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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.

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 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]

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]

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]

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]

In numerous countries, the utilization of plants for both nutritional and therapeutic purposes is a common practice. However, the inadvertent use of these plants can pose risks due to their active molecules or microbiota. The traditional use of Herniaria glabra L. (H. glabra) plant in treating various diseases is well-known; however, its application in yogurt production raises concerns. In this study, Bacillus pumilus isolated from H. glabra was identified through 16s rRNA sequencing and MALDI-TOF MS (Matriks Assisted Lazer Desorption Ionization Time of Flight Massspectrometry). The bacterium's resistance under simulated gastrointestinal tract (GIT) conditions was assessed, followed by investigations into its aggregation ability, antibiotic resistance, hemolytic activity, and antagonistic potential through in vitro tests. The study revealed that B. pumilus exhibited 100% resistance to GIT conditions. Notably, the bacterium demonstrated strong autoaggregation (34.48%) and coaggregation abilities (49.82% for Escherichia coli, 49.13% for Listeria monocytogenes), signifying a potent aggregative potential. Sensitivity to most tested antibiotics was observed, while no antagonistic activity against tested bacteria was evident. Furthermore, the bacterium exhibited β-hemolytic activity, indicative of potential virulence. The findings suggest that this resistant yet virulent bacterium, with its hemolytic activity, could disrupt the GIT balance, posing serious health risks. The study underscores the need for caution and awareness regarding the potential dangers posed by bacteria in plant microbiota in herbal therapies. [ABSTRACT FROM AUTHOR]

In recent decades, the excessive use of antibiotics has resulted in a rise in antimicrobial drug resistance (ADR). Annually, a significant number of human lives are lost due to resistant infectious diseases, leading to around 700,000 deaths, and it is estimated that by 2050, there could be up to 10 million casualties. Apart from their possible application as preservatives in the food sector, bacteriocins are gaining acknowledgment as potential clinical treatments. Not only this, these antimicrobial peptides have revealed in modulating the host immune system producing anti-inflammatory and anti-modulatory responses. At the same time, due to the ever-increasing global threat of antibiotic resistance, bacteriocins have gained attraction among researchers due to their potential clinical applications. Bacteriocins as antimicrobial peptides, represent one of the most important natural defense mechanisms among bacterial species, particularly lactic acid bacteria (LAB), that can fight against infection-causing pathogens. In this review, we are highlighting the potential of bacteriocins as novel therapeutics for inhibiting a wide range of clinically relevant and multi-drug-resistant pathogens (MDR). We also highlight the effectiveness and potential applications of current bacteriocin treatments in combating antimicrobial resistance (AMR), thereby promoting human health. [ABSTRACT FROM AUTHOR]

Objective To describe Neisseria gonorrhoeae treatment failure to the recommended antimicrobial regimens (azithromycin, cefixime and ceftriaxone). Methods Our study was a longitudinal analysis of treatment failures from an observational open cohort of gonococcal infection cases collected in Québec, Canada (n  = 2547) between September 2015 and December 2019. Epidemiological and clinical data were collected using a self-administered questionnaire, direct case interviews and chart reviews. Antimicrobial susceptibility testing was performed using the agar dilution method. To be retained as a treatment failure, cases must have had (i) a laboratory-confirmed gonococcal infection; (ii) a documented treatment; (iii) a positive test of cure (TOC) performed within a defined period and (iv) no sexual contact (vaginal, oral or anal), even protected with a condom, between the beginning of treatment and the positive TOC. A broader definition, including suspected cases, was also examined. Results Among 1593 cases where a TOC was performed, 83 had a positive TOC: 11 were retained as treatment failure, and 6 were considered suspected cases (overall = 17/1593; 1.1%). Possible explanations for retained or suspected treatment failure included resistance to the antibiotics used for treatment (n  = 1), pharyngeal infection (n  = 9, of which 5 had been treated with ceftriaxone and 4 with other regimens); and azithromycin monotherapy (n  = 1). Some cases had more than one potential explanation. Conclusions Treatment failure occurred in 1.1% of cases of Neisseria gonorrhoeae infection for which a TOC was performed, including some cases of pharyngeal infection treated with ceftriaxone. [ABSTRACT FROM AUTHOR]

