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We conducted a prospective cohort study between 1 January 2010 and 31 December 2012 at five adult and paediatric academic medical centres to identify factors associated with persistent methicillin-resistant Staphylococcus aureus (MRSA) colonisation. Adults and children presenting to ambulatory settings with a MRSA skin and soft tissue infection (i.e. index cases), along with household members, performed self-sampling for MRSA colonisation every 2 weeks for 6 months. Clearance of colonisation was defined as two consecutive negative sampling periods. Subjects without clearance by the end of the study were considered persistently colonised and compared with those who cleared colonisation. Of 243 index cases, 48 (19·8%) had persistent colonisation and 110 (45·3%) cleared colonisation without recurrence. Persistent colonisation was associated with white race (odds ratio (OR), 4·90; 95% confidence interval (CI), 1·38–17·40), prior MRSA infection (OR 3·59; 95% CI 1·05–12·35), colonisation of multiple sites (OR 32·7; 95% CI 6·7–159·3). Conversely, subjects with persistent colonisation were less likely to have been treated with clindamycin (OR 0·28; 95% CI 0·08–0·99). Colonisation at multiple sites is a risk factor for persistent colonisation and may require more targeted decolonisation efforts. The specific effect of clindamycin on MRSA colonisation needs to be elucidated. [ABSTRACT FROM PUBLISHER]

Past studies exploring risk factors for fluoroquinolone (FQ) resistance in urinary tract infections (UTIs) focused only on UTIs caused by Gram-negative pathogens. The epidemiology of FQ resistance in enterococcal UTIs has not been studied. We conducted a case-control study at two medical centres within the University of Pennsylvania Health System in order to identify risk factors for FQ resistance in enterococcal UTIs. Subjects with positive urine cultures for enterococci and meeting CDC criteria for healthcare-acquired UTI were eligible. Cases were subjects with FQ-resistant enterococcal UTI. Controls were subjects with FQ-susceptible enterococcal UTI and were frequency matched to cases by month of isolation. A total of 136 cases and 139 controls were included from 1 January 2003 to 31 March 2005. Independent risk factors [adjusted OR (95% CI)] for FQ resistance included cardiovascular diseases [2·24 (1·05–4·79), P=0·037], hospitalization within the past 2 weeks [2·08 (1·05–4·11), P=0·035], hospitalization on a medicine service [2·15 (1·08–4·30), P<0·030], recent exposure to β-lactamase inhibitors (BLIs) [14·98 (2·92–76·99), P<0·001], extended spectrum cephalosporins [9·82 (3·37–28·60), P<0·001], FQs [5·36 (2·20–13·05), P<0·001] and clindamycin [13·90 (1·21–10·49), P=0·035]. Use of BLIs, extended spectrum cephalosporins, FQs and clindamycin was associated with FQ resistance in enterococcal uropathogens. Efforts to curb FQ resistance should focus on optimizing use of these agents. [ABSTRACT FROM PUBLISHER]

Background: Staphylococcus aureus is a gram-positive bacterium commonly found in the nares and oropharynx of one in three individuals and has the potential to cause significant health problems. With antibiotic-resistant strains causing 11,000 deaths yearly and ~2% of the population nasally colonized with methicillin-resistant S. aureus , a search for predictive markers and associative relationships between carriage have been long-sought goals. Within our study, we leveraged monozygotic twin participants in concert with multi-site microbiome analyses to characterize the impacts of S. aureus on composition. Results: We recruited 147 monozygotic twin pairs and characterized three sites, i.e., the nares, oropharynx, and hand microbiomes, using 16S rRNA v3-v4 sequencing in addition to S. aureus carriage status. The prevalence of S. aureus was highest in the oropharynx followed by nares and hand with concordance between twin pairs highest in the nares, followed by oropharynx. The detection of S. aureus was statistically correlated with differences in microbiome composition across sites, as indicated by beta diversity and DESeq2 analyses. Microbiome composition was most similar in twins' nares that were S. aureus culture-positive concordant, whereas twins that were culture-negative concordant had the most similarity in the oropharynx. Of significance, Moraxella nonliquefacians and Capnocytophaga were inversely associated with S. aureus in the nares and oropharynx, respectively. Conclusions: This improved understanding of S. aureus colonization in nares, oropharynx, and hand microbiomes in monozygotic twin pairs is a further step towards unraveling the degree to which the microbiome is influenced by host genetics and S. aureus carriage. [ABSTRACT FROM AUTHOR]

Objective: Blood urea nitrogen (BUN) is a commonly used biomarker for assessing kidney function and neuroendocrine activity. Previous studies have indicated that elevated BUN levels are associated with increased mortality in various critically ill patient populations. The focus of this study was to investigate the relationship between BUN and 28-day mortality in intensive care patients. Methods: This was a multi-centre retrospective cohort study that made use of data from the eICU Collaborative Research Database. The primary exposure variable was BUN, and the outcome was 28-day mortality. The following variables were included as covariates: age, gender, BMI, white blood cell count, creatinine, GCS score, APACHE IV score, and diabetes. The statistical analyses included univariate and multivariate logistic regression, as well as generalized additive modelling, which was employed to assess the non-linear relationship between BUN and mortality. Results: A total of 63,757 elderly patients were included in the study, with a 28-day mortality of 6.5%. The univariate analysis indicated that elevated BUN quartiles were associated with an increased risk of mortality. The results of the multivariate analysis further confirmed the non-linear relationship between BUN and mortality. When BUN was less than 32 mg/dL, there was a significant positive association, with an adjusted odds ratio of 1.230 (95% CI: 1.154–1.311, p<0.0001) for every 10 mg/dL increase in BUN. However, when BUN was greater than or equal to 32 mg/dL, BUN level had no significant effect on mortality. Conclusion: BUN showed a nonlinear, threshold correlation with 28-day mortality in critically ill patients. The higher the BUN, the greater the risk of death if the BUN is below the threshold. [ABSTRACT FROM AUTHOR]

Acute respiratory infections are a significant challenge in primary care and hospital settings. Viruses are the most common etiology and the overlapping symptomatology among major respiratory viruses, such as influenza, severe acute respiratory syndrome coronavirus 2, and respiratory syncytial virus, requires the use of diagnostic tests that deliver early and accurate results. With the increasing availability of rapid antigen tests (RATS), it is tempting to prefer them over polymerase chain reaction (PCR) tests. However, compelling arguments support the existing recommendations in some European countries to maintain PCR testing for patient management throughout the year. RATs show sensitivities below 30% with lower viral loads, which are common and can have significant clinical implications. RATs perform well at lower cycle threshold (Ct) values, with sensitivity reaching 97.9% for Ct values below 20, which drops significantly for values above 25. Factors affecting viral load include disease stage, vaccination status, and viral variants, all of which can compromise the accuracy of antigen tests. Multi-target PCR tests effectively overcome these issues, ensuring reliable diagnosis. Additionally, the early detection of paucisymptomatic cases is essential in primary care and hospital settings to facilitate isolation and prevent secondary infections. Economic analyses support the use of comprehensive PCR tests, such as triplex-type tests, detecting SARS-CoV-2, influenza viruses, and RSV, as a first-line approach, as they can reduce case numbers and healthcare resource utilization. Maintaining PCR testing year-round is therefore crucial for the effective management of respiratory infections. [ABSTRACT FROM AUTHOR]

Background/Objectives: In healthcare environments with high microbial loads, effective infection control measures are critical for reducing airborne and surface contamination. One of the novel modalities in the achievement of these goals is the use of antimicrobial mists, such as droplets, in the form of dry fog. Although the usage of dry fog in the disinfection of contained healthcare microenvironments is well known, the effect of such a system in terms of a meaningful reduction in the microbial burden in an open inpatient ward is unclear. Our objective was to assess the impact of scheduled dry fogging on microbial reduction in such settings. Methods: We collected air and surface samples from rooms receiving daily, biweekly, or no fogging (controls) over six months, establishing the baseline contamination and evaluating the reduction trends in treated rooms. The "reduction effect" was measured by tracking microbial isolation trends before and after treatment, while the "degree of reduction" assessed differences across rooms with varied disinfection schedules. Results: The results indicate that scheduled dry fogging significantly reduced microbial loads in treated rooms, especially with daily disinfection (SE = 64.484, p = 0.002). The airborne contamination in treated rooms showed a strong downward trend over time (SE = 19.192, p < 0.001). Surface contamination remained challenging due to frequent recontamination; however, treated rooms exhibited a consistent reduction in microbial presence (SE = 2.002, p = 0.010), confirming dry fogging's role as a valuable adjunct to routine cleaning. Conclusions: In conclusion, this study highlights that dry fogging effectively reduces microbial loads in open, high-traffic healthcare environments, supporting its use as part of a multimodal infection control strategy. [ABSTRACT FROM AUTHOR]

