Search Results (20,556)

Necrotic enteritis (NE), caused by Clostridium perfringens, represents a major economic challenge to poultry production. This study evaluated the effects of four plant extracts—Astragalus, pomegranate peel, Sophora flavescens, and Artemisia annua—in combination with B. subtilis, as potential antibiotic alternatives for controlling NE. Using an experimentally induced NE model produced by coinfection with Eimeria maxima and C. perfringens, 288 chickens were divided into 12 groups to assess growth performance, intestinal lesions, and inflammatory markers. Compared with the enramycin group, the pomegranate peel extract group had a 9.9% increase in body weight gain (BWG), significant enhancement in claudin-2 expression, and reduced production of inflammatory factors. Compared with the infected control group, the combination of A. annua extract and B. subtilis resulted in the lowest intestinal lesion scores. The claudin-2, occludin, and zonula occludens-1 expression levels in the group treated with S. flavescens extract combined with B. subtilis increased to the highest levels compared to those in the healthy control group. These findings emphasize the potential of plant extracts, particularly pomegranate peel and A. annua with B. subtilis, as natural alternatives for NE management in poultry, providing a promising approach to reducing reliance on antibiotics. Full article

Whether exposing the microbiome to antibiotics decreases or increases the risk of blood stream infection with Pseudomonas aeruginosa, Staphylococcus aureus, Acinetobacter, and Candida among ICU patients, and how this altered risk might be mediated, are critical research questions. Addressing these questions through the direct study of specific constituents within the microbiome would be difficult. An alternative tool for addressing these research questions is structural equation modelling (SEM). SEM enables competing theoretical causation networks to be tested ‘en bloc’ by confrontation with data derived from the literature. These causation models have three conceptual steps: exposure to specific antimicrobials are the key drivers, clinically relevant infection end points are the measurable observables, and the activity of key microbiome constituents on microbial invasion serve as mediators. These mediators, whether serving to promote, to impede, or neither, are typically unobservable and appear as latent variables in each model. SEM methods enable comparisons through confronting the three competing models, each versus clinically derived data with the various exposures, such as topical or parenteral antibiotic prophylaxis, factorized in each model. Candida colonization, represented as a latent variable, and concurrency are consistent promoters of all types of blood stream infection, and emerge as harmful mediators. Full article

Background/Objectives: The work investigates the effect of the estragole complex encapsulated in beta-cyclodextrin (ES/β-CD) in modulating bacterial resistance, specifically in Staphylococcus aureus strains expressing NorA and MepA efflux pumps. Efflux pumps are mechanisms that bacteria use to resist antibiotics by expelling them from the cell. Methodology: Several compounds and antibiotics, such as ciprofloxacin and norfloxacin, were used to evaluate the antimicrobial activity and the ability of the ES/β-CD complex to reverse resistance. Methods: The study included scanning electron microscopy assays, minimum inhibitory concentration (MIC) determination, and efflux pump inhibition tests. Results: The ES/β-CD complex did not show significant direct antibacterial activity. However, it modulated the action of norfloxacin, decreasing the MIC when combined with this antibiotic in the 1199B (NorA) strain. These results suggest a potential for synergy but not a direct inhibition of efflux pumps. Conclusion: ES/β-CD can potentiate the efficacy of some antibiotics but does not directly act as an efflux pump inhibitor; it is more of an antibiotic potentiator than a direct solution to bacterial resistance. The molecular docking simulation data suggest its high affinity for forming the ES/β-CD complex. The pharmacokinetic predictions based on MPO suggest that the compound has moderate lipophilicity, highly effective cellular permeability, and low incidence of organic toxicity, pointing to a promising pharmacological principle with controlled daily oral dosing. Conclusions: These results indicate this complex’s possible and relevant association as an adjuvant in antibiotic therapy to reduce multidrug-resistant bacteria; however, new in vivo assays are necessary to confirm this effect. Full article

