Frontiers in antibiotics最新文献

Background: Antimicrobial misuse in livestock is a key driver of antimicrobial residues and resistance (AMR), yet knowledge, attitudes, and practices (KAP) among cattle keepers and stewardship awareness among animal health practitioners (AHPs) and veterinary drug retailers ((VDR) remain poorly characterized in many low-resource settings.

Methods: A total of 322 participants were interviewed in a cross-sectional study using semi-structured questionnaires and open-ended interviews. They included, 299 cattle keepers, 10 AHPs and 13 VDR. Descriptive statistics were done to compute frequencies of responses, chi square tests and linear regression analysis to assess association between dependent and independent variables while thematic analysis to analyze key informants' interviews.

Results: Awareness of antimicrobial use (AMU), residues, and AMR was generally low, with a mean score of 94 (31.4%, 95%CI: 26.2-36.6). The Mean awareness score from Linear regression showed that higher education (secondary: β = 0.878, p = 0.002; tertiary: β = 1.469, p < 0.001) and longer livestock experience (>4 years: β = 1.35, p < 0.001) were positively associated with awareness, whereas younger age groups had lower scores. Awareness significantly predicted attitudes toward responsible AMU, particularly regarding residues (β = 6.427, p < 0.001) and AMR (β = 2.473, p < 0.001). Attitudes were generally low, with an overall mean score of 2.06 (41.2%). Male sex, older age, higher education, and longer livestock experience were positively associated with more favorable attitudes. Practices were suboptimal: 99.7% (95%CI: 99.1-100) reported AMU, but only 21.1% (95%CI: 16.4-25.8) kept treatment records, hygiene was limited, and manure was frequently applied to fields (77.6%, 95%CI: 72.8-82.3). Key informants highlighted frequent non-prescription sales (AHPs: 9/10; VDR: 13/13), reliance on empirical diagnosis (AHPs: 10/10; VDR: 3/10), weak regulatory enforcement (AHPs: 8/10; VDR: 11/13), and limited knowledge of AMR (AHPs: 6/10; VDR: 3/13) as major drivers of inappropriate AMU.

Conclusion: Awareness, age, education, and livestock experience significantly influenced attitudes toward responsible AMU. Systemic gaps in veterinary services emphasize the need for integrated educational and regulatory interventions to improve antimicrobial stewardship and mitigate AMR risks.

Antibiotic resistance remains a significant public health concern. One possible solution is to develop a new type of highly accessible test for antibiotic resistance that can be rapidly and easily utilized. As new diagnostics for measuring antibiotic resistance continue to be developed, several key practical, ethical, and social factors must be considered, including the types of tests that might be useful, their potential beneficiaries, and the contexts in which they should be utilized. This study aims to gather insights from key stakeholders regarding the ethical implications, benefits, and potential risks associated with a hypothetical rapid antibiotic resistance test that may also be designed for home use. A total of 32 semi-structured interviews were conducted with three stakeholder groups: potential users, medical providers, and ethicists. While prospective users of the test were generally positive about the proposed test, this might reflect public acceptance of point of care/home tests in general, rather than one specifically measuring ABR. Medical providers and experts knowledgeable about the problems of antibiotic overuse quickly pointed out some drawbacks and areas of concern for home testing for ABR, offering helpful guidance on where further research and consideration are needed.

Background: Coastal waters contaminated by antimicrobial resistant hotspots may serve as reservoirs for third-generation cephalosporin resistant Enterobacterales (3GCR-E), extended-spectrum β-lactamase (ESBL)-producers, and carbapenem-resistant Enterobacterales (CRE), but their role in driving human carriage remains poorly understood.

Aim: We investigated intestinal carriage of 3GCR-E, ESBL-producers, and CRE in coastal and inland communities in Accra, Ghana, and examined the genomic overlap between human and wastewater-derived CRE isolates.

Methods: A comparative cross-sectional study was conducted from August 2023 to June 2024 with 800 participants (400 from coastal and 400 from inland communities). We cultured fecal samples from participants and water samples from lagoons and shorelines for 3GCR-E, ESBL-producers, and CRE. The CRE isolates from both human and wastewater were whole genome sequenced for comparison.