Background: There is no experience with ciprofloxacin for the treatment of carbapenemase-producing Gram-negative bacteria (CP-GNB) infections. Methods: This is a retrospective single-centre study where we describe the clinical evolution of all consecutive adult patients who received ciprofloxacin monotherapy for the treatment of CP-GNB infections. Primary outcomes were clinical failure (defined as death, lack of clinical improvement or a switch to another drug) at day 14 and 30-day all-cause mortality. Results: Nineteen patients were included. Fifteen (79%) were men, the median age was 74 years (IQR 66–79) and the median Charlson comorbidity index was five (IQR 3–6.5). The most frequent infections were: nine complicated urinary tract infections, three soft tissue infections and three intra-abdominal infections. Twenty CP-GNBs were isolated (one patient had a coinfection): nine VIM-type-producing Enterobacterales, nine OXA-48-type-producing Enterobacterales and two VIM-type-producing Pseudomonas aeruginosa. Six (32%) patients had positive blood cultures, and one presented with septic shock. The median duration of ciprofloxacin treatment was 14 days (IQR 10–15). One patient presented with clinical failure at day 14. There was no 30-day mortality. Two patients exhibited microbiological recurrence at day 90. There were no reported adverse effects. Conclusions: Monotherapy with ciprofloxacin may be an alternative treatment for selected, clinically stable patients with ciprofloxacin-susceptible CP-GNB infections. [ABSTRACT FROM AUTHOR]

Background: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 and European Kidney Function Consortium (EKFC) 2023 both recently updated the equations to estimate the glomerular filtration rate (eGFR) using cystatin C; however, little is known about the benefits of using the equations for the risk stratification of health outcomes. We conducted this longitudinal study to compare the cystatin C CKD-EPI and EKFC equations to track the risks of cardiovascular disease and all-cause mortality among Chinese adults. Methods: We used data from China Health and Retirement Longitudinal Study (CHARLS) between 2011 and 2018. Adjusted logistic regression models and restricted cubic spline functions were used to evaluate the relationships of cystatin C-based eGFR values with incidence of cardiovascular disease and mortality. Results: A total of 6 496 participants were finally included in this study. The mean age of the participants was 59.6 (± 9.5) years, including 2996 (46.1%) males. There were 473 deaths and 1996 cases of cardiovascular disease observed during a maximum follow-up of 7.0 years. Using cystatin C-based CKD-EPI equation, people of eGFR < 60 mL/min/1.73 m2 had an increased risk of mortality (risk ratio [RR], 1.527; 95% CI, 1.068–2.178) and incident cardiovascular disease (RR, 1.363; 95% CI, 1.006–1.844), compared to those of eGFR ≥ 90 mL/min/1.73 m2. On the contrary, we did not observe significant associations of eGFR levels by EKFC equation with mortality nor cardiovascular disease. Conclusions: The findings indicated that cystatin C-based eGFR using CKD-EPI equation is more closely associated with all-cause mortality and cardiovascular disease compared to EKFC equation among Chinese adults. The cystatin C-based eGFR by CKD-EPI equation should be monitored in health practice, which needs further validation in other populations. [ABSTRACT FROM AUTHOR]

Community-acquired urinary tract infections account for 15% of all outpatient use of antibiotics, and women are primarily affected; the major causative microorganism is uropathogenic Escherichia coli (E. coli). Treatment is indicated for cystitis and pyelonephritis and includes B-lactams (amoxicillin-clavulanic acid or third-generation cephalosporins), fluoroquinolones (ciprofloxacin or levofloxacin), nitrofurantoin, fosfomycin, and trimethoprim–sulfamethoxazole. Resistance to antibiotic treatment is of concern; several mechanisms have been associated with the acquisition of genes that confer antimicrobial resistance to fluoroquinolones, which are often associated with other patterns of resistance, especially in extended-spectrum beta-lactamase (ESBL) producers. Several studies have addressed the prevalence of uropathogens producing ESBLs, but only a few have focused on fluoroquinolone resistance, and, to our knowledge, none have addressed the prevalence of phylotypes or genes responsible for antimicrobial resistance to fluoroquinolones. The focus of the present review was to analyze recently published papers that described the E. coli phylotype causing community-acquired UTIs in association with fluoroquinolone resistance. [ABSTRACT FROM AUTHOR]

Antimicrobial stewardship (AS) Guidelines by the Infectious Diseases Society of America recommend employing prospective audit and feedback (PAF) as an effective intervention in AS programs. Since July 2022, our hospital has implemented PAF for all patients with positive blood cultures, including those with extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (EC) bacteremia. Our study examined the effect of PAF on clinical outcomes in patients with ESBL-EC bacteremia. We enrolled 62 patients diagnosed with ESBL-EC via blood culture who were undergoing antibiotic treatment. The patients were divided into the pre-PAF and post-PAF implementation groups. The rate of antibiotic de-escalation from broad-spectrum antibiotics to narrow-spectrum cefmetazole was significantly higher in the post-PAF group than in the pre-PAF group (80.7% vs. 32.4%, p = 0.0003). The treatment failure rate in the pre-PAF group was higher than that in the post-PAF group (38.7% vs. 12.9%, p = 0.04). The results of this study indicate that the implementation of PAF is advantageous not only in terms of process indicators but also in improved clinical outcomes, including reduced treatment failure rates. We hope that this study will encourage the implementation of PAF in more facilities to instigate a collective effort to reduce the incidence of antimicrobial resistance. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the correlation between computed tomography (CT) derived body composition and 30-day mortality in patients with pulmonary infections caused by carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae). Methods: A total of 89 eligible participants from a tertiary teaching hospital, enrolled between January 1, 2016, and December 31, 2020, were included in the study. We analyzed the relationship between visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), total adipose tissue (TAT), and skeletal muscle (SM) and 30-day mortality in patients infected with carbapenem-resistant K. pneumoniae (CRKP) in the pulmonary region. Furthermore, we established Cox regression models and a personalized nomogram model to predict the probability of 30-day mortality in these infected patients. Results: Individuals with high VAT exhibited a higher likelihood of 30-day all-cause mortality (P< 0.01) and 30-day mortality due to CRKP infection (P< 0.01) compared to those with low VAT. Similar results were observed for TAT. After adjusting for significant comorbidities and other clinical characteristics, Cox regression analysis revealed that male gender (adjusted HR = 4.37; 95% CI = 0.96– 19.92, P=0.06), vasopressor use (adjusted HR = 3.65; 95% CI = 1.04– 12.85, P=0.04), and VAT (adjusted HR = 1.16; 95% CI = 1.01– 1.34, P=0.03) were independent risk factors for 30-day all-cause mortality among these infectious patients. Conclusion: The study results highlight the significant prognostic value of CT-quantified visceral adipose tissue in patients with CRKP pulmonary infection. Individuals with high VAT are more prone to mortality within 30 days compared to those with low VAT. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae is well recognized as a serious cause of infection in healthcare-associated settings and immunocompromised individuals; however, accumulating evidence from resource-limited nations documents an alarming rise in community-acquired K. pneumoniae infections, manifesting as bacteremia and pneumonia as well as neonatal sepsis. The emergence of hypervirulent and antibiotic-resistant K. pneumoniae strains threatens treatment options for clinicians. Effective vaccination strategies could represent a viable alternative that would both preempt the need for antibiotics to treat K. pneumoniae infections and reduce the burden of K. pneumoniae disease globally. There are currently no approved K. pneumoniae vaccines. We review the evidence for K. pneumoniae lipopolysaccharide (LPS) as a vaccine and immunotherapeutic target and discuss the role of antibodies specific for the core or O-antigen determinants within LPS in protection against Klebsiella spp. disease. We expand on the known role of the Klebsiella spp. capsule and O-antigen modifications in antibody surface accessibility to LPS as well as the in vitro and in vivo effector functions reported for LPS-specific antibodies. We summarize key hypotheses stemming from these studies, review the role of humoral immunity against K. pneumoniae O-antigen for protection, and identify areas requiring further research. [ABSTRACT FROM AUTHOR]