Pandemics of infectious disease and growing anti-microbial resistance (AMR) pose major threats to global health, trade, and security. Conflict and climate change compound and accelerate these threats. The One Health approach recognizes the interconnectedness of human, animal, and environmental health, but is grounded in the biomedical model, which reduces health to the absence of disease. Biomedical responses are insufficient to meet the challenges. The COVID-19 pandemic is the most recent example of the failure of this biomedical model to address global threats, the limitations of laboratory-based surveillance, and the exclusive focus on vaccination for disease control. This paper examines the current paradigm through the lens of polio and the global campaign to eradicate it, as well as other infectious threats including mpox and drug-resistant tuberculosis, particularly in the context of armed conflict. Decades before vaccines became widely available, public health measures—ventilation, chlorination, nutrition and sanitation— led to longer, healthier, and even taller lives. Chlorine, our primary tool of public health, conquered cholera and transformed infection control in hospitals. The World Health Organization (WHO), part of the One Health alliance, focuses mainly on antibiotics and vaccines to reduce deaths due to superbugs and largely ignores the critical role of chlorine to control water-borne diseases (including polio) and other infections. Moreover, the One Health approach ignores armed conflict. Contemporary wars are characterized by indiscriminate bombing of civilians, attacks targeting healthcare, mass displacement and lack of humanitarian access, conditions which drive polio outbreaks and incubate superbugs. We discuss the growing trend of attacks on healthcare and differentiate between types: community-driven attacks targeting vaccinators in regions like Pakistan, and state-sponsored attacks by governments such as those of Syria and Russia that weaponize healthcare to deliberately harm whole populations. Both fuel outbreaks of disease. These distinct motivations necessitate tailored responses, yet the WHO aggregates these attacks in a manner that hampers effective intervention. While antimicrobial resistance is predictable, the escalating pandemic is the consequence of our reliance on antibiotics and commitment to a biomedical model that now borders on pathological. Our analysis reveals the international indenture to the biomedical model as the basis of disease control is the root driver of AMR and vaccine-derived polio. The unique power of vaccines is reduced by vaccination-only strategy, and in fact breeds vaccine-derived polio. The non-specific effects of vaccines must be leveraged, and universal vaccination must be supplement by international investment in water chlorination will reduce health costs and strengthen global health security. While vaccines are an important weapon to combat pandemics and AMR,, they must be accompanied by the entire arsenal of public health interventions. Full article

Background: The worldwide misuse of antibiotics is one of the main factors in microbial resistance that is a serious threat worldwide. Alternative strategies are needed to overcome this issue. Objectives: In this study, a novel strategy was adopted to suppress the growth of resistant pathogens through immobilization of silver nanoparticles (AgNPs) in gum of Moringa oleifera. Methods: The AgNPs were prepared from the leaves of Moringa oleifera and subsequently characterized through UV-spectrophotometry, FTIR, SEM, and XRD. The differential ratios of characterized AgNPs were immobilized with gum of M. oleifera and investigated for antimicrobial potential against highly resistant pathogens. Results: The immobilized AgNPs displayed promising activities against highly resistant B. subtilis (23.6 mm; 50 µL:200 µL), E. coli (19.3 mm; 75 µL:200 µL), K. pneumoniae (22 mm; 200 µL:200 µL), P. mirabilis (16.3 mm; 100 µL:200 µL), P. aeruginosa (22 mm; 175 µL:200 µL), and S. typhi (19.3; 25 µL:200 µL) than either AgNPs alone or gum. The immobilized AgNPs released positive sliver ions that easily attached to negatively charged bacterial cells. After attachment and permeation to bacterial cells, the immobilized NPs alter the cell membrane permeability, protein/enzymes denaturation, oxidative stress (ROS), damage DNA, and change the gene expression level. It has been mechanistically considered that the immobilized AgNPs can kill bacteria by damaging their cell membranes, dephosphorylating tyrosine residues during their signal transduction pathways, inducing cell apoptosis, rupturing organelles, and inhibiting cell division, which finally leads to cell death. Conclusions: This study proposes a potential alternative drug for curing various infections. Full article

Background/Objectives: The escalating challenge of antimicrobial resistance (AMR) necessitates the development of targeted antibiotic delivery platforms, minimising systemic administration. Polymer-based drug delivery emerges as a promising solution, ensuring sustained release and prolonged efficacy of bioactive compounds, ensuring long-term efficacy. Methods: This study focuses on encapsulating rifampicin (RIF), a key antibiotic for orthopaedic and wound-related infections, within Poly(d,l-lactide-co-glycolide) (PLGA), a biodegradable polymer, through solvent casting, to formulate a PLGA-RIF composite membrane. Comprehensive characterisation, employing Fourier-transformed infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), thermal analysis and X-ray Diffraction (XRD), confirmed the integrity of both the starting and produced materials. UV-Vis spectroscopy revealed a controlled drug release profile over 21 days in various media, with the chosen media influencing the drug release, notably the tryptic soya broth (TSB) caused the highest release. The quantitative assessment of the antimicrobial efficacy of the developed PLGA-RIF composite was conducted by measuring the size of the inhibition zones against both Gram-negative and Gram-positive bacteria. Results: The results confirmed the composite’s potential as a robust antibacterial biomaterial, demonstrating a rapid and effective antibacterial response. Cytocompatibility tests incorporated human fibroblast and osteoblast-like cell lines and demonstrated that the RIF:PLGA (1:8) formulation maintained eukaryotic cell viability, indicating the composite’s potential for targeted medical applications in combating bacterial infections with minimal systemic impact. Conclusions: This study presents the significance of investigating drug release within appropriate and relevant physiological media. A key novelty of this work therefore lies in the exploration of drug release dynamics across different media, allowing for a comprehensive understanding of how varying physiological conditions may influence drug release and its effect on biological responses. Full article

