Clinical Microbiology and Infection最新文献

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: Cefiderocol is a novel last-resort cephalosporin antimicrobial increasingly used for difficult-to-treat infections by multidrug-resistant microorganisms, and is effective against carbapenem-resistant Enterobacterales and Pseudomonas species. Multiple chromosomally encoded genetic determinants have been implicated in cefiderocol resistance, including mutations, deletions and/or frameshifts. However, identification of these determinants remains labour-intensive and time-consuming. Therefore, we share CefiderocolFinder, a bioinformatics pipeline to detect 25 genetic adaptations implicated in cefiderocol resistance from short-read whole-genome sequencing (WGS) data.

Methods: CefiderocolFinder was built using Python, supports WGS data of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii, and contains alignment, variant calling, annotation and filtering steps. A short-read WGS dataset (n = 98) and a validation WGS dataset (n = 21) with cefiderocol antimicrobial susceptibility testing (AST) results were used to interpret and validate CefiderocolFinder.

Results: Using CefiderocolFinder, with WGS data from 98 multidrug-resistant microorganisms collected from Ukrainian patients in 2022, six unique genetic adaptations were detected. These adaptations were associated with higher MICs in AST with cefiderocol. Loss-of-function mutations were found in the siderophore receptor cirA, the general porins oprD, ompC, ompF, negative regulator of the acrAB-tolC efflux operon acrR and a conservative in-frame insertion YRIN in ftsI encoding for penicillin-binding protein 3. The adaptations were identified in 12 of 16 E. coli (75%), 1 of 60 K. pneumoniae (1%), 6 of 17 P. aeruginosa (35%) and 0 of 5 A. baumannii (0%) isolates. CefiderocolFinder was validated using publicly available datasets.

Conclusions: CefiderocolFinder provides context to corroborate phenotypical AST from WGS data, especially when the result is in an area of technical uncertainty. For E. coli, CefiderocolFinder can be a valuable tool for informing the clinician of specific genetic adaptations associated with resistance to cefiderocol, where for K. pneumoniae and P. aeruginosa the prediction of phenotypical resistance can be improved. CefiderocolFinder is available open access at http://github.com/Bryan-vd-Brand/CefiderocolFinder.

Objectives: Controlling tuberculosis (TB) transmission is of paramount importance for combating the TB pandemic. Although TB hospitals are considered hotspots of transmission, systematic longitudinal studies examining the underlying incidence and possible risk factors of nosocomial TB transmission are lacking. The objectives of this study were to detect nosocomial transmission events over a 20-month period using whole genome sequencing (WGS) of Mycobacterium tuberculosis complex (MTBC) isolates collected from 563 patients with pulmonary TB hospitalized in the Kyrgyz Republic.

Methods: The WGS was performed on 698 MTBC isolates, including 563 first isolates recovered from participants within 4 weeks of hospitalization and 135 follow-up isolates from treatment control samples collected at least 4 weeks apart. All participants' roommates were recorded over the whole study period.

Results: The cohort represented >95% of TB patients hospitalized at the study sites during the follow-up period of 53 372 hospitalization days. Genome-based cluster analysis revealed that 173 of the 563 (30.7%) first isolates fell into 56 clusters (<5 single nucleotide polymorphism [SNPs]). Two nosocomial TB transmissions from index cases to their roommates were proven. And five potential transmissions were observed between patients who shared time, but not a room, in the hospital or where the index case was not identified. Most transmitted strains were more resistant than the previous one.

Discussion: Within-community transmission of MTBC is highly active in Kyrgyzstan. With 13.7 per 1000 patient years (95% CI: 1.6-49.5), we observed markedly higher rates of nosocomial transmission than reported in previous WGS-based studies.

Background: The global spread of multidrug-resistant gram-negative bacteria has led to the introduction of several novel antibiotics. However, emerging resistance threatens their long-term utility, emphasizing the importance of antimicrobial stewardship programmes (ASPs).

Objectives: This narrative review synthesizes current evidence on ASP interventions optimizing the use of recently approved antibiotics against multidrug-resistant gram-negative pathogens and identifies priorities for sustainable implementation.

Sources: A literature search (PubMed, Scopus, 2010-2025) identified interventional and quasiexperimental studies addressing stewardship strategies for novel agents such as ceftazidime/avibactam, ceftolozane/tazobactam, meropenem/vaborbactam, imipenem/relebactam, cefiderocol, sulbactam/durlobactam, eravacycline, and aztreonam/avibactam.

Content: Seven studies were included, encompassing educational bundles, pharmacokinetic/pharmacodynamic optimization, decision-support tools, formulary restrictions, and multidisciplinary models. Most relied on enablement strategies-education, feedback, and therapeutic monitoring-often integrated with diagnostics or digital support. These interventions improved therapy appropriateness and microbiological outcomes, though evidence remains limited by small, single-centre, and heterogeneous studies.

Implications: Effective stewardship of new gram-negative antibiotics requires combining enablement, personalized pharmacology, and selective restriction within multidisciplinary ASPs. Strengthening real-world evidence, digital infrastructure, and standardized outcome measures is essential to guide equitable and sustainable implementation.

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: We aimed to assess the diagnostic value of a battery of confirmatory tests included in the WHO guidelines for bubonic plague, combined and individually, including culture, PCR and serology, and the on-site and laboratory performance of the F1 antigen-based lateral flow rapid diagnostic test (F1RDT).

Methods: Bubo aspirates from patients (all ages) with suspected bubonic plague enrolled into the IMASOY trial (NCT04110340) underwent routine laboratory diagnosis complemented with serology to measure IgG F1 antibodies from blood samples taken on days 1, 11, and 21. The performance of the F1RDT done on site (on-site F1RDT) and at the Central Laboratory for Plague (reference laboratory F1RDT) was compared against two reference standards: RS1 (culture or PCR-positive), which is used in routine practice, and RS2 (RS1 and serology-positive), including all available confirmatory tests for plague.

Results: Of 438 suspected cases, 184 (42%) were confirmed by culture or PCR (RS1) and 211 (48%) by culture, PCR, or serology (RS2). PCR identified 179 cases (85%), culture 137 (65%), and serology 197 (93%). The combination of PCR and culture identified 87% of confirmed cases while the remaining 13% were identified by serology only. The sensitivity and specificity of on-site F1RDT were 94% (95% CI, 89.6-97.0) and 74% (95% CI, 68.2-79.3) against RS1 and 89.1% (95% CI, 84.1-93) and 77.5% (95% CI, 71.5-82.8) against RS2. The sensitivity and specificity of reference laboratory F1RDT were 91.8% (95% CI, 86.9-95.4), 97.6% (95% CI, 94.9-99.1) against RS1, and 82.0% (95% CI, 76.1-86.9) and 99.1% (95% CI, 96.9-99.9) against RS2.

Conclusions: PCR outperforms culture, the previous reference standard. While serology adds diagnostic value, it is impractical for routine use. The F1RDT done on site cannot be relied upon for clinical case management decisions. F1RDT performs better under laboratory conditions and could be implemented in peripheral laboratories for surveillance purposes in resource-constraint settings.