AmpC enzymes are a class of beta-lactamases produced by Gram-negative bacteria, including several Enterobacterales. When produced in sufficient amounts, AmpCs can hydrolyze third-generation cephalosporins (3GCs) and piperacillin/tazobactam, causing resistance. In Enterobacterales, the AmpC gene can be chromosomal- or plasmid-encoded. Some species, particularly Enterobacter cloacae complex, Klebsiella aerogenes, and Citrobacter freundii, harbor an inducible chromosomal AmpC gene. The expression of this gene can be derepressed during treatment with a beta-lactam, leading to AmpC overproduction and the consequent emergence of resistance to 3GCs and piperacillin/tazobactam during treatment. Because of this phenomenon, the use of carbapenems or cefepime is considered a safer option when treating these pathogens. However, many areas of uncertainty persist, including the risk of derepression related to each beta-lactam; the role of piperacillin/tazobactam compared to cefepime; the best option for severe or difficult-to-treat cases, such as high-inoculum infections (e.g., ventilator-associated pneumonia and undrainable abscesses); the role of de-escalation once clinical stability is obtained; and the best treatment for species with a lower risk of derepression during treatment (e.g., Serratia marcescens and Morganella morganii). The aim of this review is to collate the most relevant information about the microbiological properties of and therapeutic approach to AmpC-producing Enterobacterales in order to inform daily clinical practice. [ABSTRACT FROM AUTHOR]

Healthcare-associated infections (HAIs) caused by multidrug-resistant organisms (MDROs) represent a global threat to human health and well-being. Because transmission of MDROs to patients often occurs via transiently contaminated hands of healthcare personnel (HCP), hand hygiene is considered the most important measure for preventing HAIs. Environmental surfaces contaminated with MDROs from colonized or infected patients represent an important source of HCP hand contamination and contribute to transmission of pathogens. Accordingly, facilities are encouraged to adopt and implement recommendations included in the World Health Organization hand hygiene guidelines and those from the Society for Healthcare Epidemiology of America/Infectious Diseases Society of America/Association for Professionals in Infection Control and Epidemiology. Alcohol-based hand rubs are efficacious against MDROs with the exception of Clostridiodes difficile, for which soap and water handwashing is indicated. Monitoring hand hygiene adherence and providing HCP with feedback are of paramount importance. Environmental hygiene measures to curtail MDROs include disinfecting high-touch surfaces in rooms of patients with C. difficile infection daily with a sporicidal agent such as sodium hypochlorite. Some experts recommend also using a sporicidal agent in rooms of patients colonized with C. difficile, and for patients with multidrug-resistant Gram-negative bacteria. Sodium hypochlorite, hydrogen peroxide, or peracetic acid solutions are often used for daily and/or terminal disinfection of rooms housing patients with Candida auris or other MDROs. Products containing only a quaternary ammonium agent are not as effective as other agents against C. auris. Portable medical equipment should be cleaned and disinfected between use on different patients. Detergents are not recommended for cleaning high-touch surfaces in MDRO patient rooms, unless their use is followed by using a disinfectant. Facilities should consider using a disinfectant instead of detergents for terminal cleaning of floors in MDRO patient rooms. Education and training of environmental services employees is essential in assuring effective disinfection practices. Monitoring disinfection practices and providing personnel with performance feedback using fluorescent markers, adenosine triphosphate assays, or less commonly cultures of surfaces, can help reduce MDRO transmission. No-touch disinfection methods such as electrostatic spraying, hydrogen peroxide vapor, or ultraviolet light devices should be considered for terminal disinfection of MDRO patient rooms. Bundles with additional measures are usually necessary to reduce MDRO transmission. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic spread rapidly worldwide, including in Indonesia. As a result, people developed a fear of visiting hospitals and a tendency to ignore symptoms unrelated to COVID-19. A zygomaticomaxillary complex bone fracture is one of the most frequent midface fractures and is often accompanied by infraorbital nerve paresthesia. Purpose: This article aims to report two cases of neglected zygomaticomaxillary complex bone fractures with persistent infraorbital nerve paresthesia caused by the patient's fear of seeking medical care. Cases: The first case is a 19-year-old male with a history of trauma two weeks prior to hospital admission. He was diagnosed with a neglected zygomaticomaxillary complex bone fracture, which resulted in persistent infraorbital nerve paresthesia. This condition was due to the patient's fear of visiting the hospital. The second case is a 21-year-old female who presented with a history of persistent numbness on the left cheek and upper lip for one month prior to hospital admission. The symptoms originated from an accident where the patient fell from a ladder measuring two meters in height. Case management: Surgical intervention--open reduction and internal fixation (ORIF)--was performed on both patients to promote nerve recovery. However, there is ongoing debate regarding the safety of elective oral maxillofacial surgery procedures during the COVID-19 pandemic. After a follow-up period, both patients experienced a recovery of sensory function in the infraorbital nerve. Conclusion: Infraorbital nerve sensory disturbance along with zygomaticomaxillary complex bone fracture found during the COVID-19 pandemic should be managed with ORIF to improve nerve recovery. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) poses a significant worldwide health challenge associated with prolonged illnesses, increased healthcare costs, and high mortality rates. The present study examined the patterns and predictors of AMR among human Staphylococcus isolates obtained from diagnostic laboratories in South Africa between 2012 and 2017. This study examined data from 404 217 isolates, assessing resistance rates across different characteristics such as age, sample origin, Staphylococcus species, and study period. The highest resistance was observed against cloxacillin (70.3%), while the lowest resistance was against Colistin (0.1%). A significant (p < 0.05) decreasing trend in AMR was observed over the study period, while a significant increasing temporal trend (p < 0.05) was observed for multidrug resistance (MDR) over the same period. A significant (p < 0.05) association was observed between specimen type, species of organism, and year of isolation with AMR outcome. Significant (p < 0.05) associations were observed between specimen type and season with MDR. The observed high levels of AMR and a growing trend in MDR are concerning for public health. Clinicians should take these findings into account when deciding on therapeutic options. Continued monitoring of AMR among Staphylococcus spp. and judicious use of antimicrobials in human medicine should be promoted. [ABSTRACT FROM AUTHOR]

Introduction: Bloodstream infections caused by AmpC-producing Enterobacterales pose treatment challenges due to the risk of AmpC overproduction and treatment failure. Current guidelines recommend carbapenems or cefepime as optimal therapy. We aimed to evaluate empiric and definitive non-carbapenem regimens for these infections. Methods: In a retrospective study from June 2014 to March 2023, adult bacteremic patients with Enterobacter cloacae complex strains and Morganella morganii were evaluated. Demographic, clinical and lab data and outcomes were assessed. Results: The cohort comprised 120 bacteremic patients, 17 receiving empiric carbapenem and 103 non-carbapenem regimens. Both groups had similar Charlson and Norton scores and previous antimicrobial exposure. The most common sources of bacteremia were urinary, abdominal and central-line-associated sources. Empiric non-carbapenem regimens (primarily piperacillin–tazobactam and cephalosporins) were not associated with recurrent bacteremia or 30-day mortality. Definitive regimens included mainly carbapenems (n = 41) and ciprofloxacin (n = 46). Beta-lactams were administered to 25 patients. Recurrent bacteremia and 30-day mortality rates were similar among treatment groups. Ciprofloxacin showed comparable outcomes to carbapenems, however, severity of illness among these patients was lower. Conclusions: Empiric and definitive non-carbapenem regimens for bacteremia with AmpC-producing organisms were not associated with treatment failure or increased 30-day mortality. Ciprofloxacin appears promising for selected, stable patients, potentially enabling early discharge. [ABSTRACT FROM AUTHOR]

