Background/Objectives: Antimicrobials are regularly prescribed in general practice, yet the infrastructure to support routine review of prescribing in this setting remains limited. Integrated antimicrobial stewardship (AMS) interventions combining automated auditing of routine prescribing data with an educational component are a promising approach to addressing this gap. This qualitative study aimed to explore general practitioner (GP) and practice manager (PM) perspectives on the acceptability, feasibility, and perceived effectiveness of such an intervention implemented across 31 general practices and 97 GPs in Victoria, Australia. It also explored implementation considerations relevant to future scaling of the intervention. This is one of the first studies of GP and PM perspectives on this type of integrated program. Methods: Semi-structured interviews were conducted with 17 GPs and 5 PMs and analyzed using both inductive and deductive thematic analysis. The Theoretical Domains Framework (TDF) informed interview guide development and deductive coding; themes were generated inductively and final themes mapped to the Capability, Opportunity, Motivation–Behavior (COM-B) model for presentation. Results: Four themes were identified: (1) trust, validity, and value of audit and feedback; (2) clinical judgement and patient factors in prescribing complexity; (3) social, organizational, and professional contexts of learning and behavior change; and (4) effort, usability, and workflow in engagement with the intervention. Conclusions: Participants valued AMS activities that supported reflective practice without undermining professional autonomy. Trust in the systems managing prescribing data was a precondition for engagement with the data itself. Engagement also depended on fit with existing workflows, individualized reporting, and contextualized feedback. The social conditions under which learning occurred, such as peer interaction, moderated discussion, and collaborative reflection, mattered as much as the technical components of a program.
Background: Bedaquiline (BDQ) is critical for multidrug-resistant tuberculosis (MDR-TB) treatment, but emerging resistance threatens its efficacy. Detection of BDQ resistance relies on slow phenotypic drug-susceptibility testing (pDST), delaying treatment decisions. We determined the diagnostic accuracy of whole-genome sequencing (WGS) for predicting BDQ resistance against culture-based pDST. Methods: Mycobacterium tuberculosis isolates underwent BDQ pDST (1.0 µg/mL in MGIT) in a prospective study of patients with MDR-TB with additional resistance to fluoroquinolones or aminoglycosides in KwaZulu-Natal, South Africa (2018–2022). Isolates with single nucleotide polymorphisms showing a read depth of ≥10 and allele frequency of ≥0.7 were included. Isolates exhibiting phenotypic resistance underwent quantitative minimum inhibitory concentration (MIC) testing (ranging from 0.25 to 8.0 µg/mL) using the BACTEC MGIT 960 system. Diagnostic performance of WGS compared to MGIT-based pDST was assessed by calculating sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). Results: Analysis included 428 isolates: 88 phenotypically resistant isolates (87 with potential BDQ-resistance-associated variants (RAVs) and one wild-type) and 340 susceptible isolates (7 with potential RAVs and 333 wild-type). Presence of potential RAVs accurately predicted phenotypic resistance: sensitivity 98.9% (95% CI: 93.8–99.8), specificity 97.9% (95% CI: 95.8–99.0), PPV 92.6% (95% CI: 85.4–96.4), and NPV 99.7% (95% CI: 98.3–99.6). Among the 94 isolates with potential RAVs, we observed gene mutations in Rv0678 (88/94, 93.6%), pepQ (2/94, 2.1%), and Rv1979c (4/94, 4.3%). The median BDQ MIC for resistant isolates was 4.0 µg/mL [IQR:2.0–4.0 µg/mL]. Conclusions: Potential BDQ RAVs, predominantly in Rv0678, are strong predictors of BDQ phenotypic resistance, highlighting the potential use of genotypic catalogues to inform timely treatment decisions.
