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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.

Background: The rise of antimicrobial resistance, which is partially attributed to the overuse and/or misuse of antibiotics in health care, is one of the world's largest public health challenges. The distribution of antibiotics in absence of a prescription in pharmacies is a significant contributor to the growing global public health crisis of antibiotic resistance. A pharmacist's clinical and lawful knowledge of antibiotic provide has an impact on the proper way to dispense medication. There are few novel studies assessing pharmacists comprehension and experience in prescribing antibiotics in low- and middle-income countries, including those in the Arabian region. Objectives: (I) assess pharmacy team members Knowledge about antibiotics as reported by individuals themselves and their behavior in dispensing antimicrobial without a prescription and (ii) find potential influences on this behavior. Setting: Pharmacists were chosen from various regions in Algeria, Bahrain, Egypt, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, the United Arab Emirates, and Yemen, based on their convenience and ease of access. Methods: A descriptive cross-sectional assessment among a random sample (n = 2833) of community pharmacists was conducted Utilizing a structured, validated, and questionnaire that underwent pilot testing, a comprehensive survey with four distinct sections covering biography, knowledge, practice, and attitude domains was employed. The main outcome: Measures were knowledge, attitude, and practice toward dispensing antibiotics without prescription. Results: Of the 3100 pharmacists reached, 2833 completed and return the questionnaires (response rate 91.3%). Most of the respondents were male (57.4%). Aged between 19 and 31 years old (76.2%). Most of them held a B.Sc. Degree (78.5%). Worked as staff pharmacists (73.2%). During the survey, it was discovered that there were gaps in their knowledge regarding antibiotic usage. A total of 45.7% of the respondents were unaware that antibiotics can be used as prophylaxis, while 33.3% did not recognize the consequences of making incorrect antibiotic choices. Regarding their practice patterns, 53.8% of the pharmacists admitted that they did not consistently adhere to guidelines when dispensing antibiotics. In terms of attitudes toward antibiotic usage, 36.8% disagreed with the guidelines of not supply antibiotics without a prescription, suggesting some variation in opinions among pharmacists on this matter. Additionally, a significant percentage (75%) believed that community pharmacists had qualifications to prescribe antibiotics for infections. Conclusion: The recent survey has shed light on the differences among pharmacists in regard to dispensing antibiotics without prescriptions and their understanding of resistance. The findings are concerning, indicating a deficient in of knowledge as regards the use of antibiotics. It is crucial to implement regulations and enhance education efforts to tackle the growing problem of resistance. Collaboration between healthcare professionals and awareness campaigns is essential in addressing this issue. Impact on practice: Community pharmacists may contribute to inappropriate antibiotic usage and microbial resistance by distributing antibiotics without a prescription. It is crucial to develop and put into action a clear strategy to promote sensible antibiotic usage in a community pharmacy context. It is advised that instructional tactics regarding the prescription of antibiotics and antibiotic resistance be improved. To changing community pharmacists' dispensing practices, educational programs emphasizing attitude adjustments and acknowledging the professional code of ethics are required. Community pharmacists can modify patient behaviors and educate patients on the proper use of antibiotics. [ABSTRACT FROM AUTHOR]

Scope: The underlying medical conditions and gut dysbiosis is known to influence COVID-19 severity in high-risk patients. The current review proposed the optimal usage of nutraceuticals & pharmacological interventions can help regulate the protective immune response and balance the regulatory functionality of gut microbiota. Summary: Many studies have revealed that the probiotic interventions viz., Lactobacillus rhamnosus, L. plantarum & other bacterial spp. reduce IFNγ & TNF-α and increase IL-4 & IL-10 secretions to control the immunostimulatory effects in upper respiratory tract infection. Dietary fibres utilized by beneficial microbiota and microbial metabolites can control the NF-kB regulation. Vitamin C halts the propagation of pathogens and vitamin D and A modulate the GM. Selenium and Flavonoids also control the redox regulations. Interferon therapy can antagonize the viral replications, while corticosteroids may reduce the death rates. BCG vaccine reprograms the monocytes to build trained immunity. Bifidobacterium and related microbes were found to increase the vaccine efficacy. Vaccines against COVID-19 and season flu also boost the immunity profile for robust protection. Over all, the collective effects of these therapeutics could help increase the opportunities for faster recovery from infectious diseases. Conclusion: The nutraceutical supplements and pharmacological medicines mediate the modulatory functionalities among beneficial microbes of gut, which in turn eliminate pathogens, harmonize the activity of immune cells to secrete essential regulatory molecular receptors and adaptor proteins establishing the homeostasis in the body organs through essential microbiome. Therefore, the implementation of this methodology could control the severity events during clinical sickness and reduce the mortalities. [ABSTRACT FROM AUTHOR]

The human gut microbiome, crucial for health, can be disrupted by antibiotic treatment, leading to various health issues and the rise of antimicrobial resistance (AMR). This study investigates the impact of a probiotic on the gut microbiome's composition and antimicrobial resistance genes (ARGs) content following antibiotic treatment. Conducted as a single-centre, double-blind, randomized, placebo-controlled trial, adults taking oral antibiotics were allocated into a probiotic or placebo group. Evaluations included viable cell enumeration and shotgun metagenomic sequencing for microbiome analysis, along with ARG assessment. The probiotic maintained the numbers of lactobacilli, significantly increased the Bacteroides population and decreased numbers of enterobacteria. The lactobacilli and enterococci numbers decreased in the placebo. The alpha diversity remained stable in the probiotic group throughout the study, but significant reductions were observed in the placebo group post antibiotic treatment. There was significant spatial separation in beta diversities between groups at the end of the study. Compared to baseline levels, there was a significant reduction in the abundance of ARGs in the probiotic group at the end of the study, while ARG abundance in the placebo group was comparable with baseline levels at the end of the study. Co-occurrence network analysis observed consistent betweenness centrality and node degree within group in the probiotic group whereas scores decreased in the placebo group. This study suggests that the probiotic may minimize the disruption of antibiotic treatment on the gut microbiome by preserving microbial diversity and reducing ARG abundance. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion The management of acute exacerbations of chronic rhinosinusitis (AECRS) is understudied and the most cost‐effective management of AECRS has not been previously investigated. The aim of this study is to determine the most cost‐effective strategy for the initial management of AECRS.The study design consisted of a decision‐tree economic model comparing three different initial strategies for managing a patient perceived AECRS: observation, upfront rescue medications, or clinic visit with diagnostic nasal endoscopy (DNE). The primary study outcome was the disease burden of a single AECRS, which was determined by the health utility value and the duration of symptoms. Strategies with an incremental cost‐effectiveness ratio < $50,000/quality‐adjusted life year (QALY) or equivalently < $137/quality‐adjusted life day (QALD) were considered cost‐effective.Observation was the most cost‐effective strategy at a willingness to pay of $137 per QALD. One‐way sensitivity analysis demonstrated that observation was more effective than upfront rescue medications when the probability of bacterial infection as the cause of AECRS was <24.0%. Upfront rescue medications wer more cost effective than observation when the probability of bacterial infection exceeded 49.0%. Clinic visit with DNE was the most effective strategy to manage an AECRS, but it was not considered cost‐effective.Observation is the most cost‐effective strategy for the initial management of AECRS when there is a low likelihood of bacterial infection. When the probability of bacterial etiology of AECRS exceeds 49.0%, upfront rescue medications proved to be the most cost‐effective strategy. [ABSTRACT FROM AUTHOR]