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Introduction: Extraintestinal Escherichia coli infections represent a growing public health threat, However, current studies often overlook important factors such as temporal patterns of infection, phylogenetic and clonal background, or the host gut E. coli population, despite their likely significance. Methods: In this study, we analyzed >7000 clinical E. coli isolates from patients at the Minneapolis Veterans Affairs Health Care System (2012-2019), and concurrent fecal E. coli from uninfected veterans. We assessed phylogenetic group distribution, membership in selected sequence types (STs), and subsets thereof--including the pandemic, resistance-associated ST131-H30R, and ST1193 lineages--and strain type, as defined by pulsed-field gel electrophoresis. We then analyzed these features alongside the temporal patterns of infection in individual hosts. Results: The H30R lineage emerged as the leading lineage, both overall and among fluoroquinolone-resistant isolates, with ST1193 following among fluoroquinolone-resistant isolates. Recurrences were common, occurring in 31% of subjects and 41% of episodes, and often multiple and delayed/prolonged (up to 23 episodes per subject; up to 2655d post-index). Remarkably, these recurrences typically involved the subject's index strain (63% of recurrences), even when affecting extra-urinary sites. ST131, H30R, ST1193, and fluoroquinoloneresistant strains generally caused significantly more recurrences than did other strains, despite similar recurrence intervals. ST131 strain types shifted significantly over the study period. Infection-causing strains were commonly detectable in host feces at times other than during an infection episode; the likelihood of detection varied with surveillance intensity and proximity to the infection. H30R and ST1193 were prominent causes of fecal-clinical clonal overlap. Discussion: These findings provide novel insights into the temporal and clonal characteristics of E. coli infections in veterans and support efforts to develop anti-colonization interventions. [ABSTRACT FROM AUTHOR]

Background: Catheter ablation has become an established treatment option for premature ventricular complexes (PVCs). The use of fluoroscopy exposes patients and medical staff to potentially harmful stochastic and deterministic effects of ionizing radiations. We sought to analyze procedural outcomes in terms of safety and efficacy using a "zero fluoroscopy" approach for catheter ablation of PVCs. Methods: The present retrospective, multicenter, observational study included 131 patients having undergone catheter ablation of PVCs using "zero fluoroscopy" between 2019 and 2020 in four centers compared with another group who underwent the procedure with fluoroscopy. Results: Median age was 51.0 ± 15.9 years old; males were 77 (58.8%). Among the study population, 26 (19.8%) had a cardiomyopathy. The most frequent PVC origin was right ventricular outflow tract (55%) followed by the left ventricle (16%), LVOT and cusps (13.7%), and aortomitral continuity (5.3%). Acute suppression of PVC was achieved in 127 patients (96.9%). At 12 months, a complete success was documented in 109 patients (83.2%), a reduction in PVC burden in 18 patients (13.7%), and a failure was recorded in four patients (3.1%). Only two minor complications occurred (femoral hematoma and arteriovenous fistula conservatively treated). Conclusions: The PVC ablation with a "zero" fluoroscopy approach appears to be a safe procedure with no major complications and good rates of success and recurrence in our multicenter experience. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between blood urea nitrogen (BUN) levels and diabetic retinopathy (DR) in adults with diabetes mellitus (DM). Methods: Seven cycles of cross-sectional population information acquired from NHANES(national health and nutrition examination surveys) 2005-2018 were collected, from which a sample of diabetic adults was screened and separated into two groups based on whether or not they had DR, followed by weighted multivariate regression analysis. This study collected a complete set of demographic, biological, and sociological risk factor indicators for DR. Demographic risk factors comprised age, gender, and ethnicity, while biological risk factors included blood count, blood pressure, BMI, waist circumference, and glycated hemoglobin. Sociological risk factors included education level, deprivation index, smoking status, and alcohol consumption. Results: The multiple regression model revealed a significant connection between BUN levels and DR [odds ratio =1.04, 95% confidence interval (1.03-1.05), p-value <0.0001], accounting for numerous variables. After equating BUN levels into four groups, multiple regression modeling showed the highest quartile (BUN>20 mg/dl) was 2.22 times more likely to develop DR than the lowest quartile [odds ratio =2.22, 95% confidence interval (1.69-2.93), p- value <0.0001]. Subgroup analyses revealed that gender, race, diabetes subtype, and duration of diabetes had a regulating effect on the relationship between BUN and DR. Conclusion: BUN levels were related with an increased prevalence of DR, particularly in individuals with BUN >20 mg/dl. These findings highlight the significance of BUN level in assessing the risk of DR. [ABSTRACT FROM AUTHOR]

Classroom and staffroom floor swabs across six elementary schools in Ottawa, Canada were tested for SARS-CoV-2. Environmental test positivity did not correlate with student grade groups, school-level absenteeism, pediatric COVID-19-related hospitalizations, or community SARS-CoV-2 wastewater levels. Schools in neighbourhoods with historically elevated COVID-19 burden showed a negative but non-significant association with lower swab positivity. [ABSTRACT FROM AUTHOR]

The standardization of cystatin C (CysC) measurement has received increasing attention in recent years due to its importance in estimating glomerular filtration rate (GFR). Mass spectrometry-based assays have the potential to provide an accuracy base for CysC measurement. However, a precise, accurate and sustainable LC–MS/MS method for CysC is still lacking. The developed LC–MS/MS method quantified CysC by detecting signature peptide (T3) obtained from tryptic digestion. Stable isotope labeled T3 peptide (SIL-T3) was spiked to control matrix effects and errors caused by liquid handling. The protein denaturation, reduction and alkylation procedures were combined into a single step with incubation time of 1 h, and the digestion lasted for 3.5 h. In the method validation, digestion time-course, imprecision, accuracy, matrix effect, interference, limit of quantification (LOQ), carryover, linearity, and the comparability to two routine immunoassays were evaluated. No significant matrix effect or interference was observed with the CysC measurement. The LOQ was 0.21 mg/L; the within-run and total imprecision were 1.33–2.05 % and 2.18–3.90 % for three serum pools (1.18–5.34 mg/L). The LC–MS/MS method was calibrated by ERM-DA471/IFCC and showed good correlation with two immunoassays traceable to ERM-DA471/IFCC. However, significant bias was observed for immunoassays against the LC–MS/MS method. The developed LC–MS/MS method is robust and simpler and holds the promise to provide an accuracy base for routine immunoassays, which will promote the standardization of CysC measurement. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The impact of the difference between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFRdiff) on diabetic microvascular complications (DMCs) remains unknown. We investigated the associations of eGFRdiff with overall DMCs and subtypes, including diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy (DN). RESEARCH DESIGN AND METHODS: This prospective cohort study included 25,825 participants with diabetes free of DMCs at baseline (2006 to 2010) from the UK Biobank. eGFRdiff was calculated using both absolute difference (eGFRabdiff) and the ratio (eGFRrediff) between cystatin C- and creatinine-based calculations. Incidence of DMCs was ascertained using electronic health records. Cox proportional hazards regression models were used to evaluate the associations of eGFRdiff with overall DMCs and subtypes. RESULTS: During a median follow-up of 13.6 years, DMCs developed in 5,753 participants, including 2,752 cases of DR, 3,203 of DKD, and 1,149 of DN. Each SD decrease of eGFRabdiff was associated with a 28% higher risk of overall DMCs, 14% higher risk of DR, 56% higher risk of DKD, and 29% higher risk of DN. For each 10% decrease in eGFRrediff, the corresponding hazard ratios (95% CIs) were 1.16 (1.14, 1.18) for overall DMCs, 1.08 (1.05, 1.11) for DR, 1.29 (1.26, 1.33) for DKD, and 1.17 (1.12, 1.22) for DN. The magnitude of associations was not materially altered in any of the sensitivity analyses. CONCLUSIONS: Large eGFRdiff was independently associated with risk of DMCs and its subtypes. Our findings suggested monitoring eGFRdiff in the diabetes population has potential benefit for identification of high-risk patients. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) is a common pathogen contributing to healthcare-associated infections, which can result in multiple sites infections. The epidemiological characteristics of MRSA exhibit variability among distinct regions and healthcare facilities. The aim of this study was to investigate the molecular epidemiology and nosocomial outbreak characteristics of MRSA in a county-level hospital in China. A total of 130 non-repetitive MRSA strains were collected from December 2020 to November 2021. Whole-genome sequencing (WGS) was performed to identify antimicrobial resistance and virulence factors. Phylogenetic analysis was conducted to ascertain genetic diversity and phylogenetic relationships. Independent transmission scenarios were determined by the phylogeny derived from single nucleotide polymorphisms (SNPs) within the core genome. All the MRSA isolates were collected from the intensive care unit (30.00%, 39/130), the department of otorhinolaryngology (10.00%, 13/130) and the department of burn unit (9.23%, 12/130). The clinical samples mainly included phlegm (53.85%, 70/130), purulent fluid (24.62%, 32/130), and secretions (8.46%, 11/130). The resistance rates to erythromycin, clindamycin and ciprofloxacin were 75.38, 40.00, and 39.23%, respectively. All the isolates belonged to 11 clonal complexes (CCs), with the major prevalent types were CC5, CC59, and CC398, accounting for 30.00% (39/130), 29.23% (38/130), and 16.92% (22/130), respectively. Twenty sequence types (STs) were identified, and ST59 (25.38%, 33/130) was the dominant lineage, followed by ST5 (23.84%, 31/130) and ST398 (16.92%, 22/130). Three different SCCmec types were investigated, most of isolates were type IV (33.85%, 44/130), followed by type II (27.69%, 36/130) and type III (0.77%, 1/130). The common clonal structures included CC5-ST5-t2460-SCCmec IIa, CC59-ST59-t437-SCCmec IV and CC398-ST398-t034-SCCmec (-), with rates of 16.92% (22/130), 14.62% (19/130), and 13.84% (18/130), respectively. Only 12 panton-valentine leucocidin (PVL) positive strains were identified. Two independent clonal outbreaks were detected, one consisting of 22 PVL-negative strains belongs to CC5-ST5-t2460-SCCmec IIa and the other consisting of 8 PVL-negative strains belongs to CC5-ST5-t311-SCCmec IIa. Overall, our study indicated that the CC5 lineage emerged as the predominant epidemic clone of MRSA, responsible for nosocomial outbreaks and transmission within a county-level hospital in China, highlighting the necessity to strengthen infection control measures for MRSA in such healthcare facilities. [ABSTRACT FROM AUTHOR]

