Invasive aspergillosis (IA) is a rare but fatal disease among liver transplant recipients (LiTRs). We performed a multi-center 1:2 case-control study comparing LiTRs diagnosed with proven/probable IA and controls with no invasive fungal infection. We included 62 IA cases and 124 matched controls. Disseminated infection occurred only in eight cases (13%). 12-week all-cause mortality of IA was 37%. In multivariate analyses, systemic antibiotics usage (adjusted odds ratio [aOR], 4.74; p=0.03) and history of pneumonia (aOR, 48.7; p=0.01) were identified as independent risk factors associated with the occurrence of IA. Moreover, reoperation (aOR, 5.99; p=0.01), systemic antibiotics usage (aOR, 5.03; p=0.04), and anti-mold prophylaxis (aOR, 11.9; p=0.02) were identified as independent risk factors associated with the occurrence of early IA. Among IA cases, Aspergillus colonization (adjusted hazard ration [aHR], 86.9; p<0.001), ICU stay (aHR, 3.67; p=0.02), disseminated IA (aHR, 8.98; p<0.001), and dialysis (aHR, 2.93; p=0.001) were identified as independent risk factors associated with 12-week all-cause mortality; while recent receipt of tacrolimus (aHR, 0.11; p=0.001) was protective. Mortality among LiTRs with IA remains high in the current era. The identified risk factors and protective factors may be useful for establishing robust targeted anti-mold prophylactic and appropriate treatment strategies against IA.

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is currently a serious global concern. Antimicrobial stewardship programs (ASPs) are one of the key strategies to overcome this resistance. However, evidence about the long-term clinical and ecological impacts of ASPs is scarce. A multidisciplinary team conducted a multifaceted intervention in a CR-Kp endemic hospital over a 6-year period. We assessed the monthly long-term impacts of ASPs on carbapenem use, incidence density (ID), and crude death rates of hospital-acquired CR-Kp infections. Other variables potentially related to CR-Kp incidence and healthcare activity indicators were monitored. Carbapenem use showed a sustained reduction over the long term, with a difference of −66.19% (95% CI −87.03 to −45.34) between the expected pre-intervention trend consumption value and that obtained six years after starting the program. The ID of CR-Kp also decreased significantly and was maintained over the long term, with a relative reduction of −88.14% (95% CI; −100.4 to −75.85) at the end of the study period. The crude death rate of CR-Kp at 14 and 28 days decreased significantly after the intervention and remained steady after six years. Infection control indicator trends remained stable. This mixed ASP contributed to reducing the high incidence of infections and mortality rates of CR-Kp, achieving a sustained ecological and clinical effect.

Respiratory syncytial virus (RSV) causes a significant disease burden in adults with chronic comorbidities. Rates of severe RSV disease and death are as high, or higher in younger adults with risk factors than in healthy older adults in whom RSV vaccination is recommended. We conducted an immunobridging study using the Ad26/protein RSV preF vaccine, which previously demonstrated efficacy in adults aged ≥65 years to support extrapolation of efficacy demonstrated in an older population to younger adult populations at high risk of severe RSV disease. This Phase 3 randomized, double-blind, placebo-controlled trial assessed the safety/tolerability and immunogenicity of Ad26/protein preF RSV in adults aged 18-59 years without (Cohort 1) and with (Cohort 2) chronic cardiac or pulmonary comorbidities, compared to adults aged ≥65 years (Cohort 3) in whom efficacy against RSV disease was demonstrated. Humoral and cellular immune responses were assessed at baseline, Days 15 and 183. Reactogenicity and safety were assessed in all participants. 1118 participants were enrolled (Cohort 1: 387; Cohort 2: 388; Cohort 3: 343). Compared to adults aged ≥65 years RSV neutralizing antibody titers were non-inferior in adults aged 18-59 years, including those at high risk. Levels of pre-F A IgG antibodies and frequencies of RSV-F specific interferon-gamma T-cells increased by Day 15 post-vaccination, and remained above baseline for at least 6 months in all cohorts. Reactogenicity and safety were clinically acceptable but age-dependent, with higher rates of Grade 3 systemic adverse events in adults aged 18-59-years than adults ≥65 years. Ad26/protein preF RSV vaccine induced robust humoral and cellular immune responses in adults aged 18-59 years with or without chronic cardiac or pulmonary comorbidities, of similar magnitude to responses in older adults, allowing inference of efficacy and protection against RSV-associated respiratory disease in this population. www. govNCT05070546.