Currently, there is a high demand for novel sorbents for wastewater treatment. Nanostructured materials are often considered as more promising sorbents compared to their microsized counterparts, which, however, requires experimental verification. In this work, two types of h-BN materials (micro- and nanosized) are compared as candidates for antibiotic sorption. The initial h-BN was in the form of microsized pellets. Nanostructurued h-BN was obtained by high energy ball milling of the initial powder. The effect of ball milling on the microstructure, morphology, chemical composition and surface chemical state was investigated by SEM, TEM, STEM, EDX, XRD, XPS, FTIR and BET techniques. Adsorption properties were studied on samples in the form of pellets and powders. Activated carbon powder was used as a reference material. The antibiotic adsorption process was studied using tetracycline and linezolid. The influence of the h-BN structure on the adsorption characteristics was elucidated using DFT calculations. [ABSTRACT FROM AUTHOR]

Ahead of a United Nations meeting on the global challenge of drug-resistant infections, Nature asked health-care experts in emerging economies to describe what would address the issue in their country or region most effectively. [ABSTRACT FROM AUTHOR]

Background: Unnecessary antibiotic prescriptions in primary care are common and contribute to antimicrobial resistance in the population. Audit and feedback (A&F) on antibiotic prescribing to primary care can improve the appropriateness of antibiotic prescribing, but the optimal approach is uncertain. We performed two pragmatic randomized controlled trials of different approaches to audit and feedback. The trial results showed that A&F was associated with significantly reducing antibiotic prescribing. Still, the effect size was small, and the modifications to the A&F interventions tested in the trials were not associated with any change. Herein, we report a theory-informed qualitative process evaluation to explore potential mechanisms underlying the observed effects. Methods: Ontario family physicians in the intervention arms of both trials who were sent A&F letters were invited for one-on-one interviews. Purposive sampling was used to seek variation across interested participants in personal and practice characteristics. Qualitative analysis utilized inductive and deductive techniques informed by the Clinical Performance Feedback Intervention Theory. Results: Modifications to the intervention design tested in the trial did not alter prescribing patterns beyond the changes made in response to the A&F overall for various reasons. Change in antibiotic prescribing in response to A&F depended on whether it led to the formation of specific intentions and whether those intentions translated to particular behaviours. Those without intentions to change tended to feel that their unique clinical context was not represented in the A&F. Those with intentions but without specific actions taken tended to express a lack of self-efficacy for avoiding a prescription in contexts with time constraints and/or without an ongoing patient relationship. Many participants noted that compared to overall prescribing, A&F on antibiotic prescription duration was perceived as new information and easily actionable. Conclusion: Our findings indicate that contextual factors, including the types of patients and the setting where they are seen, affect how clinicians react to audit and feedback. These results suggest a need to test tailored feedback reports that reflect the context of how, where, and why physicians prescribe antibiotics so that they might be perceived as more personal and more actionable. Trial registration: Clinical Trial registration IDs: NCT04594200, NCT05044052. [ABSTRACT FROM AUTHOR]

Biofilm formation by Staphylococcus aureus is a major challenge in clinical settings due to its role in persistent infections. The AgrA protein, a key regulator in biofilm development, is a promising target for therapeutic intervention. This study investigates the antibiofilm potential of halogenated phenazine compounds by targeting AgrA and explores their molecular interactions to provide insights for drug development. We employed molecular docking, molecular dynamics simulations, and computational mutagenesis to evaluate the binding of halogenated phenazine compounds (C1 to C7, HP, and HP‐14) to AgrA. Binding free energy analysis was performed to assess the affinity of these compounds for the AgrA‐DNA complex. Additionally, the impact of these compounds on AgrA's structural conformation and salt bridge interactions was examined. The binding‐free energy analysis revealed that all compounds enhance binding affinity compared to the Apo form of AgrA, which has a ΔGbind of −80.75 kcal/mol. The strongest binding affinities were observed with compounds C7 (−113.84 kcal/mol), HP‐14 (−115.23 kcal/mol), and HP (−112.28 kcal/mol), highlighting their effectiveness. Molecular dynamics simulations demonstrated that these compounds bind at the hydrophobic cleft of AgrA, disrupting essential salt bridge interactions between His174‐Glu163 and His174‐Glu226. This disruption led to structural conformational changes and reduced DNA binding affinity, aligning with experimental findings on biofilm inhibition. The halogenated phenazine compounds effectively inhibit biofilm formation by targeting AgrA, disrupting its DNA‐binding function. The study supports the potential of these compounds as antibiofilm agents and provides a foundation for rational drug design targeting the AgrA‐DNA interaction. Future research should focus on further optimizing these lead compounds and exploring additional active sites on AgrA to develop novel treatments for biofilm‐associated infections. [ABSTRACT FROM AUTHOR]

Background: External Jugular Thrombophlebitis (EJT) is a rare clinical phenomenon with few reports in the literature, especially in the pediatric population. This is a report of an unusual case of right-sided EJT in a pediatric patient secondary to acute pharyngitis with sinusitis most prominent on the left side. Case presentation: A 13-year-old presented to the emergency department with worsening upper respiratory infectious (URI) symptoms and facial swelling, cough, throat pain, and emesis. The patient had traveled to Switzerland and received amoxicillin for strep throat 6 weeks before this hospitalization. Physical examination revealed nasal purulence, allodynia over the right side of the face without overlying erythema, and oropharyngeal exudate. CT scan revealed left-sided predominate sinusitis and right external jugular vein thrombosis. Blood cultures confirmed the presence of group A streptococcus infection. Treatment included IV antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), IV steroids, and anticoagulation. Follow-up imaging demonstrated improvement in thrombosis, cellulitis, and sinus disease. The patient was discharged on antibiotics for 6 weeks and anticoagulation for 10 weeks. Follow-up imaging at 6 months revealed no EJT, and medications were discontinued. Conclusions: EJT is a rare condition, and to our knowledge, no reports of EJT with sinusitis most pronounced on the contralateral side have been published. Physicians will benefit from noting clinical signs of EJT such as facial edema, headache, erythema, and palpable neck mass, especially if these symptoms occur with URI symptoms refractory to treatment. The use of anticoagulation is controversial for internal jugular vein thrombosis, and while no guidelines for EJT exist, anticoagulation is likely not necessary save for severe complications. [ABSTRACT FROM AUTHOR]

