Clinical Microbiology and Infection最新文献

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 5-10% - represents true immune-mediated hypersensitivity. Mislabelling can contribute to the development of antimicrobial resistance (AMR) 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 (ESCMID), provides evidence-based recommendations for the clinical evaluation and management of patients with reported antibiotic allergies. It is aimed at non-allergist clinicians and seeks to harmonise 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 prioritised by the panel, and relevant data were extracted using piloted Evidence to Decision (EtD) framework sheets. The panel developed recommendations by adopting, adapting or formulating new recommendations, through an iterative work-up and consensus process. All recommendations were finalised 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 (SCTK) 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 fiber infection model (HFIM) 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% reductions in AUC_CFU across all Smc isolates in SCTK assays. In the HFIM, ATM+CZA achieved ≥3-log₁₀ CFU/mL reductions 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 due to intrinsic resistance mechanisms. These findings demonstrate the therapeutic potential of ATM+CZA, and support further evaluation using murine pneumonia and bacteremia 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 is typically of a complexity that requires specific domain expertise to avoid biases, spurious findings, and other analysis pitfalls. As such, academic hospitals and research institutes are increasingly recognising the need for a dedicated microbiome research facilities that support every step in human microbiome research to a high standard.

Objectives: We aim 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 (LUMC, 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. Additionally, 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 centralise activities, innovate and validate analytical and computational methodology, foster industrial collaborations, and supports 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.

Objectives: Guidelines recommend extragenital screening for sexually transmitted infections in men having sex with men but not for women who do not report extra-vaginal intercourses. However, it has been suggested that among female commercial sex workers, limiting sexually transmitted infection screening to vaginal samples would miss a sizeable number of infections. No study exists for non-sex worker women. Therefore, our objective was to assess the potential benefit of systematically testing three anatomical sites (oral, anal and vaginal) versus only vaginal testing in women attending free sexually transmitted infection screening centres in France.

Methods: A prospective longitudinal study was conducted in seven hospitals in France between April 2023 and September 2024 in which women were offered to be tested at the three sites instead of vaginal only.

Results: A total of 1498 women were included in the study, and 1483, 1492, and 1278 oral, vaginal and anal samples, respectively, were reported. With a three-site strategy, the detection rate increased from 151/1492 (10.1%) to 179/1295 (13.8%) (p<0.001) (127 (10.0%) to 152/1268 (12.0%); p<0.001 for all patients with three-site samples) for both infections (p<0.001). Similarly, rate increased from 137/1492 (9.2%) to (160/1293) 12.4% (p<0.001)(114 (9.0%) to 135/1268(10.7%), p<0.001 for all patients with three-site samples) for C. trachomatis and from 21/1492 (1.4%) to 30/1270 (2.4%) (p=0.008)( 20 (1.6%) to 28/1268 (2.2%), p=0.01 for all patients with three-site samples) for N. gonorrhoeae. Neither symptoms nor reported sex practices were reliable predictors of infection. Among the C. trachomatis or N. gonorrhoeae infections detected, 15 (10.0%) and 25 (17.0%) were exclusively anal or anal-oral infections, respectively, without vaginal involvement.

Conclusions: Multisite testing should be considered for women to ensure accurate diagnosis and treatment of C. trachomatis and N. gonorrhoeae.

Objectives: Severe infection risk associated with tumor necrosis factor-α inhibitors (TNFi) remains a concern. We aimed to assess the association between TNFi and bloodstream infections (BSI) in a population-based setting.

Methods: Nationwide, registry-based case-control study including all adults from 2010 to 2024 with a first-time microbiologically confirmed BSI (cases) compared to age and sex-matched controls from the general population. Users were defined as individuals with TNFi exposure within six months prior to the date of BSI. Adjusted odds ratios (aOR) with 95% confidence intervals (CIs) were estimated using conditional logistic regression. We further assessed risk variation by type of TNFi, pathogen, and underlying disease.

Results: We included 174,137 cases and 1,741,294 controls. Users had significantly increased odds of BSI compared to non-users (aOR: 1.41, 95% CI: 1.30-1.52), driven by increased odds among users of adalimumab and infliximab (aOR: 1.51, 95% CI: 1.33-1.72, and aOR: 2.01, 95% CI: 1.76-2.29). Use of certolizumab pegol and etanercept was associated with lower odds of BSI, and golimumab with higher odds compared to non-use, although not statistically significant. Species-specific analyses showed increased odds of BSI with Escherichia coli (aOR: 1.33, 95% CI: 1.16-1.53), Staphylococcus aureus (aOR: 1.69, 95% CI: 1.40-2.06), Streptococcus pneumoniae (aOR: 1.46, 95% CI: 1.05-2.04), and Enterococcus faecium (aOR: 1.62, 95% CI: 1.04-2.53). Highest odds were observed in individuals with inflammatory bowel disease (aOR: 2.27, 95% CI: 1.93-2.66), followed by individuals with rheumatoid arthritis. Compared to TNFi monotherapy, concomitant glucocorticoids increased the odds (aOR: 2.63, 95% CI: 2.06-3.36).

Conclusions: TNFi use is associated with increased odds of BSI and was observed across the most frequent species. Odds varied by TNFi type and underlying disease, with highest odds among patients with inflammatory bowel disease, emphasizing the need for individualized infection risk assessment.