Background Effective management of drug–food interactions is crucial for enhancing antibiotics' efficacy/safety. Adhering to PRISMA guidelines, we conducted a systematic review to assess the impact of dietary interventions on the bioavailability of 15 macrolides and 10 tetracyclines. Methods We included studies examining the influence of food, beverages, antacids, and mineral supplements on the pharmacokinetic parameters of orally administered macrolides and tetracyclines. We searched Medline (via PubMed), Embase and Cochrane Library databases up to December 2022. Risk of bias was assessed using Cochrane and NIH tools. Quantitative analyses were conducted if two or more comparable food-effect studies were available; otherwise, a qualitative summary was provided. Results We included 120 studies from 97 reports. Meta-analyses were conducted for 8 macrolides and 4 tetracyclines, with qualitative synthesis for 10 and 9, respectively. About 64% of the studies were open-label, crossover designs. Our assessment found that 37% of the studies had a high risk of bias, while only 6% had low risk. Food significantly affected 10 of 13 macrolides (77%) and 6 of 7 tetracyclines (86%). High positive effects on bioavailability were seen with extended-release azithromycin and clarithromycin, and erythromycin estolate. High negative impacts were observed with erythromycin propionate and stearate, azithromycin capsules, demeclocycline and omadacycline. Antacids and mineral supplements significantly decreased tetracyclines absorption. Milk and grapefruit juice showed variable impacts on absorption. Discussion Interactions depend on antibiotics' physicochemical characteristics, intervention type, drug formulation and potential patient factors. The quality of evidence was rated low due to outdated studies, methodological diversity and unequal data availability. [ABSTRACT FROM AUTHOR]

Background Ceftolozane/tazobactam and ceftazidime/avibactam are commonly used in patients with MDR- Pseudomonas aeruginosa (PSA) pneumonia (PNA). This study compared outcomes between non-COVID-19 hospitalized patients with MDR-PSA PNA who received ceftolozane/tazobactam or ceftazidime/avibactam. Methods The study included non-COVID-19 adult hospitalized patients with MDR-PSA PNA in the PINC AI Healthcare Database (2016–22) who received ceftolozane/tazobactam or ceftazidime/avibactam within 3 days of index culture for ≥2 days. Outcomes were mortality, recurrent MDR-PSA PNA, discharge destination, post-index culture day length of stay (LOS) and costs (in US dollars, USD), and hospital readmission. Results The final sample included 197 patients (117 ceftolozane/tazobactam, 80 ceftazidime/avibactam). No significant differences were observed in mortality and post-index culture LOS and costs between groups. In the multivariable analyses, patients who received ceftolozane/tazobactam versus ceftazidime/avibactam had lower recurrent MDR-PSA PNA (7.9% versus 18.0%, P  = 0.03) and 60 day PNA-related readmissions (11.1% versus 28.5%, P  = 0.03) and were more likely to be discharged home (25.8% versus 9.8%, P  = 0.03). Compared with ceftazidime/avibactam patients, ceftolozane/tazobactam patients had lower adjusted median total antibiotic costs (5052 USD versus 8099 USD, P  = 0.003) and lower adjusted median comparator (ceftolozane/tazobactam or ceftazidime/avibactam) antibiotic costs (3938 USD versus 6441 USD, P  = 0.005). In the desirability of outcome ranking (DOOR) analysis, a ceftolozane/tazobactam-treated patient was more likely to have a more favourable outcome than a ceftazidime/avibactam-treated patient [DOOR probability: 59.6% (95% CI: 52.5%–66.8%)]. Conclusions Early treatment with ceftolozane/tazobactam may offer some clinical and cost benefits over ceftazidime/avibactam in patients with MDR-PSA PNA. Further large-scale studies are necessary to comprehensively understand the outcomes associated with these treatments for MDR-PSA PNA. [ABSTRACT FROM AUTHOR]

Objectives Patients with liver cirrhosis are prone to develop severe bacterial infections. Pharmacokinetics (PK) of antibiotics in cirrhosis are potentially affected by impaired biotransformation phases 0–3 and consequences of portal hypertension such as portovenous shunting, ascites formation and/or acute kidney injury (AKI). We aimed to elucidate to what extent PK of selected antibiotics and, therefore, dosage recommendations are affected in adults with cirrhosis. Methods We performed a systematic search in PubMed, Embase, Cochrane and CINAHL on effects of cirrhosis on PK profiles of ceftriaxone, fosfomycin, gentamicin, meropenem, nitrofurantoin, piperacillin/tazobactam and vancomycin in adults. Antibiotics were selected based on the lack of specific dosing recommendations for adults with cirrhosis. We included studies reporting on ≥1 of the following PK parameters: AUC, half-life (t ½), CL, volume of distribution (V d), peak (C max) or trough concentrations (C min). Results We identified 15 studies (ceftriaxone, n  = 5; gentamicin, n  = 3; meropenem n  = 5; vancomycin, n  = 2), including 379 patients with cirrhosis, of which two were of high quality. No eligible studies were identified for fosfomycin, nitrofurantoin or piperacillin/tazobactam. Ceftriaxone unbound concentration increased in cirrhosis, but was mitigated by increased renal CL. Gentamicin levels in ascitic fluid were comparable to those in plasma. Meropenem PK parameters were not altered in cirrhosis without AKI, but in the presence of AKI a decrease in CL was observed. In contrast, vancomycin CL decreased in advanced cirrhosis. Conclusions Available data in studies of mostly moderate quality suggest that PK of ceftriaxone, meropenem and vancomycin are altered in cirrhosis. More advanced PK studies are needed to provide specific dosing recommendations. [ABSTRACT FROM AUTHOR]

