Antibiotics-Basel最新文献

Background: Antibiotic overuse in Neonatal Intensive Care Units (NICUs) is a major contributor to antimicrobial resistance and adverse neonatal outcomes. This study aims to evaluate baseline antibiotic utilization (AU), identify factors influencing variability, and assess the impact of neonatal characteristics and sepsis incidence. Methods: A multicenter retrospective analysis examined AU in seven NICUs from 2019 to 2023, involving 25,532 neonatal admissions during national antibiotic stewardship program implementation. Data encompassed neonatal clinical parameters, sepsis incidence, and AU metrics, including days of therapy (DOT) per 1000 patient-days. Statistical analyses included correlation assessments and multivariate regression to identify determinants of antibiotic use. Results: Overall, 43.8% of neonates received antimicrobials, with individual NICUs ranging from 24% to 73% (p < 0.001). Antimicrobial-exposed neonates had a mean gestational age of 35.1 weeks [SD ± 4.4] and a mean birth weight of 2360 g [SD ± 970]. Antimicrobial-exposed neonates were generally more premature [35.1 (±4.4) weeks vs. 37.5 (±2.5) weeks (p < 0.001)] and had lower mean birth weight [2360 g (±971) vs. 2817 g (±686) (p < 0.001)] compared to those not exposed to antimicrobials. Total antimicrobial days varied markedly (8761 to 37,683 days), with DOT per 1000 patient-days ranging from 322 to 1031. Antimicrobial use for culture-negative sepsis varied widely among centers, from 23% to 73%. Antimicrobial-exposed neonates had higher all-cause mortality compared to those who did not [(7.5% vs. 3.2%), (p < 0.001)]. Multivariate analysis revealed individual NICU practice patterns remained significant predictors after adjusting for neonatal characteristics. Conclusions: Neonatal antimicrobial use varied significantly among NICUs, driven primarily by institutional practices rather than neonatal demographics. These findings provide nationally representative baseline data to inform neonatal antimicrobial stewardship interventions and offer transferable lessons for other countries seeking to optimize antibiotic use in NICUs amid rising global antimicrobial resistance.

The intensification of aquaculture practices has been accompanied by an increased incidence of bacterial diseases, leading to a greater reliance on antibiotics for disease control. Consequently, the widespread and often indiscriminate use of these compounds has contributed to the emergence and dissemination of antibiotic-resistant bacteria within aquaculture systems, posing a serious threat to animal health, environmental sustainability, and public health. In this regard, research efforts have focused on developing alternative strategies to reduce antibiotic use. Natural compounds have gained particular attention due to their well-documented antimicrobial and antibiofilm activities. In this context, the combined application of antibiotics and natural compounds has emerged as a promising approach to enhance antimicrobial efficacy while potentially mitigating the development of resistance. This review synthesizes the current knowledge on antibiotic resistance in aquaculture, highlights the role of biofilm formation as a key resistance mechanism, and critically examines the potential of antibiotic-natural compound combinations against major aquaculture pathogens, with particular emphasis on bacterial growth inhibition, biofilm disruption, and virulence attenuation. Collectively, the evidence discussed underscores the potential of synergistic strategies as a sustainable tool for improving disease management in aquaculture while supporting efforts to limit antibiotic resistance.

Objective: Physician assistants (PAs) are frequently involved in managing acute bacterial infections in patients with documented penicillin (PCN) allergies. Inappropriate antibiotic choice in patients with existing allergies may place them at undue risk. This study aimed to assess the knowledge and confidence among PA students in managing patients with documented PCN allergies. Methods: An electronic survey was distributed to enrolled students in participating PA programs in North and South Carolina. The survey tool consisted of 20 questions with 13 focused on knowledge and confidence primarily scored on a 5-point Likert scale. Data were collected and protected via the REDCap^® database. Primary objectives were knowledge of penicillin allergies and confidence in management decisions. Sufficient knowledge was considered a score of 80% or greater; adequate knowledge was considered 70% or greater on relevant assessments. Results: Overall, 406 students from 10 unique programs completed the survey. They were predominantly female (76%) with 43% in the first year of their program. The mean student knowledge score was 25.9%, and 30% of respondents achieved adequate knowledge. Respondents reported an average cross reactivity between penicillin and beta-lactams of 29% (10-63%), cefazolin 50% (24-75), ceftriaxone 29% (11-60), and carbapenems 26% (8-50). The majority of respondents (66.5%) reported high levels of confidence in managing patients with penicillin allergies. Conclusions: The study found significant discordance between PA students' high level of confidence in assessing patients with a PCN allergy and their comparative knowledge. PA students are likely to avoid beta-lactam antibiotics when there is a documented penicillin allergy, regardless of the documented reaction or low likelihood of cross-reactivity. Further training and education will help to encourage appropriate prescribing in these high-risk patients.

