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Objective: An altered sensation during endodontic treatment can occur due to the extrusion of endodontic materials. This study aims to discuss intentional replantation to address paresthesia resulting from an endodontic file penetrating the inferior alveolar nerve canal and provide a protocol for managing nerve injuries in such incidents. Case presentation: A 12-year-old girl developed paresthesia when an endodontic file separated and was inadvertently pushed through the apical foramen into the inferior alveolar nerve canal during root canal treatment of the mandibular left first molar. A CBCT scan revealed the file penetrating the canal towards the inferior border of the mandible. After considering the treatment options, intentional replantation was deemed suitable. The tooth was atraumatically extracted and preserved in sterile saline. The surgeon then carefully cleaned and irrigated the socket. The radiographic assessment confirmed successful file removal from the socket. The root ends were resected, and retrograde preparation and obturation were conducted using ultrasonic tips and mineral trioxide aggregate. The tooth was then replanted into the socket. Successful replantation was confirmed by tooth stability and an audible click. The patient was prescribed antibiotics and steroids. After completion of the endodontic treatment, a stainless steel crown was cemented. The successful intentional replantation procedure resulted in rapid improvement in the patient's condition. The normal sensation had been restored, indicating nerve recovery. At the 15-month follow-up, periapical bone healing and the eruption of the adjacent second molar were observed, affirming the treatment protocol's overall success. Conclusion: Prompt intervention and immediate intentional replantation facilitated direct inspection of the separated file within the socket. Collaboration between an oral maxillofacial surgeon and an endodontist ensures expedited and targeted treatment, leading to favorable outcomes. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to assess antibiotic stewardship by quantifying the use of first-dose intravenous (IV) vs oral-only antibiotics and the frequency with which antibiotic class was changed for discharged patients. Secondary aims included the following: evaluation of the relative length of stay (LOS); differences in prescribing patterns between clinician types; differences between academic and community settings; assessment of prescribing patterns among emergency department (ED) diagnoses; and frequency of return visits for patients in each group.Methods: This was a retrospective cohort study including patients presenting to EDs with infections who were discharged from our Midwest healthcare system consisting of 17 community hospitals and one academic center. We included infection type, antibiotic class and route of administration, type of infection, LOS, return visit within two weeks, clinician type, and demographics. Data were collected between June 1, 2018–December 31, 2021 and analyzed using descriptive statistics.Results: We had 77,204 ED visits for patients with infections during the study period, of whom 3,812 received IV antibiotics during their visit. There were more women (62.4%) than men included. Of the 3,812 patients who received IV antibiotics, 1,026 (34.3%) were discharged on a different class of antibiotics than they received. The most common changes were from IV cephalosporin to oral quinolone or penicillin. Patients treated with IV antibiotics prior to discharge had a longer LOS in the ED (median difference of 102 minutes longer for those who received IV antibiotics). There was not a significant difference in the use of IV antibiotics between the academic center and community sites included in the study.Conclusion: Administering IV antibiotics as a first dose prior to oral prescriptions upon discharge is common, as is shifting classes from the IV dose to the oral prescription. This offers an opportunity for intervention to improve antibiotic stewardship for ED patients as well as reduce cost and length of stay.

UNLABELLED: Coccidioidomycosis, also known as Valley fever, is a disease caused by the fungal pathogen Coccidioides. Unfortunately, patients are often misdiagnosed with bacterial pneumonia, leading to inappropriate antibiotic treatment. The soil Bacillus subtilis-like species exhibits antagonistic properties against Coccidioides in vitro; however, the antagonistic capabilities of host microbiota against Coccidioides are unexplored. We sought to examine the potential of the tracheal and intestinal microbiomes to inhibit the growth of Coccidioides in vitro. We hypothesized that an uninterrupted lawn of microbiota obtained from antibiotic-free mice would inhibit the growth of Coccidioides, while partial in vitro depletion through antibiotic disk diffusion assays would allow a niche for fungal growth. We observed that the microbiota grown on 2×GYE (GYE) and Columbia colistin and nalidixic acid with 5% sheeps blood agar inhibited the growth of Coccidioides, but microbiota grown on chocolate agar did not. Partial depletion of the microbiota through antibiotic disk diffusion revealed diminished inhibition and comparable growth of Coccidioides to controls. To characterize the bacteria grown and identify potential candidates contributing to the inhibition of Coccidioides, 16S rRNA sequencing was performed on tracheal and intestinal agar cultures and murine lung extracts. We found that the host bacteria likely responsible for this inhibition primarily included Lactobacillus and Staphylococcus. The results of this study demonstrate the potential of the host microbiota to inhibit the growth of Coccidioides in vitro and suggest that an altered microbiome through antibiotic treatment could negatively impact effective fungal clearance and allow a niche for fungal growth in vivo. IMPORTANCE: Coccidioidomycosis is caused by a fungal pathogen that invades the host lungs, causing respiratory distress. In 2019, 20,003 cases of Valley fever were reported to the CDC. However, this number likely vastly underrepresents the true number of Valley fever cases, as many go undetected due to poor testing strategies and a lack of diagnostic models. Valley fever is also often misdiagnosed as bacterial pneumonia, resulting in 60%-80% of patients being treated with antibiotics prior to an accurate diagnosis. Misdiagnosis contributes to a growing problem of antibiotic resistance and antibiotic-induced microbiome dysbiosis; the implications for disease outcomes are currently unknown. About 5%-10% of symptomatic Valley fever patients develop chronic pulmonary disease. Valley fever causes a significant financial burden and a reduced quality of life. Little is known regarding what factors contribute to the development of chronic infections and treatments for the disease are limited.

BACKGROUND: The trauma mortality rate is higher in the elderly compared with younger patients. Ageing is associated with physiological changes in multiple systems and correlated with frailty. Frailty is a risk factor for mortality in elderly trauma patients. We aim to provide evidence-based guidelines for the management of geriatric trauma patients to improve it and reduce futile procedures. METHODS: Six working groups of expert acute care and trauma surgeons reviewed extensively the literature according to the topic and the PICO question assigned. Statements and recommendations were assessed according to the GRADE methodology and approved by a consensus of experts in the field at the 10th international congress of the WSES in 2023. RESULTS: The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage, including drug history, frailty assessment, nutritional status, and early activation of trauma protocol to improve outcomes. Acute trauma pain in the elderly has to be managed in a multimodal analgesic approach, to avoid side effects of opioid use. Antibiotic prophylaxis is recommended in penetrating (abdominal, thoracic) trauma, in severely burned and in open fractures elderly patients to decrease septic complications. Antibiotics are not recommended in blunt trauma in the absence of signs of sepsis and septic shock. Venous thromboembolism prophylaxis with LMWH or UFH should be administrated as soon as possible in high and moderate-risk elderly trauma patients according to the renal function, weight of the patient and bleeding risk. A palliative care team should be involved as soon as possible to discuss the end of life in a multidisciplinary approach considering the patients directives, family feelings and representatives desires, and all decisions should be shared. CONCLUSIONS: The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage based on assessing frailty and early activation of trauma protocol to improve outcomes. Geriatric Intensive Care Units are needed to care for elderly and frail trauma patients in a multidisciplinary approach to decrease mortality and improve outcomes.