Background/Objectives: The proliferation of antibiotic resistance genes (ARGs) in agricultural soils poses a growing One Health threat. However, how hydrological fluctuations in paddy–upland rotations shape the soil resistome remains unclear. This study examined the spatiotemporal dynamics and drivers of soil ARGs in a manure-amended rice–faba bean rotation system. Methods: A one-year field experiment was conducted using quantitative PCR and 16S rRNA gene sequencing to characterize ARGs, mobile genetic elements (MGEs), and bacterial communities. Results: The hydrological regime and manure application interactively drove resistome succession. Manure introduced diverse ARGs and MGEs, whereas redox fluctuations restructured bacterial host communities and ARG–MGE networks. Compared with the wet phase, the dry phase enriched intI1 by approximately two orders of magnitude. Specifically, the log10-transformed intI1/16S rRNA gene copy-number ratio increased from −7.11 to −5.14, indicating greater potential for horizontal gene transfer. The fallow transition period represented a critical resistome-restructuring stage with lasting legacy effects. Structural equation modeling identified a dominant carbon–microbe–MGE cascade. Active organic carbon fractions, including dissolved organic carbon (DOC) and readily oxidizable carbon (ROC), shaped microbial community structure, which regulated MGE abundance and ultimately ARG dynamics. MGEs were the strongest direct driver of ARGs (path coefficient = 0.575, p < 0.001). Conclusions: Wet–dry alternation modulates soil resistance risks through the carbon–microbe–MGE cascade. The fallow transition period therefore provides a key target for managing hydrology and carbon inputs to mitigate ARG dissemination in sustainable agroecosystems.
Background/Objectives: Curcumin is a food-grade (E100) photosensitiser with promising antimicrobial properties, but its applicability is limited due to low water-solubility. Complexation of curcumin with hydroxypropyl-γ-cyclodextrin (HP-γ-CD) overcomes this constraint and may facilitate using a single photosensitiser for Photodynamic Inactivation (PDI) of pathogens along the food-production chain and within a One Health framework. Methods: In this study, a novel method to complex HP-γ-CD and curcumin (abbreviated as CD-Cur) was developed and the compound was tested against Escherichia coli, Salmonella enterica, and Candidozyma auris, in liquid culture and in situ on abiotic surfaces, food matrices, and a porcine skin model. Results: Planktonic experiments demonstrated concentration-dependent PDI efficacy with photokilling exceeding the 3 log10 threshold for all tested organisms at CD-Cur concentrations between 10 and 50 µM, illuminated with 435 nm (50 J/cm2) LED light, while dark and light toxicity remained below microbiologically relevant levels. CD-Cur induced high reductions of viable E. coli on food-contact plastic foil (3.35 log10, 100 µM, white light, 100 J/cm2) and on abiotic surfaces (5.17–5.50 log10, 30 µM, 435 nm, 25 J/cm2) with visible photobleaching of the photosensitiser after illumination. On salmon and pistachios, matrix-dependent effects were observed, but PDI still achieved practically relevant reductions (2.25–3.52 log10, 30 µM, 435 nm, 200 J/cm2) of S. enterica without visible colour alteration of the food. In a porcine skin model, CD-Cur in a 1% hydroxyethyl cellulose hydrogel reduced C. auris contamination notably. The addition of 2 mM EDTA further enhanced antifungal effects, indicating that CD-Cur can also be applied in a medical context as topical application on porcine skin (2.41 log10, 500 µM, 435 nm, 75 J/cm2). Conclusions: Together, these results show that a single, photodynamic system based on food-grade CD-Cur can provide broad antimicrobial efficacy across diverse matrices and pathogens in a One Health context.
Background/Objectives: Tuberculosis (TB) in older adults represents an increasing clinical challenge, although this population remains underrepresented in clinical studies. We compared outcomes and permanent regimen modification between age groups in adults treated for drug-susceptible pulmonary TB. Methods: This retrospective study included 3621 consecutive adults treated at an Italian referral centre between 2000 and 2023. Patients were stratified as <65 and ≥65 years for the primary analysis; additional analyses used four age groups and continuous age. Logistic regression models were adjusted for sex, WHO region, socio-economic status, clinical setting, and calendar period. Results: There were 3173 patients aged <65 years and 448 aged ≥65 years. Crude treatment success was similar (90.0% vs. 89.3%; p = 0.65), whereas death during treatment was more frequent among older adults (4.7% vs. 0.3%; p < 0.001) and loss to follow-up among younger adults (6.0% vs. 2.0%; p < 0.001). After adjustment, age ≥65 years was associated with lower odds of treatment success (aOR 0.56, 95% CI 0.39–0.81) and higher odds of death (aOR 12.24, 95% CI 4.83–31.00). Compared with patients aged 65–79 years, those aged ≥80 years had lower adjusted odds of success (aOR 0.41, 95% CI 0.22–0.78; Holm-adjusted p = 0.025) and higher odds of death (aOR 4.49, 95% CI 1.78–11.28; Holm-adjusted p = 0.004). Permanent regimen modification did not differ between the two main age groups (3.8% vs. 4.7%; p = 0.34). Conclusions: Increasing age was associated with lower treatment success and higher mortality, particularly among adults aged ≥80 years, supporting closer clinical monitoring in this population.
