Antibiotics-Basel最新文献

Background/Objectives: Rapid pathogen identification is essential to optimize antimicrobial therapy and improve patient outcomes, particularly in severe infections. Syndromic molecular diagnostics have been introduced to overcome the limitations of conventional culture-based methods. This study evaluated the diagnostic performance and real-life implementation of BioFire^® FilmArray^® syndromic panels compared with routine microbiological diagnostics. Methods: A total of 955 clinical specimens collected between 2022 and June 2025 were retrospectively analyzed, including positive blood cultures (n = 400), lower respiratory tract samples (n = 309), cerebrospinal fluid (n = 158) and stool specimens (n = 88). FilmArray^® BCID2, Pneumonia Plus, Meningitis/Encephalitis and Gastrointestinal panels were performed on the Biofire Fimarray^® instrument according to clinical indication and compared with conventional culture-based identification and phenotypic antimicrobial susceptibility testing. Results: Overall diagnostic concordance between BioFire^® FilmArray^® syndromic panels and conventional methods was high across all specimen types, with the highest positive percent agreement (PPA) observed for bloodstream infections (97.7%) and gastrointestinal pathogens (100%). In respiratory samples, the Pneumonia Plus panel detected a considerable number of microorganisms that could not be identified by culture, including viral pathogens and fastidious bacteria. Molecular detection of antimicrobial resistance markers showed excellent concordance with phenotypic profiles, with 100% agreement for CTX-M, carbapenemases (KPC, NDM, OXA-48-like, IMP), and vanA/B, while lower concordance was observed for mecA/C in staphylococci. In parallel, semi-quantitative bacterial loads provided by the Pneumonia Plus panel showed a strong essential agreement with culture-based quantification (97.4%, ±1 log₁₀). Across all panels, syndromic testing significantly reduced diagnostic turnaround time. Conclusions: Syndromic molecular panels provide rapid and reliable simultaneous detection of pathogens, as well as early resistance marker detection, thereby supporting timely antimicrobial optimization and stewardship when integrated with conventional microbiological diagnostics.

Background: Antibiotic misuse and overuse remain a critical driver of antimicrobial resistance (AMR), a global health threat associated with increased morbidity, mortality, and healthcare costs. In Greece, where antibiotic consumption and resistance rates are among the highest in Europe, community pharmacists are well-positioned to contribute to antimicrobial stewardship efforts.

Objective: This study aimed to assess the knowledge and attitudes of community pharmacists in Achaia, Western Greece, regarding antibiotic use and AMR, in order to identify knowledge gaps and inform future educational interventions.

Methods: A cross-sectional survey was conducted between May and July 2023 among 207 pharmacists using a structured, self-administered questionnaire. The survey assessed demographics, knowledge of antibiotic indications, dispensing practices, and awareness of AMR. Statistical analysis included Chi-square tests and multivariate logistic regression.

Results: Pharmacists demonstrated high levels of knowledge regarding appropriate antibiotic use in conditions such as sore throat (95%), bronchitis (76%), influenza (77.5%), and diarrhea (95%). However, knowledge was lower for rhinitis (60%) and sinusitis (56%). Almost all pharmacists (99%) were aware of AMR, and 86% perceived it as a significant public health issue in Greece. Logistic regression showed that pharmacists with 5-10 years of experience were significantly less likely to believe that antibiotics are always effective (OR = 0.08, p = 0.042).

Conclusion: Pharmacists in Western Greece are generally well-informed about antibiotic use and AMR, yet misconceptions persist, especially for viral infections. Targeted educational interventions, interprofessional collaboration, and stricter enforcement of prescription regulations are needed to strengthen the role of pharmacists in combating AMR at the community level.