Objectives Bacterial persistence is a significant cause of the intractability of chronic and relapsing infections. Despite its importance, many of the underlying mechanisms are still not well understood. Methods Antibiotic-tolerant mutants of Burkholderia thailandensis were isolated through exposure to lethal doses of AMP or MEM, followed by whole-genome sequencing to identify mutations. Subsequently, these mutants underwent comprehensive characterization via killing curves, growth curves, and persistence-fraction plots. Northern blot analysis was employed to detect uncharged tRNA, while the generation of relA and spoT null mutations served to confirm the involvement of the stringent response in this persistence mechanism. Phenotypic reversion of the persistence mutation was demonstrated by incubating the mutants without antibiotics for 2 weeks. Results We have discovered a novel mechanism of persistence triggered by specific mutations at positions 32 or 38 within the anticodon loop of tRNAAsp. This leads to heightened persistence through a RelA-dependent stringent response. Notably, this persistence can be easily reverted to wild-type physiology by losing the mutant tRNA allele within the tRNA gene cluster when persistence is no longer essential for survival. Conclusions This distinct form of persistence underscores the novel function of tRNA mutations at positions 32 or 38 within the anticodon loop, as well as the significance of the tRNA gene cluster in conferring adaptability to regulate persistence for enhanced survival. [ABSTRACT FROM AUTHOR]

Background Burkholderia cepacia complex (Bcc) is a collection of intrinsically drug-resistant Gram-negative bacteria that cause life-threatening disease in people with cystic fibrosis (CF). Standard antimicrobial susceptibility testing methods have poor predictive value for clinical outcomes in Bcc infections, probably due in part to differences between in vitro testing conditions and the environment in which Bcc grow in the lungs of people with CF. Objectives To compare the activity of commonly used antibiotics under standard in vitro testing conditions with activity in conditions mimicking those found in vivo. Methods Two Bcc strains were grown alone and with six different antibiotics (minocycline, ceftazidime, meropenem, tobramycin, levofloxacin, trimethoprim-sulfamethoxazole) in two different media: standard cation-adjusted Mueller–Hinton broth and an artificial sputum medium designed to simulate the environment in the lungs of people with CF through addition of components including mucin, free DNA and amino acids. Two different starting conditions were used for time–kill assays: a standard ∼5 × 106 cfu/mL inoculum, and a high-density inoculum in which bacteria were grown for 72 hours before addition of antibiotics. Growth detection was performed by colony enumeration and by detection of resazurin reduction. Results There were major discrepancies between standard susceptibility results and activity in our models. Some antibiotics, including ceftazidime, showed minimal activity in all time–kill assays despite low minimal inhibitory concentrations, while others, notably tobramycin, were more active in high-density growth conditions than in standard time–kill assays. Conclusions This work underscores the urgent need to develop more clinically relevant susceptibility testing approaches for Bcc. [ABSTRACT FROM AUTHOR]

Objectives Neisseria gonorrhoeae strains associated with the high-level ceftriaxone-resistant FC428 clone or containing its main resistance determinant, penA allele 60.001, have shown global transmission. In Hangzhou, China, 10% of the isolates were associated with the FC428 clone in 2019. Here, we investigated ceftriaxone resistance and the prevalence of FC428-associated strains in Hangzhou in 2020–22. Methods A total of 209 gonococcal isolates were investigated for antimicrobial susceptibility to ceftriaxone and other antibiotics by agar dilution method. Sequence types and penA alleles were determined by PCR and sequence analysis. Results Resistance to ceftriaxone (MIC > 0.125 mg/L) was observed for 16% (33/209) of the isolates, whereas 6.7% (14/209) of the isolates displayed high-level ceftriaxone resistance (MIC = 1 mg/L). These 14 high-level ceftriaxone-resistant isolates and another isolate displaying an MIC = 0.25 mg/L contained penA allele 60.001, with eight of these isolates, all from 2020 to 2021 belonging to MLST ST1903, the sequence type commonly associated with the original FC428 clone. Importantly, the six penA allele 60.001-containing isolates from 2022 belonged to MLST ST8123, ST7365 and ST7367, which are among the most frequently encountered sequence types found in China. Therefore, these results indicate that endemic lineages in China have acquired penA allele 60.001. Conclusions Here, we report continued transmission of gonococcal strains associated with the FC428 clone or containing penA allele 60.001 in Hangzhou. A major concern for public health is the acquisition of penA allele 60.001 by successful endemic lineages, which might enhance the transmission of this high-level ceftriaxone resistance trait. [ABSTRACT FROM AUTHOR]