Sepsis is a life-threatening disease caused by the overwhelming response to pathogen infections. Currently, treatment options for sepsis are limited to broad-spectrum antibiotics and supportive care. However, the growing resistance of pathogens to common antibiotics complicates treatment efforts. Excessive immune response (i.e., cytokine storm) can persist even after the infection is cleared. This overactive inflammatory response can severely damage multiple organ systems. Given these challenges, managing the excessive immune response is critical in controlling sepsis progression. Therefore, Mesenchymal stem cells (MSCs), with their immunomodulatory and antibacterial properties, have emerged as a promising option for adjunctive therapy in treating sepsis. Moreover, MSCs exhibit a favorable safety profile, as they are eventually eliminated by the host’s immune system within several months post-administration, resulting in minimal side effects and have not been linked to common antibiotic therapy drawbacks (i.e., antibiotic resistance). This review explores the potential of MSCs as a personalized therapy for sepsis treatment, clarifying their mechanisms of action and providing up-to-date technological advancements to enhance their protective efficacy for patients suffering from sepsis and its consequences. Full article

This article examines the impact of eyelid margin diseases on tear film composition and associated ocular surface disorders. It highlights the prevalence of blepharitis and meibomian gland dysfunction, discussing risk factors and diagnostic considerations. Various therapeutic approaches, including eyelid hygiene, antibiotics, and innovative treatments, are explored. Emphasizing the chronic nature of these conditions, the article underscores the need for patient compliance. Overall, it provides a concise overview of eyelid-related issues and potential management strategies. Full article

The increasing prevalence of heavy metals and antibiotic-resistant bacteria in wastewater (WW) raises serious environmental and public health concerns. This study investigates the efficiency of the microalgal strain Chlorella vulgaris EV-465 in treating wastewater and evaluates the antibiotic resistance profile of bacterial strains obtained from WW samples. Chlorella vulgaris EV-465 was used to treat four types of wastewater—domestic, municipal, hospital, and industrial wastewater—through 21 days of incubation. The findings demonstrated pH stabilization and significant decreases in nutrients (total nitrogen—TN, total phosphorus—TP), biological oxygen demand (BOD), chemical oxygen demand (COD), heavy metal (HM) concentrations, and bacterial count. Copper (Cu) showed the highest reduction, decreasing by 80% in industrial wastewater within 14 days, while lead (Pb) proved more resistant to removal, with only a 50% decrease by day 21. Additionally, the algae decreased bacterial counts, lowering colony-forming units (Log CFU/mL) from 9.04 to 4.65 in municipal wastewater over the 21-day period. Antibiotic susceptibility tests for isolated bacterial strains revealed high levels of resistance, with seven out of nine bacterial strains exhibiting multidrug resistance. Notably, Enterococcus faecium (PBI08), Acinetobacter baumannii (YBH19), and Pseudomonas aeruginosa (NBH16) displayed resistance to all nine antibiotics tested. Among the tested antibiotics, Ciprofloxacin showed the highest efficacy, with 66% susceptibility of tested bacterial strains. Cluster and phylogenetic analyses showed that the majority of the isolated bacterial strains belonged to the genera Pseudomonas and Escherichia, highlighting their genetic diversity and varied resistance mechanisms. Full article

