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Abstract Background Pneumonia is a leading diagnosis for patients requiring critical care. Prediction of the causal organisms has proved challenging, and antibiotic overuse is a burning issue. Objective This study aimed to compare the results of the BioFire FilmArray Pneumonia Panel (PN Panel) to standard diagnostic methods and evaluate its potential impact in an intensive care unit (ICU). Methods This is a retrospective study including adult patients admitted to the ICUs with a diagnosis of pneumonia. The agreement between the PN panel results and the standard diagnostic method was analyzed. Actual and potential adjustments of antimicrobials after the PN panel results were reviewed and compared. Results Two hundred ninety three patients with pneumonia were included. The PN panel identified at least one pathogen in 159 specimens (54.2%), while the standard diagnostic method identified at least one pathogen in 132 specimens (45.0%). Positive percentage agreement between the PN panel and standard‐of‐care culture reached 94%, and negative percentage agreement reached 97%. Among 293 patients, the availability of PN results led to escalation of antimicrobials in 38 (19%) patients and de‐escalation or discontinuation of antimicrobials in 95 (32.4%) patients. Conclusion This pilot study showed the PN panel could provide accurate results on the causative pathogens and detect resistant bacteria. It could reduce the use of broad‐spectrum antibiotics and overall antibiotic use. If the PN panel could be checked at the emergency department, targeted antibiotics could be administered when the patient arrived at the ICU.

Abstract Introduction Recently, antibiotics use in uncomplicated acute diverticulitis (AD) has been controversial in Europe. The American Gastroenterological Association (AGA) in their 2015 guidelines recommend their selective use. Our study highlights their role in outpatient management. Methods We queried the Diamond Network through TriNetX‐Research Network including 92 healthcare organizations. We included large intestine diverticulitis without perforation, abscess or bleeding. Exclusion criteria included any of sepsis criteria, CRP > 15 mg/L, immunodeficiency or HIV, coronary artery disease, chronic kidney disease, history of Crohn's disease or ulcerative colitis, heart failure, hypertension, diabetes or any of the following in the 3 months before study date; clostridium difficile (C. diff) infection, diverticulitis or antibiotics. Patients with AD were divided into two cohorts; patients on antibiotics, and patients not on antibiotics. Cohorts were compared after propensity‐score matching (PSM). Results 214,277 patients met inclusion criteria. 58.9% received antibiotics, and 41% did not. After PSM, both cohorts had 84,320. Rate of hospital admission was lower in the antibiotic group (3.3% vs 4.2%, p

Abstract Background Uropathogens are microorganisms that cause urinary tract infections (UTIs). Owing to higher blood glucose levels and compromised immune functions, treatment of uropathogens in diabetic patients is a challenge. Aim This study aims to assess the prevalence of uropathogens and their antibiotic susceptibility among diabetic patients at St. John of God Hospital at Duayaw Nkwanta (SJGHDN) in the Ahafo region of Ghana. Methods The cross‐sectional study recruited 175 diabetic patients at SJGHDN between August and September 2023. Questionnaires were used to collect patients’ background information. Fasting Blood Sugar (FBS) was assessed by using a glucometer. Urine samples were examined for the presence of uropathogens. A sterile inoculating loop with a calibrated volume of 2 µl was used for plating. Each colony equals 500 CFU/mL. Significant uropathogen was determined by multiplying the counted colonies by 500 to obtain CFU/mL. Positive uropathogen was defined as CFU ≥ 105/mL. Significant uropathogen was defined as ≥200 colonies per sample. The disc diffusion method was used to determine antibiotic susceptibility. Results Out of the 175 patients, 19.4% expressed various uropathogens with Escherichia coli being the predominant. Suboptimal glucose level was the most significant risk factor (p = 0.038). Glucosuria (p = 0.036), hazy urine (p = 0.028), positive leukocyte esterase (p = 0.001), and pus cells in urine sediment (p = 0.020) were significant indicators of uropathogen occurrence. Klebsiella pneumonia and Proteus mirabilis were resistant to ≥4 antibiotics. Amikacin, nitrofurantoin, levofloxacin, ciprofloxacin, and ceftriaxone demonstrated efficacy against the isolates. Conclusion This study underscores the notable prevalence of uropathogens in diabetic patients and the alarming levels of antibiotic resistance observed. The results highlight the critical need for vigilant monitoring and customized treatment approaches, particularly for diabetic patients exhibiting risk factors such as elevated urine glucose levels, cloudy urine, and presence of leukocyte esterase and pus cells in urine sediment. The significant resistance to frequently used antibiotics like co‐trimoxazole and tetracycline points to the necessity of routine susceptibility testing and the use of alternative antibiotics for effective treatment. These findings can assist healthcare providers in more effectively managing and preventing UTIs in diabetic populations.

Abstract Background Veterinary hospital antimicrobial stewardship (AMS) guidelines might help combat antimicrobial resistance (AMR). Objectives Determine the conditions and types of infection for which antimicrobial drugs (AMDs) deemed critically important (CIA) by the World Health Organization (WHO) were prescribed and assess the effect of hospital AMS guidelines on adherence to International Society for Companion Animal Infectious Diseases published guidelines for the treatment of superficial bacterial folliculitis, respiratory tract disease and urinary tract infection in these cases. Animals Dogs and cats managed at an academic veterinary hospital from 1/21 to 6/21 and 9/21 to 6/22. Methods Prescriptions of cephalosporins (third or fourth generation), glycopeptides, macrolides/ketolides, polymyxins, and quinolones were identified. Data on culture and susceptibility (C/S) testing and previous AMD exposure were collected. Frequencies were compared between time periods using Fisher's exact test with Bonferroni corrections. Results In animals prescribed ≥1 WHO‐CIA AMD, fluoroquinolones were the most frequently prescribed WHO‐CIA class in dogs (567/1724, 32.9%) and cats (192/450, 42.7%). No animals were prescribed carbapenems, dihydrofolate reductase inhibitors/sulfonamides, or polymyxins. No cats were prescribed aminoglycosides or amphenicols. Institutional guidelines were followed in 57.8% (324/561) cases. The most frequent causes of nonadherence were failure to perform C/S testing 46.0% (109/237) and unnecessary use of a higher‐tier AMD 43.0% (102/237). Bacterial C/S testing was more frequently performed after AMS guideline institution (59.7% vs. 46.8%, P = 0.0006). Conclusions and Clinical Importance Adherence to published guidelines remained poor despite an increase in C/S testing. There were no changes in the frequencies of confirmed infections, positive cultures or AMD resistance between time periods.

Abstract Background The diagnosis of pyelonephritis in cats is challenging and development of a noninvasive and accurate biomarker is needed. Hypotheses Serum amyloid A (SAA) is increased in cats with pyelonephritis, but not in cats with other urinary tract diseases. Animals A cohort of 125 cats (149 observations). Methods This was a prospective study. Group 1 included cats with a diagnosis of pyelonephritis either confirmed by bacterial culture of pelvic urine (Group 1a) or presumed (1b). Group 2 included cats for which pyelonephritis was ruled out (with certainty: Group 2a or judged unlikely: Group 2b). SAA concentration was compared between groups, and accuracy of SAA for the diagnosis of pyelonephritis was calculated using a Receiver Operating Characteristic (ROC) curve analysis. Results Median SAA concentration was significantly higher in Group 1a (86.8 mg/L [73.3; 161.5]; n = 8) than in Group 2a (4 mg/L [1.8; 5.6], n = 19; P

Abstract The prevalence of rosacea in the pediatric population is rare and treatment recommendations specific to the pediatric population are lacking. Our objective is to perform a systematic review of the published literature to identify treatments used for rosacea in the pediatric population (age