Results: Overall, 53.6% (n=429/800) of participants carried 3GCR-E, with 43.6% being ESBL-producers and 1.5% being CRE, the latter restricted only to coastal residents. In the pooled analysis, inland residence was independently associated with reduced odds of 3GCR-E carriage (aOR 0.64, 95% CI 0.48-0.85; p = 0.001). For coastal participants, not swimming was protective against ESBL carriage (aOR 0.65, 95% CI 0.42-0.95; p = 0.030). All human and wastewater CRE isolates were E. coli and clustered in mixed-source phylogenetic clades (ST10, ST940) with >95% average nucleotide identity and pairwise SNP differences as low as 2-20. Both human and wastewater sources carried the identical carbapenemase gene blaOXA-181 on overlapping plasmid replicons, with 57-80% concordance across IncFIA, IncFIB (AP001918), IncX1, and Col440I.

Conclusions: Our findings indicate a shared resistance gene pool between human and environmental sources, characterized by bidirectional CRE exchange but dominated by an environment-to-human transmission pathway. This underscores the urgent need for effective wastewater treatment and improved sanitation practices to reduce human exposure and curb the spread of antibiotic resistance.

Background: Staphylococcus epidermidis and Enterococcus faecalis are nosocomial microorganisms that have gained attention in recent times due to the increasing reports of antimicrobial-resistant strains, which are leading to infections that are progressively harder to eradicate. One of the most important resistance mechanisms employed by these two bacteria is biofilm formation, which provide them with physical and chemical protection from antimicrobial agents.

Methods: This study assessed the antimicrobial activity of crude and microencapsulated extracts of Psidium guajava L., an agro-industrial waste product widely available in guava-producing countries, using the microdilution technique. Additionally, anti-adhesion activity was analyzed in microplates and by confocal laser scanning microscopy (CLSM).

Results: Guava leaf extract reduced the growth of all three bacterial strains evaluated. For Staphylococcus epidermidis (ATCC 12228), the minimum inhibitory concentrations (MICs) were 25 mg/ml for the crude extract and 0.625 mg/ml for the microencapsulated form. In contrast, for Enterococcus faecalis (ATCC 29212 and a vaginal clinical isolate), MIC values were greater than 50 mg/ml and 5 mg/ml, respectively. Furthermore, both extracts exhibited anti-biofilm activity by reducing bacterial adhesion.

Conclusion: microencapsulation allowed a reduction in the extract concentration and guava leaf extract shows potential as an antimicrobial agent for future application.

Co-administration of simnotrelvir/ritonavir with voriconazole should be avoided, as stated in the product insert of simnotrelvir/ritonavir, due to the anticipated decrease in the plasma concentration of voriconazole. Currently, there are no published reports regarding a pharmacokinetic interaction between simnotrelvir/ritonavir and voriconazole. We present the case of an 88-year-old man with pulmonary aspergillosis and coronavirus disease 2019 (COVID-19) co-infection treated concurrently with voriconazole and simnotrelvir/ritonavir. Prior to initiating simnotrelvir/ritonavir, two trough concentrations of voriconazole were measured, yielding values of 2.8 and 2.6 mg/L. After 2 days of co-administration with simnotrelvir/ritonavir, the voriconazole trough concentration rose to 6.0 mg/L. The voriconazole dose was subsequently reduced by 25%, and simnotrelvir/ritonavir was discontinued after completion of the standard 5-day course. A week after voriconazole dose reduction (4 days after simnotrelvir/ritonavir withdrawal), the trough concentration was measured again and was found to be 3.5 mg/L. This case indicates that the trough concentration of voriconazole increased significantly during co-administration with simnotrelvir/ritonavir. Moreover, the interaction persisted even after discontinuation of simnotrelvir/ritonavir, necessitating dynamic dose adjustments guided by therapeutic drug monitoring.

Introduction: Antimicrobial resistance remains a major global public health challenge that necessitates novel drugs with a low resistance rate.

Methods: Herein, we evaluate TGV-49, a novel broad-spectrum antimicrobial agent, against multidrug-resistant Gram-negative bacteria, including ESKAPE pathogens (Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae) and pathogens from agriculture that infect humans (Ralstonia solanacearum and Aeromonas hydrophila).