Mycobacterium abscessus complex is a group of rapidly growing non-tuberculous mycobacteria (NTM), increasingly emerging as opportunistic pathogens. Current treatment options for these microorganisms are limited and associated with a high rate of treatment failure, toxicity and recurrence. In search of new therapeutic strategies, interest has grown in dual β-lactam (DBL) therapy, as research recently discovered that M. abscessus cell wall synthesis is mainly regulated by two types of enzymes (d , d- transpeptidases and l , d- transpeptidases) differently susceptible to inhibition by distinct β-lactams. In vitro studies testing several DBL combinations have shown synergy in extracellular broth cultures as well as in the intracellular setting: cefoxitin/imipenem, ceftaroline/imipenem, ceftazidime/ceftaroline and ceftazidime/imipenem. The addition of specific β-lactamase inhibitors (BLIs) targeting M. abscessus β-lactamase did not significantly enhance the activity of DBL combinations. However, in vivo data are lacking. We reviewed the literature on DBL/DBL-BLI-based therapies for M. abscessus infections to raise greater attention on this promising yet overlooked treatment option and to guide future preclinical and clinical studies. [ABSTRACT FROM AUTHOR]

Background Procalcitonin (PCT) is a blood marker used to help diagnose bacterial infections and guide antibiotic treatment. PCT testing was widely used/adopted during the COVID-19 pandemic in the UK. Objectives Primary: to measure the difference in length of early (during first 7 days) antibiotic prescribing between patients with COVID-19 who did/did not have baseline PCT testing during the first wave of the pandemic. Secondary: to measure differences in length of hospital/ICU stay, mortality, total days of antibiotic prescribing and resistant bacterial infections between these groups. Methods Multi-centre, retrospective, observational, cohort study using patient-level clinical data from acute hospital Trusts/Health Boards in England/Wales. Inclusion: patients ≥16 years, admitted to participating Trusts/Health Boards and with a confirmed positive COVID-19 test between 1 February 2020 and 30 June 2020. Results Data from 5960 patients were analysed: 1548 (26.0%) had a baseline PCT test and 4412 (74.0%) did not. Using propensity-score matching, baseline PCT testing was associated with an average reduction in early antibiotic prescribing of 0.43 days [95% confidence interval (CI): 0.22–0.64 days, P  < 0.001) and of 0.72 days (95% CI: 0.06–1.38 days, P  = 0.03] in total antibiotic prescribing. Baseline PCT testing was not associated with increased mortality or hospital/ICU length of stay or with the rate of antimicrobial-resistant secondary bacterial infections. Conclusions Baseline PCT testing appears to have been an effective antimicrobial stewardship tool early in the pandemic: it reduced antibiotic prescribing without evidence of harm. Our study highlights the need for embedded, rapid evaluations of infection diagnostics in the National Health Service so that even in challenging circumstances, introduction into clinical practice is supported by evidence for clinical utility. Study registration number ISRCTN66682918. [ABSTRACT FROM AUTHOR]

In most older patients with Helicobacter pylori infection, the risks of eradication therapy (ET) are outweighed by the benefits, which include decreases in the incidences of gastric cancer, ulcer-related bleeding, hospitalisation and death. ET involves proton pump inhibitors or potassium-competitive acid blockers, antibiotics and/or bismuth, with quadruple therapy as front-line therapy. Prescribing complexity is increased by age-related comorbidities and polypharmacy, but overall, ET is effective and well tolerated in older people. To ensure successful eradication and prevent the emergence of drug-resistant H. pylori, performing antibiotic-resistance testing, adhering to guideline-recommended treatment durations, switching antibiotics after treatment failure, and performing post-therapy examinations is recommended. [ABSTRACT FROM AUTHOR]

AbstractIntroductionMethodsResultsConclusionDuring recent years, the world—including Scandinavia—has experienced significant challenges with shortages of antibiotics. In Scandinavia, phenoxymethylpenicillin is recommended as first-line antibiotic treatment for most acute respiratory tract infections (ARTIs). However, the Scandinavian countries each constitute rather small markets for phenoxymethylpenicillin. The aim of this discussion paper is to enlighten the differences in Scandinavian ARTI antibiotic treatment recommendations. This information is fundamental for exploring the potential of harmonizing treatment recommendations in Denmark, Norway and Sweden—to help ensure sufficient future supply of phenoxymethylpenicillin.Information from national ARTI antibiotic treatment recommendations from respectively Denmark, Norway and Sweden has been collated.Several discrepancies exist in recommendations. Adult dosage varies from a minimum of 660 mg x 4 (Denmark) to a maximum of 2000 mg × 3 (Sweden). Within Norway and Sweden, variations in recommended dosage also exist between the different types of ARTIs. A main challenge is that the tablet strengths recommended, and available on the market in the three countries, differs.Also, antibiotic treatment durations vary significantly between countries and infections treated—from five to 10 days of treatment.In the capacity of a well-established network for antibiotic stewardship, we have enlightened the differences in Scandinavian ARTI antibiotic treatment recommendations. This paper is the first step moving forward to scrutinizing the potential for harmonizing recommendations for Denmark, Norway and Sweden—to help ensure continued supply of phenoxymethylpenicillin for use within the Scandinavian countries. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa, an antibiotic‐resistant opportunistic pathogen, poses significant challenges in treating infections, particularly in immunocompromised individuals. This review explores current and future innovative approaches to suppress its growth and virulence. We delve into the bacterium's virulence factors, discussing existing strategies like antibiotics, bacteriophages, probiotics, and small‐molecule inhibitors. Additionally, novel approaches, including RNA interference, CRISPR‐Cas systems, and nanotechnology, show promise in preclinical studies. Despite advancements, challenges persist, prompting the need for a multifaceted approach targeting various aspects of P. aeruginosa pathogenesis for effective infection management. This review provides a comprehensive perspective on the status and future directions of innovative strategies against P. aeruginosa. [ABSTRACT FROM AUTHOR]