ABSTRACT Objectives After the shutdown of most dental services during the COVID‐19 lockdown, the oral health community was concerned about an increase in prescribing opioids and antibiotics by dentists due to patients' limited access to dental offices. Therefore, the objective of this study was to investigate the impact of COVID‐19 pandemic on the pattern of antibiotic and opioid prescriptions by dentists in Alberta, Canada. Methods Data obtained from the Tracked Prescription Program were divided into antibiotics and opioids. Time periods were outlined as pre‐, during‐, and postlockdown (phase 1 and 2). For the number of prescriptions and average supply, each monthly average was compared to the corresponding prelockdown monthly average, using descriptive analysis. Time series analyses were conducted using regression analyses with an autoregressive error model. Data were trained and tested on monthly observations before lockdown and predicted for during‐ and postlockdown. Results A total of 1.1 million antibiotics and 400,000 opioids dispense were tracked. Decreases in the number of prescriptions during lockdown presented for antibiotics (n = 24,933 vs. 18,884) and opioids (n = 8892 vs. 6051). Average supplies (days) for the antibiotics (n = 7.10 vs. 7.55) and opioids (n = 3.92 vs. 4.05) were higher during the lockdown period. In the trend analyses, the monthly number of antibiotic and opioid prescriptions showed the same pattern and decreased during lockdown. Conclusion The COVID‐19 pandemic altered the trends of prescribing antibiotics and opioids by dentists. The full impact of COVID‐19 pandemic on the population's oral health in light of changes in prescribing practices by dentists during and after lockdown warrants further investigation.

Abstract Detailed data on safety associated with drug–drug interactions (DDIs) between Linezolid (LZD) and other antibiotics are limited. The aim of this study was to investigate the safety signals related to these DDIs and to provide a reference for clinically related adverse drug event monitoring. Adverse event (AE) information from 1 January 2004 to 16 June 2022 of the target antibiotics including LZD using alone or in combination with LZD was extracted from the OpenVigil FDA data platform for safety signal analysis. The combined risk ratio model, reporting ratio method, Ω shrinkage measure model, and chi‐square statistics model were used to analyze the safety signals related to DDIs. Meanwhile, we evaluated the correlation and the influence of sex and age between the drug(s) and the target AE detected. There were 18991 AEs related to LZD. There were 2293, 1726, 4449, 821, 2431, 1053, and 463 AE reports when LZD was combined with amikacin, voriconazole, meropenem, clarithromycin, levofloxacin, piperacillin‐tazobactam, and azithromycin, respectively. Except for azithromycin, there were positive safety signals related to DDIs between LZD and these antibiotics. These DDIs might influence the incidence of 13, 16, 7, 7, 6, and 15 types of AEs, respectively, and is associated with higher reporting rates of AEs compared with use alone. Moreover, sex and age might influence the occurrence of AEs. We found that the combinations of LZD and other antibiotics are related to multiple AEs, such as hepatotoxicity, drug resistance and electrocardiogram QT prolonged, but further research is still required to investigate their underlying mechanisms. This study can provide a new reference for the safety monitoring of LZD combined with other antibiotics in clinical practice.

Abstract Background Antimicrobial resistance (AMR) has evolved into a severe public health issue that defies all current control strategies and needs multidisciplinary, creative solutions. Antimicrobial stewardship (AMS) activities demand a set of tools and abilities that can be used by health systems. In view of the growing AMR and the difficulty for the surveillance of it in the developing country, this study was conducted to incorporate pharmacovigilance (PV) in the AMS program. Materials and Methods A cross‐sectional pilot study was conducted to collect the PV database of antimicrobials induced adverse drug reactions (ADR) from the Adverse Drug Reactions Monitoring Center (AMC) of the institute for a period of 2 months from August 2022 to September 2022. The information from the database was analyzed to estimate the usage of antibiotics from the PV database from AMC and classified it under the Anatomical Therapeutic Chemical, to assess the rationality of the antimicrobial's usage based on “Access,” “Watch,” and “Reserve” (AWaRe) classification, and to assess the ADR of the antibiotics. The analysis was done by using the SPSS version 20.0 for Windows. Results The results showed that the prevalence of ADRs were more in adults’ population with preponderance in female. The antibiotics usage was as per with World Health Organization standard and most of the antibiotics used were from the Access group of AWaRe classifications. Tetracyclines and penicillins were the most used antibiotic group of drugs. The number of patients included in the study was 70. Most of the causality assessment was “possible” (62.85%). In the study, almost 90% of the drug was withdrawn and 70% of the patients were in the recovering stage. Conclusion Using existing PV approaches to address usage of antibiotics and AMR issues would allow PV to progress as a field, and governments will get a stronger return on their PV investments.

Abstract Our previous study revealed that red kidney bean polysaccharides (RKB) exhibit a pronounced hypoglycemic effect on type 2 diabetic rats, while simultaneously exerting a significant ameliorative impact on hepatic damage in these animals. However, the precise mechanism underlying the effects of RKB on diabetes and liver metabolism remains unproven. In this study, we utilized a mouse model of type 2 diabetes induced by a high‐fat diet combined with streptozotocin to investigate the impact of RKB. We administered a combined intervention involving antibiotics, fexaramine, and RKB to elucidate the mechanism underlying RKB's effects. Our findings demonstrated that RKB significantly ameliorated liver function indices and histopathological injuries. Nevertheless, when antibiotics and fexaramine were introduced as interventions, they hindered the beneficial effects of RKB on liver function in type 2 diabetic mice. Furthermore, our nontargeted metabolomics analysis revealed that antibiotics and fexaramine exerted their inhibitory actions on RKB efficacy through modulation of distinct metabolites involved in glycerophospholipid and purine metabolic pathways.

Abstract Aquaculture developmental plans represent a nation's determination for self‐reliance on domestic fish production through resilient aquaculture. This study reviewed the 2012 Ghana National Aquaculture Development Plan (GNADP) and sought inputs from industry stakeholders to inform GNADP 2023 using the ecosystem approach to aquaculture (EAA). In furtherance of this, we also investigated the justifications for antibiotic treatments including the assessment of the sector that is supposed to regulate aquaculture growth. The findings suggest that GNADP 2023 must be strategized to address industry sustainability bottlenecks identified as input availability and quality, permitting, regulation and enforcement, financing schemes and technical expertise. In terms of technical expertise, the inclusion of women in aquaculture can diversify the skill sets for the improvement of capacity and competence in good aquaculture practices and fish health management. Sector partnerships can aid in leveraging the expertise and resources among sectors to address persistent industry issues. The justifications for antibiotic treatments are disease management, prophylactics, antibiotic availability, application, and effectiveness, capacity and competence, including regulation and enforcement. This also comprised the sense of ownership and responsibility as farmers feel they must safeguard their investment. It is therefore important for farmers to pursue preventative aquaculture biosecurity measures. The government sector was selected predominantly to regulate aquaculture growth. We however recommended a participatory approach as this could facilitate peer regulation to enhance the regulation and enforcement of aquaculture regulations. The findings in this study are worth considering as it pioneers the adoption of the EAA framework for aquaculture developmental planning in Ghana.

Abstract Background and aims The promotion of rational use of antibiotics among pregnant women is eminent not only for the risk of teratogenicity in the developing fetus but also the risk of drug resistance with its concomitant high cost of health care. Studies on antibiotic self‐medication among pregnant women in Northern Ghana are rare. Improving the knowledge and awareness among the vulnerable groups about the appropriate use of antibiotics can help in limiting the antibiotic resistance menace. We, therefore, conducted this study to assess the knowledge, attitude, and practice (KAP) toward antibiotic use among pregnant women attending an antenatal clinic at a primary health care in Tolon, Northern Region, Ghana. Method We conducted a cross‐sectional study using an interviewer‐administered questionnaire to assess the KAP of 702 pregnant women on antibiotic use. This study was conducted in the Tolon Health Center (THC) from March 2021 and ended in October 2021. Results In this study, 55.6% of pregnant women had good knowledge and 45.3% of them had engaged in self‐medication with antibiotics while pregnant. There were statistically significant associations between participants' background and obstetric characteristics and knowledge of antibiotic use and antibiotic resistance, except for age, marital status, and parity. Also, there was a significant association between pregnant women's knowledge and self‐medication or over‐the‐counter purchase of antibiotics. Conclusion We concluded that higher education level, monthly income, good practice, and good knowledge were significantly associated with a reduced likelihood of self‐medication with antibiotics. A well‐structured education that could be easily accepted and understood by pregnant women on the risks of antibiotic self‐medication should be included in the routine education at the antenatal clinics.