The emergence of antibiotic-resistant bacteria (ARB) has necessitated the development of alternative therapies to deal with this global threat. Bacteriophages (viruses that target bacteria) that kill ARB are one such alternative. Although phages have been used clinically for decades with inconsistent results, a number of recent advances in phage selection, propagation, and purification have enabled a reevaluation of their utility in contemporary clinical medicine. In most phage therapy cases, phages are administered in combination with antibiotics to ensure that patients receive the standard-of-care treatment. Some phages may work cooperatively with antibiotics to eradicate ARB, as often determined using non-standardized broth assays. We sought to develop a solid media-based assay to assess cooperativity between antibiotics and phages to offer a standardized platform for such testing. We modeled the interactions that occur between antibiotics and phages on solid medium to measure additive, antagonistic, and synergistic interactions. We then tested the method using different bacterial isolates and identified a number of isolates where synergistic interactions were identified. These interactions were not dependent on the specific organism, phage family, or antibiotic used. A priori susceptibility to the antibiotic or the specific phage were not requirements to observe synergistic interactions. Our data also confirm the potential for the restoration of vancomycin to treat vancomycin-resistant Enterococcus (VRE) when used in combination with phages. Solid media assays for the detection of cooperative interactions between antibiotics and phages can be an accessible technique adopted by clinical laboratories to evaluate antibiotic and phage choices in phage therapy.IMPORTANCEBacteriophages have become an important alternative treatment for individuals with life-threatening antibiotic-resistant bacteria (ARB) infections. Because antibiotics represent the standard-of-care for treatment of ARB, antibiotics and phages often are delivered together without evidence that they work cooperatively. Testing for cooperativity can be difficult due to the equipment necessary and a lack of standardized means for performing the testing in liquid medium. We developed an assay using solid medium to identify interactions between antibiotics and phages for gram-positive and gram-negative bacteria. We modeled the interactions between antibiotics and phages on solid medium, and then tested multiple replicates of vancomycin-resistant Enterococcus (VRE) and Stenotrophomonas in the assay. For each organism, we identified synergy between different phage and antibiotic combinations. The development of this solid media assay for assessing synergy between phages and antibiotics will better inform the use of these combinations in the treatment of ARB infections.

Carbohydrate intolerance, commonly linked to the consumption of lactose, fructose, or sorbitol, affects up to 30% of the population in high-income countries. Although sorbitol intolerance is attributed to malabsorption, the underlying mechanism remains unresolved. Here, we show that a history of antibiotic exposure combined with high fat intake triggered long-lasting sorbitol intolerance in mice by reducing Clostridia abundance, which impaired microbial sorbitol catabolism. The restoration of sorbitol catabolism by inoculation with probiotic Escherichia coli protected mice against sorbitol intolerance but did not restore Clostridia abundance. Inoculation with the butyrate producer Anaerostipes caccae restored a normal Clostridia abundance, which protected mice against sorbitol-induced diarrhea even when the probiotic was cleared. Butyrate restored Clostridia abundance by stimulating epithelial peroxisome proliferator-activated receptor-gamma (PPAR-γ) signaling to restore epithelial hypoxia in the colon. Collectively, these mechanistic insights identify microbial sorbitol catabolism as a potential target for approaches for the diagnosis, treatment, and prevention of sorbitol intolerance.

Wildfires affect soils in multiple ways, leading to numerous challenges for colonizing microorganisms. Although it is thought that fire-adapted microorganisms lie at the forefront of postfire ecosystem recovery, the specific strategies that these organisms use to thrive in burned soils remain largely unknown. Through bioactivity screening of bacterial isolates from burned soils, we discovered that several Paraburkholderia spp. isolates produced a set of unusual rhamnolipid surfactants with a natural methyl ester modification. These rhamnolipid methyl esters (RLMEs) exhibited enhanced antimicrobial activity against other postfire microbial isolates, including pyrophilous Pyronema fungi and Amycolatopsis bacteria, compared to the typical rhamnolipids made by organisms such as Pseudomonas spp. RLMEs also showed enhanced surfactant properties and facilitated bacterial motility on agar surfaces. In vitro assays further demonstrated that RLMEs improved aqueous solubilization of polycyclic aromatic hydrocarbons, which are potential carbon sources found in char. Identification of the rhamnolipid biosynthesis genes in the postfire isolate, Paraburkholderia kirstenboschensis str. F3, led to the discovery of rhlM, whose gene product is responsible for the unique methylation of rhamnolipid substrates. RhlM is the first characterized bacterial representative of a large class of integral membrane methyltransferases that are widespread in bacteria. These results indicate multiple roles for RLMEs in the postfire lifestyle of Paraburkholderia isolates, including enhanced dispersal, solubilization of potential nutrients, and inhibition of competitors. Our findings shed new light on the chemical adaptations that bacteria employ to navigate, grow, and outcompete other soil community members in postfire environments.

Aim Methods Results Conclusion To determine the association between the duration and types of antibiotic exposure and the occurrence of short‐ and long‐term outcomes among preterm, very‐low‐birthweight (VLBW) infants.Retrospective cohort study of VLBW infants born <32 weeks gestation between January 2017–December 2021. Association between antibiotic exposure and the occurrence of death and/or major morbidities, and neurodevelopmental impairment (NDI) at 18–24 months corrected age, was evaluated.A total of 728 infants were included—median gestation 28 weeks (IQR 26, 30) and median birthweight 1070g (IQR 850, 1300). Compared to no antibiotics, antibiotics exposure >3 days was significantly associated with increased risk of mortality and/or bronchopulmonary dysplasia (BPD)—adjusted odds ratio (AOR) 2.0 (95% CI 1.1–3.8; p=0.03), 3.5 (95% CI 1.6–7.8; p=0.01) and 3.8 (95% CI 1.6‐9.0; p<0.001) corresponding to antibiotic exposure of 4‐7 days, 8–14 and >14 days, respectively. Additional exposure to broad‐spectrum antibiotics was associated with AOR of 3.2 (95% CI 1.6–6.5; p<0.01) for death and/or BPD. There was no significant association between antibiotic exposure and NDI.Infants who received >3 days of antibiotics and/or additional broad‐spectrum antibiotics had significantly increased odds of death and/or BPD compared to no exposure. Antibiotic exposure was not significantly associated with NDI in our population. [ABSTRACT FROM AUTHOR]

Emergency medical services often serve as the initial point of contact for septic patients, offering crucial pre-hospital intervention opportunities. However, the efficacy of pre-hospital interventions remains uncertain. From this perspective, we'll talk about the available evidence of pre-hospital sepsis and septic shock treatment and the barriers to its implementation. [ABSTRACT FROM AUTHOR]

Shift in laying hens housing from conventional cage-based systems to alternatives has impacted their health and performance. Microorganisms colonize young chick in the early stages of their physiological and immune development. These colonizing microbes originate from parent and the environment. Escherichia coli is among the normal gut colonizing bacteria however, some E. coli strains known as avian pathogenic E. coli (APEC), cause local or systemic infections (colibacillosis) responsible of significant economic losses to the poultry industry. Potential APEC strains and other poultry gut microbiota are influenced by several factors such as housing system, and the use of feed additives (prebiotics, probiotics, symbiotic, among others). This review will discuss the status of pullets and layers immunity, gut health, and predisposing factors of colibacillosis. Dietary interventions and some colibacillosis mitigation strategies in pullets and laying hens are reviewed and discussed. With the development of sequencing technologies and the use of feed additives as alternatives to antibiotics, future studies need to understand some of the complex associations between the feed additives, the rearing environment, and their selective pressure on gut microbiota, including E. coli , and their impacts on immune development in pullets and hens. [ABSTRACT FROM AUTHOR]