Background/objectives: The expansion of intensive swine production in Córdoba, Argentina, underscores the need to assess the risks associated with antimicrobial (AM) use, whose extensive application has driven antimicrobial resistance, a major global threat within the One Health framework. This study aimed to characterize AM use practices and evaluate the epidemiological resistance profiles (non-wild-type phenotypes, NWT) of commensal Escherichia coli of fecal origin from swine farms, using epidemiological cut-off values (ECOFFs) as a surveillance criterion.

Methods: An observational cross-sectional study was conducted in 19 farrow-to-finish farms in Córdoba during 2023. Information on AM use (prophylaxis, metaphylaxis, treatment) across production categories was collected. A total of 437 E. coli isolates were obtained from fecal samples, and minimum inhibitory concentrations (MICs) were determined for 10 AMs of critical importance for human and animal health. NWT phenotypes were classified according to EUCAST ECOFFs, and multidrug resistance (MDR) was assessed.

Results: AM use was frequent and predominantly prophylactic (89.5% of farms), mainly through mass medication (66.3%), with macrolides and amoxicillin being the most commonly administered AMs. NWT proportions were extremely high (90-92%) for ampicillin, tetracyclines, and chloramphenicol and substantial for ciprofloxacin (50.6%), sulfamethoxazole (68.2%), and trimethoprim (44.9%). Extended-spectrum β-lactamase (ESBL)-producing phenotypes were detected. Alarmingly, 92% of isolates were classified as MDR E. coli, with homogeneous distribution across production categories.

Conclusions: Findings reveal intensive and largely empirical AM use that has consolidated a stable intestinal resistome in the swine population. High MDR levels, even in categories with limited direct AM exposure or involving banned compounds, suggest that co-selection and horizontal gene transfer are key drivers of resistance. This scenario highlights the urgent need to strengthen integrated surveillance and promote prudent AM use strategies under the One Health approach to preserve therapeutic efficacy.

Background/Objectives: Sepsis is a life-threatening condition associated with high mortality. Optimal dosing strategies for β-lactam antibiotics in sepsis remain controversial, particularly in patients with renal impairment. Cefepime (CFPM) is widely used as empiric therapy; however, its appropriate initial dosing in critically ill patients is unclear. This study aimed to evaluate whether high-dose CFPM administration during the first 48 h improves survival in patients with sepsis, irrespective of renal function. Methods: This single-center, retrospective, observational study included adult intensive care unit (ICU) patients with sepsis who received CFPM as initial therapy between January 2017 and December 2024. Patients were categorized into High-dose (12 g within 48 h; 2 g every 8 h) and Low-dose (<12 g/48 h) groups. The primary outcome was ICU survival. To address confounding, inverse probability of treatment weighting (IPTW) based on serum creatinine was applied, with sensitivity analyses using 1% trimmed and stabilized IPTW. Results: Of 122 eligible patients, 84 were analyzed (High-dose: n = 27; Low-dose: n = 57). After IPTW adjustment, high-dose CFPM was significantly associated with improved ICU survival (odds ratio [OR] 5.43, 95% confidence interval [CI] 1.60-18.39, p = 0.0066). This association remained consistent in the 1% trimmed IPTW analysis (OR 4.07, 95% CI 1.19-13.97, p = 0.0256). Stabilized IPTW yielded a similar effect estimate, though without statistical significance (OR 5.43, 95% CI 0.72-41.16, p = 0.1017). Overall, results were consistent in direction and magnitude across models. Conclusions: High-dose CFPM administration during the initial 48 h was associated with improved ICU survival in patients with sepsis, independent of renal function.