Abstract Microbial products are essential for developing various therapeutic agents, including antibiotics, anticancer drugs, vaccines, and therapeutic enzymes. Genetic engineering techniques, functional genomics, and synthetic biology unlock previously uncharacterized natural products. This review highlights major advances in microbial biotechnology, focusing on gene‐based technologies for medical applications.

Abstract Introduction Guidelines recommend treating asthma exacerbations (AAEs) with bronchodilators combined with inhaled and/or systemic corticosteroids. Indications for antibiotic prescriptions for AAEs are usually not incorporated although the literature shows antibiotics are frequently prescribed. Aim To investigate the antibiotic prescription rates in AAEs and explore the possible determining factors of those practices. Methods A digital survey was created to determine the antibiotic prescription rates in AAEs and the influencing factors for the prescription practices. The survey was distributed among European academy of allergy and clinical immunology (EAACI) members by mass emailing and through regional/national societies in the Netherlands, Italy, Greece, and Poland. Furthermore, we retrieved local antibiotic prescription rates. Results In total, 252 participants completed the survey. Respondents stated that there is a lack of guidelines to prescribe antibiotics in AAEs. The median antibiotic prescription rate in this study was 19% [IQR: 0%–40%] and was significantly different between 4 professions: paediatrics 0% [IQR: 0%–37%], pulmonologists 25% [IQR: 10%–50%], general practitioners 25% [IQR: 0%–50%], and allergologists 17% [IQR: 0%–33%]) (p = 0.046). Additional diagnostic tests were performed in 71.4% of patients before prescription and the most common antibiotic classes prescribed were macrolides (46.0%) and penicillin (42.9%). Important clinical factors for health care providers to prescribe antibiotics were colorised/purulent sputum, abnormal lung sounds during auscultation, fever, and presence of comorbidities. Conclusion In 19% of patients with AAEs, antibiotics were prescribed in various classes with a broad range among different subspecialities. This study stresses the urgency to compose evidence‐based guidelines to aim for more rational antibiotic prescriptions for AAE.

Abstract Understanding the mechanisms of antibiotic resistance is critical for the development of new therapeutics. Traditional methods for testing bacteria are often limited in their efficiency and reusability. Single bacterial cells can be studied at high throughput using double emulsions, although the lack of control over the oil shell permeability and limited access to the droplet interior present serious drawbacks. Here, a straightforward strategy for studying bacteria‐encapsulating double emulsion‐templated giant unilamellar vesicles (GUVs) is introduced. This microfluidic approach serves to simultaneously load bacteria inside synthetic GUVs and to permeabilize their membrane with the pore‐forming peptide melittin. This enables antibiotic delivery or the influx of fresh medium into the GUV lumen for highly parallel cultivation and antimicrobial efficacy testing. Polymer‐based GUVs proved to be efficient culture and analysis microvessels, as microfluidics allow easy selection and encapsulation of bacteria and rapid modification of culture conditions for antibiotic development. Further, a method for in situ profiling of biofilms within GUVs for high‐throughput screening is demonstrated. Conceivably, synthetic GUVs equipped with biopores can serve as a foundation for the high‐throughput screening of bacterial colony interactions during biofilm formation and for investigating the effect of antibiotics on biofilms.

Abstract Objective To improve susceptibility profiles of nosocomial bacteria, identifying the difference between infectious complications in patients undergoing endoscopic flexible ureterolithotomy (fURS) with negative urine culture (UC) that received extended antibiotic prophylaxis (EP) compared with standard antibiotic prophylaxis (SP). Methodology This is a retrospective, observational, analytical cohort study, comparing infectious complications between patients undergoing fURS with negative UC who received EP versus SP. We include patients with susccessfull fURS,

Abstract Objectives The present study aimed to identify factors related to knowledge and attitudes that influence primary care clinicians' decision‐making when diagnosing, treating, and managing suspected urinary tract infections (UTIs) in women. Understanding the factors that influence clinicians' decision‐making is important for maximising health outcomes in women and reducing suboptimal use of antibiotics and antimicrobial resistance. Design A qualitative think‐aloud study design was employed. Methods Semi‐structured qualitative interviews were conducted with primary care clinicians in England over Microsoft Teams. Interviews were transcribed and coded in two ways. First, clinicians' responses for each scenario were coded as either following (optimal), not following evidence‐based national guideline or incorrectly citing certain diagnosis, treatment, and management procedures (suboptimal). Second, the knowledge and attitude factors that influenced decision‐making were coded according to an empirically informed umbrella framework. Clinicians external to the study team reviewed the findings to promote their trustworthiness and utility. Results Ten clinicians (six female) took part. Clinicians prescribing decisions were mostly influenced by knowledge rather than attitude factors. Despite clinicians expressing high awareness of relevant evidence‐based guidelines (a knowledge factor) and high confidence (an attitude factor), more than half of their decisions (60%) were suboptimal in some way thereby impacting women's health. Most clinicians relied on their experiential knowledge rather than using evidence‐based guidelines. Our results suggest that knowledge could impede adherence, for example, where local guidelines conflict with national guidelines of when to perform a urine dipstick test. Conclusions Suboptimal prescribing decisions could result from a combination of different knowledge and attitude factors leading to negative outcomes in women's health such as inappropriate treatment of asymptomatic bacteriuria in women over 65 years old. To optimise antibiotic prescribing in women, policy‐level interventions could increase concordance across local and national guidelines, or more tailored individual‐level interventions could help clinicians recognise where their experiential knowledge causes deviations from evidence‐based guidelines when diagnosing, treating and managing UTIs.

Abstract Background and Aim Biliary obstruction causes bacteriobilia and significant morbidity and high mortality, which necessitates prompt and effective treatment for a good clinical outcome. Hence, the aim of this study was to determine updated knowledge of biliary microbial spectrum, antibiotic sensitivity pattern, and key clinical factors of bacteriobilia. Methods This is a prospective study conducted during the period between November 2021 and December 2022 at Ibn Sina specialized hospital, Khartoum, Sudan, on 50 patients diagnosed with obstructive jaundice and symptomatic bacteriobilia who underwent open biliary surgeries electively. Bile samples were aspirated intra‐operatively and cultured, and antibiotic sensitivity tests were performed. Results Fifty‐four percent of patients diagnosed with obstructive jaundice who underwent elective open biliary surgeries were males with the ratio (2:1). Forty‐six percent of patients were between 61 and 75 years (elderly). The most frequent cause of obstructive jaundice was migrating biliary stones (48% of cases). Thirty‐two percent of patients were diabetic with bacteriobilia. The predominant isolated bacterial pathogen in this study was Escherichia coli (36% of cases). These biliary pathogens were sensitive to meropenem in 54% of cases and ciprofloxacin in 46%. Eventually, in all patients in this study, biliary bacterial pathogens were found to be resistant to a broad spectrum of antibiotics. Conclusion Careful selection of empirical antibiotic therapy based on surveillance of routine bile cultures during biliary tree procedures in patients with high risk of bacteriobilia will potentially help in improving the surgical outcomes and optimizing treatment of acute cholangitis, which is associated with high mortality.