A metagenomic library consisting of 15,000 clones was constructed from the mangrove sediment. An antimicrobially active clone from the metagenomic library PS49 was identified by function- based screening. This paper presents the results of the biochemical characterization and metagenomic library screening of the marine-derived antibiotic, 8-demethoxy-10-deoxysteffimycin. Plasmid libraries were constructed, and clones were produced using a metagenomic approach. Out of 15,000 clones, 81 clones were screened for antimicrobial activity, and five potential clones were selected. The activity of one clone was characterized and named as PS49. The bioactive compounds from the selected clone were checked for antimicrobial, antioxidant, and anticancer activities. The clone PS49 was tested against various pathogens including bacteria and fungi and it showed inhibitory effects against all the tested pathogens. The antimicrobially active fractions were then crystallized and subjected to spectroscopic analysis such as FTIR, NMR and LC–MS analysis. The substance from clone PS49 has finally been recognized, and the compound from clone PS49 has been identified as 8-demethoxy-10-deoxysteffimycin. The substances isolated from the PS49 clone exhibited strong anticancer activity against skin cancer-cell lines SK-MEL2. The compounds showed a reduction in cell viability with an increase in the compound concentration. The compounds obtained from clone PS49 showed an IC50 value of 85 µg/ml. [ABSTRACT FROM AUTHOR]

Abstract\nHIGHLIGHTSAntibiotic resistance has expanded as a result of the careless use of antibiotics in the medical field, the food industry, agriculture, and other industries. By means of genetic recombination between commensal and pathogenic bacteria, the microbes obtain antibiotic resistance genes (ARGs). In bacteria, horizontal gene transfer (HGT) is the main mechanism for acquiring ARGs. With the development of high-throughput sequencing, ARG sequence analysis is now feasible and widely available. Preventing the spread of AMR in the environment requires the implementation of ARGs mapping. The metagenomic technique, in particular, has helped in identifying antibiotic resistance within microbial communities. Due to the exponential growth of experimental and clinical data, significant investments in computer capacity, and advancements in algorithmic techniques, the application of machine learning (ML) algorithms to the problem of AMR has attracted increasing attention over the past five years. The review article sheds a light on the application of bioinformatics for the antibiotic resistance monitoring. The most advanced tool currently being employed to catalog the resistome of various habitats are metagenomics and metatranscriptomics. The future lies in the hands of artificial intelligence (AI) and machine learning (ML) methods, to predict and optimize the interaction of antibiotic-resistant compounds with target proteins.The global issue of antibiotic resistance has an impact on people’s health.Antibiotic resistance genes mapping is crucial for the prevention of antimicrobial resistance.Metagenomics is the most sophisticated method for cataloging the resistome.Artificial intelligence (AI) can help to optimize the antibiotic-resistant compounds interaction with target proteins.The global issue of antibiotic resistance has an impact on people’s health.Antibiotic resistance genes mapping is crucial for the prevention of antimicrobial resistance.Metagenomics is the most sophisticated method for cataloging the resistome.Artificial intelligence (AI) can help to optimize the antibiotic-resistant compounds interaction with target proteins. [ABSTRACT FROM AUTHOR]

The use of highly potent but very toxic antibiotics such as colistin has become inevitable due to the rise of antimicrobial resistance. We aimed for a chemically‐triggered, controlled release of colistin at the infection site to lower its systemic toxicity by harnessing the power of click‐to‐release reactions. Kinetic experiments with nine tetrazines and three dienophiles demonstrated a fast release via an inverse‐electron‐demand Diels–Alder reaction between trans‐cyclooctene (TCO) and the amine‐functionalised tetrazine Tz7. The antibiotic activity of colistin against Escherichia coli was masked by TCO units, but restored upon reaction with d‐Ubi−Tz, a tetrazine functionalised with the bacterial binding peptide d‐Ubi29–41. While standard TCO did not improve toxicity against human proximal tubular kidney HK‐2 cells, the installation of an aspartic acid‐modified TCO masking group reduced the overall charge of the peptide and entry to the kidney cells, thereby dramatically lowering its toxicity. The analog Col−(TCO‐Asp)1 had favourable pharmacokinetic properties in mice and was successfully activated locally in the lung by d‐Ubi−Tz in an in vivo infection model, whereas it remained inactive and non‐harmful without the chemical trigger. This study constitutes the first example of a systemically acting two‐component antibiotic with improved drug tolerability. [ABSTRACT FROM AUTHOR]

Current photocatalysts endowed with oxidation and reduction capabilities for pharmaceuticals and heavy metals removal face numerous challenges, such as a lack of sufficient reactive sites, poor electron-hole separation, and limited oxidation and reduction capabilities. In this study, we aimed to overcome these limitations by employing a simple solvothermal method to fabricate a novel S-scheme heterojunction, Cd 0.5 Zn 0.5 S/CeO 2. The optimal Cd₀.₅Zn₀.₅S/CeO 2 heterojunction achieved a maximum ciprofloxacin degradation efficiency of 86 % within 30 min, showing a remarkable improvement of 2.4 and 4.6 times compared to pristine Cd₀.₅Zn₀.₅S and CeO 2 , respectively. The heterojunction also demonstrated a remarkable 100 % photoreduction efficiency of Cr(VI) within 30 min, which is double the photodegradation performance of the individual materials. The combination of Cd₀.₅Zn₀.₅S with CeO 2 to form the Cd₀.₅Zn₀.₅S/CeO 2 S-scheme heterojunction effectively enhanced spatial photo-carrier separation and optimized the photo-redox capability, resulting in a substantial improvement in photocatalytic performance and stability. Through radical trapping experiments, the primary reactive species responsible for CIP degradation were identified as h⁺, OH•, and •O₂⁻. Additionally, e⁻ was determined to be the key species responsible for the photoreduction of Cr(VI). Based on these findings, we proposed a plausible photocatalytic reaction pathway for the simultaneous elimination of both CIP and Cr(VI). This study underscores the significant potential of the Cd 0.5 Zn 0.5 S/CeO 2 S-scheme heterojunction for advanced wastewater treatment applications, highlighting its innovative approach and superior performance. [ABSTRACT FROM AUTHOR]

The increasing prevalence of multidrug-resistant pathogens is a critical public health issue, necessitating the development of alternative antibacterial agents. Examples of these pathogens are methicillin-resistant Staphylococcus aureus (MRSA) and the emergence of "pan-resistant" Gram-negative strains, such as Pseudomonas aeruginosa and Acinetobacter baumannii, which occurred more recently. This review examines various emerging materials with significant antibacterial activities. Among these are nanomaterials such as quantum dots, carbon quantum dots, metal–organic frameworks (MOFs), covalent organic frameworks (COFs), and layered double hydroxides, all of which demonstrate excellent antibacterial properties. Interestingly, including antibacterial agents within the structure of these materials can help avoid bacterial resistance and improve the long-term efficacy of the materials. Additionally, the antibacterial potential of liquid solvents, including ionic liquids and both deep eutectic solvents and natural deep eutectic solvents, is explored. The review discusses the synthesis methods, advantages, and antibacterial efficacy of these new materials. By providing a comprehensive overview of these innovative materials, this review aims to contribute to the ongoing search for effective solutions to combat antibiotic resistance. Key studies demonstrating antibacterial effects against pathogens like Escherichia coli, Staphylococcus aureus, and multidrug-resistant strains are summarized. MOFs have exhibited antibacterial properties through controlled ion release and surface interactions. COFs have enhanced the efficacy of encapsulated antibiotics and displayed intrinsic antibacterial activity. Other nanomaterials, such as quantum dots, have generated reactive oxygen species, leading to microbial inactivation. This review aims to provide insights into these new classes of antibacterial materials and highlight them for addressing the global crisis of antibiotic resistance. Key points: • Nanomaterials show strong antibacterial effects against drug-resistant bacteria • Emerging solvents like ionic liquids offer novel solutions for bacterial resistance • MOFs and COFs enhance antibiotic efficacy, showing promise in combating resistance [ABSTRACT FROM AUTHOR]

