Other specific DSP article suggested by Editorial Board
Harnessing host-derived biomarkers for personalized diagnosis of invasive fungal infections.
Authors: Scott J et al
Abstract
Introduction: Invasive fungal infections (IFIs) remain a major clinical challenge due to the expansion of high-risk patient groups and drawbacks of conventional diagnostics which contribute to the devastating mortality rates associated with these diseases. Areas covered: Current mycological diagnostics suffer from limitations of sensitivity, specificity, and the capacity to determine invasive infection. Here,advancements in omics technologies are explored which present opportunities to gain insights into the host response to invasive infection. Developments in genomics, transcriptomics, proteomics, and metabolomics and their applications for investigating host-pathogen interactions during IFIs are discussed. The literature search was conducted in the PubMed database for the period between January 2020 and August 2025. Expert opinion/commentary: The focus is on the potential of host-based biomarkers to facilitate personalized medicine at every stage of disease management. Covering initial risk stratification, diagnosis, prognosis, choice of antifungal therapy, disease monitoring, and antifungal stewardship. The possibility of exploiting these biomarkers in a proactive and preventative approach to allows early and personalized antifungal treatment of IFIs is underscored. To maximize the potential of the data gathered, the utility of frameworks is highlighted that integrate and optimize existing diagnostic expertise.
Other specific DSP article suggested by Editorial Board
aiGeneR 3.0: an enhanced deep network model for resistant strain identification and multi-drug resistance prediction in Escherichia coli causing urinary tract infection using next-generation sequencing data.
Authors: Nayak DSK et al
Abstract
Background: Infectious diseases pose a global health threat, with antimicrobial resistance (AMR) exacerbating the issue. Considering Escherichia coli (E. coli) is frequently linked to urinary tract infections, researching antibiotic resistance genes in this context is essential for identifying and combating the growing problem of drug resistance.
Objective: Machine learning (ML), particularly deep learning (DL), has proven effective in rapidly detecting strains for infection prevention and reducing mortality rates. It is proposed that aiGeneR 3.0, a simplified and effective DL model employing a long-short-term memory mechanism for identifying multi-drug resistant and resistant strains in E. coli. The aiGeneR 3.0 paradigm for identifying and classifying antibiotic resistance is a tandem link of quality control incorporated with DL models. Cross-validation was adopted to measure the ROC-AUC, F1-score, accuracy, precision, sensitivity, specificity, and overall classification performance of aiGeneR 3.0. It is hypothesized that the aiGeneR 3.0 would be more effective than other baseline DL models for antibiotic resistance detection with an effective computational cost. Here, it is assessed how well this model can be memorized and generalized.
Results: The aiGeneR 3.0 can handle imbalances and small datasets, offering higher classification accuracy (93%) with a simple model architecture. The multi-drug resistance prediction ability of aiGeneR 3.0 has a prediction accuracy of 98%. aiGeneR 3.0 uses deep networks (LSTM) with next-generation sequencing (NGS) data, making it suitable for novel antibiotics and growing resistance identification in the future.
Conclusion: This work uniquely integrates SNP-level insights with DL, offering potential clinical utility in guiding antibiotic stewardship. It also enables a robust, generalized, and memorized model for future use in AMR analysis.
Other specific DSP article suggested by Editorial Board
Effectiveness of imipenem-relebactam for multidrug-resistant Pseudomonas aeruginosa in pneumonia and bloodstream infections in the United States (MIRAGE).
DOI: 10.1128/aac.01325-25
Authors: Wangchinda W et al
Abstract
Imipenem-relebactam demonstrates in vitro activity against multidrug-resistant (MDR) Pseudomonas aeruginosa, but real-world effectiveness data are limited. MIRAGE was a multicenter, retrospective, observational study of imipenem-relebactam for MDR P. aeruginosa pneumonia and bacteremia. Patients were included if they received imipenem-relebactam for >48 h within 7 days of index P. aeruginosa culture. The primary outcome was clinical success at day 30, defined as survival, resolution of signs and symptoms of infection, completion of intended treatment course, and absence of recurrent infection. Secondary outcomes included 30- and 90-day mortality, infection recurrence, and development of non-susceptibility. Sixty-three patients were included. Median (IQR) age was 61 (51-70) years, and the median Charlson Comorbidity Index was 5 (3-6). Forty-six percent of patients had an immunocompromising condition, 79% were in the intensive care unit, 76% were receiving mechanical ventilation, and 48% required vasopressors. Median SOFA score was 7 (5-12). Forty percent of index isolates that were tested displayed non-susceptibility to both ceftolozane-tazobactam and ceftazidime-avibactam. Fifty-six percent of patients achieved clinical success at day 30. All-cause 30- and 90-day mortality rates were 18% and 29%, respectively. Recurrent infections were documented in 37% of patients within 90 days, and resistance developed in 39% (16/41) of evaluable patients. Clinical outcomes following imipenem-relebactam for treatment of MDR P. aeruginosa were comparable to those reported in real-world studies for other novel β-lactam agents. Our data suggests that imipenem-relebactam has a role in the treatment of patients infected with MDR P. aeruginosa.