Aims: 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. Methods: 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. Results: 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. Conclusions: 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]

Acne fulminans (AF) is a severe form of inflammatory acne commonly associated with adolescents. It is characterized by an abrupt onset of painful nodules and plaques and can progress to suppurative, ulcerative, and hemorrhagic lesions. AF can be associated with systemic symptoms such as fever, arthralgia, and bone pain. The etiology of AF is unknown but it has been linked to the use of certain medications and has been rarely found in autoinflammatory syndromes. In previous years, there have been reports of <200 cases in the literature; however, AF may be more common in clinical practice than reported. The most common presentation of AF is seen in adolescents starting isotretinoin therapy. Diagnosis of AF is determined based on its clinical findings. The main purpose of this article is to provide clinicians with a practical approach to treating AF. Current evidence for its treatment is limited to case reports and case series. The mainstay treatment of AF is a combination of prednisone and isotretinoin. It is important to taper or discontinue any exacerbating or precipitating medications such as isotretinoin, antibiotics, or androgens when AF is identified. Along with treatment of AF, it is important to treat associated scarring. Early identification and treatment of AF in adolescents is crucial to minimize both acute symptoms and long-term scarring, and further research is needed to determine optimal management. [ABSTRACT FROM AUTHOR]

Purpose An advisory panel of experts was convened by the ASHP Foundation as a part of its Medication-Use Evaluation Resources initiative to provide commentary on an approach to antibiotic stewardship in the treatment of skin and soft tissue infections (SSTIs), with a focus on oral antibiotics in the emergency department (ED) setting for patients who will be treated as outpatients. Considerations include a need to update existing guidelines to reflect new antibiotics and susceptibility patterns, patient-specific criteria impacting antibiotic selection, and logistics unique to the ED setting. Summary While national guidelines serve as the gold standard on which to base SSTI treatment decisions, our advisory panel stressed that institutional guidelines must be regularly updated and grounded in local antimicrobial resistance patterns, patient-specific factors, and logistical considerations. Convening a team of experts locally to establish institution-specific guidelines as part of a comprehensive antibiotic stewardship program can ensure patients receive the most appropriate oral therapy for the outpatient treatment of SSTIs in patients visiting the ED. Conclusion SSTI treatment considerations for antibiotic selection in the ED supported by current, evidence-based guidelines, including guidance on optimal oral antibiotic selection for patients discharged for outpatient treatment, are a useful tool to improve the quality and efficiency of care, enhance patient-centric outcomes and satisfaction, decrease healthcare costs, and reduce overuse of antibiotics. [ABSTRACT FROM AUTHOR]

Objective: To characterize the institutional utilization of pneumococcal vaccination during an index hospital admission for acute cerebrospinal fluid (CSF) leakage and associated infectious and clinical outcomes. Methods: This retrospective cohort study included patients hospitalized and treated for an acute CSF leak from January 2017 to June 2022. The primary outcome evaluated the incidence of pneumococcal vaccination during the index admission in patients without prior vaccination. Secondary outcomes evaluated the incidence of meningitis, time from CSF leak identification to meningitis, and mortality within 1 year of the index admission. Results: A total of 94 patients were included. Nineteen (20.2%) patients received pneumococcal vaccination prior to admission. Of the 75 patients without prior vaccination, 4 (5.3%) patients received vaccination during the admission. Meningitis occurred in 5/94 (5.3%) patients and occurred 4-24 days from CSF leak identification. Mortality was observed in 9/94 (9.6%) patients. None of the meningitis cases were attributed to culture-positive findings of pneumococcal disease. Conclusions: The results of this study demonstrate an overall low institutional utilization of pneumococcal vaccination in patients with an acute CSF leak. Infectious and clinical outcomes reflected comparable to previous reported literature. Further evaluation into the risk-benefit relationship of vaccination omission is warranted in this patient population. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether oral microbiome diversity is associated with all‐cause mortality in the general US population and in individuals with chronic diseases. Materials and Methods: We included 8224 individuals with oral microbiome diversity data from the National Health and Nutrition Examination Survey (2009–2012), representing 164,000,205 US adults, using a survey‐weighted analysis method. Cox regression analyses were performed to identify the association between oral microbiome diversity and all‐cause mortality. Results: During a survey‐weighted mean follow‐up period of 8.86 years, 429 all‐cause deaths (survey‐weighted number: 7,124,920) occurred in 8224 participants. Cox regression analysis revealed that higher oral microbiome diversity was significantly associated with a lower all‐cause mortality risk. Significant differences in all‐cause mortality risk were observed among the different clusters based on oral microbiome β‐diversity (log‐rank p < 0.001). Subgroup analyses revealed that the oral microbiome diversity was independently associated with all‐cause mortality in individuals with diabetes mellitus and hypertension. A multivariate logistic regression model showed that current smoking and antibiotic use were significantly associated with lower oral microbiome α diversity. Conclusions: Higher oral microbiome diversity was significantly associated with a lower all‐cause mortality risk in the general US population and in individuals with diabetes mellitus and hypertension. [ABSTRACT FROM AUTHOR]