Abstract Achromobacter xylosoxidans is a common bacterium that rarely causes pneumonia. Determining whether A. xylosoxidans is the cause of lung infection in patients suspected of having chronic infectious lung disease is challenging because it can present with colonization. We report a case of a 56‐year‐old immunocompetent woman suspected of having non‐tuberculous mycobacteria (NTM) infection on imaging examination and monitored for 3 years. Sputum examinations revealed A. xylosoxidans several times, and it was determined to be a colonization. A. xylosoxidans was isolated from bronchial lavage fluid and aspirated sputum, but no evidence of NTM was observed. She was diagnosed with A. xylosoxidans infection and given ceftazidime for 2 weeks. Her symptoms and imaging findings improved rapidly after treatment, without recurrences. A. xylosoxidans rarely causes chronic lower respiratory tract infections similar to NTM in immunocompetent patients. A. xylosoxidans may be a target for treatment when detected in lower respiratory tract specimens.

Abstract Background Given that there is already evidence of a neural network that connects the brain and gut and that the gut microbiota actively modulates gut health, it is crucial to know which foods, supplements, and medications to use or avoid when treating any disease that causes dementia or cognitive impairment. Previous research has examined the relationships between vitamins, antibiotics, and gut microbiota and the correlations between these factors and dementia. The question arises of how these three factors interact together and if evidence suggests one element is more important than the others in the pathogenesis and development of dementia. Methods The Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) standards were followed when conducting this review. The papers' publication dates varied from (2012−2022). Cochrane/EMBASE, PEDro, and PubMed/Medline databases were searched. The precise terms “gut microbiota,” vitamins,” antibiotics,” and “dementia” were included in the search method, along with the conjunctions “OR” and “AND.” Results Gut dysbiosis has a significant impact on cognition, brain function, and the development and progression of dementia. The two most popular probiotics used in studies linked to cognition benefits were Lactobacillus and Bifidobacterium. Numerous scales were used to evaluate cognition, but the mini‐mental state examination was the most popular, and the most prevalent impairment was Alzheimer's disease. The supplements with the most significant impact on gut microbiota were vitamin B‐12 and folic acid. Conclusion This systematic review concluded that vitamins, gut microbiota and antibiotics have a close association with the development of dementia. More research is required to establish causality and elucidate the underlying mechanisms because there is still little evidence connecting the interactions of vitamins, medications, and microbiota with dementia. The complexity of interactions between genetics, lifestyle factors, and comorbidities, as well as the heterogeneity of dementia, may make it more challenging to interpret the findings.

Abstract In the age of antimicrobial resistance, the urgency by which novel therapeutic approaches need to be introduced into the clinical pipeline has reached critical levels. Antimicrobial blue light (aBL), as an alternative approach, has demonstrated promise as a stand‐alone therapeutic method, albeit with a limited window of antimicrobial activity. Work by others indicates that treatment with antibiotics increases the production of reactive oxygen species (ROS) which may, in part, contribute to the bactericidal effects of antibiotics. These findings suggest that there may be potential for synergistic interactions with aBL, that similarly generates ROS. Therefore, in this study, the mechanism of aBL is investigated, and the potential for aBL to synergistically promote antibiotic activity is similarly evaluated. Furthermore, the translatability of using aBL and chloramphenicol in combination within a mouse model of Acinetobacter baumanii burn infection is assessed. It is concluded that porphyrins and hydroxyl radicals driven by “free iron” are paramount to the effectiveness of aBL; and aBL is effective at promoting multiple antibiotics in different multidrug‐resistant bacteria. Moreover, rROS up‐regulation, and promoted antibiotic uptake are observed during aBL+antibiotic exposure. Lastly, aBL combined with chloramphenicol appears to be both effective and safe for the treatment of A. baumannii burn infection. In conclusion, aBL may be a useful adjunct therapy to antibiotics to potentiate their action.

Abstract Background It is unknown whether serum procalcitonin (PCT) concentration monitoring can differentiate between bacterial infection or cytokine release syndrome (CRS) when chimeric antigen receptor T‐cell (CAR‐T) recipients present with a constellation of signs and symptoms that may represent both complications. Objective The objective of the study was to assess the utility of serum PCT concentrations as a biomarker of bacterial infection in CAR‐T recipients. Study design This single‐center, retrospective, medical record review evaluated patients prescribed CAR‐T therapy until death or 30 days after infusion. Logistic regression modeling determined the association between elevated serum PCT concentrations within 48 h of fever onset and microbiologically confirmed infection. Secondary outcomes included clinically suspected infection, CAR‐T toxicity rates, and broad‐spectrum antibiotic usage. Predictive performance of PCT was assessed by area under the receiver operating characteristic curve (AUC). Results The 98 included patients were a median age of 63 (IQR: 55–69) years old, 47 (48%) were male, and 87 (89%) were Caucasian. Baseline demographics and clinical characteristics were similar between patients with and without a bacterial infection. Serum PCT >0.4 ng/mL within 48 h of fever was significantly associated with a microbiologically confirmed bacterial infection (OR: 2.75 [95% CI: 1.02–7.39], p = 0.045). Median PCT values in patients with and without confirmed infections were 0.40 ng/mL (IQR: 0.26, 0.74) and 0.26 ng/mL (IQR: 0.13, 0.47), respectively. The AUC for PCT to predict bacterial infection was 0.62 (95% CI 0.48–0.76). All patients experienced CRS of some grade, with no difference in CRS severity based on elevated PCT. Broad‐spectrum antibiotics were used for a median of 45% and 23% of days in those with and without confirmed infection, respectively (p = 0.075). Conclusion Elevated serum PCT concentrations above 0.4 ng/mL at time of first fever after CAR‐T infusion was significantly associated with confirmed bacterial infection. Furthermore, rigorous, prospective studies should validate our findings and evaluate serial PCT measurements to optimize antimicrobial use after CAR‐T therapy.

Abstract Background No recent studies have evaluated the association between clinical signs of lower urinary tract disease (LUTD) and positive urine culture in dogs with diabetes mellitus. Objective Determine the prevalence of subclinical bacteriuria (ie, positive urine culture without signs of LUTD) in dogs with diabetes mellitus. Animals One hundred seven dogs with diabetes mellitus were evaluated at a university veterinary hospital. Methods Retrospective study evaluating diabetic dogs with a single sample paired urinalysis and urine culture. Relationship between the presence of signs of LUTD, pyuria, and bacteriuria and urine culture results were compared using Fisher exact testing. Results Fifteen dogs (14%) had a positive urine culture via cystocentesis or free catch, of which 8 (53%) had pyuria, and 4 (27%) had signs of LUTD. Of the 88 dogs (82%) without signs of LUTD, 11 (13%) had a positive culture. A significant association was found between a positive urine culture and pyuria (OR infinity; 95% CI 20.34‐infinity, P

Abstract Background and Aims Antimicrobial resistance (AMR) is among the top public health concerns around the globe. Migrants, especially forced migrants, could be at higher risk of acquiring and transmitting AMR during their journeys or in host countries. There is limited understanding regarding migrants' living conditions and the wider factors contributing to their risk of acquiring infections, and behaviors around antimicrobial use, and AMR development. In this study, we aimed to explore transit experiences, living conditions, and antibiotic use of migrants living in the United Kingdom. Methods We conducted semistructured qualitative interviews with 27 participants and identified five themes regarding migrants' journey and their living conditions during transit and after arriving in the United Kingdom, their access to water, sanitation and hygiene (WASH), and their use of antibiotics. Results Migrants, particularly forced migrants, experienced unfavorable living conditions, poor access to WASH, and challenges in accessing healthcare, which further contributed to health conditions like urinary and skin problems. Isolation and difficulty in accessing healthcare played significant roles in migrants' perceived need for storing and using antibiotics as a safety net. Conclusion The findings highlight the need for coordinated and multilevel interventions to address these challenges and contribute toward tackling AMR and improving the health of this population group.