Cattle manure or its digestate, which often contains antibiotic residues, can be used as an organic fertilizer and copper (Cu) as a fungicide in agriculture. Consequently, both antibiotics and Cu are considered soil contaminants. In this work, microcosms were performed with soil amended with either manure or digestate with Cu and an antibiotic (sulfamethoxazole, SMX) co-presence and the planting of Lactuca sativa. After the addition of the organic amendments, a prompt increase in the microbial activity and at the same time of the sul1 and intI1 genes was observed, although ARGs generally decreased over time. In the amended and spiked microcosms, the microbial community was able to remove more than 99% of SMX in 36 days and the antibiotic did not bioaccumulate in the lettuce. Interestingly, where Cu and SMX were co-present, ARGs (particularly sul2) increased, showing how copper had a strong effect on resistance persistence in the soil. Copper also had a detrimental effect on the plant-microbiome system, affecting plant biomass and microbial activity in all conditions except in a digestate presence. When adding digestate microbial activity, biodiversity and lettuce biomass increased, with or without copper present. Not only did the microbial community favour plant growth, but lettuce also positively influenced its composition by increasing bacterial diversity and classes (e.g., Alphaproteobacteria) and genera (e.g., Bacillus), thus indicating a good-quality soil. Key points: • Cattle digestate promoted the highest microbial activity, diversity, and plant growth • Cattle digestate counteracted detrimental contaminant effects • Cu presence promoted antibiotic cross-resistance in soil [ABSTRACT FROM AUTHOR]

The study was conducted on 60 L of suckling piglets out of 775 piglets, of which 227 piglets had diarrhea litres of piglets, and out of 775 piglets, 227 piglets had diarrhoea syndrome. There were 3 interventions in separate trials as follows: 1 and 2 involved antibiotic use (Enrofloxacin and Gentamicin); Trial 3 used the supplement Lectin C (LvCLT3 and LvCLT4) for a treatment period of 3–7 days. Intervention results on 227 piglets with diarrhea showed the highest cure rate when supplemented with Lectin C, with no mortality rate, longer treatment time, and no reinfection rate. While the two antibiotic trials still had lower cure rates, mortality and reinfection rates were higher. After 05 days of recovery, piglets were tested for MCV, MCH, and MCHC, showing an apparent decrease in the group supplemented with Lectin C, while the two groups using antibiotics still had high rates, with a confidence level of P < 0.05; 0.01 and 0.001. Antibiotics treat piglets in their early stages, so there is a risk of immunodeficiency and low infection response. It is necessary to supplement substances derived from dietary supplements. Supplementing Lectin C increases resistance, enhances immune response, improves the effectiveness of treating diarrhoea syndrome in piglets, and ensures safe meat quality in the future. Lectin C supplementation will improve piglet health and breed quality efficiency. This heralds a promising future for the pig industry with improved meat quality and reduced environmental impact. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Discussion Guidelines for vancomycin therapeutic monitoring recommend using a Bayesian approach with a population pharmacokinetic model to estimate the 24 h area under the concentration‐time curve over first‐order equations. Thus, we performed an external evaluation of population pharmacokinetic models of vancomycin in neonates and compared Bayesian results with those observed in clinical practice via pharmacokinetic equations to improve therapeutic monitoring by proposing optimized initial dosing nomograms and assessing the feasibility of reduced blood sampling strategies using the most predictive models.Models were identified from the literature and evaluated via an external neonatal population. A priori predictive performance was first assessed by prediction‐based diagnostics, then by simulation‐based diagnostics and a posteriori analyses only if deemed satisfactory; model‐informed vancomycin exposure was also compared with reference first‐order pharmacokinetic equations. The best‐performing models were ultimately subjected to Monte Carlo simulations to develop new initial dosing nomograms offering the highest probability of achieving therapeutic target.A total of 28 population pharmacokinetic models were evaluated in the external dataset, which includes 72 neonates and 380 vancomycin concentrations. Eleven models had an adequate predictive performance with bias ≤ ± 15% and imprecision ≤$$ \le $$ 30%, while the Bayesian approach yielded over 75% agreement with reference exposure values in most cases. Nonetheless, Capparelli et al. and Mehrotra et al. models performed the best overall, showing the lowest imprecisions of 16.8% and 16.9%, respectively; both models recommended higher dosage regimens than the theoretical nomogram currently applied to favor therapeutic target attainment.We externally evaluated numerous neonatal population pharmacokinetic models of vancomycin and used the most predictive ones to advocate new initial dosing nomograms. Clinical implementation of the Bayesian approach could reduce the time needed to reach therapeutic target and limit the number of blood samples in newborns compared with traditional pharmacokinetic equations. [ABSTRACT FROM AUTHOR]

Burkholderia thailandensis has emerged as a nonpathogenic surrogate for Burkholderia pseudomallei, the causative agent of melioidosis, and an important Gram-negative model bacterium for studying the biosynthesis and regulation of secondary metabolism. We recently reported that subinhibitory concentrations of trimethoprim induce vast changes in both the primary and secondary metabolome of B. thailandensis. In the current work, we show that the folate biosynthetic enzyme FolE2 is permissive under standard growth conditions but essential for B. thailandensis in the presence of subinhibitory doses of trimethoprim. Reasoning that FolE2 may serve as an attractive drug target, we screened for and identified ten inhibitors, including dehydrocostus lactone (DHL), parthenolide, and ß-lapachone, all of which are innocuous individually but form a chemical-synthetic lethal combination with subinhibitory doses of trimethoprim. We show that DHL is a mechanism-based inhibitor of FolE2 and capture the structure of the covalently inhibited enzyme using X-ray crystallography. In vitro, the combination of subinhibitory trimethoprim and DHL is more potent than Bactrim, the current standard of care against melioidosis. Moreover, unlike Bactrim, this combination does not affect the growth of most commensal and beneficial gut bacteria tested, thereby providing a degree of specificity against B. pseudomallei. Our work provides a path for identifying antimicrobial drug targets and for utilizing binary combinations of molecules that form a toxic cocktail based on metabolic idiosyncrasies of specific pathogens. [ABSTRACT FROM AUTHOR]

Summary Crop diseases cause significant quality and yield losses to global crop products each year and are heavily controlled by chemicals along with very limited antibiotics composed of small molecules. However, these methods often result in environmental pollution and pest resistance, necessitating the development of new bio‐controlling products to mitigate these hazards. To identify effective antimicrobial peptides (AMPs) considered as potential sources of future antibiotics, AMPs were screened from five bacterial strains showing antagonism against a representative phytopathogenic fungus (Rhizoctonia Solani) through the Bacillus subtilis expression system, which has been developed for identifying bacterial AMPs by displaying autolysis morphologies. A total of 5000 colonies were screened, and five displaying autolysis morphologies showed antagonism against R. solani. A novel AMP with the strongest antagonism efficiency was determined and tentatively named HR2‐7, which is composed of 24 amino acids with an alpha‐helical structure. HR2‐7 has strong and broad‐spectrum antimicrobial activity, tested against 10 g‐positive and ‐negative bacteria and four phytopathogenic fungi by contact culture in plates with minimal lethal concentrations of 4.0 μM. When applied as purified peptide or in fermented B. subtilis culture solution, HR2‐7 showed strong controlling efficiency on plants against diverse fungal and bacterial pathogens. Based on current understanding, HR2‐7 is recognized as the first AMP derived from an agricultural antagonistic bacterium. It exhibits wide‐ranging and notable antimicrobial efficacy, offering a supplementary approach for managing plant diseases, in addition to conventional chemical pesticides and antibiotics. [ABSTRACT FROM AUTHOR]

