Clinical Microbiology and Infection最新文献

Background: Severe infections and sepsis are characterized by a disruption of intestinal and respiratory microbial communities. Loss of obligate gut anaerobes and depletion of immunomodulatory metabolites disrupt mucosal integrity, impair immune homeostasis, and increase susceptibility to secondary infection and organ failure.

Objectives: To summarize the current understanding of gut and lung microbiome dynamics during severe infections, describe immunometabolic crosstalk along the gut-lung axis, and identify microbiome-targeted strategies to improve outcomes.

Sources: Peer-reviewed preclinical and clinical studies on microbiota composition, metabolite signalling, and therapeutic modulation in severe infections published up to October 2025.

Content: In health, obligate anaerobes such as Faecalibacterium and Blautia species are thought to support mucosal homeostasis through short-chain fatty acids, secondary bile acids, and tryptophan-derived indoles that calibrate systemic immunity and suppress overgrowth of opportunistic pathogens. Sepsis-associated inflammation, hypoperfusion, and antibiotic exposure deplete obligate anaerobes, shifting the gut ecosystem towards Enterococcus, Enterobacterales, and Candida species, accompanied by disruption of metabolite-mediated immune homeostasis. The lungs, which contain their own low-biomass microbiota, similarly undergo a loss of diversity with overrepresentation of Proteobacteria during critical illness, a pattern that has been linked to impaired alveolar immunity and adverse outcomes. Experimental studies indicate that gut-derived metabolites and migrating immune cells shape pulmonary responses, and loss of gut-lung compartmentalization may permit bacterial translocation and contribute to systemic inflammation. Defined live anaerobic consortia and postbiotics represent promising experimental strategies to restore microbial balance during severe infections, but the most immediate opportunity lies in antibiotic stewardship that limits unnecessary anaerobe-active coverage.

Implications: The obligately anaerobic microbiome is central to host-pathogen interactions in severe infection. Preserving and restoring anaerobic and pulmonary microbial communities through rational antimicrobial use and mechanistically informed microbiome-based interventions may improve outcomes and recovery after critical illness.

Scope: Antibiotic allergies remain one of the most frequently documented drug allergies in clinical records. It is well established that only a small proportion-estimated at 5% to 10%-represents true immune-mediated hypersensitivity. Mislabelling can contribute to the development of antimicrobial resistance via prescription of suboptimal antimicrobial therapy (i.e. unnecessary avoidance of first-line antibiotics), increased use of broad-spectrum agents, and complications such as drug toxicity. This guideline, developed by the European Society of Clinical Microbiology and Infectious Diseases, provides evidence-based recommendations for the clinical evaluation and management of patients with reported antibiotic allergies. It is aimed at nonallergist clinicians and seeks to harmonize practice across healthcare settings in Europe and beyond.

Methods: The guideline was developed by a multidisciplinary panel of 16 experts in infectious diseases, allergy, pharmacy, paediatrics and clinical microbiology, following a modified GRADE-ADOLOPMENT process. Systematic searches were conducted in PubMed and the Trip Database (2015-2023) to identify relevant guidelines, complemented by an additional systematic search for primary studies (2021-2024). The included guidelines were assessed using the AGREE Global Rating Scale. Four existing guidelines, from 2022 and 2023, met methodological quality criteria and were included. Key questions were identified and prioritized by the panel, and relevant data were extracted using piloted Evidence to Decision framework sheets. The panel developed recommendations by adopting, adapting or formulating new recommendations, through an iterative work-up and consensus process. All recommendations were finalized through panel discussion and formal voting, with consensus defined as agreement by ≥ 80% of members.

Recommendations: The guideline recommends a structured clinical assessment to evaluate a reported antibiotic allergy, taking into consideration the characteristics of the index reaction. Where the clinical history suggests a very low or low likelihood of true allergy, direct delabelling or performing a controlled drug challenge test is appropriate. By supporting allergy evaluation and prudent prescribing practices, the recommendations aim to improve individual patient outcomes and reinforce antimicrobial stewardship goals.

Objectives: Stenotrophomonas maltophilia is a multidrug-resistant Gram-negative pathogen causing serious infections in vulnerable populations, including individuals with cystic fibrosis and immunocompromised patients. We evaluated the activity of aztreonam (ATM) and ceftazidime/avibactam (CZA) against S. maltophilia complex (Smc) isolates.

Methods: Interactions between ATM and CZA were evaluated using static concentration time-kill assays across 11 Smc isolates. A mechanism-based pharmacokinetic/pharmacodynamic model was developed to characterize bacterial killing dynamics and guide regimen selection. Selected regimens were then evaluated in the hollow fibre infection model under clinically relevant drug exposures. Emergence of resistance was assessed via population analysis profiles, and scanning electron microscopy visualized antibiotic-induced morphological changes.

Results: Clinically relevant ATM + CZA exposures produced 31-74% reduction in area under the log-transformed bacterial count versus time curve across all Smc isolates in static concentration time-kill assays. In the hollow fibre infection model, ATM + CZA achieved ≥3-log₁₀ CFU/mL reduction at 24 hours from an initial ∼7.5-log₁₀ CFU/mL inoculum. This effect was sustained over 168 hours against GG6 strain. Against the non-GG6 strain, both continuous-infusion and standard-dosing regimens showed ∼2-log10 regrowth after 72 hours, but overall suppressed resistant subpopulations more effectively than trimethoprim/sulfamethoxazole.

Conclusions: Smc infections remain challenging because of intrinsic resistance mechanisms. These findings demonstrate the therapeutic potential of ATM + CZA, and support further evaluation using murine pneumonia and bacteraemia models of S. maltophilia.

Background: The increasing number of therapeutic intervention studies in the microbiome field has sparked broad interest among clinicians and scientists to incorporate microbiome analyses in their research. However, microbiome study design, data generation, bioinformatics, and statistical data analysis are typically of a complexity that require specific domain expertise to avoid biases, spurious findings, and other analysis pitfalls. As such, academic hospitals and research institutes are increasingly recognizing the need for dedicated microbiome research facilities that support every step in human microbiome research to a high standard.

Objectives: We aimed to offer an experience-based approach on what we consider essential aspects of such a microbiome research facility.

Sources: Insights and recommendations are based on our experiences with establishing and running a microbiome research facility at the Leiden University Medical Center (Leiden, the Netherlands), which was initiated in 2017.

Content: This review uses an existing microbiome research facility as an example to provide information on its advantages, structure, and financial and legal frameworks. In addition, key portfolio items of such an expertise centre are discussed.

Implications: A dedicated microbiome research facility can support microbiome research in clinical studies, and provides opportunities to centralize activities, innovate and validate analytical and computational methodology, foster industrial collaborations, and support competitive funding applications through a dedicated infrastructure. Central facilities to support clinicians and scientists in the design, execution, and interpretation of microbiome analyses constitutes a key step towards conducting high-quality gut microbiome research and education.