Key Clinical Message A 97‐year‐old woman with gastrostomy had a drastic enhancement for PT‐INR after starting antibiotic therapy. Possible causes include (1) vitamin K deficiency due to fasting and (2) a combination of warfarin and antibiotics. Abstract Geriatric and Asian‐descent patients are more sensitive to the effects of warfarin, a key anticoagulant drug. In this report, we present a 97‐year‐old bedridden woman being treated with warfarin for cardiogenic cerebral infarction and femoral neck replacement as part of in‐home medical care with a gastrostomy and was admitted to our hospital after developing pneumonia. We discontinued warfarin and started antibiotics, and her pneumonia‐related symptoms improved. Eleven days after restarting warfarin, the patient's PT‐INR surpassed the upper limit for measurement (over 10). We considered the mechanism might be triggered by (1) fasting, low nutrition status; and (2) antibiotics secondary to risk factors such as gastrostomy and being a super‐geriatric woman. We recommend careful monitoring of PT‐INR in patients treated with warfarin and antibiotics, especially in the setting of gastrostomy or older persons.

Key Clinical Message The main type of urinary tract infection in hospitalized diabetics in Antananarivo is acute pyelonephritis; Escherichia coli is the most isolated uropathogen; imipenem, amikacin, fosfomycin and ceftriaxone are the major antibiotics for which Escherichia coli retain good sensitivity; Type 2 diabetes is predictive factor for infection by multidrug resistant bacteria. Abstract This study aimed to describe the epidemiological‐clinical profiles of diabetics hospitalized for bacterial urinary tract infections in the Endocrinology Department of Befelatanana Hospital, to identify the main bacteria responsible, their antibiotic sensitivity profile and the factors associated with multidrug‐resistant bacterial infection. A cross‐sectional study was conducted between March 2017 and March 2020 involving all diabetics hospitalized for documented community‐acquired bacterial urinary tract infection during this period. The hospital prevalence of urinary tract infections was 4.64%. The mean age of the patients was 59.06 ± 14.26 years and the sex ratio was 0.15. The main sign was fever (55.76%). The main clinical form was uncomplicated acute pyelonephritis (38.46%). Fifty‐seven bacterial uropathogens were isolated. The most frequent was Escherichia coli (77.19%). Escherichia coli was sensitive to ertapenem and nitrofurantoin in 100% of cases, to Amikacin in 97.5% of cases, to Fosfomycin in 94.4% of cases and to Ceftriaxone in 80.65% of cases. Thirteen patients were infected with multidrug‐resistant bacteria, all of them are extended‐spectrum beta‐lactamase‐producing Enterobacteriaceae. Only the type of diabetes was associated with multidrug‐resistant bacteria infection. The epidemiological‐clinical and biological characteristics of urinary tract infections in our diabetics are similar to those reported in the literature. Compliance with the rules of proper antibiotic use is imperative to limit the emergence and spread of multidrug‐resistant bacteria.

Abstract Antimicrobial peptides (AMPs) are essential elements of thehost defense system. Characterized by heterogenous structures and broad‐spectrumaction, they are promising candidates for combating multidrug resistance. Thecombined use of AMPs with other antimicrobial agents provides a new arsenal ofdrugs with synergistic action, thereby overcoming the drawback of monotherapiesduring infections. AMPs kill microbes via pore formation, thus inhibitingintracellular functions. This mechanism of action by AMPs is an advantage overantibiotics as it hinders the development of drug resistance. The synergisticeffect of AMPs will allow the repurposing of conventional antimicrobials andenhance their clinical outcomes, reduce toxicity, and, most significantly,prevent the development of resistance. In this review, various synergies ofAMPs with antimicrobials and miscellaneous agents are discussed. The effect ofstructural diversity and chemical modification on AMP properties is firstaddressed and then different combinations that can lead to synergistic action,whether this combination is between AMPs and antimicrobials, or AMPs andmiscellaneous compounds, are attended. This review can serve as guidance whenredesigning and repurposing the use of AMPs in combination with other antimicrobialagents for enhanced clinical outcomes.

Abstract Between January 2010 and December 2015, we enrolled 28 patients with stage IEI/IIE1 extragastric mucosa‐associated lymphoid tissue (MALT) lymphoma who received first‐line antibiotic treatment, after informing them about the pros and cons of alternative therapies. In addition, during the same period, 64 patients with stage IE/IIE1 disease who received conventional treatment were selected as the control group. The most common primary sites were the ocular adnexal area (17 cases), followed by the salivary glands (four cases), pulmonary (three cases), and thyroid, trachea, larynx, and colon region (one case each). First‐line antibiotic treatment resulted in an overall response rate of 57.1%: 12 patients achieved complete remission (CR), while four achieved partial remission (antibiotic‐responsive tumors). Monoclonal gammopathy was significantly prevalent in antibiotic‐unresponsive tumors than in antibiotic‐responsive tumors (50.0% [6/12] vs. 12.5% [2/16], p = 0.044). After a median follow‐up of 7 years, all patients with CR remained lymphoma‐free, with 7‐year event‐free survival (EFS) and overall survival (OS) rates of 62.7% and 96.4%, respectively. The 7‐year EFS and OS rates of patients who received conventional treatments were 73.1% and 91.1%, respectively. Compared with that noted in patients who received conventional treatment, antibiotic treatment was effective in some patients with localized extragastric MALT lymphoma.

Abstract Background The use of antibiotics has been associated with increased risks of various cancers. Comprehensive information on the association of antibiotic use with the risk of glioma is lacking. Methods We performed a large case–control study based on the Clinical Practice Research Datalink (CPRD) GOLD from the United Kingdom. We identified 4423 glioma cases recorded between 1995 and 2020 and matched them to controls (1:10) on the date of diagnosis (i.e., the index date), age, sex, general practice, and number of years of medical history in the database prior to the index date. We conducted conditional logistic regression analyses to calculate odds ratios (ORs) with 95% confidence intervals (CIs). The exposures of interest were the use of antimicrobial drugs, including antibacterial, antiviral, antifungal, antiprotozoal, and anthelmintic drugs with specific subclasses, where possible. Results We found no substantially increased risk of glioma after ever‐use of antibiotics (OR 1.13, 95% CI 1.03–1.24). The risk did not increase with the increasing number of prescriptions received or with increasing time from first use to cancer diagnosis. The use of polyenes was associated with a weakly decreased risk of glioma (OR 0.81, 95% CI 0.67–0.96).

Abstract Natural plant extracts (NPEs) may offer an effective alternative to minimize the consequences caused by antibiotic resistance in the marine industry. In this study, the anti‐Vibrio parahaemolyticus activities of several antibiotics and NPEs alone and in combinations were evaluated. The results indicated that the best combination was the 1/4 minimum inhibitory concentration (MIC) oxytetracycline +1/4 MIC hawthorn extract with fractional inhibitory concentration of 0.50. As a result, the survival rate of Exopalaemon carinicauda challenged by V. parahaemolyticus was improved to 53.3 ± 4.7% (as compared to 23.3 ± 2.3% in control) because of exposure to the combination of oxytetracycline +1/4 MIC hawthorn extract. Furthermore, the combination of upregulated digestive enzyme activities (cellulose, lipase, and pepsin), Toll receptor expressions, and immune parameters (alkaline phosphatase, and lysozyme) improved tolerance of E. carinicauda to V. parahaemolyticus infection. The synergistic anti‐V. parahaemolyticus functions may be associated with improved digestibility and immunity of E. carinicauda. Therefore, as a supplementary therapy to inhibit V. parahaemolyticus, the combinations of NPEs + antibiotics will hold better application potential for reducing antibiotic dosage and resistance.