Background: High-pressure injection injuries are rare injuries and are frequently underestimated due to the limited external damage. Because of their association with occupational activities, these injuries are predominantly seen in hands. Facial involvement in such traumas is extremely rare. The difference in facial anatomy compared to the extremities demands careful consideration of both associated complications and treatment options. Case: A 6-year-old girl with no significant medical history was presented to the Emergency Department with a high-pressure injection injury to her right eye with a high-pressure cleaner. This resulted in injection of air at a pressure of 8 bar into the eye. She developed significant subcutaneous emphysema in the facial and neck regions. Additionally, intraorbital and intracranial emphysema were identified without any fractures. Treatment consisted of inpatient observation and antibiotic treatment. The patient was discharged after one day of observation for continued antibiotic treatment at home. Two weeks later, the patient had no residual symptoms and there were no signs of secondary infection. Conclusion: High-pressure injection injuries to the face are rare and demand a different approach compared to the most common high-pressure injection injuries to the extremities. The nature of the injected material is paramount in choosing the appropriate treatment. This case illustrates that a high-pressure injection injury with air in the facial region, leading to extensive emphysema, can be managed conservatively with antibiotic therapy and inpatient observation. [ABSTRACT FROM AUTHOR]

Purpose Materials and Methods Results Conclusion To investigate antibiotic usage practices in ophthalmic surgeries in Germany.An online questionnaire was sent to veterinary surgeons (general veterinarians and veterinarians with additional qualification in ophthalmology) inquiring about their antibiotic preferences, administration methods, and factors affecting antibiotic usage in ophthalmic surgical procedures.A total of 417 questionnaires were analyzed. Postoperative antibiotics (systemic/topical in percent when used) were used all or most of the time by 69% of veterinarians following enucleation (99/6), by 62% after eyelid surgery (54/69), by 68% after third eyelid (TEL) surgery (19/92) and by 80% after keratectomy (6/99). The most commonly used systemic antibiotic was amoxicillin with clavulanic acid and the most commonly used topical antibiotic was chloramphenicol.WHO “watch‐group” antibiotics were infrequently administered systemically but frequently utilized topically; including in 13% of eyelid surgery, 15% of TEL surgery, and 35% of keratectomies. Factors influencing antibiotic use included fear of complications (67%), personal experience (63%), diagnostic uncertainty (21%), and owner expectations (9%). Participants following institutional guidelines used fewer antibiotics in enucleations (p = .002) and were less likely to choose fluoroquinolones post‐eyelid surgery (p = .044).The potential for reducing antibiotic use following ophthalmic soft tissue surgery is significant. Addressing barriers such as concerns about postoperative complications and the reliance on individual clinical experience, the implementation of standardized guidelines could facilitate a shift toward more judicious antibiotic practices. [ABSTRACT FROM AUTHOR]

ABSTRACT Sea turtles face various threats to survival, primarily due to human activities, such as bycatch, vessel strikes, pollution, and climate change. Many of these activities can lead to illness or injuries, increasing the risk of infection. Treating infections appropriately and effectively requires knowledge of antimicrobial properties and their ability to eradicate microbes without harm to the sea turtle. Robust pharmacokinetic studies, therefore, are important for appropriate dosing. Herein, we review the studies detailing the pharmacokinetic properties of antimicrobials in sea turtles conducted to date. [ABSTRACT FROM AUTHOR]

This review aimed to summarize the current literature on antibiotic distribution in orthopedically relevant tissues and settings where dynamic sampling methods have been used. PubMed and Embase databases were systematically searched. English‐published studies between 2004 and 2024 involving systemic antibiotic administration in orthopedically relevant tissues and settings based on dynamic measurements were included. In total, 5385 titles were identified. After title and abstract screening, 97 eligible studies (43 different antibiotic drugs) were included. The studies covered both preclinical (42%) and clinical studies including healthy and infected tissues (21%) and prophylactic and steady‐state situations (35%). Microdialysis emerged as the predominant sampling method in 98% of the studies. Most of the presented antibiotics (80%) were only assessed once or twice. Among the most extensively studied antibiotics were cefuroxime (18 studies), linezolid (9 studies) and vancomycin (9 studies). This review presents valuable insights into the microenvironmental distribution of antibiotics in orthopedically relevant target tissues and settings and seeks to provide a basis for improving dosing recommendations and treatment outcomes. However, it is important to acknowledge that our findings are limited to the specific drug, dosing regimens, administration method and target tissue, and are crucially linked to the selected PK/PD target. [ABSTRACT FROM AUTHOR]

Ribosomal RNA (rRNA) modifications are involved in multiple biological processes. KsgA is a 16S rRNA adenine dimethyltransferase that methylates at the adenines 1518 and 1519 (A1518/1519) positions, which are located near the ribosome decoding center. These methylations are conserved and important for ribosome biogenesis and protein translation. In this study, we demonstrated the absence of A1518/1519 methylation in the 16S rRNA of a Pseudomonas aeruginosa ksgA mutant. Biolog phenotypic microarrays were used to screen the phenotypes of the ksgA mutant against various antimicrobial agents. The loss of ksgA led to increased sensitivity to menadione, a superoxide generator, which was, at least in part, attributed to decreased in a superoxide dismutase (SOD) activity. Interestingly, the decrease in SOD activity in the ksgA mutant was linked to a decrease in the SodM protein levels, but not the sodM mRNA levels. Furthermore, the ksgA mutant strain exhibited sensitivity to hygromycin B and tylosin antibiotics. The tylosin-sensitive phenotype was correlated with decreased transcriptional levels of tufA, tufB, and tsf, which encode elongation factors. Additionally, the ksgA mutant showed resistance to kasugamycin. Collectively, these findings highlight the role of KsgA in oxidative stress responses and antibiotic sensitivity in P. aeruginosa. [ABSTRACT FROM AUTHOR]

The increasing incidence of surgical site infections (SSIs) following caesarean sections highlights the necessity for updated protocols that address risk factors throughout the preoperative, intraoperative, and postoperative stages. Negative Pressure Wound Therapy (NPWT) and hydrocolloid dressings have demonstrated potential for improving wound management and reducing complications, particularly by enhancing dressing integrity. Nevertheless, the application of NPWT requires careful consideration and adherence to local trust guidelines to ensure both its safety and efficacy. [ABSTRACT FROM AUTHOR]

Apidaecin 1b (Api), the first characterized Type II Proline-rich antimicrobial peptide (PrAMP), is encoded in the honey bee genome. It inhibits bacterial growth by binding in the nascent peptide exit tunnel of the ribosome after the release of the completed protein and trapping the release factors. By genome mining, we have identified 71 PrAMPs encoded in insect genomes as pre-pro-polyproteins. Having chemically synthesized and tested the activity of 26 peptides, we demonstrate that despite significant sequence variation in the N-terminal sequence, the majority of the PrAMPs that retain the conserved C-terminal sequence of Api are able to trap the ribosome at the stop codons and induce stop codon readthrough—all hallmarks of Type II PrAMP mode of action. Some of the characterized PrAMPs exhibit superior antibacterial activity in comparison with Api. The newly solved crystallographic structures of the ribosome complexed with Api and with the more active peptide Fva1 from the stingless bee demonstrate the universal placement of the PrAMPs' C-terminal pharmacophore in the post-release ribosome despite variations in their N-terminal sequence. Synopsis: This study identifies new Type II proline-rich antimicrobial peptides from insects that trap ribosomes at stop codons and presents the structure of one of the most active peptides in complex with the bacterial ribosome. Genome mining identified new apidaecin-like Type II proline-rich antimicrobial peptides encoded in insect genomes. These peptides target bacterial ribosomes trapping them at stop codons and inducing stop codon readthrough. The pharmacophore of a peptide from Frieseomelitta varia interacts with the ribosomal nascent peptide exit tunnel. This study identifies new ribosome-targeting Type II proline-rich antimicrobial peptides in insect genomes that trap the ribosome at stop codons and presents the structure of one of the most active peptides in complex with the bacterial ribosome. [ABSTRACT FROM AUTHOR]