Other specific DSP article suggested by Editorial Board
Clinical Impact of Implementing a Specific Clinical Pathway for the Management of Clostridioides difficile Infection.
Authors: Rodriguez-Fernandez M et al
Abstract
Introduction: Despite Clostridioides difficile infection (CDI) being a leading healthcare-associated infection with high morbimortality, there is little evidence on specific antimicrobial stewardship program (ASP) interventions for CDI. The objective of this study was to assess the clinical impact of implementing a specific clinical pathway for CDI management at two Spanish hospitals.
Methods: This was a quasi-experimental pre-post intervention study, and three periods were evaluated: historical (2014-2017), educational-ASP (2018-2020), and intervention (2021-2023), after implementation of a CDI-specific measures bundle. Key measures included: (1) updated local CDI guidelines; (2) 24/7 diagnostic testing and real-time positive results notification to ASP-CDI team; (3) systematic evaluation of new cases; (4) optimizing CDI antibiotic treatment and overall management; and (5) structured follow-up until 8 weeks post-treatment. Primary outcome was first CDI recurrence, and secondary outcomes were readmissions during recurrent CDI episodes and 30-day all-cause mortality.
Results: In total, there were 1435 patients with CDI included: 370 in the historical period (2014-2017), 537 in the educational-ASP period (2018-2020), and 528 in the CDI-specific clinical pathway period (2021-2023). First CDI recurrence rates significantly declined across periods in high-risk groups: immunocompromised patients, 29% in 2014-2017, 22% in 2018-2020, and 15% in 2021-2023 (p = 0.038); those with severe/fulminant initial CDI, from 38% to 34% to 24% (p = 0.027); and patients aged 65-79 years, from 29% to 31% to 13% (p = 0.003). Hospitalization during recurrent CDI episodes and mortality were significantly reduced in the CDI-specific clinical pathway period: readmissions, 11% (2014-2017), 13% (2018-2020), and 6% (2021-2023) (p = 0.017); mortality, 7%, 6%, and 4% (p = 0.023).
Conclusions: The implementation of a structured, multifaceted clinical pathway specifically designed for CDI management had significant clinical benefits, including a reduction of recurrences in high-risk groups, readmissions, and mortality.
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Rate and Predictors of Urine Culture Positivity Following Single-Dose Antibiotic Administration: a Prospective Single-Center Study
Authors: Neta Sror
Abstract
Introduction: International guidelines advocate obtaining urine cultures prior to antibiotic administration in hospitalized patients with suspected urinary tract infection (UTI). However, adherence remains suboptimal. The aim of this study was to evaluate the positivity rate of urine cultures following a single empiric antibiotic dose and to identify factors associated with post-antibiotic culture positivity.
Methods: A prospective observational study was conducted in an internal medicine ward between December 2019 and June 2024. Patients diagnosed with UTI who had both pre- and post-antibiotic urine cultures were included. Positivity rates of post-antibiotic urine cultures were assessed. Factors associated with culture positivity were examined using logistic regression.
Results: A total of 132 patients were included in the analysis (59% female; median age 79 years). Eighty-eight patients (67%) had a positive post-antibiotic urine culture. The positivity rate in patients with a sensitive and resistant uropathogen to the empirically administrated antibiotic was 58% and 100%, respectively. Independent predictors for urine culture positivity included older age (adjusted odds ratio [aOR] 1.04, confidence interval [CI] 1.01–1.07, p = 0.007) and recent urinary catheter use in the last 30 days (aOR 14.7, CI 1.66–128, p = 0.016). Culture sampling more than 9 h after antibiotic administration was a negative predictor for culture positivity (aOR 0.41, CI 0.18–0.96, p = 0.041).
Conclusion: Urine culture positivity remains high after a single antibiotic dose in hospitalized patients with UTI. In cases where pre-antibiotic urine cultures are missed, a timely post-antibiotic urine sampling remains clinically relevant for pathogen identification and appropriate antibiotic selection.”
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Optimizing Polymyxin B Therapy in Critical Care: Pharmacokinetic Insights and Clinical Outcomes in a Retrospective Cohort Study.
Authors: Qingyun Peng
Abstract
Introduction: Carbapenem-resistant Gram-negative bacteria pose significant global health threats due to high infection rates and limited treatment options. Polymyxin B (PMB) has reemerged as a last-line therapy against these pathogens, despite nephrotoxicity and neurotoxicity concerns. However, the precise correlation between PMB exposure and response/toxicity has not been well established. The objective of this study was to assess the impact of polymyxin B pharmacokinetics on clinical outcomes in critically ill patients.