Although most countries recommend amoxicillin for paediatric pneumonia, there is a long tradition of treatment with penicillin V (PcV) in Sweden, thus not empirically covering Haemophilus influenzae. There are, however, large regional differences in treatment practice. The aim was to compare clinical outcomes (treatment failure and severe complications), in children aged 1–59 months treated with PcV vs. amoxicillin for pneumonia. This population-based emulated target trial included all children born in Sweden between 2001 and 2021, using national health, sociodemographic, and population registers. All pneumonia cases from hospitals and paediatric outpatient clinics in children aged 1–59 months treated as outpatients with PcV or amoxicillin between July 2005 and December 2021, were identified. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for treatment failure (newly dispensed antibiotic prescription or pneumonia-associated hospitalization day 1–14) and severe complications (lung complications, an invasive bacterial disease, admission to intensive care unit or death day 1–28) were calculated with logistic regression analysis. PcV was prescribed in 14 766 cases and amoxicillin in 10 566. Treatment failure occurred in 7.7% with PcV vs. 4.7% with amoxicillin, aOR 1.76 (95% CI: 1.54–2.00). Severe complications were rare, with no significant difference between PcV and amoxicillin (0.3% vs. 0.2%, aOR 0.96, 95% CI: 0.53–1.73). Sensitivity and interaction analyses showed consistent results. PcV treatment compared with amoxicillin, was associated with an increased risk for treatment failure but not for severe complications. The absolute risks for adverse outcomes were low in both groups suggesting a minor role of H. influenzae in paediatric pneumonia. [ABSTRACT FROM AUTHOR]

Background: The infection rate among patients with head-and-neck cancer (HNC) undergoing chemoradiotherapy (CRT) is approximately 19%, with sepsis-related death ranging from 3–9%. A previous study at our institute found a 12% sepsis-related death rate in HNC patients during CRT. The objective of this study is to investigate the utilization of sepsis surveillance and early intervention in reducing the occurrence of sepsis-related deaths in locally advanced HNC patients receiving CRT. Methods: This retrospective analysis examined 54 patients with locally advanced HNC undergoing CRT who underwent sepsis surveillance between January 2018 and December 2021. The study recorded the utilization of oral and intravenous antibiotics, G-CSF, early admissions and their reasons, and the incidence of early mortality. Data analysis was conducted using SPSS v.24 software. Results: Twenty-one (38.9%) patients were prescribed oral antibiotics, and 14 (25.9%) received G-CSF on an outpatient basis. Twenty-nine (54%) patients required hospital admission. Among the admitted patients, 28 (96%) received intravenous antibiotics, and G-CSF was administered in 18 (62%) patients. In 8 cases, antibiotic treatment was intensified due to persistent fever and deteriorating neutropenia. The median time for receiving antibiotics and G-CSF after starting CRT was 5th week (range: 3–8 weeks). Five patients required readmission. Only one patient succumbed to sepsis. Among the 54 patients, 48 (89%) completed the scheduled RT, while 14 (25.9%) received all 6 cycles of chemotherapy. Conclusion: Sepsis surveillance and the prompt use of antibiotics and G-CSF, along with early hospitalization, when necessary, reduces the occurrence of sepsis-related early deaths in HNC patients undergoing CRT. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 12-year-old girl who presented with lower abdominal pain, ultimately diagnosed with hematometrocolpos due to an imperforate hymen. Topics discussed include the importance of considering uncommon gynecological causes for abdominal pain in pubescent females, the significance of a thorough gynecological history and examination, and the need for increased training in performing gynecological assessments in emergency medicine.