Abstract Background Antibiotics may alter colorectal cancer (CRC) risk due to gut dysbiosis. We aimed to study the specific and temporal effects of various antibiotics on CRC development in older individuals. Methods This was a territory‐wide retrospective cohort study. Subjects aged 60 years and older who did not have CRC diagnosed on screening/diagnostic colonoscopy diagnosed between 2005 and 2013 were recruited. Exclusion criteria were history of CRC, colectomy, inflammatory bowel disease, and CRC diagnosed within 6 months of index colonoscopy. Exposure was use of any antibiotics up to 5 years before colonoscopy. The primary outcomes were CRC diagnosed >6 m after colonoscopy. Covariates were patient demographics, history of colonic polyps/polypectomy, concomitant medication use (NSAIDs, COX‐2 inhibitors, aspirin, and statins), and performance of endoscopy centers (colonoscopy volume and polypectomy rate). Stratified analysis was conducted according to nature of antibiotics and location of cancer. Results Ninety seven thousand one hundred and sixty‐two eligible subjects (with 1026 [1.0%] cases of CRC) were identified, 58,704 (60.4%) of whom were exposed to antibiotics before index colonoscopy. Use of antibiotics was associated with a lower risk of cancer in rectum (adjusted hazard ratio [aHR]: 0.64, 95% CI: 0.54–0.76), but a higher risk of cancer in proximal colon (aHR: 1.63, 95%CI: 1.15–2.32). These effects differed as regards the anti‐anaerobic/anti‐aerobic activity, narrow‐/broad‐spectrum, and administration route of antibiotics. Conclusions Antibiotics had divergent effects on CRC development in older subjects, which varied according to the location of cancer, antibiotic class, and administration route.

Abstract Rapid detection and quantification of outer membrane vesicle (OMV) are of both scientific value and clinical implications. However, limited tools are available for investigations of OMVs. Herein, we report a novel fluorescent probe with aggregation‐induced emission (AIE) characteristics, namely, OEO‐TPE‐MEM (OTM), for OMV detection. OTM emits faintly in an aqueous medium, but its fluorescence could be effectively turned on upon interacting with bacteria bodies and OMVs produced by Gram‐negative bacteria. Notably, OTM could provide quantitative information on bacterial membrane remodeling and OMV secretion and be applied to high‐throughput screening of OMV‐inducing agents. This study presents a powerful AIE probe for imaging and quantitative analysis of bacteria envelop and derived OMVs, which might be applied for evaluating research and clinical antimicrobial materials in future studies.

Key Clinical Message Necrotizing fasciitis (NF) is a rare soft‐tissue infection generally treated by emergency surgical intervention. We report a case of successfully drug treatment for NF in older patient with comorbidities thus avoiding surgical intervention.

Abstract Background The frequency of surgical site infection (SSI) following orthopaedic implant placement in horses has been reported but not compared with respect to specific antibiotic protocols administered. Objectives To determine factors associated with SSI in horses undergoing proximal interphalangeal joint (PIPJ) arthrodesis including perioperative antibiotic protocols. Methods Records were evaluated (2010–2019), and horses undergoing PIPJ arthrodesis were identified. Patient signalment, supervising surgeon, reason for surgery, limb, implants placed, anaesthetic time, duration casting/coaptation postoperatively, antibiotic regimen and incidence/onset SSI were recorded. Bayesian and frequentist logistic regressions were used to estimate the contribution of covariates to infection occurrence. Results Fifty‐four PIPJ arthrodeses were performed. SSI occurred in 2/54 (3.7%) on day 15,30. Arthrodesis was performed most commonly for osteoarthritis (33/54, 61.1%), fracture (11/54, 20.4%), and subluxation (5/54, 9.3%). Perioperative systemic antibiotics were administered 1–3 days (15/54, 27.8%) or > 3 days (39/54, 72.2%). Antibiotic protocols included cefazolin/gentamicin (20/54, 37%), cefazolin/gentamicin/doxycycline (14/54, 25.9%) and potassium penicillin/gentamicin (10/54, 18.5%). Regional limb perfusion was performed preoperatively 31/54 (57.4%) and postoperatively 7/54 (13%). Survival to dismissal was 98.1% (53/54 horses) with one horse euthanized due to support limb laminitis. No association was identified between antibiotic selection or duration (1–3 vs. > 3 days), pre‐operative regional antibiotic perfusion, intraoperative antibiotic lavage or anaesthetic time ( 3 h) and SSI; however, modelling was complicated by quasi‐complete or complete separation of the data. Bayesian analysis (but not frequentist analysis) indicated an association between post‐operative regional antibiotic perfusion and SSI. Limitations include the retrospective nature of data collection and the low rate of infection overall. Conclusions The prevalence of SSI in this population was lower than that in previous reports of equine orthopaedic internal fixation. There was no difference in SSI rate in cases administered systemic antibiotics for 1–3 days or >3 days, or for those horses that did or did not receive preoperative regional antibiotic perfusion.

Abstract Background Urinary tract infections (UTI) caused by Escherichia coli and Enterococcus spp., which are frequently coisolated in polymicrobial UTI, cause morbidity among dogs and warrant antimicrobial therapy. Objectives To evaluate clinical features of dogs with polymicrobial E. coli and Enterococcal UTI. Animals Forty‐four client‐owned dogs with polymicrobial bacteriuria and groups of 100 client‐owned dogs with E. coli and Enterococcal monomicrobial bacteriuria. Methods Retrospective cohort study of medical records of dogs at a university teaching hospital from 2014 to 2019. Prevalence of recurrent UTI and isolate antimicrobial resistance were determined. Clinical outcomes of dogs with recurrent UTI from groups including cost and hospital visits were compared. Results Recurrent UTI was more prevalent (P = .05) in dogs with polymicrobial bacteriuria (57%, 95% confidence interval [95% CI]: 42%‐70%) compared to the Enterococcal monomicrobial group (40%, 95% CI: 31%‐50%). Escherichia coli from polymicrobial bacteriuria were more frequently resistant to doxycycline (P

Abstract Background and Aim Environmental factors play a key role in development of Crohn's disease (CD), thought to be mediated by changes in the gut microbiota. We aimed to delineate the potential contribution of antibiotic exposure to subsequent development of CD, across diverse geographical populations. Methods This case–control study in Australia and three cities in China (Hong Kong, Guangzhou, and Kunming) included four groups: patients with CD, at‐risk individuals including non‐affected first‐degree relatives (FDRs) and household members of CD patients (HM), and unrelated healthy controls (HCs). Environmental risk factors, including childhood antibiotic use and 13 other categories, were assessed using a self‐developed questionnaire. Logistic regression and conditional logistic regression were used to determine environmental factors associated with CD development. Results From 2017 to 2019, a total of 254 patients with CD (mean age: 37.98 ± 13.76 years; 58.3% male), 73 FDR (mean age: 49.35 ± 13.28 years; 46.6% male), 122 HMs (including FDR) (mean age: 45.50 ± 13.25 years; 47.5% male), and 78 HC (mean age: 45.57 ± 11.24; 47.4% male) were included. Comparing CD patients with their FDR and HMs, antibiotic use before 18 years old was a risk factor for CD development (adjusted odds ratio [OR] 3.46, 95% confidence interval [CI] 1.38–8.69; P = 0.008). There were no significant differences in other childhood environmental risk factors between CD and their FDR or HMs. Subgroup analysis showed that antibiotic use

Abstract Despite the successes achieved so far with the Global Programme to Eliminate Lymphatic Filariasis, there is still an appreciable number of lymphatic filarial patients who need alternative treatment and morbidity management strategies. The unresponsiveness of some cohorts to the drugs used in the mass drug administration program is currently raising a lot of questions and this needs urgent attention. Natural medicinal plants have a long‐standing history of being effective against most disease conditions. Countries such as India have been able to integrate their natural plant remedies into the treatment of lymphatic filarial conditions, and the results are overwhelmingly positive. Components of Azadirachta indica A. Juss, Parkia biglobosa, Adansonia digitata, and Ocimum spp have been shown to have anti‐inflammatory, anticancerous, and antimicrobial activities in animal models. Therefore, this review calls for attention toward the use of natural plant components as an alternate treatment against lymphatic filariasis to help reduce the World Health Organization's burden of providing drugs for people in need of treatment every year.