Background: To evaluate the impact of implementation of 2019 European respiratory distress syndrome (RDS) guidelines on the incidence of bronchopulmonary dysplasia (BPD). Method: We retrospectively collected the clinical data of very preterm infants (VPIs) born before 32 gestational weeks from January 1st 2018 to December 31st 2021. VPIs were divided into group A and group B according to their birth date which was before or at/after January 1st 2020, when the 2019 European RDS guidelines were introduced. BPD is considered as primary outcome. We statistically analyzed all the data, and we compared the general characteristics, ventilation support, medication, nutrition and the outcomes between the two groups. Results: A total of 593 VPIs were enrolled, including 380 cases in group A and 213 cases in group B. There were no statistic differences regarding to gender ratio, gestational age, birth weight and delivery mode between the two groups. Compared with group A, group B showed higher rate of antenatal corticosteroid therapy (75.1% vs. 65.5%). The improvement of ventilation management in these latter patients included lower rate of invasive ventilation (40.4% vs. 50.0%), higher rate of volume guarantee (69.8% vs. 15.3%), higher positive end expiratory pressure (PEEP) [6 (5, 6) vs. 5 (5, 5) cmH2O] and higher rate of synchronized nasal intermittent positive pressure ventilation (sNIPPV) (36.2% vs. 5.6%). Compared with group A, group B received higher initial dose of pulmonary surfactant [200 (160, 200) vs. 170 (130, 200) mg/Kg], shorter antibiotic exposure time [13 (7, 23) vs. 17 (9, 33) days], more breast milk (86.4% vs. 70.3%) and earlier medication for hemodynamically significant patent ductus arteriosus (hsPDA) treatment [3 (3, 4) vs. 8 (4, 11) days] (p < 0.05). As the primary outcome, the incidence of BPD was significantly decreased (16.9% vs. 24.2%) (p < 0.05), along with lower extrauterine growth retardation (EUGR) rate (39.0% vs. 59.7%), while there were no statistic differences regarding to other secondary outcomes, including mortality, intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), retinopathy of preterm (ROP) and necrotizing enterocolitis (NEC). However, in the subgroups of infants less than 28 gestational weeks or infants less than 1,000 g, the incidence of BPD was not significantly decreased (p > 0.05). Conclusions: After implementation of 2019 European RDS guidelines, the overall incidence of BPD was significantly decreased in VPIs. Continuous quality improvement is still needed in order to decrease the incidence of BPD in smaller infants who are less than 28 gestational weeks or less than 1,000 g. [ABSTRACT FROM AUTHOR]

Background: Despite the worldwide increasing incidence of Group A Streptococcus (GAS) infections reported since December 2022, data on noninvasive GAS (nGAS) infections in the post COVID-19 era are limited. By a self-reported survey performed in an outpatient setting, we investigated the number and clinical features of GAS infections, the diagnostic work-up and the type of treatment utilized. In addition, the rate of influenza vaccination was evaluated. Methods: In June 2023 family pediatricians involved in the study sent the survey to parents of patients aged 0–16 years. The survey included questions on GAS infections that occurred from January 1 to May 31, 2023. Results: Among 3580 children, 20.3% had a GAS infection (0,8% < 1 year, 16,4% 1–3 years, 42,3% 3–6 years, 26,5% 6–9 years, 11,4%, 9–12 years, and 2,6% 12–16 years). Symptoms reported were sore throat (76.9%), fever (75.2%), tonsillar exudate (25.2%), lymphadenopathy (21.8%), and scarlet fever (14.7%). A single patient was hospitalized due to GAS meningitis. Twenty four percent of children had more than one GAS infection. In this group, frequencies of symptoms reported in the first and in the following infection were similar, except for fever and scarlet fever which were less frequent during relapses. GAS was identified by rapid antigen detection test in 81.0% of children. Eighty-nine per cent of children were treated with antibiotics, mostly amoxicillin/clavulanate (40.4%) and amoxicillin (39.4%). Thirty four percent of children received influenza vaccine. No difference was observed among immunized and not immunized regarding the number and characteristics of GAS infection. Conclusions: We reported a certain prevalence of nGAS infections in children, mainly those aged 3–6 years age, who were mostly characterized by a low score of symptoms, and in most of the cases diagnosed and treated using a microbiological test as confirmatory tool. In this new clinical setting, a national study would be useful to reach more significant data for the definition of a correct diagnosis and clinical management of nGAS infections in children. Moreover, it is important to improve flu vaccination campaign and coverage to protect children from coinfections that could worsen the disease and misdiagnose the etiology of pharyngitis. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions Healthcare accounts for 5% of global greenhouse gas emissions, with medicines making a sizeable contribution. Product‐level medicine emission data is limited, hindering mitigation efforts. To address this, we created Medicine Carbon Footprint (MCF) Classifier, to estimate, standardize, stratify and visualize medicine carbon footprints.We used molecular weight and chemical structure to estimate the process mass intensity and global warming potential of the active pharmaceutical ingredient in small molecule medicines. This allowed us to estimate medicine carbon footprints per dose, which we categorized into MCF Ratings, accessible via a searchable web application, MCF Formulary. We performed comparison and sensitivity analyses to validate the ratings, and stratification analyses by therapeutic indication to identify priority areas for emission reduction interventions.We generated standardized medicine carbon footprints for 2214 products, with 38% rated LOW, 35% MEDIUM, 25% HIGH and 2% VERY HIGH. These products represented 2.2 billion NHS England prescribed doses in January 2023, with a total footprint of 140 000 tonnes CO2e, equivalent to the monthly emissions of 940 000 cars. Notably, three antibiotics—amoxicillin, flucloxacillin and penicillin V—contributed 15% of emissions. We estimate that implementing the recommended 20% antibiotic prescription reduction could save 4200 tonnes CO2e per month, equivalent to removing 29 000 cars.Standardized medicine carbon footprints have utility in assessing and addressing the carbon emissions of medicines, and the potential to inform and catalyse changes needed to align better healthcare and net zero commitments. [ABSTRACT FROM AUTHOR]

Photocatalysis is regarded as a potent alternative to conventional treatment methods with low removal efficiency (e.g., activated sludge process) against refractory/recalcitrant antibiotics in wastewater. Here, the potential utility of bismuth oxyiodide (BiOI)-based materials has been evaluated as visible-light–driven photocatalysts (bandgap energy < 2.0 eV) with unique optical structure for the enhanced treatment of tetracyclines (TCs) as a representative antibiotic product. The effects of key modification strategies (e.g., elemental doping and heterojunction formation) on the photocatalytic activity of BiOI-based photocatalysts are assessed against TCs in terms of the key performance metrics such as quantum efficiency (QE) and space-time yield (STY). This review also highlights the challenges and promising opportunities for the photocatalytic application of BiO-based materials against TCs in real effluents. Accordingly, zinc-doped BiOI is recognized to have the maximum efficiency with QE of 2.95 × 10−5 molecules photon−1 and STY of 2.95 × 10−7 molecules photon−1 mg−1. This review is expected to help deepen the exploration path to the construction of efficient BiOI-based systems based on their performance evaluation along with the discussions on their perspectives. [ABSTRACT FROM AUTHOR]