Introduction: The global rise in antimicrobial resistance poses a growing threat to public health, particularly in low- and middle-income countries where diagnostic capacity and surveillance systems remain limited. In these settings, optimizing empiric antibiotic prescribing is critical, and syndromic antibiograms offer a promising approach to support evidence-based decision-making. This study examines anticipated barriers and facilitators to the adoption of syndromic antibiograms from the perspectives of pediatric clinicians and laboratory professionals at Maputo Central Hospital in Mozambique. Methods: Guided by the Dynamic Adaptation Process (DAP) framework, this qualitative study used semi-structured interviews with eighteen healthcare professionals to explore empiric antibiotic prescribing practices, perceptions of syndromic antibiograms, and system-level barriers and facilitators. Data were analyzed thematically using deductive codes derived from the DAP framework alongside inductive codes generated from participants' narratives. Results: Barriers were identified at individual, organizational, and systems levels. Individual barriers included limited awareness, reliance on traditional practices, and resistance to change. Organizational barriers included weak leadership support, insufficient training, poor communication between clinicians and laboratory staff, suboptimal sample collection, heavy workloads, and staff shortages. Systems-level barriers comprised shortages of laboratory supplies and medicines, delays in laboratory results, and weak monitoring mechanisms. Facilitators included health worker motivation for evidence-based practice, organizational collaboration, peer and team support, and the presence of influential champions. Systems-level enablers included functional laboratory services, supportive institutional environments, alignment with clinical guidelines, and recognition of clinical utility. Conclusions: Successful implementation of syndromic antibiograms in LMIC will require addressing systemic and organizational barriers while fostering professional motivation, collaboration, and institutional support. Sustainable integration will depend on coordinated strategies-including resource strengthening, continuous training, supportive leadership, and structured monitoring-that collectively strengthen antimicrobial stewardship and inform health policy.

Background/Objectives: This study aimed to describe the population pharmacokinetics of cefazolin (CFZ) using unbound serum and periprostatic adipose tissue concentrations and to optimize dosing regimens for patients undergoing robotic-assisted radical prostatectomy (RARP). Methods: We investigated the population pharmacokinetics of CFZ using 295 unbound serum and 67 periprostatic adipose tissue samples from 67 individuals. CFZ concentrations were determined in all samples. A nonlinear mixed-effects model was developed. The pharmacodynamic target was defined as maintaining unbound trough and periprostatic adipose tissue concentrations exceeding the minimum inhibitory concentration (MIC) against methicillin-susceptible Staphylococcus aureus (MSSA) for over 90% of the dosing interval (MIC₉₀; 0.5 mg/L). Results: Systemic clearance of unbound CFZ was significantly associated with creatinine clearance (CLcr). In patients with normal renal function, simulations showed that a 1 g CFZ infusion over 15 min maintained unbound concentrations exceeding the MSSA MIC₉₀ for >90% of the 3 h interval after the initial dose. Notably, in patients with mild renal impairment (CLcr ≤ 80 mL/min), a 5 h dosing interval also achieved a >90% probability of maintaining the target CFZ concentration. Conclusions: The simulations demonstrated that the probability of target attainment of >90% was maintained for up to 5 h in patients with mild renal impairment (CLcr ≤ 80 mL/min). These findings provide a pharmacokinetic rationale suggesting that the standard additional dose may not be necessary for this subgroup; however, future clinical studies are needed to validate safety and efficacy.

In the face of rising antimicrobial resistance, food insecurity, and climate change, bacteriophages are gaining renewed attention as promising biological alternatives to antibiotics across human, animal, and plant health sectors. Their high specificity, self-replicating capacity, and biodegradability make them valuable tools for combating antimicrobial or pesticide resistance and promoting sustainable biocontrol. This review discusses commonly accepted selection criteria for therapeutic phages, such as avoiding temperate types and screening for undesirable genes, while acknowledging ongoing debates and exceptions in specific clinical or ecological contexts. An overview of phage-based applications within a One Health framework is provided, spanning human medicine, veterinary practice, aquaculture, food safety and crop protection. Particular attention is given to agricultural biocontrol, where several successful plant protection strategies are highlighted, illustrating the feasibility and diversity of phage-based approaches. Despite their potential, key challenges remain regarding phage stability, formulation, and persistence under environmental conditions. Emerging innovations such as encapsulation, carrier bacteria, and protective formulations aim to enhance field performance. Furthermore, this review emphasizes the need to assess the environmental safety of phage applications, particularly their impacts on natural ecosystems, microbial communities, and ecological functions. Finally, the regulatory and policy challenges that currently limit the large-scale deployment of phages, particularly in the European Union, where they remain evaluated under conventional chemical pesticide frameworks are discussed. The development of dedicated regulatory pathways, better adapted to the specificities of phages, is argued to be essential for supporting their integration into agroecological transition strategies and next-generation antimicrobial policies.