Fever in infants presenting to pediatric emergency departments (PEDs) often results in significant return visits (RVs). This retrospective study aimed to identify factors associated with RVs in febrile infants aged 0 to 90 days. Data from infants presenting to PED between 2018 and 2021 and returning within 7 days (RV group) were compared to age-matched febrile infants without RVs (control group). Each group had 95 infants with similar demographics and medical history. RVs were primarily due to positive cultures and persistent fever. The control group had higher initial hospitalization rates, longer PED stays, and increased antibiotic treatment. Prevalence of serious bacterial infections (SBIs) did not significantly differ. Higher hospitalization, prolonged PED stays, and initial antibiotic treatment were associated with reduced RV incidence despite similar SBI rates. Return visits in infants <90 days were primarily driven by persistent fever and positive cultures. Addressing these factors through targeted parental education and improved care protocols may reduce RVs. [ABSTRACT FROM AUTHOR]

Background: Neomycin is an aminoglycoside antibiotic that may cause contact allergy. It was withdrawn as a medicine for human use in Denmark in October 2009 but is still found in some vaccines. Objectives: To identify time trends in contact allergy to neomycin in the period from 2000 to 2023. Methods: A cross‐section study of patients ≥18 years consecutively patch‐tested with neomycin sulfate (20% in pet.) at Gentofte Hospital, Denmark, during the period 2000–2023 was conducted. Results: The overall prevalence of contact allergy to neomycin was 1.4%. The prevalence was significantly lower in the period '2010–2023' (1.2%) than in '2000–2009' (1.8%) (p < 0.005). Contact allergy to neomycin was significantly positively associated with facial dermatitis and age >40 years, and significantly negatively associated with occupational dermatitis and hand dermatitis. No changes in sex, occupational dermatitis, atopic dermatitis, hand dermatitis, leg dermatitis, facial dermatitis, or age > 40/≤40 (the MOAHLFA‐index) were identified when comparing neomycin contact allergic‐patients in the two periods '2010–2023' and '2001–2009'. Conclusion: Neomycin is a rare cause of contact allergy in Denmark with a significantly lower prevalence following its withdrawal as a medicinal product for human use in Denmark in 2009. [ABSTRACT FROM AUTHOR]

Epimedium is a Chinese herb known as "yin and yang fire," first mentioned in the Compendium of Materia Medica. Many of the proprietary Chinese medicines used in clinical practice contain Epimedium as an ingredient, and its main active constituents include icariin, icaritin, and icariside II, among others. In addition to its traditional use in treating fatigue and sexual problems, modern research has confirmed that the main bioactive compounds in Epimedium have pharmacological effects such as antidepressant, antibacterial, antiviral, antioxidant, and anti-inflammatory properties, as well as inhibiting bone destruction, promoting bone growth, improving immune regulation and protecting the cardio-cerebral vascular system. With the continuous development of extraction and purification techniques, the development and use of bioactive compounds in Epimedium have significantly progressed, and the anticancer effect has received widespread attention. Since natural herbs have few side effects on the human body and do not easily develop drug resistance, they have long been the direction of research in cancer treatment. This review summarizes the latest research on the anticancer effects of Epimedium and its extracts, describes the bioactive compounds, pharmacological efficacy, and antitumor mechanism of Epimedium, and gives a new view on the administration and development of Epimedium. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infection (UTI) in infants is a common, potentially life-threatening bacterial infection, and must be managed carefully through the entire chain of care from diagnosis, choice of treatment, follow-up and risk stratification of future complications. This Swedish nationwide study of infant UTI was conducted to evaluate the current management of infant UTI, yield of investigations and the Swedish UTI guidelines' ability to detect abnormalities of importance in the urinary tract. Methods: Infants < 1 year with a first episode of UTI were included in a prospective multicenter study. Treatment and follow-up were provided by local pediatricians. Clinical and laboratory findings and imaging results were reported to the coordinating center. The current management and results were compared with a previous Swedish study. Results: One thousand three hundred six infants were included. Urine sampling was performed with clean catch technique in 93% of patients. Initial oral antibiotic treatment was used in 63%, predominantly third generation cephalosporines. Permanent kidney abnormalities were found in 10% and dilating vesicoureteral reflux (VUR) in 8%. Higher rates of male gender, non-E. coli infection and ultrasound dilatation were seen in infants < 1 month. UTI recurrences were reported in 18%. Conclusions: Infant UTI is still generating a considerable amount of follow-up examinations. There is a significant shift towards clean catch as the main urine sampling method. Voiding cystourethrography is performed less frequently reducing the findings of low grade VUR. The incidence of renal scarring is comparable with earlier studies which suggests that the Swedish guidelines are able to identify individuals with risk for long-term complications. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