Results: TGV-49 was highly effective in overcoming resistance to conventional antibiotics. The experimental evolution of A. baumannii using a morbidostat revealed minimal development of resistance.

Conclusion: Our findings suggest TGV-49 as a potential alternative for combating MDR infections in clinical and agricultural settings.

Antibiotic stewardship programs and controlled antibiotic usage have long been considered fundamental strategies in healthcare systems, and these approaches were traditionally viewed as the primary defense against bacterial resistance development. But recent studies reveal a surprising disconnect between antibiotic usage and resistance patterns, with socioeconomic factors showing stronger correlations than clinical drug use. Multiple factors beyond antibiotic consumption now influence resistance patterns, including agricultural antibiotic use, increasing urbanization, and the evolution of mobile genetic elements. Therefore, while antibiotic stewardship remains crucial for preventing side effects and reducing healthcare costs, its role in controlling bacterial resistance requires fundamental reassessment. This understanding necessitates a strategic shift in stewardship programs to focus on more attainable goals, such as patient safety and cost reduction, while developing new, comprehensive approaches to address antibiotic resistance that account for the complex interplay of biological, environmental, and socioeconomic factors.

Antimicrobial resistance (AMR) in poultry production poses a growing public health threat due to the emergence of multidrug-resistant (MDR) bacteria and the risk of transmission to humans through direct or indirect contact with these germs. In Tunisia, limited data on antibiotic use and veterinary prescribing practices hinder the development of effective AMR mitigation strategies, particularly in a sector with high antibiotic consumption. A cross-sectional study was conducted among veterinarian prescribers in avian medicine in Tunisia to assess their antibiotic prescribing behaviours and related practices and to evaluate their potential contribution to AMR emergence and spread. The most frequently reported first and second-line antibiotics were enrofloxacin (20/52 and 14/52), florfenicol (14/52 and 14/52), and doxycycline (7/52 and 6/52). Colistin (10/52) was the most used third-line antibiotic. These antibiotics were often administered without microbiological confirmation. Although 69% had access to accredited labs, 42% relied on rapid antimicrobial susceptibility tests (RASTs). Waste management practices were inadequate, with 50% disposing of biological waste in regular trash and 42% discarding expired antibiotics into the environment. Additionally, 77% reported frequent farmer self-medication. These findings highlight the urgent need for targeted training, improved surveillance, and the application of the One Health approach to tackle AMR in Tunisia's poultry sector.

Introduction: Clostridium perfringens strains may cause foodborne illness, and 95% of human infections are linked to the consumption of contaminated meat, including chicken products. In poultry, C. perfringens infection may cause necrotic enteritis, and infections are associated with high mortality rates partially due to antibiotic resistance, which hampers efficient treatment. In-vitro screening approaches of alternative treatment options, for instance, specific phages, represent a promising strategy for the selection of novel interventions to combat infections.

Material and methods: In this study, we explored the application of a C. perfringens strain LMG 11264-specific phage #7 introduced at 10⁴ pfu/mL to inhibit the growth of C. perfringens at 10⁶ cfu/mL compared to two antibiotics (amoxicillin at 10 µg/mL and clindamycin at 10 µg/mL) within complex chicken cecal microbiota in vitro. Samples for gDNA isolation, qPCR, and metagenome sequencing were taken at the beginning and after 24 and 48 h of incubation.

Results: The C. perfringens strain LMG 11264 proliferated within the untreated complex microbiota and reached levels of approximately 10⁸ and 10⁹ genome equivalents per mL after 24 and 48 h of incubation, respectively. The phage intervention with phage #7 inhibited the growth of C. perfringens LMG 11264 significantly; the inhibitory effects were similar to those exerted by the antibiotic intervention with amoxicillin and stronger than the inhibitory effects with clindamycin. In the absence of the C. perfringens challenge, we found a significant effect of amoxicillin (p = 0.040) or clindamycin (p = 0.000017) compared to the untreated control after 24 h of incubation, and the phage addition did not affect the alpha diversity expressed as Chao index significantly (p = 1). In addition, the endogenous C. perfringens in the chicken microbiota appeared insensitive to phage #7. The phage titer of phage #7 only increased in the presence of the inoculated C. perfringens strain LMG 11264. In conclusion, the i-screen model can be implemented to test the efficacy and specificity of phage therapy in vitro.