Background/Objectives: Gramicidin S (GS) is a cyclic antimicrobial peptide with strong antibacterial activity but significant cytotoxicity toward mammalian cells. This study evaluated GS-induced cytotoxicity in L929 fibroblast cells using both traditional 2D monolayer cultures and more physiologically relevant 3D spheroid models, and assessed whether liposomal encapsulation could mitigate toxicity and improve biocompatibility. Methods: L929 cells were cultured in monolayers and spheroids and treated with free GS or GS encapsulated in liposomes of varying lipid compositions. Cell viability and morphology were evaluated after 24 h of exposure using standard cytotoxicity assays. Results: Control liposomes, regardless of tested lipid type or concentration, showed no adverse effects on cell morphology or viability. Free GS caused pronounced, dose-dependent cytotoxicity in monolayers, decreasing viability to 11.0 ± 1.9% and 0.5 ± 1.1% at 50 and 75 µg/mL, respectively. By contrast, encapsulation in liposomes significantly reduced toxicity (p < 0.05), preserving 80.3-82.2% viability at 75 µg/mL depending on formulation, corresponding to protection factors exceeding 160-fold (80.3% vs. 0.5%). Spheroid cultures showed slightly higher resistance to GS; free GS reduced viability to 2.9%, while liposomal GS preserved it above 84.8%, depending on lipid composition. Conclusions: Liposomal encapsulation effectively reduces GS-induced cytotoxicity, likely by limiting direct membrane disruption. Moreover, spheroid models provide a more physiologically relevant and predictive platform for toxicity testing, while the results support nanoliposomes as a practical delivery strategy to enhance the safety of antimicrobial peptides during preclinical development.

Background: AMR is a public health concern which leads to high global morbidity and mortality. Immunocompromised patients, who are more susceptible to contracting potentially life-threatening infections, are faced with reduced treatment options due to emerging AMR. Ceftolozane/tazobactam is a novel β-lactam/β-lactamase inhibitor which displays effectiveness against resistant Gram-negative infections. Methods: SPECTRA was a multinational, observational study conducted in seven countries including 617 patients who received ≥48 h of ceftolozane/tazobactam. Medical-record data were collected up to 6 months before treatment and 30 days after the final dose or until death. This analysis describes clinical outcomes and healthcare resource use in patients with sepsis or who were immunocompromised, specifically in patients with hematologic malignancy with and without solid tumor, febrile neutropenia, and solid organ transplant patients. Results: Clinical success ranged from 50.0% in patients with hematologic malignancy and solid tumor to 69.4% in 38 patients with febrile neutropenia. All-cause in-hospital mortality was 23.1-42.9%, with the lowest rates in patients with solid organ transplant. ICU admission was 46.4-68.2% across subpopulations (excluding febrile neutropenia) with the lowest rates in patients with hematologic malignancy. ICU length of stay was lowest within transplant patients (9 days) and highest within the hematologic malignancy and solid tumor population (32 days). Conclusions: The results from this sub analysis of SPECTRA showed that ceftolozane/tazobactam was associated with clinical success in the selected immunocompromised and sepsis patient populations and may lead to reduced morbidity, mortality, and healthcare-resource use. Further research is required to standardize treatment protocols and improve patient outcomes.