This article reports on the development of an atmospheric pressure filtering electrospray ionization (FESI) source – composed of a syringe, a filter, and the ESI source – for the determination of furazolidone, amoxicillin, nitrofurantoin, and nitrofural, common antibiotics. Spiked food samples were also analyzed; the analytes were placed in the filter head, and the flow rate of the extraction solution from the syringe pump was adjusted. Using a mixture of oleic acid and antibiotics, hydrophilic and hydrophobic filters were compared, demonstrating the advantage of FESI in reducing the background and noise for the mixture. The device simplifies not only the experimental procedure but also the sample pretreatment process. Additionally, the limits of detection of the antibiotics were determined to be 1 mg L−1 for furazolidone, amoxicillin, and nitrofurantoin and 2 mg L−1 for nitrofural. The linear regression coefficients (R2) of the antibiotic standard solutions were all ≥0.99. Furthermore, the spiked recovery rates of pork, chicken, and egg samples ranged from 73.3% to 107.5%, with relative standard deviations (RSDs) from 1.1% to 15.6%. This study uncovers the potential capabilities of ion trap mass spectrometry (ITMS) for the on-site detection of antibiotics and offers a new method for ensuring food safety. [ABSTRACT FROM AUTHOR]

Objective: To identify and analyze antibiotics' prescription patterns and associated factors among terminally ill patients at a hospital in southern Peru. Methodology: A cross-sectional analytical study was conducted on adult patients who died in Hospital III Daniel Alcides Carrion in Tacna, Peru, 2023. Data were collected from electronic medical records, focusing on antibiotic use during the last hospitalization. Univariate, bivariate, and multivariate analyses were performed using Poisson regression to adjust for potential confounders. Results: The study included 239 patients with an average age of 76. Antibiotics were administered to 93.72% of patients, with 42.46% lacking an identified infectious focus. Ceftriaxone, Meropenem, and Vancomycin were the most used antibiotics. A lower use of antibiotics within 72 hours prior to death was associated with hospitalizations longer than 18 days and having 2 or more comorbidities. Conclusion: The high prevalence of antibiotic use at the end of life, often without an infectious focus, suggests a need for better guidelines and education on palliative care to avoid inappropriate antibiotic prescribing. Improved communication between healthcare providers, patients, and families is essential for optimizing end-of-life care. [ABSTRACT FROM AUTHOR]

Bacterial evolution, particularly in hospital settings, is leading to an increase in multidrug resistance. Understanding the basis for this resistance is critical as it can drive discovery of new antibiotics while allowing the clinical use of known antibiotics to be optimized. Here, we report a photoactive chemical probe for superresolution microscopy that allows for the in situ probing of antibiotic-induced structural disruption of bacteria. Conjugation between a spiropyran (SP) and galactose via click chemistry produces an amphiphilic photochromic glycoprobe, which self-assembles into glycomicelles in water. The hydrophobic inner core of the glycomicelles allows encapsulation of antibiotics. Photoirradiation then serves to convert the SP to the corresponding merocyanine (MR) form. This results in micellar disassembly allowing for release of the antibiotic in an on-demand fashion. The glycomicelles of this study adhere selectively to the surface of a Gram-negative bacterium through multivalent sugar-lectin interaction. Antibiotic release from the glycomicelles then induces membrane collapse. This dynamic process can be imaged in situ by superresolution spectroscopy owing to the "fluorescence blinking" of the SP/MR photochromic pair. This research provides a high-precision imaging tool that may be used to visualize how antibiotics disrupt the structural integrity of bacteria in real time. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare targeted next-generation sequencing (tNGS) with metagenomic next-generation sequencing (mNGS) for pathogen detection in infants with severe postoperative pneumonia after congenital heart surgery. Methods: We conducted a retrospective observational study using data from the electronic medical record system of infants who developed severe pneumonia after surgery for congenital heart disease from August 2021 to August 2022. Infants were divided into tNGS and mNGS groups based on the pathogen detection methods. The primary outcome was the efficiency of pathogen detection, and the secondary outcomes were the timeliness and cost of each method. Results: In the study, 91 infants were included, with tNGS detecting pathogens in 84.6% (77/91) and mNGS in 81.3% (74/91) of cases (P = 0.55). No significant differences were found in sensitivity, specificity, PPA, and NPA between the two methods (P > 0.05). tNGS identified five strains with resistance genes, while mNGS detected one strain. Furthermore, tNGS had a faster detection time (12 vs. 24 h) and lower cost ($150 vs. $500) compared to mNGS. Conclusion: tNGS offers similar sensitivity to mNGS but with greater efficiency and cost-effectiveness, making it a promising approach for respiratory pathogen detection. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus (S. aureus) infection is a primary cause of otitis media (OM), the most common disease for which children are prescribed antibiotics. However, the abuse of antibiotics has led to a global increase in antimicrobial resistance (AMR). Nanozymes, as promising alternatives to traditional antibiotics, are being extensively utilized to combat AMR. Here, we synthesize a series of single-atom nanozymes (metal-C3N4 SANzymes) by loading four metals (Ag, Fe, Cu, Ru) with antibacterial properties onto a crystalline g-C3N4. These metal-C3N4 display a rob-like morphology and well-dispersed metal atoms. Among them, Ru-C3N4 demonstrates the optimal peroxidase-like activity (285.3 U mg-1), comparable to that of horseradish peroxidase (267.7 U mg-1). In vitro antibacterial assays reveal that Ru-C3N4 significantly inhibits S. aureus growth compared with other metal-C3N4 even at a low concentration (0.06 mg mL-1). Notably, Ru-C3N4 acts as a narrow-spectrum nanoantibiotic with relative specificity against Gram-positive bacteria. Biofilms formed by S. aureus are easily degraded by Ru-C3N4 due to its high peroxidase-like activity. In vivo, Ru-C3N4 effectively eliminates S. aureus and relieves ear inflammation in OM mouse models. However, untreated OM mice eventually develop hearing impairment. Due to its low metal load, Ru-C3N4 does not exhibit significant toxicity to blood, liver, or kidney. In conclusion, this study presents a novel SANzyme-based antibiotic that can effectively eliminate S. aureus and treat S. aureus-induced OM. [ABSTRACT FROM AUTHOR]

