Frontiers in antibiotics最新文献

Because of the global spread of multi- and pan-resistant bacteria, there is a need to identify, research, and develop new strategies to combat these pathogens. In a previous proof-of-concept study, we presented an innovative strategy by genetically modifying lytic T7 bacteriophages. We integrated DNA fragments encoding for derivatives of the antimicrobial peptide (AMP) apidaecin into the phage genome to induce the production and release of apidaecin within the T7 infection cycle, thereby also targeting phage-resistant Escherichia coli bacteria. In this follow-up study, we optimized the apidaecin encoding insert to improve the expression of the apidaecin derivative Api805 by adding the secretion signal peptide of the OmpA protein. This prevented the detrimental effects of the peptide on the producing bacterial cell after its production. The integration of two copies of the OmpA-Api805 insert into the phage genome resulted in T7Select-2xOmpA-Api805 phages, which had a partially improved activity in inhibiting phage-resistant E. coli compared to the T7Select phages without insert and with only one copy of the OmpA-Api805 insert. Additionally, we showed that the combinatorial use of the lytic bacteriophage T7Select with the highly active and lytic AMPs CRAMP (cathelicidin-related AMP) and melittin against E. coli made the lysis process of the phage and the peptides more effective and prevented the growth of potentially AMP- and phage-resistant E. coli strains. The integration of DNA sequences derived from CRAMP and melittin into the phage genome resulted in the created T7Select-(M)CRAMP and T7Select-(M)melittin phages, which showed a lysis behavior like the phage without insert and partially inhibited the growth of potentially phage-resistant E. coli strains after the phage-mediated lysis.

Background: Patients' adherence to antibiotic treatment and related prevention of AMR is significant. Understanding healthcare professionals' strategies for advising and educating patients in primary care settings is crucial.

Aim: From the perspectives of professionals and patients, to explore how physicians, pharmacists, and nurses educate patients about antibiotic use and antimicrobial resistance in primary care settings.

Methods: A qualitative systematic literature review was conducted in MEDLINE, EMBASE, CINAHL Complete, Eric, SocINDEX, PsycInfo, Web of Science and Scopus. The study included 102 publications, followed PRISMA recommendations and was registered in PROSPERO (reg.no. CRD4202455761). The studies were screened and selected based on specific inclusion and exclusion criteria using Covidence. Quality appraisal followed the Critical Appraisal Skills Program (CASP) qualitative study checklist. Data were extracted, and the analysis consisted of a descriptive numerical summary analysis and a qualitative thematic analysis.

Results: The analyzed studies spanned multiple countries and settings and included perspectives of primary care physicians, pharmacists, nurses and patients. Two main themes emerged: (1) Relationships between professionals and patients influenced educational strategies, showing that trust and rapport between healthcare professionals and patients played a crucial role in shaping educational strategies around antibiotic use; (2) The organizational structures challenged professionals in guiding and educating patients, highlighting how limited resources, time constraints, and system-level pressures hindered healthcare professionals' ability to provide consistent and effective education. Often, structural challenges led to not educating the patients on the risks of antibiotic misuse and antimicrobial resistance. The use of delayed prescriptions emerged as a strategy for improved AMR stewardship and to meet patients' expectations for antibiotic treatment, though it raised concerns about undermining professional responsibility and authority in ensuring appropriate antibiotic use.

Conclusion: Healthcare professionals' role in educating patients about antibiotic use and AMR in primary care settings was complex, with different challenges faced by nurses, pharmacists and primary care physicians. These challenges extended beyond the clinical level, including relational, social and structural factors. Power dynamics, trust issues, and time pressures often hindered effective education on antibiotic use. Addressing gaps in education on antibiotic use and AMR requires acknowledging these multifaceted challenges, with future efforts focusing on better supporting healthcare professionals in this context.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD4202455761.