Purpose: Donor-derived infection (DDI) has become an important factor affecting the prognosis of lung transplantation patients. The risks versus benefits of using donor organs infected with multidrug-resistant organisms (MDRO), especially carbapenem-resistant organisms (CRO), are frequently debated. Traditional microbial culture and antimicrobial susceptibility testing at present fail to meet the needs of quick CRO determination for donor lungs before acquisition. In this study, we explored a novel screening method by using Xpert® Carba-R assay for CRO in donor lungs in a real-time manner to reduce CRO-associated DDI mortality. Methods: This study was registered on chictr.org.cn (ChiCTR2100053687) on November 2021. In the Xpert Carba-R screening group, donor lungs were screened for CRO infection by the Xpert Carba-R test on bronchoalveolar fluid (BALF) before acquisition. If the result was negative, donor lung acquisition and subsequent lung transplantation were performed. In the thirty-five potential donors, nine (25.71%) with positive Xpert Carba-R results in BALF were declined for lung transplantation. Twenty-six recipients and the matching CRO-negative donor lungs (74.29%) were included in the Xpert Carba-R screening group. In the control group, nineteen recipients underwent lung transplants without Xpert Carba-R screening. The incidence and mortality of CRO-associated DDI were collected and contrasted between the two groups. Results: Multivariate analysis showed that CRO-related death due to DDI within 60 days was significantly lower in the Xpert Carba-R screening group than that in the control group (OR = 0.05, 95% CI 0.003–0.74, p = 0.03). Conclusion: Real-time CRO screening of donor lungs before transplantation at the point of care by the Xpert Carba-R helps clinicians formulate lung transplantation strategies quickly and reduces the risk of subsequent CRO infection improving the prognosis of lung transplantation. [ABSTRACT FROM AUTHOR]

The increasing prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections is a global concern. Elderly patients have a diminished immune response and functional reserve, and are thus more vulnerable to bacterial infection. This study aimed to investigate the risk factors and outcomes in elderly patients with community-acquired CRKP infections. We performed a retrospective cohort study in a tertiary medical center between 1 January 2021, and 31 December 2021. All elderly patients who visited the emergency department during this period with culture-positive K. pneumoniae were enrolled, and their baseline demographics, laboratory profiles, management strategies, and outcomes were recorded and analyzed. We identified 528 elderly patients with K. pneumonia infection, and the proportion of patients with CRKP infection was 10.2% (54/528). Recent intensive care unit (ICU) admission and prior carbapenem use are independent risk factors for CRKP infection in elderly patients. Compared to patients with carbapenem-sensitive K. pneumoniae infection, those with CRKP infection had a significantly higher risk of adverse outcomes, including ICU care, respiratory failure, septic shock, and 90-day mortality. CRKP infection was also identified as an independent risk factor for 90-day mortality. Clinicians should be aware of the increasing prevalence of CRKP infections in elderly patients and judiciously choose appropriate antibiotics for these patients. [ABSTRACT FROM AUTHOR]

Background Due to scarce therapeutic options, hospital-acquired infections caused by Klebsiella pneumoniae (KP), particularly carbapenem-resistant KP (CRKP), pose enormous threat to patients' health worldwide. This study aimed to characterize the epidemiology and risk factors of CRKP among nosocomial KP infections. Method MEDLINE, Embase, PubMed, and Google Scholar were searched for studies reporting CRKP prevalence from inception to 30 March 2023. Data from eligible publications were extracted and subjected to meta-analysis to obtain global, regional, and country-specific estimates. To determine the cause of heterogeneity among the selected studies, prespecified subgroup analyses and meta-regression were also performed. Odds ratios of CRKP-associated risk factors were pooled by a DerSimonian and Laird random-effects method. Results We retained 61 articles across 14 countries and territories. The global prevalence of CRKP among patients with KP infections was 28.69% (95% CI, 26.53%–30.86%). South Asia had the highest CRKP prevalence at 66.04% (95% CI, 54.22%–77.85%), while high-income North America had the lowest prevalence at 14.29% (95% CI, 6.50%–22.0%). In the country/territory level, Greece had the highest prevalence at 70.61% (95% CI, 56.77%–84.45%), followed by India at 67.62% (95% CI, 53.74%–81.79%) and Taiwan at 67.54% (95% CI, 58.65%–76.14%). Hospital-acquired CRKP infections were associated with the following factors: hematologic malignancies, corticosteroid therapies, intensive care unit stays, mechanical ventilations, central venous catheter implantations, previous hospitalization, and antibiotic-related exposures (antifungals, carbapenems, quinolones, and cephalosporins). Conclusions Study findings highlight the importance of routine surveillance to control carbapenem resistance and suggest that patients with nosocomial KP infection have a very high prevalence of CRKP. [ABSTRACT FROM AUTHOR]

Simple Summary: Nosema ceranae (N. ceranae), a highly aggressive pathogen that affects honeybees, can rapidly spread infection under suboptimal conditions for honeybee breeding, consequently reducing honey production. Preventing and treating Nosema infection remains challenging since symptoms are often manifested in bees only after several million Nosema spores are present in the bee midgut. In this study, specialized methods, namely a sandwich enzyme-linked immunosorbent assay (ELISA) and an immunochromatography assay (ICG), were developed for diagnosing N. ceranae infections, and their effectiveness in diagnosing Nosema infections was evaluated. The sandwich ELISA method effectively detected Nosema infection; comparatively, the ICG approach was less efficient. This comparison between the two diagnostic methods provides insights into their respective strengths and limitations, facilitating future investigations and potential improvements in the development of more effective diagnostic approaches for detecting and managing N. ceranae infections in honeybees. Nosema ceranae (N. ceranae) infection is prevalent globally, causing a decline in bee populations and significant economic losses to apiarists. Although several methods have been proposed for diagnosing Nosema infections, limitations in these methods have hindered their broad applications. Therefore, this current study aimed to develop a specialized method for diagnosing Nosema infections. To achieve this, a sandwich enzyme-linked immunosorbent assay (ELISA) and immunochromatography assay (ICG) were developed, and their effectiveness in screening and diagnosing Nosema infection was assessed. In sandwich ELISA, the combination of the monoclonal antibodies (mAb) 19B2 and biotinylated-19B2 exhibited stronger binding affinity to the antigen than did other combinations of mAbs that were tested. Furthermore, the antigen detection limit achieved with the sandwich ELISA surpassed that previously reported with Western blotting. The ICG was designed using the same antibody combination as that used in sandwich ELISA; however, the assay exhibited a lower diagnostic ability for Nosema infection than the ELISA. The diagnostic models developed in this study offer practical applications for conducting rapid nosemosis detection tests. These innovative techniques will help to improve the timely identification and management of nosemosis. [ABSTRACT FROM AUTHOR]