Methods: This single-center, retrospective study included 146 critically ill patients treated with PMB from January 2020 to July 2023. The primary outcome was 28-day mortality, while secondary outcomes included clinical efficacy, length of hospital and intensive care unit (ICU) stay and new onset acute kidney injury (AKI).
Results: The 28-day mortality rate was 43.2%. Multivariable Cox regression analysis showed PMB pharmacokinetic parameters, an area under the concentration–time curve across 24 h at steady state (AUCss, 24 h), C6h, and Cmin were associated with mortality. The receiver operating characteristic (ROC) analysis indicated an AUCss, 24 h cutoff of 81.6 mg·h/l for predicting mortality. AKI occurred in 40.6% of patients. Logistic regression revealed that baseline estimated glomerular filtration rate (eGFR) (adjusted OR 0.979, 95% CI 0.963–0.994, P = 0.007) and PMB treatment duration (adjusted OR 1.101, 95% CI 1.007–1.204, P = 0.034) were independent risk factors for AKI.
Conclusions: PMB pharmacokinetics are closely related to patient outcomes. An AUCss, 24 h ≥ 81.6 mg·h/l may reduce mortality. Baseline eGFR and PMB treatment duration are independent risk factors for AKI during PMB therapy.”
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Prevalence of colorectal cancer in patients with Enterococcus faecalis blood stream infection: A nationwide study
Authors: L Østergaard
Abstract
Background: Some studies have suggested an association between Enterococcus faecalis blood stream infection (BSI) and colorectal cancer (CRC) suggesting that screening for CRC could be reasonable. However, these studies were limited by small numbers with low generalizability.
Methods: Danish nationwide registries were used to identify patients with first-time E. faecalis BSI from 2010 –2021 without previous colorectal neoplasia (CRN). Age-, sex- and calendar-matched comparators from the general population was identified (1:5). We estimated the six-month cumulative incidence of CRC and CRN and a multivariable adjusted Cox analysis was used for relative comparison between groups.
Results: We identified 4,664 patients with E. faecalis BSI (median age: 74.9 years, 73.4% males) and 23,320 comparators from the general population. For patients with E. faecalis BSI the six-month incidence of CRC was 0.45% (95% CI: 0.28-0.72%) and of CRN 2.34% (95% CI: 1.88-2.88). For matched comparators the incidence of CRC was 0.12% (95% CI: 0.08-0.17) and of CRN 0.48% (95% CI: 0.39-0.57). In adjusted analysis, patients with E. faecalis BSI had a higher HR of CRC (HR=3.70 (95% CI: 1.91-7.19) and CRN (HR=4.64 (95% CI: 3.40-6.34) than matched comparators. The six-month mortality was 36.3% in patients with E. faecalis BSI while this was 1.7% among comparators.
Conclusion: In patients with first-time E. faecalis BSI the six months incidence of CRC was around 0.5% and 2.3% for the diagnosis of CRN, which were 3-4 times higher than in a matched cohort from the general population. Nevertheless, the absolute risks do not justify systematic screening for CRC or CRN in patients with E. faecalis BSI.
Keywords: Enterococcus faecalis
colorectal cancer
colorectal neoplasia”
Other specific DSP article suggested by Editorial Board
Association between pre-diagnostic fluoroquinolone exposure and possible acquired fluoroquinolone resistance in Mycobacterium tuberculosis in Shanghai: an EHR-based case-control study using whole-genome sequencing
Authors: Yangyi Zhang
Abstract
Objectives: Fluoroquinolones (FQ) are one of the most prescribed broad-spectrum antibiotics and a cornerstone of tuberculosis (TB) treatment. TB patients may have had FQ resistance before treatment initiation. However, the association between pre-diagnostic FQ exposure and acquired FQ-resistant TB remains unclear.
Methods: A case-control study was conducted among all pulmonary TB patients in Shanghai during 2022-2023. Cases were TB patients who had possible acquired FQ resistance identified through whole-genome sequencing (WGS), while controls were FQ susceptible patients. Pre-diagnostic FQ prescriptions were extracted from the Shanghai Electronic Health Record (EHR) platform.
Results: Among 3,496 patients, 7.4% had FQ-resistant TB, with 93.5% (243/260) phylogenetically inferred as possible acquired resistance. Multivariate analysis revealed FQ exposure was the strongest predictor of possible acquired FQ resistance with an aOR of 4.31 for a single prescription and 13.18 for multiple prescriptions. A nonlinear dose-response relationship between resistance probability and prescription number was found. Most prescriptions to cases were from non-TB-designated tertiary hospitals for non-TB respiratory diseases, with an exposure interval of ≥61 days prior to TB diagnosis.
Conclusion : Acquired resistance dominates FQ resistance in Shanghai TB patients. The dose-response relationship between pre-diagnostic FQ exposure and possible acquired resistance underscores the need for judicious FQ use.”