Introduction: The intensification of tilapia production has increased animal density in tanks, leading to more frequent exposure to pathogenic agents and compromising the quality of fish products. Antimicrobial resistance is a global concern that affects human treatment, and sentinel microorganisms like Escherichia coli are crucial for monitoring production chains, especially in aquaculture, where research is still limited. The aim of this study was to identify the presence of E. coli and investigate its antimicrobial resistance profiles throughout the entire tilapia production chain.

Methods: A total of 240 samples were collected from various points in the production process: carcasses before scaling (Ca), scaling wastewater (Sw), filleting wastewater (Fw), fillet washing wastewater (Tw), fillet handling surfaces (Su), and pre-packaged fillets (Pf). The samples were collected during 10 visits, each corresponding to animals from different farms. E. coli isolates were identified using MacConkey agar and biochemical tests. Phenotypic resistance profiles were determined using nine classes of antimicrobials. Extended- spectrum b-lactamase (ESBL) production was identified with ceftazidime and cefotaxime and confirmed by a double-disc synergy test. Isolates were classified as sensitive or resistant based on the inhibition zone. Multidrug-resistant (MDR) was defined as resistance to at least one agent in three or more antimicrobial categories, while extensively drug-resistant (XDR) was defined as resistance to at least one agent in all but two or fewer categories.

Results: Overall, 50.8% of the samples (122/240) tested positive for E. coli, with 403 isolates identified. Of these, 33% (133/403) were resistant to at least two antimicrobials, and 20% (48/240) of the samples had MDR isolates, with the highest frequency found at the filleting point (Fw), which also had the only XDR profile. Resistance was most commonly observed against amoxicillin (35.73%), tetracycline (30.77%), and ciprofloxacin (26.30%).

Discussion: These findings emphasize the importance of E. coli as an indicator of antimicrobial resistance throughout tilapia processing and highlight the need for good production practices and qualified technical support to mitigate risks to public health, animal health, and the environment.

Correct use of antibiotics is paramount to present global health. Among other actions, antimicrobial stewardship emphasizes de-escalation and suspension whenever possible. Nonetheless, roadblocks can be encountered (e.g., lack of culture results or availability of specific antibiotic classes). Furthermore, in an ever-increasing interconnected world, global success relies on local success. In this perspective, a particular case study in a resource-limited setting is an example of the many difficulties encountered in the fight against antimicrobial resistance that could hamper global advancements.

Salmonella is a foodborne pathogenic bacterium that causes salmonellosis worldwide. Also, Salmonella is considered a serious problem for food safety and public health. Several antimicrobial classes including aminoglycosides, tetracyclines, phenols, and β-Lactams are used to treat Salmonella infections. Antibiotics have been prescribed for decades to treat infections caused by bacteria in human and animal healthcare. However, intensive use of antibiotics resulted in antibiotic resistance (AR) among several foodborne bacteria including Salmonella. Furthermore, multi-drug resistance (MDR) of Salmonella has increased dramatically. In addition to MDR Salmonella, extensively drug resistant (XDR) as well as pan drug resistant (PDR) Salmonella were reported globally. Therefore, increasing AR is becoming a serious universal public health crisis. Salmonella developed many mechanisms to ensure its survival against antimicrobials. The most prominent defense mechanisms against these antibiotics include enzymatic inactivation, expelling drugs from the cell through efflux pumps, altering the structure of drugs, and changing or protecting the targets of drugs. Additionally, the formation of biofilms and plasmid-mediated AR by Salmonella, enhancing its resistance to various antibiotics, making it a challenging pathogen in both healthcare and food industry settings. This review focuses exclusively on providing a detailed overview of the mechanisms of AR in Salmonella.

Introduction: Antimicrobial resistance (AMR) represents a persistent and ascensive global threat influenced by antibiotic misuse and overuse. In the Romanian context, patterns of antibiotic consumption and resistance within the healthcare system are marked in the red scenario on the European map. General practitioners and pharmacists, among others, play a major role in stewardship towards AMR.

Aim: To explore the practices, strategies, and challenges in antibiotic treatment and prevention of antimicrobial resistance from the perspectives of Romanian community pharmacists and general practitioners.