Mitochondrial translation is essential to maintain mitochondrial function and energy production. Mutations in genes associated with mitochondrial translation cause several developmental disorders, and immune dysfunction is observed in many such patients. Besides genetic mutations, several antibiotics targeting bacterial ribosomes are well‐established to inhibit mitochondrial translation. However, the effect of such antibiotics on different immune cells is not fully understood. Here, we addressed the differential effect of mitochondrial translation inhibition on different subsets of helper T cells (Th) of mice and humans. Inhibition of mitochondrial translation reduced the levels of mitochondrially encoded electron transport chain subunits without affecting their nuclear‐encoded counterparts. As a result, mitochondrial oxygen consumption reduced dramatically, but mitochondrial mass was unaffected. Most importantly, we show that inhibition of mitochondrial translation induced apoptosis, specifically in Th2 cells. This increase in apoptosis was associated with higher expression of Bim and Puma, two activators of the intrinsic pathway of apoptosis. We propose that this difference in the sensitivity of Th1 and Th2 cells to mitochondrial translation inhibition reflects the intrinsic metabolic demands of these subtypes. Though Th1 and Th2 cells exhibit similar levels of oxidative phosphorylation, Th1 cells exhibit higher levels of aerobic glycolysis than Th2 cells. Moreover, Th1 cells are more sensitive to the inhibition of glycolysis, while higher concentrations of glycolysis inhibitor 2‐deoxyglucose are required to induce cell death in the Th2 lineage. These observations reveal that selection of metabolic pathways for substrate utilization during differentiation of Th1 and Th2 lineages is a fundamental process conserved across species. [ABSTRACT FROM AUTHOR]

We have created a novel synthetic biology expression system allowing easy refactoring of biosynthetic gene clusters (BGCs) as monocistronic transcriptional units. The system is based on a set of plasmids containing a strong kasOp* promoter, RBS and terminators. It allows the cloning of biosynthetic genes into transcriptional units kasOp *-gene(s)-terminator flanked by several rare restriction cloning sites that can be sequentially combined into the artificial BGC in three compatible Streptomyces integration vectors. They allow a simultaneous integration of these BGCs at three different attB sites in the Streptomyces chromosome. The system was validated with biosynthetic genes from two known BGCs for aromatic polyketides landomycin and mithramycin. • A new synthetic biology-based system for investigating antibiotic biosynthesis. • Efficient rabelomycin production using the initial landomycin biosynthetic genes. • Efficient 4-DMPC production using the initial mithramycin biosynthetic genes. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is a global health threat. This randomized controlled trial evaluates the impact of experiential virtual reality (VR) versus information provision via VR or leaflet on prudent antibiotic use. A total of 249 (239 analyzed) participants were randomized into three conditions: VR Information + Experience, VR Information, or Leaflet Information. All participants received AMR information, while those in the VR Information + Experience condition additionally engaged in a game, making treatment decisions for their virtual avatar's infection. Participants in the VR Information + Experience condition showed a significant increase in prudent use intentions from baseline (d = 1.48). This increase was significantly larger compared to the VR Information (d = 0.50) and Leaflet Information (d = 0.79) conditions. The increase in intentions from baseline remained significant at follow-up in the VR Information + Experience condition (d = 1.25). Experiential VR communication shows promise for promoting prudent antibiotics use. [ABSTRACT FROM AUTHOR]

The application of antibiotics in the poultry and veterinary sectors is very common practice in India. Owing to the seriousness of antimicrobial resistance (AMR), the present study has illustrated the overall scenario of AMR in the poultry and veterinary sectors in India through an in-depth scoping review and key informant interview (KII). In the poultry sector, most of the studies reviewed have reported resistant bacteria isolated from chicken meat, eggs, cloacal swabs, and fecal samples, and only a few have reported the presence of resistant bacteria in and around the environment of poultry farms. The major resistant bacteria that have been reported are E. coli, Salmonella spp., S. aureus, Campylobacter jejuni, and K. pneumoniae. These bacterial isolates exhibited resistance to various antibiotics, such as azithromycin (21.43%), tetracycline (11.30-100%), chloramphenicol (4.76-100%), erythromycin (75-83.33%), ciprofloxacin (5.7-100%), gentamicin (17-100%), amikacin (4.76%), cotrimoxazole (42.2-60%), trimethoprim (89.4%), ceftriaxone (80%), and cefotaxime (14.29-70%). Like the poultry sector, different antibiotics are also used for treating clinical and subclinical bovine mastitis, which is one of the major problems plaguing the dairy sector. Several AMR bacterial strains, such as E. coli, Staphylococcus aureus, S. epidermidis, and Klebsiella pneumoniae, have been reported by many researchers and showed resistance against tetracycline (74%), oxytetracycline (47.37%), ciprofloxacin (51%), streptomycin (57.89%), cephalosporin (100%), and trimethoprim (70%). The KIIs have revealed several reasons behind these AMR scenarios, of which the growing need for the production of food animals and their products with inadequate infrastructure and a lack of proper knowledge on farm management among the farmers are the major ones. Though several government legislations and policies have been laid down, proper implementation of these policies, strict surveillance on antibiotic application in the poultry and veterinary sectors, awareness generation among farmers, and infrastructure development can help minimize the development and transmission of AMR bacteria within and from these sectors. [ABSTRACT FROM AUTHOR]