Cancer remains a leading cause of death worldwide. Also threatening the public is the emergence of antibiotic resistance to existing medicines. Despite the challenge to produce viable natural products to market, there continues to be a need within public health to provide new chemotherapeutic drugs such as those exhibiting cytotoxicity and tumor cell growth-inhibitory properties. As marine genomic research advances, it is apparent that marine-derived sediment harbors uniquely potent bioactive compounds compared to their terrestrial counterparts. The Streptomyces genus in particular produces more than 30% of all secondary metabolites currently approved for human health, thus harboring unexplored reservoirs of chemotherapeutic and antibiotic agents to combat emerging disease. The present study identifies the presence of Streptomyces hygroscopicus and rapamycinicus in environmental sediment at locations within the U.S. Stellwagen Bank National Marine Sanctuary (SBNMS) from 2017 to 2022. Sequencing and bioinformatics methods catalogued biosynthetic gene clusters (BGCs) that drive cytotoxic and antibiotic biochemical processes in samples collected from sites permittable and protected to fishing activity. Poisson regression models confirmed that Sites 1 and 3 had significantly higher occurrences of rapamycinicus than other sites (p < 0.01). Poisson regression models confirmed that Sites 1, 2 and 3 had significantly higher occurrence for Streptomyces hygroscopicus across sites (p < 0.05). Interestingly, permitted fishing sites showed a greater prevalence of both species. Statistical analyses showed a significant difference in aligned hits with polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs) by site and between species with hygroscopicus showing a greater quantity than rapamycinicus among Streptomyces spp. (p < 0.05; F = 4.7 > F crit). Full article

Background/Objectives: Adaptation can reduce or completely eliminate the effectiveness of antibiotics and antiseptics at clinical concentrations. To our knowledge, no studies have examined fungal adaptation to antiseptics. This study aimed to preliminarily investigate the potential for Candida albicans adaptation to eight antiseptics. Methods: The minimal inhibitory concentration (MIC), drug susceptibility, adaptation to antiseptics, and Karpinski Adaptation Index (KAI) of C. albicans strains were assessed. Results: The antiseptics with the most effective MICs activity against C. albicans were octenidine dihydrochloride (OCT), chlorhexidine digluconate (CHX), and polyhexamethylene biguanide (polyhexanide, PHMB). Sodium hypochlorite (NaOCl) and ethacridine lactate (ET) demonstrated moderate activity, while boric acid (BA), povidone–iodine (PVI), and potassium permanganate (KMnO₄) showed the weakest activity. The MIC values for NaOCl and KMnO₄ were close to or equal to the clinical concentrations used in commercial products. The studied strains were susceptible to econazole, miconazole, and voriconazole. Resistance to other drugs occurred in 10–30% of the strains. Antifungal resistance remained unchanged after antiseptic adaptation testing. The lowest KAI values, indicating very low resistance risk, were observed for CHX, OCT, and PHMB. PVI and BA presented a low risk, ET a moderate risk. KMnO₄ and NaOCl had the highest KAI values, indicating high and very high resistance risk in Candida yeasts. Conclusions: C. albicans strains can adapt to antiseptics to varying extents. For most antiseptics, adaptation does not significantly affect their clinical efficacy. However, due to adaptation, NaOCl and KMnO₄ may become ineffective against C. albicans strains even at clinical concentrations. Full article

The gut dysbiosis present in chronic kidney disease (CKD) has been associated with anemia. Factors such as the accumulation of gut-derived uremic toxins, increased gut barrier permeability-induced inflammation, and a reduced intestinal production of short-chain fatty acids (SCFAs), all associated with changes in the intestinal microbiota composition in CKD, may lead to the development or worsening of anemia in renal patients. Understanding and addressing these mechanisms related to gut dysbiosis in CKD patients can help to delay the development of anemia and improve its control in this population. One approach is to avoid or reduce the use of drugs linked to gut dysbiosis in CKD, such as phosphate binders, oral iron supplementation, antibiotics, and others, unless they are indispensable. Another approach involves introducing dietary changes that promote a healthier microbiota and/or using prebiotics, probiotics, or symbiotics to improve gut dysbiosis in this setting. These measures can increase the presence of SCFA-producing saccharolytic bacteria and reduce proteolytic bacteria, thereby lowering the production of gut-derived uremic toxins and inflammation. By ameliorating CKD-related gut dysbiosis, these strategies can also improve the control of renal anemia and enhance the responsiveness to erythropoiesis-stimulating agents (ESAs) in ESA-resistant patients. In this review, we have explored the relationship between gut dysbiosis in CKD and renal anemia and propose feasible solutions, both those already known and potential future treatments. Full article