Method and materials: Semi-structured interviews were conducted with six general practitioners and five community pharmacists in Romania from January to March 2024. An inductive, Goffman theory-inspired thematic analysis was conducted, inspired by Braun and Clarke's thematic analysis method, consisting of familiarization with the data, iterative coding guided by theoretically inspired questions, and identification and refinement of (sub)themes. Goffman's theory of social interaction, focusing on the concepts of front stage, backstage, and roles, guided the analytical questions.

Results: The results were presented in three overarching themes: 'Knowledge acquired backstage to support challenges and performance on front stage', 'Adapting roles and performances on the front stage: A mix of structured and twisted acts', and 'Interprofessional Collaboration: A latent part in the play's roles and performances'. Professionals prepared their understandings of AMR and antibiotics backstage, with an awareness of the challenges rooted in the Romanian context. The front stage scenario evolved from structured antibiotic performances led by AMR strategies with compliant actors to challenging performances influenced by actors which changed the course of performances and intended AMR strategies. The revealed competition between general practitioners and pharmacists further complicated antibiotic use and AMR-related performances.

Conclusion: The Romanian socio-political system influenced the course of antibiotic treatment and the professionals' intended antibiotic related practices and AMR strategies. The study showed a theory-practice gap in health professionals' practices, leading to limited strategy integration towards AMR and increased antibiotic use. The study underscores the need for context-specific policies and interventions to minimize identified gaps.

Neonatal sepsis causes substantial morbidity and mortality, the burden of which is carried by low-income countries (LICs). The emergence of multidrug-resistant pathogens in vulnerable neonatal populations poses an urgent threat to infant survival. Acinetobacter spp. are increasingly responsible for severe disease in neonates globally. The cause of this escalation remains unclear, but host, pathogen and environmental factors are all likely to contribute. Acinetobacter spp. strains are frequently resistant to the first line empirical treatment for neonatal sepsis as recommended by the World Health Organization (WHO), ampicillin and gentamicin, rendering these antibiotics ineffectual in many critically ill neonates. The resultant escalation to broader spectrum antibiotic regimens in neonatal intensive care units (NICUs) worldwide has led to the emergence of more resistant strains, including carbapenem-resistant Acinetobacter baumanii (CRAB), resulting in infections that are ever more difficult to treat. While some existing antimicrobial agents are under consideration for treatment of Acinetobacter spp. infections, the majority remain a long way from clinical use in neonates. Further research into the clinical phenotype of these infections, transmission dynamics and preventative measures are urgently needed to reduce neonatal deaths. This review aims to summarise the role of Acinetobacter spp. in neonatal sepsis, including host, pathogen and environmental factors, the global epidemiology and clinical features of the disease, the treatment options, and future research priorities.

Rifamycin and its derivatives are natural products that belong to the class of antibiotic-active polyketides and have significant therapeutic relevance within the therapy scheme of tuberculosis, a worldwide infectious disease caused by Mycobacterium tuberculosis. Improving the oral bioavailability of rifamycin B was achieved through semisynthetic modifications, leading to clinically effective derivatives such as rifampicin. Genetic manipulation of the rifamycin polyketide synthase gene cluster responsible for the production of rifamycin B in the Amycolatopsis mediterranei strain S699 represents a promising tool to generate new rifamycins. These new rifamycins have the potential to be further derivatized into new, ideally more effective, clinically usable compounds. However, the resulting genetically engineered strains only produce these new derivatives in low yields. One example is the strain DCO36, in which rifAT6 was replaced by rapAT2, resulting in the production of rifamycin B and the new derivative 24-desmethyl rifamycin B. Here we describe the successful method adaptation of the PCR-targeting Streptomyces gene replacement approach to Amycolatopsis mediterranei S699 and further on the implementation of genetic modifications that enable an increased production of the derivative 24-desmethyl rifamycin B in the mutant strain DCO36. The described genetic modifications resulted in a mutant strain of DCO36 with rifQ deletion showing a 62% increase in 24-desmethyl rifamycin B production, while a mutant with rifO overexpression showed a 27% increase.