The emission of glyphosate and antibiotic residues from human activities threatens the diversity and functioning of the microbial community. This study examines the impact of a glyphosate-based herbicide (GBH) and common antibiotics on Gram-negative bacteria within the ESKAPEE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli). Ten strains, including type and multidrug-resistant strains for each species were analysed and eight antibiotics (cefotaxime, meropenem, aztreonam, ciprofloxacin, gentamicin, tigecycline, sulfamethoxazole-trimethoprim, and colistin) were combined with the GBH. While most combinations yielded additive or indifferent effects in 70 associations, antagonistic effects were observed with ciprofloxacin and gentamicin in five strains. GBH notably decreased the minimum inhibitory concentration of colistin in eight strains and displayed synergistic activity with meropenem against metallo-β-lactamase (MBL)-producing strains. Investigation into the effect of GBH properties on outer membrane permeability involved exposing strains to a combination of this GBH and vancomycin. Results indicated that GBH rendered strains sensitive to vancomycin, which is typically ineffective against Gram-negative bacteria. Furthermore, we examined the impact of GBH in combination with three carbapenem agents on 14 strains exhibiting varying carbapenem-resistance mechanisms to assess its effect on carbapenemase activity. The GBH efficiently inhibited MBL activity, demonstrating similar effects to EDTA (ethylenediaminetetraacetic acid). Chelating effect of GBH may have multifaceted impacts on bacterial cells, potentially by increasing outer membrane permeability and inactivating metalloenzyme activity. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance in agriculture is a global concern that is growing every day. As a result, there is increasing interest in investigating different approaches to disease control in both plants and animals. Research on the identification and synthesis of antimicrobial compounds derived from plants and microbes has exploded in the last few years. The purpose of this review is to give a broad overview of the current knowledge regarding antimicrobials derived from plants and microbes and their possible uses in agricultural practises. It discusses a number of topics, such as the origins of these antimicrobial agents, how they work, and how well they work to fight infections in plants and animals. Furthermore, the difficulties pertaining to their execution and potential outcomes are examined. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion One of the goals established by the United States National Action Plan to Combat Antibiotic‐Resistant Bacteria is to reduce inappropriate outpatient antibiotic prescriptions by 50% by 2020. Recent data on the achievement of this goal is lacking. The objective of our study was to examine recent trends in the appropriateness of oral antibiotic prescriptions dispensed to a commercially insured population in outpatient settings in the United States to quantify the relative trend in inappropriate antibiotic prescribing from 2010 to 2018.Our cross‐sectional analysis examined oral antibiotic prescriptions dispensed in outpatient settings using the IBM MarketScan Commercial Data from January 2010 to December 2018. Trends in the annual proportion of antibiotic prescriptions classified as appropriate, potentially appropriate, inappropriate, or without any medical visit during a 7 days look‐back period were estimated using multivariable generalized linear models with Poisson distribution adjusting for beneficiaries' demographic and infectious conditions.Approximately 170 million oral antibiotic prescriptions were dispensed to 86 million beneficiaries during 2010 to 2018. The mean age of the study population was 34.5 (±19.1) years, with 58.4% females and 24.6% children. We observed a 12.9% (95% Confidence Interval [CI] = 12.6%–13.2%; p < 0.01) decline in rates of antibiotic use, from 832 to 727 prescriptions per 1000 beneficiaries, from 2010 to 2018. The proportion of prescriptions classified as appropriate increased by 36.7% (95% CI = 36.4%–36.9%; p < 0.01); potentially appropriate prescriptions increased by 9.3% (95% CI = 9.1%–9.4%; p < 0.01); whereas inappropriate prescriptions and those without a medical visit declined by 11.3% (95% CI = 11.2%–11.4%; p < 0.01) and 14.0% (95% CI = 13.9%–14.2%; p < 0.01), respectively. Similar declining trends were observed in use and proportion of inappropriate prescriptions for broad‐spectrum antibiotics. In 2018, amoxicillin and azithromycin were the most common appropriate and inappropriate prescription fills, respectively.Although antibiotic use and inappropriate prescribing declined steadily from 2010 to 2018 in the United States, this study demonstrates that we have not achieved the national goal of reducing inappropriate antibiotic prescribing by 50%. [ABSTRACT FROM AUTHOR]

Objective: To investigate the diagnostic value of metagenomic next-generation sequencing (mNGS) in detecting pathogens from joint infection (JI) synovial fluid (SF) samples with previous antibiotic exposure. Methods: From January 2019 to January 2022, 59 cases with suspected JI were enrolled. All cases had antibiotic exposure within 2 weeks before sample collection. mNGS and conventional culture were performed on SF samples. JI was diagnosed based on history and clinical symptoms in conjunction with MSIS criteria. The diagnostic values, including sensitivity, specificity, positive/negative predictive values (PPV/NPV), and accuracy, were in comparison with mNGS and culture. Results: There were 47 of the 59 cases diagnosed with JI, while the remaining 12 were diagnosed with non-infectious diseases. The sensitivity of mNGS was 68.1%, which was significantly higher than that of culture (25.5%, p<0.01). The accuracy of mNGS was significantly higher at 71.2% compared to the culture at 39.0% (p <0.01). Eleven pathogenic strains were detected by mNGS but not by microbiological culture, which included Staphylococcus lugdunensis, Staphylococcus cohnii, Finegoldia magna, Enterococcus faecalis, Staphylococcus saprophytics, Escherichia coli, Salmonella enterica, Pseudomonas aeruginosa, Acinetobacter pittii, Brucella ovis, andCoxiella burnetii. Antibiotic therapy was adjusted based on the mNGS results in 32 (68.1%) patients, including 12 (25.5%) and 20 (42.6%) patients, in whom treatment was upgraded and changed, respectively. All JI patients underwent surgery and received subsequent antibiotic therapy. They were followed up for an average of 23months (20-27 months), and the success rate of treatment was 89.4%. Out of the 33 patients who had positive results for pathogens, reoperation was performed in 1 case (3.03%), while out of the 14 cases with negative results for both mNGS and cultures, reoperation was performed in 4 cases (28.6%). Conclusions: mNGS has advantages over conventional culture in detecting pathogens in SF samples from JI patients previously treated with antibiotics, potentially improving clinical outcomes. [ABSTRACT FROM AUTHOR]

Key Points: Question: Do commonly prescribed oral antibiotics carry differential risks of cutaneous adverse drug reactions (cADRs) leading to an emergency department visit or hospitalization? Findings: In this population-based, nested case-control study spanning 2 decades, sulfonamide antibiotics and cephalosporins carried the highest risk of serious cADRs relative to macrolides, followed by nitrofurantoin, penicillins, and fluoroquinolones. Meaning: All commonly prescribed oral antibiotics are associated with an increased risk of serious cADRs compared with macrolides, with sulfonamide antibiotics and cephalosporins carrying the highest risk. Importance: Serious cutaneous adverse drug reactions (cADRs) are potentially life-threatening drug hypersensitivity reactions involving the skin and internal organs. Antibiotics are a recognized cause of these reactions, but no studies have compared relative risks across antibiotic classes. Objectives: To explore the risk of serious cADRs associated with commonly prescribed oral antibiotics, and to characterize outcomes of patients hospitalized for them. Design, Setting, and Participants: Nested case-control study using population-based linked administrative datasets among adults aged 66 years or older who received at least 1 oral antibiotic between 2002 and 2022 in Ontario, Canada. Cases were those who had an emergency department (ED) visit or hospitalization for serious cADRs within 60 days of the prescription, and each case was matched with up to 4 controls who did not. Exposure: Various classes of oral antibiotics. Main Outcomes and Measures: Conditional logistic regression estimate of the association between different classes of oral antibiotics and serious cADRs, using macrolides as the reference group. Results: During the 20-year study period, we identified 21 758 older adults (median age, 75 years; 64.1% female) who had an ED visit or hospitalization for serious cADRs following antibiotic therapy and 87 025 matched controls who did not. In the primary analysis, sulfonamide antibiotics (adjusted odds ratio [aOR], 2.9; 95% CI, 2.7-3.1) and cephalosporins (aOR, 2.6; 95% CI, 2.5-2.8) were most strongly associated with serious cADRs relative to macrolides. Additional associations were evident with nitrofurantoin (aOR, 2.2; 95% CI, 2.1-2.4), penicillins (aOR, 1.4; 95% CI, 1.3-1.5), and fluoroquinolones (aOR, 1.3; 95% CI, 1.2-1.4). The crude rate of ED visits or hospitalization for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions; 95% CI, 4.86-4.99) and sulfonamide antibiotics (3.22 per 1000 prescriptions; 95% CI, 3.15-3.28). Among the 2852 case patients hospitalized for cADRs, the median length of stay was 6 days (IQR, 3-13 days), 9.6% required transfer to a critical care unit, and 5.3% died in the hospital. Conclusion and Relevance: Commonly prescribed oral antibiotics are associated with an increased risk of serious cADRs compared with macrolides, with sulfonamides and cephalosporins carrying the highest risk. Prescribers should preferentially use lower-risk antibiotics when clinically appropriate. This population-based case-control study assesses the association of commonly prescribed oral antibiotics with serious cutaneous adverse drug reactions and characterizes outcomes of patients hospitalized for them. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial stewardship (AMS) aims to improve antibiotic use while reducing resistance and its consequences. There is a paucity of data on the availability of AMS programmes in southern Nigeria. Further, there is no data on Nigerian healthcare professionals' knowledge of the WHO 'Access, Watch and Reserve' (AWaRe) classification of antibiotics. This study sought to assess knowledge of AMS and the AWaRe classification of antibiotics among frontline healthcare professionals in Akwa Ibom State, Nigeria. Methods: This was a cross-sectional survey of 417 healthcare professionals, comprising medical doctors, pharmacists and nurses, across 17 public hospitals in Akwa Ibom State, Nigeria. A paper-based self-completion questionnaire was used to collect data from the participants during working hours between September and November 2023. Statistical analysis was done using SPSS version 25.0, with p < 0.05 indicating statistical significance. Results: Four hundred and seventeen out of the 500 healthcare professionals approached agreed to participate, giving an 83.4% response rate. Most of the participants were female (62.1%) and nurses (46.3%). Approximately 57% of participants were familiar with the term antibiotic/antimicrobial stewardship, however, only 46.5% selected the correct description of AMS. Majority (53.0%) did not know if AMS programme was available in their hospitals. 79% of participants did not know about AWaRe classification of antibiotics. Among the 87 (20.9%) who knew, 28.7% correctly identified antibiotics into the AWaRe groups from a given list. Only profession significantly predicted knowledge of AMS and awareness of the AWaRe classification of antibiotics (p < 0.001). Pharmacists were more likely to define AMS correctly than medical doctors (odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.16–3.52, p = 0.012), whereas nurses were less likely to be aware of the WHO AWaRe classification of antibiotics than medical doctors (OR = 0.36, 95% CI = 0.18–0.72, p = 0.004). Conclusions: There was a notable knowledge deficit in both AMS and the AWaRe classification of antibiotics among participants in this study. This highlights the need for educational interventions targeted at the different cadres of healthcare professionals on the role of AMS programmes in reducing antimicrobial resistance and its consequences. [ABSTRACT FROM AUTHOR]

