Clinical Microbiology and Infection最新文献

Objectives: Metagenomic next-generation sequencing (mNGS) is a promising tool for diagnosing central nervous system 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 15 CSF samples was designed to evaluate CSF mNGS performance across laboratories, including 3 replicate samples, 5 serial concentration-gradient samples, 3 anti-interference samples with added human serum albumin or increased host nucleic acids, and 3 simulated clinical case samples, along with 1 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 analysed.

Results: Overall performance across 127 laboratories was favourable (average F1-score 0.98, reflecting overall accuracy by balancing sensitivity and specificity). Most false-positive results (83.43%) were due to experimental contamination, whereas 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 central nervous system infections.

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.

Background: Antibiotics are essential for treating and preventing bacterial infections, yet inappropriate use drives the development of antimicrobial resistance, posing a major global health challenge. Antimicrobial stewardship aims to optimize 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 (HICs). The secondary objective was to describe levels of inappropriate prescribing in HICs.

Methods: A 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 of 128 gave quantifiable outcomes for inappropriateness of prescribing, which when standardized ranged from 2% to 88%.

Conclusions: This review provides a comprehensive catalogue and categorization of both PSPR and proxy indicators of antibiotic prescribing appropriateness across HICs. 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.

Objectives: To evaluate the diagnostic performance, particularly specificity, of the MucorGenius® PCR assay for detecting pulmonary mucormycosis in bronchoalveolar lavage fluid (BALF) samples from at-risk patients.

Methods: This is a retrospective diagnostic accuracy study using prospectively collected BALF samples. All consecutive BALF samples obtained from patients who were considered to be at risk for invasive mould infections (IMIs) were prospectively collected. Patients were retrospectively classified according to European Organization for Research and Treatment of Cancer and Mycoses Study Group Education and Research Consortium and adapted Invasive Fungal Diseases in Adult Patients in Intensive Care Unit definitions. All samples were retrospectively tested with the MucorGenius® assay.

Results: A total of 1407 BALF samples obtained from 1330 patients had been included and tested for Mucorales DNA. A total of 256 patients (19.6%) fulfilled European Organization for Research and Treatment of Cancer and Mycoses Study Group Education and Research Consortium host factors and 664 (49.9%) Invasive Fungal Diseases in Adult Patients in Intensive Care Unit host factors. Proven or probable pulmonary mucormycosis was routinely diagnosed (without Mucorales PCR) in four patients (0.3%), 26 patients had proven or probable invasive pulmonary aspergillosis (IPA) (2%), and 25 (1.9%) had possible IMI. Overall, 32 positive MucorGenius® results had been observed. Per patient the MucorGenius® assay gave a specificity of 98.6% (95% CI: 97.8-99.2; n = 1251/1269) and a sensitivity of 100% (95% CI: 39.8-100; n = 4/4). Two cases with IPA were routinely diagnosed with mixed Mucorales infection and three additional IPA cases had a positive MucorGenius® PCR. In total, 5 of 26 IPA cases were therefore diagnosed with a mixed mould infection. Six of the 25 possible IMI cases (24%) also turned out positive on MucorGenius® PCR. Nineteen Mucorales PCR-positive samples had been obtained from patients without any routinely diagnosed IMI.

Conclusions: We observed a near-to-perfect specificity of the MucorGenius® assay in BALF, making diagnosis of pulmonary mucormycosis very likely in patients with a positive PCR. In addition, the test was able to identify mucormycosis in a relevant proportion of cases with possible IMI and probable IPA, potentially indicating otherwise missed mixed-mould infections.

Background: Patients treated with glucagon-like peptide-1 (GLP-1) receptor agonists and sodium glucose co-transporter 2 (SGLT2) inhibitors often have underlying conditions that predispose them to infection. While these agents offer cardiometabolic benefits, concerns persist regarding their impact on infectious risk. Existing literature has not comprehensively assessed their dose-dependent influence on severe infections such as sepsis.