Febrile infections in children are a common cause of presentation to the emergency department (ED). While viral infections are usually self-limiting, sometimes bacterial illnesses may lead to sepsis and severe complications. Inflammatory biomarkers such as C reactive protein (CRP) and procalcitonin are usually the first blood exams performed in the ED to differentiate bacterial and viral infections; nowadays, a better understanding of immunochemical pathways has led to the discovery of new and more specific biomarkers that could play a role in the emergency setting. The aim of this narrative review is to provide the most recent evidence on biomarkers and predictor models, combining them for serious bacterial infection (SBI) diagnosis in febrile children. Literature analysis shows that inflammatory response is a complex mechanism in which many biochemical and immunological factors contribute to the host response in SBI. CRP and procalcitonin still represent the most used biomarkers in the pediatric ED for the diagnosis of SBI. Their sensibility and sensitivity increase when combined, and for this reason, it is reasonable to take them both into consideration in the evaluation of febrile children. The potential of machine learning tools, which represent a real novelty in medical practice, in conjunction with routine clinical and biological information, may improve the accuracy of diagnosis and target therapeutic options in SBI. However, studies on this matter are not yet validated in younger populations, making their relevance in pediatric precision medicine still uncertain. More data from further research are needed to improve clinical practice and decision making using these new technologies. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine the genetic relatedness between Methicillin-resistant Staphylococcus aureus (MRSA) isolated from pet animals and human. In that context, 561 swabs were collected from dogs (n=238) and cats (n=323). In addition, 30 MRSA positive isolates from Qasr Elainy hospital, from different patients were also included. The collected samples were subjected for bacteriological examination for isolation of S. aureus. The recovered S. aureus isolates that were resistant to oxacillin and cefoxitin were tested for the presence of mecA, mecC, spa, and nuc genes by PCR, followed by a sequence analysis of the mecA gene in seven selected isolates. Out of 238 swab samples collected from dogs and 323 swab samples collected from cats, 13 (5.46%) and 8 (2.48%) isolates respectively were confirmed to be MRSA. In addition, the 30 human isolates were all categorized as MRSA. The mecA gene was successfully identified in all isolates from dogs, cats and human, while spa was harbored by 13, 4 and 30 isolates from dogs, cats and human respectively. Furthermore 13, 4 and 23 isolates from dogs, cats and human were positive for the nuc gene. mecC was not identified from all examined isolates. The phylogenetic analysis of the mecA gene sequence in seven selected MRSA isolates demonstrated a high degree of similarity among isolates originating from dogs, cats, and humans. This study confirms the zoonotic spread of S. aureus and suggests that dogs and cats are probably contributing to the spread of MRSA to human. [ABSTRACT FROM AUTHOR]

Bacteremia and endocarditis are two clinical syndromes that, for decades, were managed exclusively with parenteral antimicrobials, irrespective of a given patient's clinical condition, causative pathogen, or its antibiotic susceptibility profile. This clinical approach, however, was based on low-quality data and outdated expert opinions. When a patient's condition has improved, gastrointestinal absorption is not compromised, and an oral antibiotic regimen reaching adequate serum concentrations is available, a switch to oral antibacterials can be applied. Although available evidence has reduced the timing of the oral switch in bacteremia to three days/until clinical improvement, there are only scarce data regarding less than 10-day intravenous antibiotic therapy in endocarditis. Many standard or studied oral antimicrobial dosages are smaller than the approved doses for parenteral administration, which is a risk factor for treatment failure; in addition, the gastrointestinal barrier may affect drug bioavailability, especially when the causative pathogen has a minimum inhibitory concentration that is close to the susceptibility breakpoint. A considerable number of patients infected by such near-breakpoint strains may not be potential candidates for oral step-down therapy to non-highly bioavailable antibiotics like beta-lactams; different breakpoints should be determined for this setting. This review will focus on summarizing findings about pathogen-specific tailoring of oral step-down therapy for bacteremia and endocarditis, but will also present laboratory and clinical data about antibiotics such as beta-lactams, linezolid, and fosfomycin that should be studied more in order to elucidate their role and optimal dosage in this context. [ABSTRACT FROM AUTHOR]

Acute pyelonephritis (APN) is a relatively common community-acquired infection, particularly in women. The early appropriate antibiotic treatment of this potentially life-threatening infection is associated with improved outcomes. The international management guidelines for complicated urinary tract infections and APN recommend using oral antibiotics with <10% resistance among urinary pathogens. However, increasing antibiotic resistance rates among Escherichia coli and other Enterobacterales to fluoroquinolones, trimethoprim-sulfamethoxazole (TMP-SMX), and beta-lactams has left patients without reliable oral antibiotic treatment options for APN. This narrative review proposes using precision medicine concepts to improve empirical antibiotic therapy for APN in ambulatory settings. Whereas resistance rates to a particular antibiotic class may exceed 10% at the population-based level, the predicted antibiotic resistance rates based on patient-specific risk factors fall under 10% in many patients with APN on the individual level. The utilization of clinical tools for the prediction of fluoroquinolones, TMP-SMX, and third-generation cephalosporin resistance improves the ambulatory antibiotic management of APN. It may also reduce the need to switch antibiotic therapy later based on the in vitro antibiotic susceptibility testing results of bacterial isolates in urinary cultures. This approach may mitigate the burden of increasing antibiotic resistance in the community by ensuring that the initial antibiotic prescribed has the highest likelihood of treating APN appropriately. [ABSTRACT FROM AUTHOR]

Antimicrobial-resistant (AMR) infections have increased in community settings. Our objectives were to study the epidemiology of community-onset bloodstream infections (BSIs), identify risk factors for AMR-BSI and mortality-related factors, and develop the empirical antimicrobial treatment-decision algorithm. All adult, positive blood cultures at the emergency room and outpatient clinics were evaluated from 08/2021 to 04/2022. AMR was defined as the resistance of organisms to an antimicrobial to which they were previously sensitive. A total of 1151 positive blood cultures were identified. There were 450 initial episodes of bacterial BSI, and 114 BSIs (25%) were AMR-BSI. Non-susceptibility to ceftriaxone was detected in 40.9% of 195 E. coli isolates and 16.4% among 67 K. pneumoniae isolates. A treatment-decision algorithm was developed using the independent risk factors for AMR-BSI: presence of multidrug-resistant organisms (MDROs) within 90 days (aOR 3.63), prior antimicrobial exposure within 90 days (aOR 1.94), and urinary source (aOR 1.79). The positive and negative predictive values were 53.3% and 83.2%, respectively. The C-statistic was 0.73. Factors significantly associated with 30-day all-cause mortality were Pitt bacteremia score (aHR 1.39), solid malignancy (aHR 2.61), and urinary source (aHR 0.30). In conclusion, one-fourth of community-onset BSI were antimicrobial-resistant, and one-third of Enterobacteriaceae were non-susceptible to ceftriaxone. Treatment-decision algorithms may reduce overly broad antimicrobial treatment. [ABSTRACT FROM AUTHOR]

Hunting dogs may be a potential source of transmission of pathogenic, zoonotic, or drug-resistant bacteria to people since they may carry the pathogenic bacteria in their oral cavities. As a result of clinic-based cross-sectional study conducted to evaluate the level of multidrug resistant bacteria, colonization of the bacteria in the oral cavities of hunting dogs that appeared apparently healthy were found in Maiduguri. Oral swab samples were taken from one hundred and ninety-three (193) apparently healthy hunting dogs. Using colony morphology and oxidase, catalase, starch hydrolysis, casein hydrolysis, indole, methyl-red and Voges-Proskauer test (MR-VP) the bacteria were isolated and identified. The isolates were tested for antibiotic susceptibility to ten (10) different antibiotics using the Kirby-Bauer disk diffusion method in accordance with standard procedure. Escherichia coli (E. coli) accounted for the greater proportion of 100 (51.8%) of the isolates. Others were Staphylococcus spp. 19 (18.8%), Klebsiella spp. 13 (6.7%), and Streptococcus spp. 7 (3.6%). Escherichia coli isolates were highly resistant to Penicillin 100 (100%), Ceftriaxone (100%) and Tetracycline (80%) while Klebsiella spp. was found resistant to Amikacin (100%), Gentamicin (100%) and Ceftriaxone (100 %). Similarly, Staphylococcus spp. obtained in the current study was found to be resistant to Ciprofloxacin (100%), Gentamicin (100%) and Amikacin (100%) while Streptococcus isolates were resistant to Tetracycline (100%), Penicillin (100%) and Chloramphenicol (100%). Susceptibility of the isolates were E. coli 100 (100%) for Chloramphenicol. Owners of dogs should refrain from using antibiotics indiscriminately. In conclusion, the study revealed the presence of dissimilar bacteria in the oral cavities of hunting dogs using cultural isolation, biochemical and antibiotics sensitivity tests in the study area. [ABSTRACT FROM AUTHOR]