New, first-in-class oral antibiotics like zoliflodacin, developed in a public–private partnership, require an optimal introduction strategy while ensuring antibiotic stewardship. Zoliflodacin, given as a single dose for uncomplicated urogenital gonorrhoea, recently demonstrated non-inferiority to ceftriaxone plus azithromycin and safety in a phase 3 randomised controlled trial. Following regulatory approval, zoliflodacin could improve sexually transmitted infection (STI) management and help address the threat of untreatable gonorrhoea, as levels of resistance to current first-line treatments increase. The Global Antibiotic Research & Development Partnership (GARDP) convened an expert meeting during the 2023 STI and HIV World Congress to discuss key questions about the introduction of zoliflodacin in low- and middle-income countries (LMICs). The questions included: which patients to treat in which situations, the timing of introduction, and what additional evidence is needed to change policy for the use of new antibiotics for gonorrhoea. Recommendations from the expert group included: the generation of evidence for the role of a drug like zoliflodacin in clinical treatment failures; the need for additional antimicrobial resistance surveillance; investigation of the role of novel diagnostic approaches, such as point-of-care tests, to improve stewardship; study of preferences and values among the population in need; and modelling of the emergence of N. gonorrhoeae resistance and transmission in different scenarios. Forthcoming World Health Organization (WHO) global guidelines could outline recommendations for a new oral antibiotic like zoliflodacin based on existing evidence, and rational approaches for certain populations or use cases, while the evidence base is further strengthened. [ABSTRACT FROM AUTHOR]

Background: Severe trauma is the leading cause of disability and mortality in the patients under 35 years of age. Surgical site infections (SSI) represent a significant complication in this patient population. However, they are often inadequately investigated, potentially impacting the quality of patient outcomes. The aim of this study was to investigate the epidemiology of SSI and risk factors in severe trauma patients. Methods: We conducted a multicenter retrospective cohort study screening the severe trauma patients (STP) admitted to two intensive care units of an academic institution in Marseille between years2018 and 2019. Those who underwent orthopedic or spinal surgery within 5 days after admission were included and classified into two groups according to the occurrence of SSI (defined by the Centers for Disease Control (CDC) international diagnostic criteria) or not. Our secondary goal was to evaluate STP survival at 48 months, risk factors for SSI and microbiological features of SSI. Results: Forty-seven (23%) out of 207 STP developed an SSI. Mortality at 48-months did not differ between SSI and non-SSI patients (12.7% vs. 10.0%; p = 0.59). The fractures of 22 (47%) severe trauma patients with SSI were classified as Cauchoix 3 grade and 18 (38%) SSI were associated with the need for external fixators. Thirty (64%) severe trauma patients with SSI had polymicrobial infection, including 34 (72%) due to Gram-positive cocci. Empirical antibiotic therapy was effective in 31 (66%) cases. Multivariate analysis revealed that risk factors such as low hemoglobin, arterial oxygenation levels, hyperlactatemia, high serum creatinine and glycemia, and Cauchoix 3 grade on the day of surgery were associated with SSI in severe trauma patients. The generated predictive model showed a good prognosis performance with an AUC of 0.80 [0.73–0.88] and a high NPV of 95.9 [88.6–98.5] %. Conclusions: Our study found a high rate of SSI in severe trauma patients, although SSI was not associated with 48-month mortality. Several modifiable risk factors for SSI may be effectively managed through enhanced perioperative monitoring and the implementation of a patient blood management strategy. [ABSTRACT FROM AUTHOR]

Biofilm formation and toxin production are some of the virulence factors of Clostridioides difficile (C. difficile), which causes hospital-acquired C. difficile infection (HA-CDI). This work investigated the prevalence and distribution of different strains recovered from HA-CDI patients hospitalized in 4 medical centres across Israel, and characterized strains' virulence factors and antibiotic susceptibility. One-hundred and eighty-eight faecal samples were collected. C. difficile 's toxins were detected by the CerTest Clostridium difficile GDH + Toxin A + B combo card test kit. Toxin loci PaLoc and PaCdt were detected by whole-genome sequencing (WGS). Multi-locus sequence typing (MLST) was performed to classify strains. Biofilm production was assessed by crystal violet. Antibiotic susceptibility was determined using Etest. Fidaxomicin susceptibility was tested via agar dilution. Sequence type (ST) 42 was the most (13.8%) common strain. All strains harboured the 2 toxins genes; 6.9% had the binary toxin. Most isolates were susceptible to metronidazole (98.9%) and vancomycin (99.5%). Eleven (5.85%) isolates were fidaxomicin-resistant. Biofilm production capacity was associated with ST (p < 0.001). In conclusion, a broad variety of C. difficile strains circulate in Israel's medical centres. Further studies are needed to explore the differences and their contribution to HA-CDI epidemiology. [ABSTRACT FROM AUTHOR]