Background/Objectives: Bacteraemia can be fatal without antibiotic intervention. Antibiotic Susceptibility Testing (AST) provides the necessary information for targeted antibiotic therapy; however, the traditional method using disc diffusion can take over two days from a positive blood culture. Inappropriate empiric therapy is associated with increased mortality and increased antibiotic resistance, highlighting the need for more rapid turnaround times for AST. By making changes to an established method, turnaround times can be reduced. Methods: Eighty-two patient positive blood culture samples were collected from January to April 2022, representing the range of common bacteria causing sepsis. This followed the normal methodology in the laboratory of inoculating agar from positive blood cultures in preparation for European Committee on Antimicrobial Susceptibility Testing (EUCAST) disc diffusion AST method. EUCAST methodology outlines that disc diffusion should be performed on isolates from an overnight culture of 16–24 h. This study looked at comparing disc diffusion results from cultures with 6 h of incubation to those with incubation times of 24 h, after organism identification by MALDI-ToF. Results from 6-h and 24-h cultures were compared by disc zone sizes and by interpreted susceptibility reading following EUCAST guidelines of sensitive, resistant, susceptible with increased exposure, or an area of technical uncertainty. Results: A total of 99.65% interpreted susceptibility readings matched across all organisms to all relevant antibiotics, with an average zone size difference of 1.08 mm between results from 6 h versus 24 h cultures. Conclusions: This method offers a non-automated way of using the traditional disc diffusion method, reducing turnaround times while still producing reliable and accurate results. This would mean validated ASTs can be set up in the same day as a blood culture flags positive rather than waiting for a longer culture. As this method is widely used within the laboratory already, it would mean that additional training is not required, as the process is the same, and only incubation time varies. This would positively impact patient outlook due to the shorter use of empiric therapy, and benefit antimicrobial stewardship (AMS). Full article

Background: An external ventricular drain (EVD) is used to release elevated intracranial pressure by draining cerebrospinal fluid (CSF) from the brain’s ventricles. The establishment of an EVD is one of the most commonly performed neurosurgical procedures to treat intracranial pressure in patients. Nevertheless, infections are very frequent complications. Identifying the risk factors for EVD-related infections is a key to improving patient safety and outcomes. Methods: We conducted a retrospective, single-center study of patients who underwent EVD implantation between January 2022 and March 2024. Patients were classified into infected and non-infected groups based on their clinical symptoms, as well as laboratory and microbiological results. Patient characteristics and possible risk factors for infection were compared between the two groups. Results: In total, 123 patients treated with 156 EVDs were included in this study, with a mean age of 55.8 (range: 25–84) years. EVD-associated infections were observed in 37 patients (30%). We found no significant association between infection risk and patient characteristics, including gender, primary diagnosis, craniotomy, or immunosuppression. There was no significant difference in terms of EVD insertion, i.e., whether the insertion took place in the operating room (OR) with antibiotic prophylaxis or outside the OR with no periprocedural antibiotic treatment. However, within the intensive care unit (ICU), EVD infection was much lower (13%) if EVD insertion took place in a single-bed room compared to multiple-bed room insertions (34%). Furthermore, there were significant differences in terms of the duration of first EVD (both single and multiple catheterizations) (p < 0.0001) and the total catheterization time (p = 0.0001). Additionally, there was a significant association with patient days in the ICU and EVD catheterization. Conclusions: Revisiting infection control measures is necessary, with special attention to the replacement of EVDs in single-bed ICU rooms, to introduce antibiotic prophylaxis in the ICU. Minimizing unnecessary EVD manipulation during catheterization is crucial in order to decrease the risk of EVD infection. Full article

Auditory hair cell damage induced by aminoglycoside antibiotics (AmAn) leads to hearing loss, which has a serious effect on people’s mental and physical health. This ototoxicity is thought to be related with the excessive accumulation of reactive oxygen species (ROS) in hair cells. However, therapeutic agents that protect hair cells are limited. Marine peptides have been shown to have excellent potential applications in disease prevention and treatment. Therefore, this study investigated the protective effects of an active peptide from Neptunea arthritica cumingii against AmAn-induced hair cell damage using the model of hair cell damage zebrafish. We identified the number, ultrastructure, and function of hair cells using fluorescence probes and scanning electron microscopy. The uptake of AmAn, ROS level, mitochondrial permeability transition pore, and apoptosis in hair cells were also tested by fluorescence labeling and TUNEL assay. The molecular mechanism for hair cell protection exerted by the peptide was detected by a real-time quantitative PCR assay. The results indicated that the peptide suppressed the uptake of AmAn but did not damage the function of hair cells mediating hearing. It also prevented ROS accumulation, decreased the occurrence of apoptosis, and rescued the abnormal opening and expressions of mitochondrial permeability transition pore and genes related to antioxidants. The peptide may be an effective therapeutic agent for AmAn-induced ototoxicity. In the future, we plan to use mammalian models to further investigate the otoprotective effect of the peptide. Full article