Abstract Diabetic foot infection (DFI) is an important cause of morbidity and mortality. Antibiotics are fundamental for treating DFI, although bacterial biofilm formation and associated pathophysiology can reduce their effectiveness. Additionally, antibiotics are often associated with adverse reactions. Hence, improved antibiotic therapies are required for safer and effective DFI management. On this regard, drug delivery systems (DDSs) constitute a promising strategy. We propose a gellan gum (GG)‐based spongy‐like hydrogel as a topical and controlled DDS of vancomycin and clindamycin, for an improved dual antibiotic therapy against methicillin‐resistant Staphylococcus aureus (MRSA) in DFI. The developed DDS presents suitable features for topical application, while promoting the controlled release of both antibiotics, resulting in a significant reduction of in vitro antibiotic‐associated cytotoxicity without compromising antibacterial activity. The therapeutic potential of this DDS was further corroborated in vivo, in a diabetic mouse model of MRSA‐infected wounds. A single DDS administration allowed a significant bacterial burden reduction in a short period of time, without exacerbating host inflammatory response. Taken together, these results suggest that the proposed DDS represents a promising strategy for the topical treatment of DFI, potentially overcoming limitations associated with systemic antibiotic administration and minimizing the frequency of administration.

Abstract Inflammatory bowel disease (IBD), including both ulcerative colitis and Crohn's disease, is a chronic inflammatory disease of the gastrointestinal tract that is thought to arise from a combination of environmental, genetic and immunological factors. The gut microbiome, a diverse ecosystem of microorganisms residing in the digestive tract, has been proposed to play a role in the pathogenesis of IBD. There is an unmet clinical need for microbiome‐based therapies. This review will discuss the landscape of microbiome‐based therapeutics in IBD. Microbiome‐targeted therapeutics, such as antibiotics, pre‐/probiotics and faecal microbiota transplant (FMT), are based on the premise that restoring a healthy gut microbiome can attenuate mucosal inflammation. Antibiotics work directly to impede growth or eradicate specific gut microorganisms. Antibiotics may play a role in inducing clinical remission and treating refractory pouchitis and may be associated with immunogenicity to anti‐TNF biologics in IBD. Prebiotics are the molecular metabolic building blocks for commensal gut bacteria. Probiotics artificially introduce gut microorganisms thought to be beneficial to the local microenvironment and maybe be associated with symptom relief in IBD. FMT similarly introduces bacteria found in higher proportions of healthy persons, though in a more direct manner than probiotics. FMT has been associated with increased rates of clinical remission in IBD, but heterogeneity in FMT response may be influenced by IBD subtype, FMT donor selection and delivery protocols. Current evidence suggests that microbiome‐targeted therapeutics may have some benefit for IBD. Several studies are underway exploring the targeting of specific gut microbes or microbial pathways as therapy in IBD.

Abstract Background Early antibiotic treatment changes susceptibility to disease in rodent models for type 1 diabetes, but the impact that gestational antibiotics may have on pancreatic embryogenesis and β cell function later in life is still unknown. Methods Our aim was to determine whether gestational antibiotics could change islet neogenesis and function in female non‐obese diabetic mouse offspring. Stereology of pancreatic islets and insulin measurements were therefore applied to 2‐week‐old pups from mothers either exposed or not to a broad‐spectrum cocktail of ampicillin (1 g/L), vancomycin (0.5 g/L) and neomycin (1 g/L) during pregnancy. The degree of insulitis, glycated haemoglobin (HbA1c), serum cytokines and endotoxin, fasting glucose and insulin, and glucose tolerance were tested in the prediabetic pups later in life. Inflammatory and glycaemic measurements were made on the breeding females, and the gut microbiota was analysed by 16S sequencing in both the mothers and pups. Results Antibiotics depleted the maternal microbiome and perturbed the normal gut colonisation trajectory in the pups. While Akkermansia and Rikenellaceae were later enriched in the treated pups, Bacteroides failed to colonise post‐treatment. Antibiotic treatment reduced blood glucose in the mothers, weight of the pups, and HbA1c and insulitis in the adult offspring and increased anti‐inflammatory CD4+ natural killer T cells. This was preceded by more than 50% increase in total islet number and volume, and increased insulin levels in postnatal life. No changes were observed in their homeostatic model assessment of insulin resistance (HOMA‐IR) and β cell function (HOMA‐β), serum endotoxin or cytokine levels later in life, but the glucose tolerance response was altered in the treated offspring, which suggested an improvement in β cell exhaustion that may have left the islets less vulnerable to destruction. Conclusion Our study highlights the importance of considering maternal microbiota‐modulating factors as determinants that may mitigate or aggravate diabetes via changes in islet maturation and β cell function in perinatal life.

Abstract Background Septicaemia in the neonatal foal is caused by both Gram positive and Gram negative bacteria. The life‐threatening nature of this condition requires treatment to be initiated with broad spectrum antimicrobial drugs pending antimicrobial susceptibility testing. Potentiated sulphonamides, for example, trimethoprim combined with sulfadiazine, could be clinically relevant options but their pharmacokinetics in the neonatal foal are unknown. Objectives To describe the plasma disposition of trimethoprim and sulfadiazine in neonatal foals and to relate the results to patterns in the minimum inhibitory concentration (MIC) for Escherichia coli, a recognized pathogen in neonatal foal sepsis. Method A total of five doses of trimethoprim (2.5 mg/kg) and sulfadiazine (12.5 mg/kg) were administered intravenously every 12 h to eight neonatal foals that were 3 days old at inclusion. A non‐linear mixed effects model was fitted to the trimethoprim and sulfadiazine experimental data. The 24 h area under the free plasma trimethoprim and sulfadiazine concentration‐time curves (fAUC) and the pharmacokinetic/pharmacodynamik (PK/PD)‐index fAUC/MIC was calculated to evaluate the potential clinical benefits of the administered dose. Results For trimethoprim, the typical values were 1.99 L/kg, 0.33 L/h·kg and 4.2 h for the apparent volume of distribution, clearance and terminal half‐life, respectively. The 24 h fAUC for trimethoprim was 11.3 μg·h/ml (7.2–15.2) and the fAUC/MIC ratio for E. coli was 23 (16.4–29.2) (population mean (range)). For sulfadiazine, the typical values were 0.61 L/kg, 0.09 L/h·kg and 5.3 h for the apparent volume of distribution, clearance and terminal half‐life, respectively. The 24 h fAUC for sulfadiazine was 246.8 μg·h/ml (175.6–335.4). Conclusion For trimethoprim, the plasma exposure is insufficient in some foals to successfully treat bacterial infections with an MIC‐value of 0.5 μg/ml using the studied dosing regimen.

Abstract Objective To evaluate the effects of the concomitant use of proton pump inhibitors (PPIs) and/or antibiotics (Abs) on oncological outcomes in patients with advanced urothelial carcinoma. Patients and methods We retrospectively evaluated 155 patients with advanced urothelial carcinoma who were treated with immune checkpoint inhibitors (ICIs) between August 2015 and April 2021. The concomitant use of PPI or Abs was defined as any PPI or Abs administered within 30 days before ICI initiation and during ICI therapy. The primary outcomes were the effect of PPI and/or Abs use on the objective response rate (ORR) and immune‐related adverse events (irAEs). The secondary outcomes were the effects of PPI and/or Abs use on progression‐free survival (PFS) and overall survival (OS) after ICI therapy analyzed using the inverse probability of treatment weighting‐adjusted Cox regression analysis. Results Of the 155 patients enrolled in the study, 99 (64%) were PPI users and 56 (36%) Abs users. PPI users were associated with a significantly poorer ORR than non‐PPI users (41% vs. 20%, respectively), whereas Abs use was not significantly associated with changes in ORR. The rate of irAEs was not significantly associated with the use of PPIs or Abs. Multivariate inverse probability of treatment weighting‐adjusted Cox regression analysis revealed significantly poorer PFS and OS in PPI users than in non‐PPI users, whereas Abs use was not associated with poorer outcomes. Conclusion The concomitant use of PPI may adversely affect oncological outcomes in patients with locally advanced or metastatic urothelial carcinoma treated with ICI therapy.