Italy was the first country in Europe to be hit by the Severe Acute Respiratory Syndrome Coronavirus 2. Little research has been conducted to understand the economic impact of providing care for SARS-CoV-2 patients during the pandemic. Our study aims to quantify the incremental healthcare costs for hospitalizations associated to being discharged before or after the first SARS-CoV-2 case was notified in Italy, and to a positive or negative SARS-CoV-2 notified infection. We used data on hospitalizations for 9 different diagnosis related groups at a large Italian Research Hospital with discharge date between 1st January, 2018 and 31st December 2021. The median overall costs for a hospitalization increased from 2410EUR (IQR: 1588–3828) before the start of the pandemic, to 2645EUR (IQR: 1885–4028) and 3834EUR (IQR: 2463–6413) during the pandemic, respectively for patients SARS-CoV-2 negative and positive patients. Interestingly, according to results of a generalized linear model, the highest increases in the average costs sustained for SARS-CoV-2 positive patients with respect to patients discharged before the pandemic was found among those with diagnoses unrelated to COVID-19, i.e. kidney and urinary tract infections with CC (59.71%), intracranial hemorrhage or cerebral infarction (53.33), and pulmonary edema and respiratory failure (47.47%). Our study highlights the economic burden during the COVID-19 pandemic on the hospital system in Italy based on individual patient data. These results contribute to the to the debate around the efficiency of the healthcare services provision during a pandemic. [ABSTRACT FROM AUTHOR]

In contrast, a European multi-centre study on the incidence of ventilator-associated lower respiratory tract infections suggested that MDRO was lower in the COVID-19 patients than in the non-COVID comparators [[5]]. Co-infection and ICU-acquired infection in COIVD-19 ICU patients: a secondary analysis of the UNITE-COVID data set. Patients who develop severe coronavirus disease 2019 (COVID-19) suffer nosocomial infections that were not only the commonest single category of complications, affecting over 50% of COVID-19 patients in intensive care unit (ICU) [[1]], but also sit at the intersection of two pandemics, namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and antimicrobial resistance (AMR). However, studies examining COVID-19 and non-COVID-19 patients managed in the same unit under the same PPE conditions do not support local infection prevention and control (IPC) breaches as the dominant driver of MDRO transmission [[12]]. [Extracted from the article]

Background: The spread of antibiotic-resistant bacteria may be driven by human–animal–environment interactions, especially in regions with limited restrictions on antibiotic use, widespread food animal production, and free-roaming domestic animals. In this study, we aimed to identify risk factors related to commercial food animal production, small-scale or "backyard" food animal production, domestic animal ownership, and practices related to animal handling, waste disposal, and antibiotic use in Ecuadorian communities. Methods and findings: We conducted a repeated measures study from 2018 to 2021 in 7 semirural parishes of Quito, Ecuador to identify determinants of third-generation cephalosporin-resistant E. coli (3GCR-EC) and extended-spectrum beta-lactamase E. coli (ESBL-EC) in children. We collected 1,699 fecal samples from 600 children and 1,871 domestic animal fecal samples from 376 of the same households at up to 5 time points per household over the 3-year study period. We used multivariable log-binomial regression models to estimate relative risks (RR) of 3GCR-EC and ESBL-EC carriage, adjusting for child sex and age, caregiver education, household wealth, and recent child antibiotic use. Risk factors for 3GCR-EC included living within 5 km of more than 5 commercial food animal operations (RR: 1.26; 95% confidence interval (CI): 1.10, 1.45; p-value: 0.001), household pig ownership (RR: 1.23; 95% CI: 1.02, 1.48; p-value: 0.030) and child pet contact (RR: 1.23; 95% CI: 1.09, 1.39; p-value: 0.001). Risk factors for ESBL-EC were dog ownership (RR: 1.35; 95% CI: 1.00, 1.83; p-value: 0.053), child pet contact (RR: 1.54; 95% CI: 1.10, 2.16; p-value: 0.012), and placing animal feces on household land/crops (RR: 1.63; 95% CI: 1.09, 2.46; p-value: 0.019). The primary limitations of this study are the use of proxy and self-reported exposure measures and the use of a single beta-lactamase drug (ceftazidime with clavulanic acid) in combination disk diffusion tests for ESBL confirmation, potentially underestimating phenotypic ESBL production among cephalosporin-resistant E. coli isolates. To improve ESBL determination, it is recommended to use 2 combination disk diffusion tests (ceftazidime with clavulanic acid and cefotaxime with clavulanic acid) for ESBL confirmatory testing. Future studies should also characterize transmission pathways by assessing antibiotic resistance in commercial food animals and environmental reservoirs. Conclusions: In this study, we observed an increase in enteric colonization of antibiotic-resistant bacteria among children with exposures to domestic animals and their waste in the household environment and children living in areas with a higher density of commercial food animal production operations. In a repeated-measures study conducted between 2018-2021 in 7 semi-rural parishes of Quito, Ecuador, Heather Kathleen Amato and colleagues aim to identify determinants of antibiotic resistant E.coli infection in children. Author summary: Why was this study done?: An estimated 1.27 million deaths in 2019 were attributable to bacterial antibiotic-resistant infections, 89% of which occurred in low- and middle-income countries (LMICs). Small-scale and commercial-scale food animal production is expanding rapidly in middle-income countries like Ecuador and antibiotic use in food animals is increasing at the fastest rate in these settings, fueling the emergence and selection of multidrug-resistant bacteria. Evidence is needed to inform action against the spread of antibiotic resistance in communities with varying degrees of both small-scale or "backyard" and commercial food animal production, especially in South America where research on community-acquired antibiotic resistance is lacking. What did the researchers do and find?: We conducted a repeated measures study in a food animal-producing region in Ecuador to compare the risk of antibiotic-resistant bacterial (ARB) carriage among children with varying degrees of exposure to backyard and commercial food animals. We used multivariable log-binomial regression models to estimate relative risks (RR) of ARB carriage, adjusting for child sex and age, caregiver education, household wealth, and recent child antibiotic use. Living within 5 km of >5 commercial food animal operations, household pig or dog ownership, child contact with pets, and placing animal feces on household crops were identified as significant risk factors for ARB carriage in children. What do these findings mean?: This study underscores the need for improved waste management and surveillance of antibiotic resistance in LMICs with widespread food animal production. A significant challenge remains: There is a lack of available data on antibiotic usage and resistance in commercial food animal operations and their effluent, in Ecuador and globally, due to limited oversight and surveillance. In future studies, researchers should work with local and national governments to monitor antibiotic use and resistance in food animals, food animal production waste, nearby environmental reservoirs, and food animal products in order to more accurately characterize sources of exposure and transmission routes of community-acquired ARB. The primary limitations of this study are the use of proxy and self-reported exposure measures and the use of a single beta-lactamase drug (ceftazidime with clavulanic acid) in combination disk diffusion tests for ESBL confirmation, potentially underestimating phenotypic ESBL production among cephalosporin-resistant E. coli isolates. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a chronic disease that, untreated or poorly controlled, can lead to serious complications, reducing life expectancy and quality. Diabetic patients are more likely to develop infections, including many common infections, but also pathognomonic ones such as emphysematous pyelonephritis, malignant otitis externa, mucormycosis and Fournier's gangrene. Considering the fact that diabetic patients experience more frequently urinary tract infections (UTIs) with a worse prognosis than non-diabetic people, we conducted a review study based on data in the literature, following the particularities of UTIs in this group of patients, the risk factors, the mechanisms involved and the challenges in their management. The findings highlight that UTI in diabetic patients have some particularities, including a more frequent evolution to bacteremia, increased hospitalizations, and elevated rates of recurrence and mortality than non-diabetic patients. The possible risk factors identified seem to be female gender, pregnancy, older age, UTI in the previous six months, poor glycemic control and duration of diabetes. The mechanisms involved are related to glucosuria and bladder dysfunction, factors related to bacterial strains and host response. The bacterial strains involved in UTIs in diabetic patients and their antibiotic susceptibility profile are, with some exceptions, similar to those in non-diabetic people; however, the antimicrobial agents should be carefully chosen and the duration of the treatment should be as those required for a complicated UTI. The data related to the risk of developing UTIs in patients treated with SGLT-2 inhibitors, a new class of oral hypoglycaemic agents with cardiovascular and renal benefits, are controversial; overall, it was evidenced that UTIs occurred at the initiation of the treatment, recurrent infection was uncommon and the majority of UTIs responded to treatment with standard antibiotics. Moreover, interruption or discontinuation of SGLT-2 inhibitor as a result of UTI was rare and SGLT-2 inhibitors did not increase the risk of severe infections such as urosepsis and pyelonephritis. [ABSTRACT FROM AUTHOR]