Background: While the benefits of sonication for improving periprosthetic joint infection (PJI) are well-documented, its potential therapeutic effect against bacterial biofilm remains unstudied. This study aimed to investigate the safety and efficacy of a novel nanoparticle ultrasonication process on methicillin-resistant Staphylococcus aureus (MRSA) bacterial biofilm formation in a PJI rat model. Methods: This novel ultrasonication process was designed to remove attached bacterial biofilm from implant and peri-articular tissues, without damaging native tissues or compromising implant integrity. Twenty-five adult Sprague–Dawley rats underwent a surgical procedure and were colonized with intra-articular MRSA, followed by the insertion of a titanium screw. Three weeks after the index surgery, the animals received a second procedure during which the screws were explanted, and soft tissue was sampled. The intraoperative use of the nanoparticle sonication treatment was employed to assess the device's safety, while ex vivo treatment on the retrieved tissue and implants was used to evaluate its efficacy. Results: Clinical and histological assessments did not indicate any macro- or micro-damage to the host tissue. Sonication of the retrieved tissues demonstrated an average bacterial removal of 2 × 103 CFU/mL and 1 × 104 CFU/gram of tissue. Compared to the standard-of-care group (n = 10), implants treated with sonication (n = 15) had significantly lower remaining bacteria, as indicated by crystal violet absorbance measurements (P = 0.012). Conclusions: This study suggests that nanoparticle sonication technology can successfully remove attached bacterial biofilms from explanted orthopedic hardware and the joint capsule, without negatively affecting native tissue. The study provides initial results supporting the potential of nanoparticle sonication as an adjuvant treatment option during a DAIR (debridement, antibiotics, and implant retention) procedure for PJI, paving the way for future clinical trials. [ABSTRACT FROM AUTHOR]

Sore throat represents one of the main causes of antibiotic overprescription in children. Its management is still a matter of debate, with countries considering streptococcal pharyngotonsillitis a benign and self-limiting condition and others advocating for its antibiotic treatment to prevent suppurative complications and acute rheumatic fever. Italian paediatricians frequently prescribe antibiotics on a clinical basis regardless of microbiological results. Moreover, broad-spectrum antibiotics are inappropriately prescribed for this condition. In this regard, an intersociety consensus conference was issued to promote the judicious use of antibiotic therapy in paediatric outpatient settings. A systematic review of the literature was performed, and updated recommendations were developed according to the GRADE methodology. Antibiotic treatment with amoxicillin (50 mg/kg/day) for 10 days is recommended in all children with proven streptococcal pharyngitis. Benzathine-penicillin could be prescribed in children with impaired intestinal absorption or inability to tolerate enteral intake and in those at high risk of suppurative complications with low compliance to oral therapy. In children with suspected amoxicillin allergy, third-generation cefalosporins for five days are recommended in low-risk patients, and macrolides are recommended in high-risk ones. Candidates for tonsillectomy due to recurrent pharyngitis could be treated with amoxicillin-clavulanic acid, clindamycin, or combined therapy with amoxicillin plus rifampicin for four days, in an attempt to avoid surgery. [ABSTRACT FROM AUTHOR]

The rising prevalence of antibiotic resistance threatens human health. While more sophisticated strategies for antibiotic discovery are being developed, target elucidation of new chemical entities remains challenging. In the postgenomic era, expression profiling can play an important role in mechanism-of-action (MOA) prediction by reporting on the cellular response to perturbation. However, the broad application of transcriptomics has yet to fulfill its promise of transforming target elucidation due to challenges in identifying the most relevant, direct responses to target inhibition. We developed an unbiased strategy for MOA prediction, called perturbation-specific transcriptional mapping (PerSpecTM), in which large-throughput expression profiling of wild-type or hypomorphic mutants, depleted for essential targets, enables a computational strategy to address this challenge. We applied PerSpecTM to perform reference-based MOA prediction based on the principle that similar perturbations, whether chemical or genetic, will elicit similar transcriptional responses. Using this approach, we elucidated the MOAs of three molecules with activity against Pseudomonas aeruginosa by comparing their expression profiles to those of a reference set of antimicrobial compounds with known MOAs. We also show that transcriptional responses to small-molecule inhibition resemble those resulting from genetic depletion of essential targets by clustered regularly interspaced short palindromic repeats interference (CRISPRi) by PerSpecTM, demonstrating proof of concept that correlations between expression profiles of small-molecule and genetic perturbations can facilitate MOA prediction when no chemical entities exist to serve as a reference. Empowered by PerSpecTM, this work lays the foundation for an unbiased, readily scalable, systematic reference-based strategy for MOA elucidation that could transform antibiotic discovery efforts. [ABSTRACT FROM AUTHOR]

The rational design of bifunctional photocatalysts with high adsorption and enrichment characteristics and excellent photocatalytic redox activity is an effective way to address environmental pollution and energy shortage crisis. In this study, cyclophosphazene‐derived porous organic polymer (PCPD) microspheres with P─N linkage are coated with graphene oxide (GO) and loaded with Ag0 nanoparticles (NPs) to prepare covalently bonded xAg‐rGO/PCPD composites. The catalyst with the highest specific surface area (denoted as 2.5Ag‐rGO/PCPD) shows excellent adsorption capacity for fluoroquinolone antibiotics, removing 96.2% of ciprofloxacin (CIP) through adsorption. By applying the catalyst with the best photocatalytic redox activity (denoted as 5Ag‐rGO/PCPD), 82.97% of refractory sulfonamide antibiotics are removed through adsorption‐degradation, and 635.3 µmol g−1 of CO and 162.3 µmol g−1 of CH4 are generated as products of CO2 photoreduction alone. Among the co‐catalytic systems, the highest CO yield of 9.16 µmol g−1 is obtained by coupling CO2 reduction with levofloxacin (LVX) degradation to harness the electron‐donating power of the pollutant molecule. This study is expected to provide useful guidance for the rational design of bifunctional photocatalysts. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionWhen chest tube drainage does not adequately resolve thoracic empyema, video assisted thoracoscopic surgery (VATS) is often needed. However, the proper duration of antibiotics after VATS is poorly defined. Consequently, the objective of this study was to evaluate if short antibiotic durations post-VATS was equally effective compared to longer durations.Patients with thoracic empyema treated with VATS were identified retrospectively by a query of the hospital billing database. The bacterial causes of the empyema were divided into 8 different categories while the antibiotic duration after VATS was divided into two groups which included antibiotics ˂ 14 days and antibiotics >14 days. The primary outcome measured was rates of empyema recurrence. Statistical comparisons were conducted between the antibiotic duration groups overall and when stratified based on the different bacterial causes.137 patients were included in this study with the main cause of empyema being culture negative empyema (37.2%) while alpha haemolytic Streptococcus spp. was the most cultured bacteria (26.3%). There was no statistical difference (p = 0.5168), in the rates of empyema recurrence, when short antibiotic durations (median 11.6 days)were compared to longer antibiotic durations (median 29.1 days)post-VATS. Nor was there a statistical difference in recurrence rates when stratifying based on bacterial cause.This study reinforces that antibiotic durations less than 14 days post-VATS are equally effective as prolonged antibiotic durations. However, to determine the proper duration of antibiotic therapy post-VATS, a prospective clinical trial is needed to reduce complications of prolonged antibiotic therapies for these patients. [ABSTRACT FROM AUTHOR]