Background: Acute rhinosinusitis (ARS) is one of the most encountered conditions in primary care and otolaryngology clinics. However, little is known about how antibiotic prescription practices following a diagnosis of ARS compare to guidelines set forth by the American Academy of Otolaryngology in 2015. Objective: To investigate the epidemiology of ARS and the corresponding antibiotic prescribing practices by physicians and compare to published guidelines. Methods: Using the TriNetX Live database, we identified all patients diagnosed with ARS using the ICD10 code J01 between April 2015 and December 2022 across the state of Tennessee. After investigating the demographics of this cohort, we compared the first prescribed antibiotic within one day of ARS diagnosis to published guidelines. Antibiotics were grouped into their respective classes. Results: Of 81 310 patients diagnosed with ARS identified in the specified time frame, 66% were Female, 49% were African American, 44% were White, and the mean age was 47 ± 20 years. The six most common initial antibiotics prescribed for ARS were erythromycins/macrolides [14 609 (25.8%)], amoxicillin/clavulanate [14 322 (25.3%)], amoxicillin [9300 (16.4%)], third generation cephalosporins [7733 (13.6%)], quinolones [3648 (6.4%)] and tetracyclines [2235 (3.9%)]. Of this cohort, 56 719 patients (69.8%) of patients were prescribed an antibiotic within one day of diagnosis. Conclusion: Despite published guidelines recommending amoxicillin with or without clavulanic acid as first-line treatment for ARS, only 42.2% of prescribed antibiotics followed this guideline in our cohort. While accounting for patients with penicillin allergy, the second-most represented antibiotics were erythromycins/macrolides, which are specifically recommended against due to high rates of S. Pneumonia e resistance. Our results suggest that further investigation into the causes of erythromycin/macrolide prescriptions as first line treatment for ARS and practices at other institutions should be conducted. In addition, building awareness around published ARS guidelines for physicians may be useful in improving antibiotic stewardship in treatment of ARS. [ABSTRACT FROM AUTHOR]

Dog bites are common within the United Kingdom, with their incidence increasing over recent years. Bites to the head and neck region can have substantial and multifactorial implications for victims, and can provide a challenge to maxillofacial departments. This study is a 10-year retrospective review of head and neck dog bites that required input from the maxillofacial team within the Cwm Taf Morgannwg University Health Board. Data collected included demographics of the patients involved, relationship with and breed of dog, nature of the injury, treatment received, and nature of any complications. In total, 168 records matched our inclusion criteria. The median age of our cohort was 12 years, with 57.1% of patients being younger than 15. Of the patients, 52.4% were female. Eighty-three per cent of cases involved a known dog, with Jack Russells being the breed most commonly involved. The upper lip was the most commonly affected area (30.3%), followed by the cheek (24.5%). Twenty-eight per cent of patients were admitted for management in theatre, with 8% of the total patients experiencing a complication. In conclusion, head and neck dog bites most commonly affect children and the upper lip. [ABSTRACT FROM AUTHOR]

The increasing threat of antibiotic resistance and shrinking treatment options for infections have pushed mankind into a difficult position. The looming threat of the return of the pre-antibiotic era has caused a sense of urgency to protect and conserve the potency of antibiotic therapy. One of the perverse effects of antibiotic resistance is the dissemination of its causative agents from non-clinically important strains to clinically important strains and vice versa. The popular saying "Prevention is better than cure" is appropriate for tackling antibiotic resistance. On the one hand, new and effective antibiotics are required; on the other hand, better measures for the use of antibiotics, along with increased awareness in the general public related to antibiotic use, are essential. Awareness, especially of appropriate antibiotic use, antibiotic resistance, its dissemination, and potential threats, can help greatly in controlling the use and abuse of antibiotics, and the containment of antibiotic resistance. Antibiotic drugs' effectiveness can be enhanced by producing novel antibiotic analogs or adding adjuvants to current antibiotics. Combinatorial therapy of antibiotics has proven successful in treating multidrug-resistant (MDR) bacterial infections. This review aims to highlight the current global situation of antibiotic resistance and discuss the methods used to monitor, prevent, inhibit, or reverse bacterial resistance mechanisms in the fight against antibiotic resistance. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a bacterial pathogen of considerable significance in public health, capable of inducing a diverse range of infectious diseases. One of the most notorious mechanisms used by S. aureus to survive and colonize the site of infection is its ability to form biofilms. Diflunisal, a non-steroidal antiinflammatory drug (NSAID), is a known inhibitor of the Agr system in S. aureus, which is key in regulating biofilm formation. This study evaluated the effect of broad-spectrum antibiotics in combination with diflunisal on S. aureus biofilm density. Eight antibiotics were tested independently at different concentrations and in combination with diflunisal to assess their effect on S. aureus biofilm formation. When using the antibiotics alone and with diflunisal, a significant control effect on biofilm formation was observed (p < 0.05), irrespective of diflunisal presence, but did not achieve a complete biofilm growth inhibition. Over time, diflunisal influenced biofilm formation; however, such an effect was correlated with antibiotic concentration and exposure time. With amikacin treatments, biofilm density increased with extended exposure time. In the case of imipenem, doripenem, levofloxacin, and ciprofloxacin, lower doses and absence of diflunisal showed higher control over biofilm growth with longer exposure. However, in all cases, diflunisal did not significantly affect the treatment effect on biofilm formation. In the absence of antibiotics, diflunisal significantly reduced biofilm formation by 53.12% (p < 0.05). This study suggests that diflunisal could be a potential treatment to control S. aureus biofilms, but it does not enhance biofilm inhibition when combined with antibiotics. [ABSTRACT FROM AUTHOR]