Background/Objectives: Stenotrophomonas maltophilia is an opportunistic pathogen causing severe infections, particularly in patients with cystic fibrosis (CF). Its intrinsic multidrug resistance and biofilm-forming capacity complicate treatment. Although biofilms are generally associated with antimicrobial tolerance, the relationship between biofilm formation and planktonic antibiotic resistance in S. maltophilia remains poorly understood. This study investigated the association between antibiotic resistance profiles and biofilm production in clinical isolates from CF and non-CF patients. Methods: A total of 86 clinical isolates (40 from CF airways and 46 from non-CF patients) were analyzed. Susceptibility to seven antibiotics was assessed by disk diffusion, and multidrug resistance profiles were defined using standard criteria. Biofilm formation was quantified after 24 h using a crystal violet microtiter plate assay and categorized by using a semiquantitative scale. Results: High resistance rates were observed, particularly to meropenem (87.2%), ciprofloxacin (80.2%), and rifampicin (72.1%). CF isolates exhibited significantly higher resistance to piperacillin/tazobactam and a greater prevalence of multidrug resistance. Biofilm formation was detected in 94.2% of isolates, with strong or powerful producers predominating. However, CF isolates formed significantly less biofilm than non-CF isolates. Notably, resistance to piperacillin/tazobactam and meropenem was associated with reduced biofilm biomass and a lower proportion of high biofilm producers. Across all isolates, an inverse correlation was observed between the number of antibiotic resistances and biofilm biomass. These trends persisted after stratification by clinical origin, although some comparisons did not reach statistical significance. Conclusions: This study reveals an unexpected inverse relationship between planktonic antibiotic resistance and biofilm-forming capacity in S. maltophilia. Enhanced biofilm production may represent an alternative persistence strategy in more antibiotic-susceptible strains, with important implications for infection management and therapeutic failure.

Background/Objectives: The increasing trend of foodborne zoonotic pathogens exhibiting antimicrobial resistance (AMR) represents a growing threat to food safety and public health in sub-Saharan Africa (SSA). Resistant strains of foodborne zoonotic pathogens compromise treatment efficacy, raise illness, and threaten sustainable food systems in human and animal health. However, regional understanding and policy response are limited due to the fragmentation of data and the inadequacy of surveillance. This systematic review and meta-analysis aimed to achieve the following: (1) estimate the pooled prevalence of AMR, including multidrug resistance (MDR) in selected foodborne pathogens; (2) compare subgroup variations across countries, pathogen species, and antibiotic classes; and (3) evaluate temporal trends. Methods: Following PRISMA 2020 guidelines, studies published between 2010 and June 2025 reporting AMR and MDR in Salmonella, Campylobacter, or E. coli from food or animal sources in SSA were systematically reviewed. Data on pathogen prevalence, AMR profile, and MDR were extracted. Random-effects meta-analysis using R software was implemented to estimate the pooled prevalence and the 95% confidence intervals (95% CI). Subgroup analyses were performed to explore heterogeneity across countries, antibiotic class, and bacterial species. Results: Ninety studies from 16 sub-Saharan African countries were included, encompassing 104,086 positive isolates. The pooled foodborne pathogen prevalence was 53.1% (95% CI: 51.5-54.7), AMR prevalence was 61.6% (95% CI: 59.4-63.9), and MDR prevalence was 9.1% (95% CI: 8.3-10.0). The highest resistance was reported in Campylobacter spp. (43.6%), followed by Salmonella spp. (29.1%) and E. coli (22.8%). High heterogeneity was observed across studies (I² = 95-99%, p < 0.001). Conclusions: It is concluded that substantial AMR burden exists in food systems, highlighting an urgent need for integrated One Health surveillance, antimicrobial stewardship, and policy harmonization in SSA. Strengthening laboratory capacity, enforcing prudent antimicrobial use, and promoting regional data sharing are critical for the management of antimicrobial resistance in sub-Saharan Africa.

