 2% to 88%.

Conclusions: This review provides a comprehensive catalogue and categorisation of both patient-specific/prescription-related and proxy indicators of antibiotic prescribing appropriateness across high-income countries. Recurring themes reflect shared stewardship principles: prescribing the correct antibiotic, dose, frequency, and duration, in-line with guidance, and tailored to the clinical context. These findings provide a valuable resource for those monitoring antibiotic prescribing practices.

Background: Nocardia spp. can cause a range of clinical syndromes in immunocompromised individuals, such as solid organ transplant recipients, haematopoietic stem cell transplant recipients, and people with HIV (PWH) with advanced HIV disease. Owing to its rarity as an opportunistic infection, its nonspecific clinical presentation, and the difficulties in establishing a definitive diagnosis, clinicians often face challenges in recognizing this infection. Furthermore, the limited literature and the lack of evidence-based guidelines leave clinicians without clear indications in the management of this condition.

Objectives: We aimed to provide guidance on the diagnosis and treatment of nocardiosis in transplant recipients and PWH.

Sources: We performed a review of case reports, case series, original articles, meta-analyses, and systematic reviews retrieved from PubMed.

Content: We reviewed and discussed the most challenging steps in the management of nocardiosis in solid organ transplant and haematopoietic stem cell transplant recipients and PWH through a clinical vignette including epidemiologic changes after the introduction of antiretroviral therapy for PWH; the clinical presentation and differential diagnosis; the role of immune reconstitution; diagnostic challenges and treatment options for an underresearched condition, and the possible role of primary prophylaxis for other opportunistic infections.

Implications: Nocardiosis is a rare but clinically significant opportunistic infection, especially in transplant recipients and PWH with advanced HIV disease. Diagnosis is challenging owing to its nonspecific clinical presentation and the difficulties associated with prolonged culture incubation. Therapeutic management is complex, owing to interspecies variability in antibiotic susceptibility, tolerability of first-line regimens and limited evidence available to guide treatment decisions.

Background: Clinical practice guidelines (CPGs) must be effectively implemented to result in meaningful improvements in patient care, support evidence-based decision-making, and drive high-quality, standardized medical practice.

Objectives: This paper is a guide to current best practices for quality implementation of CPGs, with a focus on the European Society of Clinical Microbiology and Infectious Diseases guidelines for the prevention, diagnosis, and management of infection.

Sources: The guide is informed by implementation science and based on the RE-AIM/PRISM implementation framework, one of the most used frameworks for planning and monitoring research-supported change in healthcare.

Content: A systematic approach to CPG implementation should be guided by three key principles commonly acknowledged in implementation science and reflected in the RE-AIM/PRISM model: (1) understanding the context into which the guideline will be embedded, (2) tailoring the guideline and its implementation to this context, and (3) monitoring guideline implementation.

Implications: To improve the applicability, effectiveness, and sustainability of novel CPGs, future advancements should prioritize their intentional, well-planned dissemination and implementation, and the rigorous evaluation of CPG outcomes.