Abstract Background Respiratory infections are the main indication for antimicrobial use in calves. Optimal treatment duration currently is unknown, but shorter duration would likely decrease selection for antimicrobial resistance. Hypothesis/Objectives Determine differences in cure rate and healing time between animals treated with florfenicol and oxytetracycline in a natural outbreak of respiratory disease using reaeration observed on thoracic ultrasound examination as healing criterion. Animals Commercial farm housing 130, 3 to 9 month old Belgian blue beef calves. Methods Randomized clinical trial during an outbreak of respiratory disease. Metaphylactic treatment was initiated, randomly treating animals with either florfenicol or oxytetracycline. Ultrasonographic follow‐up was done the first day and every other day for a 14‐day period. At the individual animal level, treatment was discontinued when reaeration of the lungs occurred. Differences in cure rate and healing time were determined. Results Of the 130 animals studied, 67.7% developed a lung consolidation ≥0.5 cm. The mean ultrasonographic healing time was 2.5 days in the florfenicol group compared to 3.1 days in the oxytetracycline group (P = .04). After single treatment, 80.6% and 60.3% had no consolidations in the florfenicol and oxytetracycline groups, respectively (P = .01). A Mycoplasma bovis strain was genetically and phenotypically determined to be susceptible to both antimicrobials. Conclusions and Clinical Importance Ultrasonographic lung reaeration shows potential as a cure criterion to rationalize antimicrobial use for outbreaks of pneumonia. In our study, florfenicol resulted in a faster cure and higher reduction in antimicrobial usage than did oxytetracycline.

Abstract Background Urethral obstruction (UO) has a negative effect on welfare of cats. Objectives This study aimed to determine incidence, case management, and outcomes of UO in cats in primary‐care practice in the United Kingdom. Animals All male cats under veterinary care within the VetCompass database in 2016. Methods A retrospective cohort study was performed. The electronic records of all male cats with a clinical note during the study period were searched for UO cases and were manually reviewed for inclusion. Additional demographic and clinical information were extracted on cases. Results From the study cohort of 237 825 male cats, there were 1293 incident cases. The estimated UO incidence risk during 2016 was 0.54 (95% CI: 0.51‐0.57). Demographic and clinical data were available for 1108 cases. Antibiotics were administered to 641/1108 (57.9%) cases. Overall repeat catheterization rate was 253/854 (29.6%). Repeat catheterization at 48 hours was less frequent in patients with indwelling catheters (10.1%) vs those that had a catheter placed and then immediately removed (14.8%; P = .04). Death during a UO episode was 329/1108 (29.6%), and 285/329 (88.0%) deaths involved euthanasia. Conclusions and Clinical Importance Antibiotics were commonly prescribed in cats for treatment of UO despite minimal evidence in the clinical records of bacterial cystitis. Repeat catheterization was common and case fatality rate during a UO episode was high. Repeat catheterization within 48 hours of elective removal of a urethral catheter was less common in cats that had previously had indwelling catheters. The majority of cats requiring repeat catheterization survived until the end of the study.

Abstract Background and Aim Filarial infections affect over 150 million people in the tropics. One of the major forms of filarial pathologies is lymphedema; a condition where the immune response is significantly altered, resulting in changes in the normal flora. Staphylococcus hominis, a human skin commensal, can also be pathogenic in immunocompromised individuals. Therefore, there is the possibility that S. hominis could assume a different behavior in filarial lymphedema patients. To this end, we investigated the levels of antibiotic resistance and extent of mecA gene carriage in S. hominis among individuals presenting with filarial lymphedema in rural Ghana. Method We recruited 160 individuals with stages I–VII lymphedema, in a cross‐sectional study in the Ahanta West District of the Western Region of Ghana. Swabs from lymphedematous limb ulcers, pus, and cutaneous surfaces were cultured using standard culture‐based techniques. The culture isolates were subjected to Matrix‐Assisted Laser Desorption/Ionization Time of Flight (MALDI‐TOF) mass spectrometry for bacterial identification. Antimicrobial susceptibility testing (AST) was performed using the Kirby–Bauer method. mecA genes were targeted by polymerase chain reaction for strains that were cefoxitin resistant. Results In all, 112 S. hominis were isolated. The AST results showed resistance to chloramphenicol (87.5%), tetracycline (83.3%), penicillin (79.2%), and trimethoprim/sulphamethoxazole (45.8%). Of the 112 strains of S. hominis, 51 (45.5%) were resistant to cefoxitin, and 37 (72.5%) of the cefoxitin‐resistant S. hominis haboured the mecA gene. Conclusion This study indicates a heightened level of methicillin‐resistant S. hominis isolated among filarial lymphedema patients. As a result, opportunistic infections of S. hominis among the already burdened filarial lymphedema patients in rural Ghana may have reduced treatment success with antibiotics.

Aim It is not clear whether evaluating the clinical response to antibiotic use at day 7 among critically ill patients accurately predicts outcomes. We aimed to evaluate the relationship between clinical response to the initial empiric therapy on day 7 and mortality. Methods The determinants of antimicrobial use and de‐escalation in critical care (DIANA) study was an international, multicenter, observational study on antibiotic use in the intensive care unit (ICU). ICU patients ages over 18 years in whom an empiric antimicrobial regimen in Japan was initiated were included. We compared patients who were evaluated as cured or improved (“effective”) 7 days after starting antibiotic treatment with patients who were evaluated as deteriorated (“failure”). Results Overall, 217 (83%) patients were in the effective group, and 45 (17%) were in the failure group. Both the infection‐related mortality rate in the ICU and the in‐hospital infection‐related mortality rate in the effective group were lower than those in the failure group (0% versus 24.4%; P

Abstract In the case report presented, three cases of large endodontic lesions, which were the consequences of endodontic treatment failure, were studied. In all cases, a novel combination of triple antibiotics was used to successfully manage and heal the lesions, showing the promising potential of the antibiotic combination in resolving pathosis.

Abstract Objectives Sepsis is defined as the host's inflammatory response to a life‐threatening infection. The endothelium is implicated in immunoregulation during sepsis. Macrolides have been proposed to display immunomodulatory properties. The goal of this study was to analyze whether macrolides can exert immunomodulation of endothelial cells (ECs) in an experimental model of sepsis. Methods Human ECs were stimulated by proinflammatory cytokines and lipopolysaccharide before exposure to macrolides. ECs phenotypes were analyzed by flow cytometry. Cocultures of ECs and peripheral blood mononuclear cells (PBMCs) were performed to study the ECs ability to alter T‐cell viability and differentiation in the presence of macrolides. Soluble factor production was assessed. Results ECs act as non‐professional antigen presenting cells and expressed human leukocyte antigen (HLA) antigens, the adhesion molecules CD54, CD106, and the coinhibitory molecule CD274 after septic stimulation. Incubation with macrolides induced a significant decrease of HLA class I and HLA class II HLA‐DR on septic‐stimulated ECs, but did not alter either CD54, CD106, nor CD274 expression. Interleukin‐6 (IL‐6) and IL‐8 production by stimulated ECs were unaltered by incubation with macrolides, whereas Clarithromycin exposure significantly decreased IL‐6 gene expression. In cocultures of septic ECs with PBMCs, neither the proportion of CD4 + , CD8 + T nor their viability was altered by macrolides. T‐helper lymphocyte subsets Th1, Th17, and Treg polarization by stimulated ECs were unaltered by macrolides. Conclusion This study reports phenotypic and gene expression changes in septic‐stimulated ECs exposed to macrolides, without resulting in altered immunogenicity of ECs in co‐cultures with PBMCs. In vivo studies may help to further understand the impact of macrolide therapy on ECs immune homeostasis during sepsis.