Objectives: The study aims to assess the strategies used to estimate antimicrobial consumption (AMC) and the barriers encountered in data collection. It also addresses the perception about AMC based on the World Health Organization (WHO) definition. Methodology: The qualitative study adhered to the standard consolidated criteria for reporting qualitative studies (COREQ) guidelines. It involved stakeholders from diverse sectors, i.e., regulatory bodies, the pharmaceutical industry, international health organizations, policy experts, medical professionals, veterinary doctors, and academia (nursing, medicine, and pharmacy). A total of 37 in-depth interviews were conducted using a semi-structured interview schema. The interviews were recorded and transcribed verbatim. Codes were generated afterward and organized into themes. Results: Data analysis yielded five themes consisting of (i) Perception about Antimicrobial Consumption, AWaRe (Access, Watch, Reserve) classification and related terms, (ii) Antimicrobial Consumption: Policy Design, (iii) Data management and record keeping for the Estimation of Antimicrobial Consumption, (iv) Levels of Estimation for Antimicrobial consumption and Organizations, and (v) Challenges and suggested solutions in estimation of AMC: One health approach is the way forward. Conclusions: The study concluded that AMC and AMR are two sides of the same coin. The solution to AMR and excessive AMC is to re-evaluate the policy and implement legislation strictly. Efforts focused on irrational prescribing and unsupervised OTC sales of antimicrobials. This will help in reducing the consumption of broad-spectrum antimicrobials.

Antimicrobials are common drugs used to treat and prevent infectious diseases in plants, animals, and humans. Since their discovery in the mid-20th century, their use has dramatically increased for the benefit of humanity, and also for animal care. However, antimicrobial resistance soon appeared, which, according to the WHO, will limit or impede their use at the horizon of 2050. Indeed, antimicrobial resistance (AMR), which is a natural phenomenon in bacteria increased dramatically over the last 3 decades mainly due to the overuse and misuse of antibiotics in humans, animals, and plants. Apart from affecting human health, drug-resistant diseases also adversely affect plant and animal health, reduce agricultural productivity, and threaten food security. AMR affects all countries, regardless of economic status, and imposes high costs on health systems and national economies. Therefore, antimicrobial resistance should be studied and analyzed under the One Health paradigm. In mind of the One Health paradigm, to reduce and overcome AMR, we must take at least 3 complementary and integrated actions: (i) monitoring the resistome; (ii) developing protective strategies against antibiotic resistance; (iii) taking curative actions by designing new and original treatments. Moreover, the three actions must be conducted simultaneously due to the continuous adaptation of bacteria.

Background/Objectives: Bacterial biofilms formed by Escherichia coli pose a significant challenge in veterinary medicine due to their intrinsic resistance to antibiotics. Antimicrobial peptides (AMPs) represent a promising alternative. AMPs exert their bactericidal activity by binding to negatively charged phospholipids in bacterial membranes via electrostatic interactions, leading to membrane disruption and rapid cell lysis. Methods: In vitro assays including MIC determination, biofilm eradication testing (crystal violet, colony counts, and CLSM), swimming motility, and EPS quantification were performed. CRISPR/Cas9 was used to construct and complement a kduD mutant. A transposon mutagenesis library was screened for biofilm-defective mutants. In an in vivo murine excisional wound infection model treated with the mouse cathelicidin-related antimicrobial peptide (CRAMP-34), wound closure and bacterial burden were monitored. Gene expression changes were analyzed via RT-qPCR. Results: CRAMP-34 effectively eradicated pre-formed biofilms of a clinically relevant, porcine-origin E. coli strain and promoted wound healing in the murine infection model. We conducted a genome-wide transposon mutagenesis screen, which identified kduD as a critical gene for robust biofilm formation. Functional characterization revealed that kduD deletion drastically impairs flagellar motility and alters exopolysaccharide production, leading to defective biofilm architecture without affecting growth. Notably, the anti-biofilm activity of CRAMP-34 phenocopied aspects of the kduD deletion, including motility inhibition and transcriptional repression of a common set of biofilm-related genes. Conclusions: This research highlights CRAMP-34 as a potent anti-biofilm agent and unveils kduD as a previously unrecognized regulator of E. coli biofilm development, which is also targeted by CRAMP-34.