Camellia reticulata , an ancient plant species endemic to Yunnan Province, China, remains underexplored in terms of its endophytic bacterial communities. The plant tissue pedicel serves as the connection between the flower and the stem, not only delivers nutrients but also transmits metabolic substances from endophytic bacteria to the nectar during long-term microbial colonization and probably improves the antagonistic activity of nectar against yeast. Hence, 138 isolates of endophytic bacteria have been isolated in this study from the pedicels of 12- and 60-year-old C. reticulata. Comparative analysis revealed significantly higher density of endophytic bacteria in older trees. Among these isolates, 29 exhibited inhibitory effects against nectar yeasts. Most of the isolates displayed positive results for Gram staining, catalase reaction, gelatin liquefaction, and motility. Additionally, the isolates demonstrated the ability to utilize diverse substrates, such as glucose, nitrate, and starch. Based on 16S rRNA molecular biology analysis, these isolates were identified to be 11 different species of 6 genera, with the majority belonging to Bacillus genus. Notably, C1 isolate, identified as Bacillus spizizenii , exhibited strongest antagonistic effect against three yeasts, i.e., Metschnikowia reukaufii, Cryptococcus laurentii , and Rhodotorula glutinis , with minimum inhibitory concentration values below 250 μg/mL. Major metabolites of B. spizizenii were aminoglycosides, beta-lactams, and quinolones, which possess antimicrobial activities. Furthermore, KEGG enrichment pathways primarily included the synthesis of plant secondary metabolites, phenylpropanoids, amino acids, alkaloids, flavonoids, neomycin, kanamycin, and gentamicin. Therefore, antagonistic activity of B. spizizenii against yeasts could be attributed to these antibiotics. The findings highlight the diverse endophytic bacteria associated with C. reticulata , indicating their potential as a valuable resource of bioactive metabolites. Additionally, this study provides new insights into the role of endophytic bacteria of pedicels in enhancing nectar resistance against yeasts. [ABSTRACT FROM AUTHOR]

The 9th symposium on Antimicrobial Resistance in Animals and the Environment (ARAE) was held in Tours, France in July 2023, attracting 170 participants from 23 countries. The conference focused on various aspects of antibiotic resistance, including epidemiology, resistance mechanisms, microbiota, and whole genome sequencing. Research presented at the symposium covered topics such as polyether ionophore resistance, multidrug-resistant Salmonella, and methodologies for rapid typing of MDR bacterial isolates. The event also highlighted the need for harmonization in bacterial culture and identification methods in veterinary clinical laboratories. The proceedings of the symposium are available online, and the next edition of ARAE is scheduled for July 2025 in Berlin, Germany. [Extracted from the article]

Background: Fixed orthodontic appliances act as a niche for microbial growth and colonization. Coating orthodontic wires with antimicrobial silver nanoparticles (AgNPs) and nanocomposite was adopted in this study to augment the biological activity of these wires by increasing their antibacterial and antibiofilm properties and inhibiting bacterial infections that cause white spot lesions and lead to periodontal disease. Methods: Three concentrations of biologically synthesized AgNPs were used for coating NiTi wires. The shape, size, and charge of the AgNPs were determined. Six groups of 0.016 × 0.022-inch NiTi orthodontic wires, each with six wires, were used; and coated with AgNPs and nanocomposites. The antimicrobial and antibiofilm activities of these coated wires were tested against normal flora and multidrug-resistant bacteria (Gram-positive and Gram-negative bacterial isolates). The surface topography, roughness, elemental percentile, and ion release were characterized. Results: AgNPs and nanocomposite coated NiTi wires showed significant antimicrobial and antibiofilm activities. The chitosan-silver nanocomposite (CS-Ag) coated wires had the greatest bacterial growth inhibition against both Gram-positive and Gram-negative bacteria. The surface roughness of the coated wires was significantly reduced, impacting the surface topography and with recorded low Ni and Ag ion release rates. Conclusions: NiTi orthodontic wires coated with AgNPs, and nanocomposites have shown increased antimicrobial and antibiofilm activities, with decreased surface roughness, friction resistance and limited- metal ion release. [ABSTRACT FROM AUTHOR]

Introduction: Restoring a balanced, healthy gut microbiota through fecal microbiota transplantation (FMT) has the potential to be a treatment option for sepsis, despite the current lack of evidence. This study aimed to investigate the effect of FMT on sepsis in relation to the gut microbiota through a sepsis model in juvenile mice. Methods: Three-week-old male mice were divided into three groups: the antibiotic treatment (ABX), ABX-FMT, and control groups. The ABX and ABX-FMT groups received antibiotics for seven days. FMT was performed through oral gavage in the ABX-FMT group over the subsequent seven days. On day 14, all mice underwent cecal ligation and puncture (CLP) to induce abdominal sepsis. Blood cytokine levels and the composition of fecal microbiota were analyzed, and survival was monitored for seven days post-CLP. Results: Initially, the fecal microbiota was predominantly composed of the phyla Bacteroidetes and Firmicutes. After antibiotic intake, an extreme predominance of the class Bacilli emerged. FMT successfully restored antibiotic-induced fecal dysbiosis. After CLP, the phylum Bacteroidetes became extremely dominant in the ABX-FMT and control groups. Alpha diversity of the microbiota decreased after antibiotic intake, was restored after FMT, and decreased again following CLP. In the ABX group, the concentrations of interleukin-1β (IL-1β), IL-2, IL-6, IL-10, granulocyte macrophage colony-stimulating factor, tumor necrosis factor-α, and C-X-C motif chemokine ligand 1 increased more rapidly and to a higher degree compared to other groups. The survival rate in the ABX group was significantly lower (20.0%) compared to other groups (85.7%). Conclusion: FMT-induced microbiota restoration demonstrated a protective effect against sepsis. This study uniquely validates the effectiveness of FMT in a juvenile mouse sepsis model, offering potential implications for clinical research in critically ill children. [ABSTRACT FROM AUTHOR]

Introduction: Acute diverticulitis represents a significant disease burden in the United States and developed world. This article examines current trends in the treatment of acute diverticulitis and concentrates on the utility of antibiotics in acute uncomplicated cases managed in the outpatient setting. Methods: The literature was reviewed for randomized controlled trials (RCTs) to discern the best practice and recommendations for antibiotics for diverticulitis. The time period included relevant RCTs after 2000. Results: Four recent RCTs examine the use of antibiotics in acute uncomplicated diverticulitis. The AVOD study was an RCT that managed inpatients with either antibiotics or IV fluids alone and demonstrated non-inferiority of non-antibiotic management with respect to recovery, complication rates, or recurrence. The DIABLO trial randomized first episodes of acute uncomplicated diverticulitis admitted to the hospital with antibiotics or supportive care and found no difference in morbidity or mortality between the two groups and longer hospital stay for patients treated with antibiotics. The DINAMO study examined outpatients managed with antibiotics by mouth or without and found no difference in morbidity in 90 day follow-up. The STAND study was the only of these four to use a placebo and found no difference between hospital stay or other adverse events at 30 days. In response to this, the ASCRS, AAFP and other societies now recommend against the routine use of antibiotics in acute uncomplicated diverticulitis. Conclusions: Several quality studies found similar outcomes in cases of acute uncomplicated diverticulitis treated with or without antibiotics. Based on these findings, societal guidelines do not recommend routine antibiotics for acute diverticulitis. [ABSTRACT FROM AUTHOR]