(1) Background: Understanding the physicians' knowledge, attitudes, and antimicrobial prescribing behavior is a crucial step towards designing strategies for the optimal use of these agents. (2) Methods: A cross-sectional online survey was conducted among clinicians across India between May and July 2022 using a self-administered questionnaire in English comprising 35 questions pertaining to demographic characteristics, knowledge, attitude, and practices domains. (3) Results: A total of 544 responses were received from 710 physicians contacted. Sixty percent of participants were males, with mean age of 34.7 years. Mean ± Standard Deviation scores for knowledge, attitude, and practices domains were 8 ± 1.6, 20.2 ± 3.5, and 15.3 ± 2.1, respectively. Higher scores were associated with basic [odds ratio (95% Confidence Interval), p value: 2.95 (1.21, 7.2), 0.02], medical and allied sciences [2.71 (1.09, 6.67), 0.03], and central zone [3.75 (1.39, 10.12), 0.009]. A substantial proportion of dissatisfactory responses were found regarding hospital antibiograms, antibiotics effective against anaerobes, WHO AWaRe (access, watch, and reserve) classification of antibiotics, and the role of infection prevention and control (IPC) measures in the containment of antimicrobial resistance (AMR). (4) Conclusions: There is a need to sensitize and educate clinicians on various issues related to antimicrobial use, such as antibiograms, double anaerobic cover, IPC practices, and guideline-based recommendations, to curb the AMR pandemic. [ABSTRACT FROM AUTHOR]

Italy was the first country in Europe to be hit by the Severe Acute Respiratory Syndrome Coronavirus 2. Little research has been conducted to understand the economic impact of providing care for SARS-CoV-2 patients during the pandemic. Our study aims to quantify the incremental healthcare costs for hospitalizations associated to being discharged before or after the first SARS-CoV-2 case was notified in Italy, and to a positive or negative SARS-CoV-2 notified infection. We used data on hospitalizations for 9 different diagnosis related groups at a large Italian Research Hospital with discharge date between 1st January, 2018 and 31st December 2021. The median overall costs for a hospitalization increased from 2410EUR (IQR: 1588–3828) before the start of the pandemic, to 2645EUR (IQR: 1885–4028) and 3834EUR (IQR: 2463–6413) during the pandemic, respectively for patients SARS-CoV-2 negative and positive patients. Interestingly, according to results of a generalized linear model, the highest increases in the average costs sustained for SARS-CoV-2 positive patients with respect to patients discharged before the pandemic was found among those with diagnoses unrelated to COVID-19, i.e. kidney and urinary tract infections with CC (59.71%), intracranial hemorrhage or cerebral infarction (53.33), and pulmonary edema and respiratory failure (47.47%). Our study highlights the economic burden during the COVID-19 pandemic on the hospital system in Italy based on individual patient data. These results contribute to the to the debate around the efficiency of the healthcare services provision during a pandemic. [ABSTRACT FROM AUTHOR]

Italy was the first country in Europe to be hit by the Severe Acute Respiratory Syndrome Coronavirus 2. Little research has been conducted to understand the economic impact of providing care for SARS-CoV-2 patients during the pandemic. Our study aims to quantify the incremental healthcare costs for hospitalizations associated to being discharged before or after the first SARS-CoV-2 case was notified in Italy, and to a positive or negative SARS-CoV-2 notified infection. We used data on hospitalizations for 9 different diagnosis related groups at a large Italian Research Hospital with discharge date between 1st January, 2018 and 31st December 2021. The median overall costs for a hospitalization increased from 2410EUR (IQR: 1588–3828) before the start of the pandemic, to 2645EUR (IQR: 1885–4028) and 3834EUR (IQR: 2463–6413) during the pandemic, respectively for patients SARS-CoV-2 negative and positive patients. Interestingly, according to results of a generalized linear model, the highest increases in the average costs sustained for SARS-CoV-2 positive patients with respect to patients discharged before the pandemic was found among those with diagnoses unrelated to COVID-19, i.e. kidney and urinary tract infections with CC (59.71%), intracranial hemorrhage or cerebral infarction (53.33), and pulmonary edema and respiratory failure (47.47%). Our study highlights the economic burden during the COVID-19 pandemic on the hospital system in Italy based on individual patient data. These results contribute to the to the debate around the efficiency of the healthcare services provision during a pandemic. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) poses a significant global health challenge, exacerbated by the COVID-19 pandemic. Antimicrobial stewardship programs (ASPs) are crucial in managing this crisis, with diagnostic stewardship (DS) emerging as a key component. DS refers to the appropriate use of diagnostic tests to optimize patient outcomes, improve antimicrobial use, and combat multi-drug-resistant (MDR) organisms. Despite its potential, understanding and application of DS remain ambiguous in multiple respects, which, however, do not directly implicate the implementation of such initiatives. DS is particularly important for resident physicians who are often at the forefront of patient care and can significantly influence future AMR strategies. This review provides a comprehensive overview of DS, discussing its importance, potential challenges, and future directions. It emphasizes the need for resident physicians to understand DS principles and integrate them into their clinical practice from the beginning of their careers. The review also highlights the role of various stakeholders in implementing DS and the importance of continuous education and training. Ultimately, DS is not just a clinical tool but a philosophy of care, essential for a more responsive, humane, and effective healthcare system. [ABSTRACT FROM AUTHOR]

Simple Summary: Atrial fibrillation (AF), the most prevalent sustained dysrhythmia, is accountable for substantial mortality and morbidity. Accumulating convincing evidence highlights the predominant roles of heritable components in the initiation and maintenance of AF. Here, through pan-genomic genotyping with genetic markers followed by a genetic linkage study in an AF family, a novel AF-causing locus was located at human chromosome 7p14.2–p14.3. An exome-wide sequence assay unveiled that, at the defined locus, the mutation in TBX20, NM_001077653.2: c.695A>G; p.(His232Arg), was solely co-segregated with AF in the family. Additionally, a Sanger sequencing assay of TBX20 in another AF family uncovered a novel mutation, NM_001077653.2: c.862G>C; p.(Asp288His). Neither of the two mutations were found in 600 control persons. Functional investigations demonstrated that the two mutations both significantly reduced the transactivation of the target gene KCNH2 and the ability to bind the promoter of KCNH2, while they had no effect on the nuclear distribution of TBX20. These findings strongly indicate that TBX20 is a new AF-predisposing gene, shedding light on the mechanism underlying AF and suggesting clinical significance for the individually tailored treatment of AF. Atrial fibrillation (AF), the most prevalent type of sustained cardiac dysrhythmia globally, confers strikingly enhanced risks for cognitive dysfunction, stroke, chronic cardiac failure, and sudden cardiovascular demise. Aggregating studies underscore the crucial roles of inherited determinants in the occurrence and perpetuation of AF. However, due to conspicuous genetic heterogeneity, the inherited defects accounting for AF remain largely indefinite. Here, via whole-genome genotyping with genetic markers and a linkage assay in a family suffering from AF, a new AF-causative locus was located at human chromosome 7p14.2-p14.3, a ~4.89 cM (~4.43-Mb) interval between the markers D7S526 and D7S2250. An exome-wide sequencing assay unveiled that, at the defined locus, the mutation in the TBX20 gene, NM_001077653.2: c.695A>G; p.(His232Arg), was solely co-segregated with AF in the family. Additionally, a Sanger sequencing assay of TBX20 in another family suffering from AF uncovered a novel mutation, NM_001077653.2: c.862G>C; p.(Asp288His). Neither of the two mutations were observed in 600 unrelated control individuals. Functional investigations demonstrated that the two mutations both significantly reduced the transactivation of the target gene KCNH2 (a well-established AF-causing gene) and the ability to bind the promoter of KCNH2, while they had no effect on the nuclear distribution of TBX20. Conclusively, these findings reveal a new AF-causative locus at human chromosome 7p14.2-p14.3 and strongly indicate TBX20 as a novel AF-predisposing gene, shedding light on the mechanism underlying AF and suggesting clinical significance for the allele-specific treatment of AF patients. [ABSTRACT FROM AUTHOR]