Clinical Microbiology and Infection最新文献

Background: The global rise of extended-spectrum β-lactamase (ESBL) and plasmid-borne cephalosporinase (pAmpC) producing Enterobacterales is a major health concern. Their increasing prevalence in both humans and animals underscores the need for One Health surveillance, for which Escherichia coli has been recognized as a key indicator. While many studies have investigated the circulation of ESBL/pAmpC-producing E. coli (ESBL/pAmpC-Ec) across human, animal, and environmental sectors, the extent to which animals contribute to human acquisition remains unclear.

Objectives: This review provides an overview of the intersectoral circulation of ESBL/pAmpC-Ec and evaluates the potential role of animals as a reservoir for human colonization.

Sources: Publications (2010-2024) identified through PubMed, Scopus, and Google Scholar, on ESBL/pAmpC-Ec circulation across human, animal, and environmental sectors (excluding studies on human-environment, animal-environment, and human-food only) were reviewed considering the included sectors, comparison methods, and geographical context.

Content: Surveillance approaches varied widely between studies, shaped by sampling strategies, geographical context, and isolated comparison methods. Advances in genomic methods have refined our understanding of ESBL/pAmpC-Ec circulation between sectors. Early studies, mostly conducted in high-income countries (HICs), suggested human-animal transmission based on comparisons of ESBL/pAmpC-Ec sequence types, resistance genes, and plasmid replicons. However, these findings were challenged by the introduction of more discriminating comparison methods such as whole-genome sequencing, which revealed a largely compartmentalized circulation of ESBL/pAmpC-Ec in HICs. Similar studies in low- and middle-income countries (LMICs) shifted this paradigm, demonstrating frequent cross-sectoral transmission across humans, animals, and the environment. Many authors also highlighted the likely underestimated role of plasmids in the circulation of ESBL/pAmpC genes.

Implications: Despite the heterogeneity of the studies, two distinct scenarios emerged: predominantly intrasectoral ESBL/pAmpC-Ec circulation in HICs and significant intersectoral circulation in LMICs. These findings underscore the need for region-specific antimicrobial resistance control strategies, focusing on limiting human-to-human transmission in HICs and enhancing sanitation and biosecurity in LMICs.

Objectives: Fluoroquinolones can exert excitatory effects on the central nervous system. Our population-based cohort study assessed whether fluoroquinolones are associated with an increased risk of seizures.

Methods: We used German claims data from the InGef database (2016-2023) to assemble a cohort of patients initiating fluoroquinolones or amoxicillin. Patients were followed using a 30-day intention-to-treat approach. Inverse-probability-of-treatment-weighting based on propensity scores incorporating many potential confounders was used for confounding control. Cox proportional hazards models estimated hazard ratios (HRs) and 95% CIs of seizures associated with use of fluoroquinolones versus use of amoxicillin. Secondary analyses stratified by potential effect modifiers. All analyses were repeated using macrolides as an alternate comparator to control for residual confounding.

Results: Our cohort included 3 250 916 patients (mean age [standard deviation], 51 [18] years; 54% female) initiating treatment with fluoroquinolones or amoxicillin. Fluoroquinolones versus amoxicillin were not associated with the risk of seizures in the overall population (HR, 1.10; 95% CI, 0.995-1.23). There were increased risks among older adults (HR, 1.29; 95% CI, 1.07-1.47), patients without prior epilepsy (HR, 1.34; 95% CI, 1.11-1.61) and patients with chronic kidney disease (HR, 1.43; 95% CI, 1.11-1.85). Using macrolides as comparator led to no associations with the risk of seizures overall (HR, 0.89; 95% CI, 0.72-1.09) and in the different subgroups except for patients with chronic kidney disease (HR, 1.65; 95% CI, 1.03-2.63).

Conclusions: Our large cohort study showed that fluoroquinolones were not associated with the risk of seizures overall. An increased risk among patients with chronic kidney disease is possible.

Background: Critically ill patients in the intensive care unit represent a highly heterogeneous population with large variations in the pharmacokinetics (PK) of antimicrobials (antibiotics, antifungals, and antiviral agents), complicating optimal dosing strategies. This becomes even more complex in those receiving continuous renal replacement therapy (CRRT), because CRRT significantly alters drug clearance. Nonetheless, many PK studies exclude patients undergoing CRRT and existing studies often suffer from methodological limitations and small sample sizes, reducing their generalizability. Accordingly, there remains a critical gap in robust, evidence-based dosing guidelines for antimicrobials in intensive care unit patients on CRRT, despite the clear clinical need.

Objectives: To conduct a scoping review of the literature on factors affecting the PK of antimicrobials in critically ill patients undergoing CRRT, provide practical recommendations, and develop a CRRT-PK checklist for designing and conducting PK research in this patient group.

Methods: Embase, Medline, and Cochrane databases, and the reference lists of relevant publications were searched from database inception to 24 June 2025. Data were extracted independently by two reviewers (AW and TJLS) and disagreements were resolved through discussion until consensus was reached. No quality appraisal was performed. Extracted data were synthesized descriptively, grouped by the type of influencing factor (CRRT-, patient-, or drug-related).

Results: Of 811 articles identified in the search strategy, a total of 96 articles were included in the review. All relevant CRRT-, patient-, and drug-related factors that may influence the PK of antimicrobials are discussed. Moreover, we provided practical considerations and a CRRT-PK checklist for an appropriate study design and output.

Conclusions: This review, along with the checklist, can form the foundation for designing and conducting high-quality PK studies in critically ill patients undergoing CRRT. By improving the consistency and reproducibility of future studies, this is the first step towards robust, evidence-based dosing guidelines for antimicrobials in critically ill patients undergoing CRRT.