Objectives: To investigate the effect of GLP-1 receptor agonists and SGLT2 inhibitors on infection risk.

Data sources: PubMed, Embase, ClinicalKey, Cochrane CENTRAL, ProQuest, ScienceDirect, Web of Science, and ClinicalTrials.gov up to December 18, 2024.

Study eligibility criteria: Randomized controlled trials reporting target infection outcomes related to GLP-1 receptor agonists or SGLT2 inhibitor prescription.

Participants: Individuals without evidence of ongoing infection at study initiation.

Interventions: GLP-1 receptor agonists or SGLT2 inhibitors.

Assessment of risk of bias: Cochrane risk of bias tool version 2.0.

Methods of data synthesis: A frequentist random-effects model was used to assess the comparative incidence of infectious complications-classified as sepsis, abscess/gangrene, or other infections (e.g., pneumonia and urinary tract infection). Drop-out rates served to reflect acceptability. Sensitivity analyses included Bayesian modelling and subgroup analyses of diabetic status and treatment duration.

Results: Based on 105 randomized controlled trials with 219 283 participants, no significant association was found between GLP-1 receptor agonists or SGLT2 inhibitors and controls, except for high-dose canagliflozin (300 mg/day), which was the only intervention significantly associated with reduced sepsis risk versus control. This effect persisted in participants with diabetes. No significant associations were found between any other GLP-1 receptor agonist or SGLT2 inhibitor and risk of sepsis, abscess, gangrene, or other infections. Subgroup and meta-regression analyses confirmed robustness. Bayesian modelling yielded comparable results. Treatment duration had minimal influence on primary outcomes.

Conclusions: This analysis identifies no significant evidence of infection-related adverse events related to GLP-1 receptor agonist or SGLT2 inhibitor prescription.

Objectives: Nearly a million people have received the recombinant vesicular stomatitis virus-based vaccine expressing the surface glycoprotein of Ebola virus (rVSVΔG-ZEBOV-GP), whose immune durability is unknown. We evaluated the safety and immunogenicity of the DNA vaccine candidate INO-4201 in volunteers primed with the rVSVΔG-ZEBOV-GP vaccine.

Methods: This investigator-initiated phase Ib double-blind, placebo-controlled, single-centre trial randomly assigned healthy adults (≥18 years) primed with rVSVΔG-ZEBOV-GP to intradermal INO-4201 (1 mg) or placebo (4:1), both followed with electroporation. The coprimary outcome was incidence of adverse events at 14 days and geometric mean EBOV-GP-binding antibody titres (GMT) at 28 days (clinicaltrials.gov NCT04906629).

Results: Forty-six participants were enrolled. Median age was 52 years (interquartile range 44-57); 26 (57%) were male. Thirty-six participants received INO-4201 and 10 participants received placebo. No serious adverse events occurred. There was little reactogenicity. At 14 days, 20 of 36 (56%) vaccinees versus 5 of 10 (50%) placebo recipients (relative risk 1.11 [95% CI 0.56-2.20]) experienced adverse events. Peak T-cell responses were significantly increased in INO-4201 recipients (median percentage of CD4 cells producing interferon-gamma at postboost peak versus day 0: 0.09 [range 0.00-14.48] versus 0.00 [0.00-1.33], p 0.004). Filovirus Animal Non-Clinical Group-based EBOV-GP-binding titres were significantly higher after boosting for vaccinees at all time points (GMT at 4 weeks versus day 0: 3221.7 [95% CI 2629.8-3946.8] vs 704.3 [513.8-965.3]). Neutralizing antibody titres were also significantly higher after boosting for vaccinees at all time points measured (GMT at 4 weeks versus day 0: 21.3 [95% CI 13.8-32.7] versus 2.4 [1.5-3.9]).

Conclusions: In adults primed with rVSVΔG-ZEBOV-GP, INO-4201 demonstrated favourable safety and significant immunogenicity.