Clinical Microbiology and Infection最新文献

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.

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.

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-center trial randomized healthy adults (≥18 years) primed with rVSVΔG-ZEBOV-GP to intradermal INO-4201 (1 mg) or placebo (4:1), both followed with electroporation. The co-primary 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 (IQR 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, 20/36 (56%) vaccinees versus 5/10 (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 post-boost peak versus day 0: 0.09 [range 0.00-14.48] versus 0.00 [0.00-1.33], p=.004). FANG-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]).

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

Background: Patients treated with GLP-1 receptor agonists and 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 (RCTs) reporting target infection outcomes related to GLP-1 receptor agonists or SGLT2 inhibitors 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, UTI). Drop-out rates served to reflect acceptability. Sensitivity analyses included Bayesian modeling and subgroup analyses of diabetic status and treatment duration.

Results: Based on 105 RCTs 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 modeling 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 inhibitors prescription.

Trial registration: PROSPERO CRD42024628901.

Background: Colonisation of the gastrointestinal tract by multidrug-resistant organisms (MDROs) is a precursor to endogenous infection and onward transmission. The gut microbiome provides colonisation resistance (CR) - the ability to prevent or limit the establishment of pathogens, including MDROs - through nutrient and niche competition, production of inhibitory metabolites, and immune modulation. However, its integrity is threatened by antibiotics, adverse diet, and healthcare exposures.

Objectives: To describe mechanistic, epidemiological, and interventional evidence on the role of the gut microbiome in MDRO colonisation and infection, and to highlight implications for clinical practice, policy, and research.

Sources: PubMed/MEDLINE, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched from 1 January 2000 to 30 September 2025, supplemented by hand-searching of key international guidelines (EUCIC/ESCMID, WHO, CDC/ECDC, NICE/UKHSA) and reference lists.

Content: CR is shaped by microbial and host factors, including metabolic interactions, immune responses, and environmental exposures. Antimicrobials, non-antimicrobial drugs, diet, travel, and healthcare contact can disrupt the microbiota, predisposing to MDRO acquisition and infection. Observational data link gut microbial composition to risk of colonisation and infection outcomes, but predictive models are imperfect. Interventions to preserve or restore CR - such as diet-based strategies, probiotics, and faecal microbiota transplant - show promise but require robust and repeated, context-specific evaluation.

Implications: Protecting the microbiome must be a clinical and policy priority. Short-course, microbiome-sparing antimicrobial regimens, microbiome-aware diagnostics, and public health measures that support microbiome resilience could reduce MDRO burden and infections. Rigorous trials of microbiota-based therapies and integration of microbiome stewardship into antimicrobial resistance strategies are essential for translating mechanistic insights into patient benefit.