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening skin lesion triggered by hypersensitive drug reaction. They are characterized by extensive epidermal necrosis and skin exfoliation. Fulminant type 1 diabetes mellitus (FT1DM) is featured by a rapid-onset of hyperglycemia with ketoacidosis due to severely destroyed β-cell function. Fulminant type 1 diabetes mellitus as a sequela of SJS/TEN has rarely been reported. Case presentation: We present a 73-year-old female patient who developed SJS/TEN skin allergic reaction after taking carbamazepine and phenytoin for 35 days. Then, hyperglycemia and diabetic ketoacidosis occurred 20 days after discontinuation of antiepileptic drugs. A very low serum C-peptide level (8.79 pmol/l) and a near-normal glycosylated hemoglobin level met the diagnostic criteria for fulminant T1DM. Intravenous immunoglobulin (IVIG) and insulin were promptly administered, and the patient recovered finally. Conclusions: This rare case indicates that monitoring blood glucose is necessary in SJS/TEN drug reaction, and comprehensive therapy with rehydration, insulin, antibiotics, and IVIG may improve the prognosis. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To evaluate the available literature on ureteric stent‐related infections, the use of antibiotics and bacterial colonisation to identify the current incidence of stent‐related infections, unveil knowledge gaps and generate potential hypotheses for future research.A literature review was conducted using PubMed, Cochrane and urological association websites identifying relevant English literature published between 1983 and January 2024.There is a worldwide lack of guidelines for antibiotic prophylaxis for stent placement, exchange or extraction. In patients with a negative preoperative urine culture undergoing ureteroscopy and stent placement, it may be considered to only provide prophylaxis in presence of risk factors. However, in pre‐stented patients a preoperative urine culture is important to guide prophylaxis during endourological surgery. During stent indwell time, antibiotic prophylaxis does not show any advantage in preventing urinary tract infections (UTIs). There is no strong evidence to support the use of antibiotics at time of stent removal. In the absence of any clear evidence, management strategies for treating UTIs in patients with ureteric stents vary widely. Stent exchange could be considered to remove the biofilm as a potential source of bacteria. Stent culture can help to guide treatment during infection as urine culture and stent culture can differ.In terms of good antibiotic stewardship, urologists should be aware that unnecessary use of antibiotics provokes bacterial resistance. There is a great need for further research in the field of antibiotic prophylaxis and stent‐related infections to develop evidence that can help shape clear guidelines for this very common urological practice. [ABSTRACT FROM AUTHOR]

Introduction Bloodstream infections are a significant threat to soldiers wounded in combat and contribute to preventable deaths. Novel and combination therapies that can be delivered on the battlefield or in lower roles of care are urgently needed to address the threat of bloodstream infection among military personnel. In this manuscript, we tested the antibacterial capability of silver ions (Ag+), with long-appreciated antibacterial properties, against ESKAPEE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, and Escherichia coli) pathogens. Materials and Methods We used the GENESYS (RAIN LLC) device to deliver Ag+ to Gram-positive and Gram-negative ESKAPEE organisms grown in broth, human blood, and serum. Following the Ag+ treatment, we quantified the antibacterial effects by quantifying colony-forming units. Results We found that Ag+ was bactericidal against 5 Gram-negative organisms, K pneumoniae, A baumannii, P aeruginosa , E cloacae , and E coli , and bacteriostatic against 2 Gram-positive organisms, E faecium and S aureus. The whole blood and serum inhibited the bactericidal activity of Ag+ against a common agent of bloodstream infection, P aeruginosa. Finally, when Ag+ was added in conjunction with antibiotic in the presence of whole blood, there was no significant effect of Ag+ over antibiotic alone. Conclusions Our results confirmed that Ag+ has broad-spectrum antibacterial properties. However, the therapeutic value of Ag+ may not extend to the treatment of bloodstream infections because of the inhibition of Ag+ activity in blood and serum. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to create resorbable nanoparticles (NPs) using poly(lactic-co-glycolic acid) (PLGA) to develop novel antibacterial therapeutics for the treatment of chronic wound infections that are susceptible to recurrent infections. By first performing a release study, it was possible to predict the behavior of the different PLGA NP formulations and assess the efficacy of the nanocomposite drug delivery system. These PLGA NP formulations consisted of varying ratios of PLGA without polyvinyl alcohol (PVA) and PLGA with PVA (PLGA-PVA) (i.e. 25:75[PLGA25], 50:50[PLGA50], and 75:25[PLGA75]). Then, different antibiotics (i.e. ciprofloxacin and gentamicin) were incorporated into the PLGA NP formulations to test the antibacterial efficacy of these antimicrobial NPs against different pathogens (i.e. methicillin-resistant Staphylococcus aureus USA300 [MRSA], Pseudomonas aeruginosa FRD1, and Acinetobacter baumannii BAA1605). Of particular interest was testing against the MRSA strain USA300 and the P. aeruginosa strain FRD1. This was possible by measuring the zone of inhibition. A 3-day period was used to monitor the antibacterial efficacy of the different PLGA NP formulations (i.e. PLGA25, PLGA50, and a 1:1 combination of PLGA25:PLGA50) against A. baumannii BAA1605 , MRSA, and P aeruginosa FRD1. Throughout the study, A. baumannii was a negative control and was resistant to all the PLGA NP formulations loaded with ciprofloxacin and gentamicin. At the end of the 3-day period, the PLGA and PLGA50 ciprofloxacin-loaded formulations produced zones of inhibition of 27 mm and 23 mm, respectively, against P. aeruginosa FRD1. This indicated that P. aeruginosa FRD1 was susceptible to both formulations. The mixed formulations with equal parts PLGA25:PLGA50 loaded with ciprofloxacin produced a zone of inhibition (i.e. 25 mm). This again indicated that P. aeruginosa FRD1 was susceptible to ciprofloxacin. The formulations tested against MRSA showed that only gentamicin-loaded formulations produced intermediate results, and that ciprofloxacin-loaded formulations were ineffective. The PLGA25 and the PLGA50 NP formulations loaded with gentamicin both produced zones of inhibition of 13 mm. This indicated that MRSA was intermediate to both the formulations. The PLGA25:PLGA50 loaded with gentamicin produced a zone of inhibition of 14 mm, which again showed that MRSA was intermediate to this formulation. Overall, these PLGA NP formulations showed the sustained antibacterial potential of a burst release, followed by a sustained release of antibiotics from antibiotics loaded PLGA NPs in a controlled manner. In the future, this can help prevent the emergence of recurrent infections in the treatment of chronic wounds and reduce the number of medical dressing changes. [ABSTRACT FROM AUTHOR]