Background: Intensive poultry production systems can act as reservoirs for antibiotic-resistant and multidrug-resistant (MDR) Escherichia coli, posing a public health risk through food and environmental transmission. Methods: This study investigated the genomic characteristics of antibiotic-resistant E. coli isolated from an intensive poultry production system in the uMgungundlovu District, KwaZulu-Natal, South Africa. Chicken litter, wastewater, and floor swab samples were collected over three consecutive production cycles. Putative E. coli isolates were detected using the Colilert-18 system, cultured on eosin methylene blue agar, and genomically confirmed by quantitative PCR (q-PCR) targeting the uidA gene. Whole genome sequencing was performed using the Illumina MiSeq platform, followed by bioinformatic analyses to assess resistance genes, mobile genetic elements, and phylogenetic relationships. Results: Of 150 presumptive E. coli, 70 were genomically confirmed as E. coli and resistant to at least one antibiotic, with 74% exhibiting multidrug resistance. Resistance was highest to tetracycline (100%), ampicillin (94%), and trimethoprim-sulfamethoxazole (76%), while ciprofloxacin resistance was rare (3%). Genomic analysis identified multiple antibiotic resistance genes conferring resistance to fluoroquinolones, β-lactams, aminoglycosides, amphenicols, fosfomycin, and sulfonamides, as well as the disinfectant resistance gene qacI. These genes were frequently associated with mobile genetic elements, including plasmids, integrons, transposons, and insertion sequences. Predominant sequence types included ST155, ST48, ST1286, and ST602, with phylogenetic relatedness to poultry-associated isolates from Cameroon, Ghana, Nigeria, and Tanzania, as well as environmental E. coli strains previously identified in South Africa and Ghana. Conclusions: The detection of diverse, mobile MDR E. coli lineages in poultry environments clearly signals a substantial risk for resistance gene dissemination into the food chain and surrounding ecosystems. Immediate attention and intervention are warranted to mitigate public health threats.

Background/objectives: As part of the European Union's harmonized monitoring framework, Belgium conducts antimicrobial resistance (AMR) monitoring in commensal bacteria from livestock. The aim of this study was to conduct a cost analysis of the national AMR monitoring in livestock, and to explore sampling size scenarios in relation to their associated costs and statistical performance (power and confidence) of monitoring.

Methods: To our knowledge, this is the first published cost evaluation using unit cost aggregation of a national AMR monitoring program in animals.

Results: The testing of the different sample size scenarios showed that if the sample size increases, the costs increase linearly. A sample size increase of 10 samples/isolates (e.g., from 170 to 180) can increase the yearly total costs per animal species by 5.2%. Moreover, the testing of the different scenarios showed that if the sample size increases, the power and the confidence level also increase, providing a higher level of trust in the results of the monitoring program. The highest total monitoring costs per animal category were estimated for fattening pigs, broilers and veal calves (over 18% of total costs each, using 2024 data). Among the various monitoring activities, antimicrobial susceptibility testing emerged as the costliest component, representing 50.2% of the total monitoring costs.

Conclusions: The approach presented allows it to be used by other countries aiming to estimate the cost of their national AMR monitoring in animals or other similar activities. This economic and scenario testing analysis can be used to suggest informed suggestions to improve AMR monitoring in animals.

Background: Septic shock is a leading cause of mortality worldwide, with community-acquired (CA) and hospital-acquired (HA) infections representing distinct clinical entities. The differences in clinical characteristics, immune response profiles, and effects of sepsis treatments between CA and HA septic shock have not been fully elucidated. Methods: This retrospective cohort study included 726 adults with septic shock who were admitted to two ICUs at Modena University Hospital between January 2006 and September 2024. Patients were classified as having CA or HA septic shock based on the origin of the infection. Clinical, microbiological, and immunological data, treatments, and outcomes were analysed. Immune cell dynamics were assessed during the first week after the onset of the shock. Multivariable Cox regression models were used to identify predictors and the effects of treatment on ICU mortality. Results: Among 344 patients with CA and 382 with HA septic shock, those with CA had higher severity scores but lower ICU and in-hospital mortality. Patients with HA exhibited a higher prevalence of multidrug-resistant organisms and more comorbidities. Immunologically, CA survivors showed increasing lymphocyte counts over time, whereas HA survivors mainly demonstrated recovery in T helper cells. Therapeutic strategies were similar between groups; however, continuous renal replacement therapy was more frequent in patients with HA. Neither appropriate empiric antibiotics nor steroids or immunoglobulin therapy independently improved mortality in the multivariate analyses. Conclusions: CA and HA septic shock differ significantly in terms of clinical severity, microbiological aetiology, immune recovery patterns, and outcomes. The lack of mortality benefit from standard treatments highlights the need for personalised management strategies that integrate clinical, immunological, and microbiological data to optimise care in septic shock subpopulations.