Objectives: Multidrug-resistant organisms (MDROs) are becoming increasingly prevalent among patients with advanced cancer referred for palliative care (PC), and may adversely impact the quality of end-of-life care.

Methods: We conducted a retrospective cohort study of patients with advanced cancer who were referred for PC at a tertiary hospital in South Korea between January 2018 and December 2022 and died before June 2023. Clinical data of patients were linked to nationwide health insurance claims data, enabling comprehensive longitudinal assessment of the end-of-life trajectory beyond a single institution. MDRO status was defined as the detection of resistant organisms in any clinical specimen at the time the patient was referred for PC. Outcomes included utilization of hospice services, in-hospital death at tertiary care centres, receipt of aggressive end-of-life interventions, and total medical costs. Adjusted associations were estimated using logistic and γ regression models.

Results: Among 6151 patients, 523 (8.5%) had MDROs detected. MDRO status was associated with significantly lower use of community-based hospice care, including inpatient hospice (24.1% vs. 37.8%; adjusted odd ratios [aOR], 0.56, 95% CI, 0.45-0.70; p < 0.001) and home hospice (2.7% vs. 7.4%; aOR, 0.39, 95% CI, 0.22-0.67; p = 0.001). It was also associated with more frequent deaths in tertiary hospitals (aOR, 1.74; 95% CI, 1.43-2.12, p < 0.001), and higher intensive care unit admissions (aOR, 2.18; 95% CI, 1.51-3.16, p < 0.001) and renal replacement therapy (aOR, 1.63; 95% CI, 1.03-2.60, p = 0.039). The medical costs were consistently higher in the MDRO group throughout the last 6 months of life.

Conclusions: MDRO status could be associated with lower quality of end-of-life care, including reduced access to community-based hospice and more aggressive interventions, in patients with advanced cancer referred for PC. These findings underscore the need for infection control strategies that support high-quality, patient-centred care near the end-of-life.

Objectives: Patients on haemodialysis (HD) are commonly treated with teicoplanin for Gram-positive infections. Kidney replacement therapy is known to alter drug pharmacokinetics (PK), which impacts treatment success. This study aimed to characterize teicoplanin PK, explore potential covariate predictors for interindividual variability, and derive an evidence-based dosing strategy for patients undergoing maintenance HD.

Methods: A monocentric prospective observational PK study in patients undergoing maintenance HD was conducted at the Ghent University Hospital and its low care at the General Hospital Aalst. Total and unbound teicoplanin concentrations were used to inform the development of a teicoplanin population PK model. Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) for predialysis teicoplanin concentrations (C_predialysis) of 20-50 mg/L across dosing regimens. The impact of administration of a predialysis dose and therapeutic drug monitoring (TDM) on target attainment was evaluated.

Results: This study included 31 patients on teicoplanin therapy undergoing maintenance HD or haemodiafiltration (HDF). The final model consists of a two-compartment population PK model with a semimechanistic dialyser flow. High clearance variability was observed across the cohort. The standard 12 mg/kg thrice-weekly regimen achieved PTA of 13.6% (HD) and 6.8% (HDF) after the first dose, which increased to approximately 50% with subsequent doses. A fixed-dose regimen was proposed with a single 1600 mg loading dose, followed by an 800 mg maintenance dose (1200 mg for 3-day interdialytic periods). The proposed dosing regimen increased PTA to 71.7% (HD) and 66.9% (HDF) after the first loading dose, with week 1 averages of 61.1% and 59.9%, respectively. C_predialysis-based TDM further improved PTA to >70% in both groups.

Conclusions: This study proposed an optimized dosing strategy to maximize PTA in patients undergoing maintenance HD, although prospective validation is recommended before clinical implementation. Furthermore, the estimated high clearance variability underscores the need for TDM in teicoplanin dosing for this population.

Background: Invasive mould infection (IMI) is a major cause of morbidity and mortality in immunocompromised children. Outcomes for paediatric patients with IMI remain poor, due in part to the limitations of available diagnostic tools and therapeutic agents.

Objectives: To summarize current and emerging modalities for diagnosis and treatment of IMI in immunocompromised children, focusing on recent advances and remaining barriers.

Sources: A comprehensive literature search of tools for diagnosis and management of IMI in children was conducted using PubMed, including clinical and preclinical studies, relevant consensus guidelines, and reviews.

Content: Initial diagnosis of IMI, particularly for invasive aspergillosis (IA), often relies on computed tomography imaging of the chest, yet imaging findings are not specific to mould infection and cannot differentiate between IA and nonaspergillus moulds. Fluorodeoxyglucose-positron emission tomography imaging may have advantages, but diagnostic sampling remains essential. Traditional microbiological and histopathological work up of blood, fluid and tissue samples are the mainstay of laboratory diagnosis of IMI in children, yet limitations related to test sensitivity, turnaround time, as well as potential complications associated with invasive sampling remain. Nonculture-based biomarkers, including galactomannan for IA, have a role in diagnosis of paediatric IMI, although interpretation requires consideration of test limitations and patient factors. Molecular assays have shown promise and will be an important diagnostic tool in future. Novel antifungal agents, including isavuconazole, olorofim, fosmanogepix, and ibrexafungerp, have significantly broadened the range of agents with activity against IMI, yet paediatric data are required to facilitate use in children. Similarly, immunotherapeutic approaches have potential to improve outcomes in paediatric IMI, yet data in children remain limited.

Implications: There has been much progress in IMI management with recent development of novel diagnostic methods, new antifungals, and immunotherapeutic approaches. Ongoing paediatric studies are required to inform optimal implementation of these tools into clinical practice.