The cutoff value of the commercial interferon (IFN)-γ release assay (QuantiFERON-CMV) proposed by the manufacturer is assumed to be predictive. We aimed to determine the optimal cutoff value for protection against clinically significant cytomegalovirus (CMV) infection within 30 days. We analyzed two different cohorts: adult CMV seropositive kidney transplant (KT) recipients with antithymocyte globulin (ATG) induction from the TIMOVAL study and seropositive lung transplant (LT) patients from the CYTOCOR study. The optimal cutoff value was established using Youden’s index. We estimated the predictive capacity of the cutoff value through the AUROC and assessed the diagnostic accuracy of the assay at the different cutoff values. We finally evaluated clinical variables that could improve the predictive ability of the assay on a predictive score. Four hundred-four samples from 130 transplant recipients were analyzed. The optimal cutoff value was ≥2.2 IU/mL for both populations, with a positive predictive value of 99% and 99.5% (95% CI, 98–100%) for KT and LT recipients, respectively. The AUROC of the predictive score was 0.85 (95% CI, 0.73–0.97). Using the proposed cutoff value and the Quanti-CMV score may allow the individualization of preventive strategies and serve as an objective tool to support clinical decision-making.

Infections caused by KPC-producing Klebsiella pneumoniae (KPC-KP) represent a persistent public health challenge. This prospective study examines ten-year trends, clinical features, and genomic epidemiology of hospital-onset (HOI) and non-hospital-onset (non-HOI, including healthcare-associated [HcAI] and community-acquired [CA]) KPC-KP infections following a 2012 outbreak. We evaluated the impacts of a 2014 antimicrobial stewardship program (ASP) and COVID-19-related infection prevention and control (IPC) measures, with emphasis on hospital-to-community dissemination. We analysed a prospective, longitudinal cohort of patients (2012–2022) in a tertiary referral hospital. Interrupted time series and ARIMA models assessed ASP and IPC impacts on incidence density (ID). Cross-correlation analysis explored temporal associations between HOI and non-HOI trends. Whole-genome sequencing and PERMANOVA evaluated the genomic structure of ST512/KPC-3 isolates. Multivariable regression analysed the association between infection type and clinical outcomes. Among 467 patients, 33.2% had non-HOI (ID 0.53/1,000 admissions/month) and 66.8% HOI (ID 0.30, p = 0.39). Urinary tract infections predominated in non-HOI (52.9%), while bloodstream and respiratory infections were more common in HOI. Incidence density of HOI and non-HOI infections declined significantly following ASP implementation, with a 4-month lag suggesting sequential transmission dynamics. These reductions were maintained during the pandemic. Genomic data confirmed ST512/KPC-3 dominance and hospital-to-community spread, with temporal factors—rather than acquisition type—explaining genetic variation. Adjusted analyses showed similar 30-day mortality and treatment responses across HOI and non-HOI. ASP and COVID-19 IPC measures contributed to maintaining low KPC-KP incidence. Genomic evidence underscores the role of temporal dynamics and clonal expansion in ST512/KPC-3 dissemination. Non-HOI infections are clinically significant and require targeted, system-wide surveillance and control strategies.

Background: The competencies required of life sciences graduates to participate in clinical trial research teams are poorly defined. Objective: This study aimed to establish a structured consensus on the core competencies that students must acquire during their degree programs. Methods: A RAND-modified Delphi procedure was conducted using 2 rounds of online questionnaires, a virtual meeting, and a final review. The process began with a questionnaire completed by experts from the University of Córdoba and the Maimonides Institute for Biomedical Research of Córdoba (3 principal investigators, 1 study coordinator, and 1 data manager). The 48 competencies initially proposed were reviewed by a panel of 18 experts representing 6 clinical research groups from universities and biomedical research institutes in Andalusia, Spain. The relevance of each proposed competency was rated on a 9-point Likert scale. Competencies were accepted if they achieved a mean score of 7 points or higher and at least 70% of ratings in the top tertile (scores of 7-9). Results: The 18 experts achieved 100% consensus on a panel of 48 competencies organized into 3 sections: fundamental concepts (n=23, 47.9% of the competencies), clinical trial development (n=23, 47.9% of the competencies), and certifications (n=2, 4.2% of the competencies). Conclusions: This consensus defines the core competencies required of undergraduate life sciences students for entry-level participation in clinical trial research. It also provides a framework for designing training strategies in both undergraduate and graduate programs of study.