Monitoring the concentration of antibiotics rapidly and cost-effectively is crucial for accurate clinical medication and timely identification of drug-induced illnesses. Here, we constructed a novel fluorescent assay kit to monitor Zavicefta, an effective antibiotic composed of avibactam (AVI) and ceftazidime (CFZ) to treat carbapenem-resistant gram-negative bacteria infections. AVI can emit fluorescence, but CFZ cannot. To enable simultaneous measurement of both in one kit, we designed molecularly imprinted polymer (MIP) modified quantum dots (QDs) for CFZ determination. MIPs have received significant attention as an artificial antibody due to their exceptional specificity for various targets, particularly drugs with small molecular weight. Under the excitation wavelength of 350 nm, the detection process involves a decrease in QDs' fluorescence signal at 600 nm owing to the "gate effect" between MIP and CFZ and the internal filtration effect between CFZ and QDs. Simultaneously, a fluorescence emission characteristic peak at 420 nm for AVI emerges. In addition, to simplify the operation procedure and improve determination throughput, the detection agents were incorporated into a hydrogel and placed in a 96-well plate, enabling concurrent quantification of AVI and CFZ within the respective range of 80–1000 μM and 1–1000 μM. The developed assay kit successfully determined AVI and CFZ in human serums and therapeutic drug monitoring in a live rabbit model. Recoveries of AVI and CFZ were 92.7–114%, with relative standard deviations below 6.0%. Moreover, a smartphone was employed to read the fluorescence signals, which was beneficial for cost reduction and out-of-lab analysis. This study will deliver a pragmatic resolution to developing high-throughput assay kits for drug determination. [ABSTRACT FROM AUTHOR]

Huanglongbing is a severe citrus disease that causes significant tree and crop losses worldwide. It is caused by three Candidatus liberibacter species and spread by psyllids and infected budwood. Various methods have been used to diagnose and understand HLB, including recent advances in molecular and biochemical assays that explore the pathogen's mode of action and its impact on the host plant. Characterization is essential for developing sustainable HLB management strategies. Nanotechnology, particularly nano sensors and metal nanoparticles, shows potential for precise disease diagnosis and control. Additionally, antibiotics, nanomaterials, and genetic engineering techniques like transgenesis offer promising avenues for mitigating HLB. These diverse approaches, from conventional to cutting-edge, contribute to developing integrated HLB management strategies for sustainable citrus cultivation. The review highlights the significant advancements in conventional and advanced molecular and biochemical characterization of HLB, aiding in early detection and understanding of the infection mechanism. It emphasizes the multidimensional efforts required to characterize disease and devise innovative management strategies. As the citrus industry faces unprecedented challenges, exploring new frontiers in HLB research provides hope for sustainable solutions and a resilient future for global citrus cultivation. [ABSTRACT FROM AUTHOR]

Background: Surgeons are sometimes reluctant to manage uncomplicated appendicitis non‐operatively. Reasons cited include the risk of recurrent appendicitis and the risk of missed appendiceal malignancy. The aim of this study was to address these uncertainties and determine the long‐term efficacy of antibiotic versus operative management of appendicitis. Method: One‐year follow‐up of patients enrolled in the multicentre, COVID:HAREM cohort study during March‐June 2020 was performed. Initial operative or non‐operative management was determined on a case‐by‐case basis by the responsible surgeon. Outcomes were appendicectomy rate at 1‐year, histology of removed appendix and predictors of unsuccessful antibiotic treatment. Results: A total of 625 patients who had non‐operative management were included. Emergency appendicectomy had been performed by 1‐year in 24% (149/625), with a median time to appendicectomy of 12 days [IQR 1–77] from presentation. Thirty‐one patients had elective appendicectomy. Normal histology was reported in 6% of emergency procedures and 58% of elective ones. There were 7 malignancies and 3 neuroendocrine tumors identified at histology. All patients with malignant histology had ≥1 risk factors for malignancy at initial presentation. Faecolithiasis (hazard ratios (HR) 2.3, 95% confidence intervals (CI) 1.51–3.49) and a high Adult Appendicitis Score (AAS >16; HR 2.44, 95% CI 1.52–3.92) were independent risk factors for unsuccessful non‐operative management. Conclusion: At 1 year, 71% of patients managed non‐operatively did not undergo an appendicectomy. Recurrence of appendicitis was associated with faecolithiasis and a high AAS. Patients at higher risk for appendiceal malignancy should have targeted follow‐up. These factors should be considered when counseling patients on non‐operative management. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background: The use of silver nanoparticles (AgNPs) in biomedicine has emerged in a big way owing to its antibacterial and anti-inflammatory properties. We hypothesize that combining the AgNPs with antibiotics for coating sutures will enhance the antibacterial property of sutures with the added advantage of the immunomodulatory effect of AgNPs on tissue healing. Materials and Methods: Polyglactin sutures were coated with AgNPs using the dip-coating method. The uniform coating and morphology of AgNPs on the suture surface were confirmed using scanning electron microscopy (SEM). Each type of suture – polyglactin plain, antibiotic coated (Triclosan), AgNP coated, and dually coated (antibiotic and AgNP) – was assessed for their antibacterial properties against Gram-positive bacteria, Gram-negative bacteria, and anaerobes. These sutures were utilized in an abdominal and systemic inflammatory mice model for ileal anastomosis. The intestinal tissue was evaluated for acute and chronic inflammation and collagen deposition to assess the healing and inflammatory response. Results: The SEM and energy dispersive X-ray analysis showed successful coating of AgNPs on plain and antibiotic-coated sutures. In comparison with the other groups, the dually coated suture had the best in vitro antibacterial efficacy. The AgNP-coated sutures were able to decrease both acute and chronic inflammatory cell infiltration, but the collagen synthesis and deposition were enhanced. Conclusion: AgNPs can be coated on Polyglactin suture either alone or in combination with antibiotics with preserved antibacterial effects. The dual coating of sutures gives a synergistic antibacterial effect. The AgNP diminishes immune response in the presence of preserved extracellular matrix generation. [ABSTRACT FROM AUTHOR]

• Both sexes gained weight on high-fat (HF) diet + low-dose streptozotocin (STZ). • Both sexes developed impaired oral glucose tolerance. • Only males developed fasting hyperglycemia. • Only males developed hyperinsulinemia and insulin resistance. • Principal component analysis revealed overall metabolic derangement for males only. • HF diet + low-dose STZ is not useful for studying insulin resistance in female mice. Translation of preclinical findings on the efficacy of dietary interventions for metabolic disease to human clinical studies is challenging due to the predominant use of male rodents in animal research. Our objective was to evaluate a combined high-fat (HF) diet and low-dose streptozotocin (STZ) model for induction of type-2 diabetes (T2D) in male and female C57BL/6J mice. We hypothesized that T2D biomarkers would differ significantly between sexes. Mice were administered either a low-fat (LF) diet (10% kcal from fat), or HF diet (60% kcal from fat) + STZ injections (30 mg/kg/d for 3 days). Both sexes gained weight and developed impaired postprandial oral glucose tolerance on the HF+STZ treatment compared to LF. Only male mice on HF + STZ developed fasting hyperglycemia, fasting hyperinsulinemia and insulin resistance, suggesting that the underlying causes of postprandial hyperglycemia differed between sexes. Principal component analysis of measures such as body weights, glucose and insulin concentrations indicated metabolic derangement for males only on HF+STZ treatment, while LF group males and both groups of females significantly overlapped. Based on our data, we accept our hypothesis that the combined high-fat diet and low-dose STZ model for T2D phenotypes differs significantly in its effect on mice based on sex. The HF diet + low-dose STZ model is not useful for studying insulin resistance in females. Other models are needed to model T2D, and study the effects of dietary interventions in this disease, in females. Sexual dimorphism remains a significant challenge for both preclinical and clinical research. We attempted to induce type-2 diabetes in mice with high-fat diet and low-dose streptozotocin. Both sexes developed impaired oral glucose tolerance. Only males developed fasting hyperglycemia, hyperinsulinemia and insulin resistance. The high-fat diet and low-dose streptozotocin model primarily recapitulates type-2 diabetes in males. Studies of dietary interventions thus require other models to study their effects in females, complicating translation of preclinical findings to humans. Abbreviations: F, Female; HF, high-fat, HOMA-IR, Homeostatic Model Assessment for Insulin Resistance; LF, low-fat; M, male; PC, principal component; STZ, streptozotocin. [Display omitted] [ABSTRACT FROM AUTHOR]