Antimicrobial resistance (AMR), particularly among extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE), represents a major challenge at the human-animal-environment interface. We conducted a nationwide study assessing faecal carriage of ESBL-PE in free-ranging hedgehogs, a synanthropic species well adapted to urban environments. Between December 2022 and September 2023, 246 hedgehogs rescued across Israel and admitted to the country's sole wildlife hospital were screened on admission, with all isolates undergoing antimicrobial susceptibility testing. Overall, 71% of hedgehogs carried at least one ESBL-PE isolate, and 2% harboured carbapenem-resistant Enterobacterales. Escherichia coli was the predominant species, followed by Citrobacter, Klebsiella, and Enterobacter spp. High resistance rates were observed to quinolones (83%) and trimethoprim-sulfamethoxazole (46%). Carriage prevalence varied over time, with higher rates observed during months associated with holiday periods and increased outdoor recreational activity. These findings suggest that free-ranging hedgehogs may serve as a complementary sentinel species for monitoring AMR patterns in One Health contexts.

Background: This study evaluated the utility of fluconazole disk diffusion on CHROMagar Candida Plus for differentiating Candidozyma auris from Candida parapsilosis. Methods: In this in vitro study, clinical isolates of both C. auris and C. parapsilosis were used. Antifungal susceptibility testing was performed via broth microdilution and disk diffusion with different fluconazole concentrations on both CHROMagar Candida Plus and RPMI agar. Colony color was also assessed. Results: This study demonstrates high categorical agreement between disk diffusion on CHROMagar Candida Plus and broth microdilution for both species. An optimal cut-off zone diameter of 10 mm was identified on CHROMagar Candida Plus with 50 µg fluconazole, providing 91% sensitivity and 90% specificity for differentiating the two species. Notably, at 24 h, 83 out of 88 (94.3%) C. auris isolates exhibited a bluish, blue-green, or turquoise coloration on the reverse side of the plate, suggesting that reverse-side colony color on CHROMagar may serve as a supportive phenotypic indicator when combined with disk diffusion testing, to differentiate C. auris from C. parapsilosis in the laboratory setting. Conclusions: Fluconazole disk diffusion on CHROMagar Candida Plus, supplemented by reverse-side colony coloration, offers a practical, low-cost adjunctive strategy to aid in the differentiation of C. auris and C. parapsilosis in clinical laboratories.

Amid the rising prevalence of antimicrobial resistance (AMR), attention is increasingly directed toward investigating additional factors that may contribute to or mediate its development, among which companion animals have emerged as a potential reservoir and transmission interface. Despite this, the contribution of free-roaming animal populations living in proximity to humans and domestic animals has yet to be thoroughly investigated worldwide. Accordingly, this study aimed to determine the prevalence and antimicrobial resistance patterns of extended-spectrum β-lactamase (ESBL)-producing Enterobacterales in free-roaming cats in Israel. Rectal swabs were collected from 214 free-roaming cats admitted to two veterinary clinics between 2023 and 2024. ESBL-PE were recovered from 51 cats (23.8%), yielding 61 isolates, which were tested for susceptibility to multiple antimicrobials. Eleven bacterial species were identified, with Escherichia coli being the most frequently recovered (62.3%, 38/61). Nine purposively selected E. coli isolates underwent whole-genome sequencing (WGS). Multidrug resistance (MDR), defined as non-susceptibility to at least one agent in three or more antimicrobial categories, was observed in 72.1% (44/61) of isolates, and four isolates were carbapenemase-producing Enterobacterales (CPE). These findings suggest that free-roaming cats may serve as a previously overlooked ‘One Health’ link, possibly connecting environmental contamination to human and animal health risks.

BACKGROUND:In 2024, Israel faced a major West Nile virus (WNV) disease outbreak. We aimed to evaluate the efficacy and safety of WNV-neutralizing plasma for hospitalized patients with WNV disease. METHODS:We conducted a randomized, double-blind, placebo-controlled trial. Patients hospitalized with laboratory-confirmed symptomatic WNV disease, 60 years of age or older, or 18 to 59 years of age and immunocompromised, were eligible. Participants were randomly assigned (2:1) to donor-derived WNV-neutralizing plasma or placebo. The primary outcome was a composite of all-cause mortality and any functional deterioration at 30 days, defined as a decrease of more than 5 points from baseline on the Barthel Index (range 0-100; higher scores indicate greater independence) for activities of daily living (i.e., failure to return to pre-illness functional status). Key secondary outcomes included mortality, functional capacity (Barthel Index), and cognitive score (Modified Mini-Mental State Examination; range 0-30; higher scores indicate higher cognitive ability) at 30 and 90 days. RESULTS:Of the 34 participants enrolled, 22 were randomly assigned to the intervention group and 12 to placebo. Median age was 74 (interquartile range, 64-82), 50% were women, and 91% had neuroinvasive disease at enrollment. At 30 days, 11/22 (50%) and 6/12 (50%) patients in the treatment and placebo group, respectively, died or had functional deterioration (risk ratio [RR], 0.96; 95% confidence interval [CI], 0.51-1.79). Two patients (2/22) died in the intervention group, compared with 4 (4/12) in the placebo group (RR, 0.33, 95% CI, 0.09-1.15). The intervention was associated with higher functional capacity (Barthel Index 85 in the intervention group vs. 78 in the placebo group; RR, 1.15; 95% CI, 1.05-1.27), and higher cognitive scores (Mini-Mental score 25 vs. 22; RR, 1.24; 95% CI, 1.04-1.47) at 30 days. One (4.5%) allergic reaction was observed in the intervention group. CONCLUSIONS:In this small, randomized trial of predominantly severe neuroinvasive WNV, treatment with WNV-neutralizing plasma did not reduce the composite outcome of death or functional deterioration at 30 days compared to placebo. It was associated with improved cognitive and functional outcomes. Potential differences in mortality warrant further evaluation. (ClinicalTrials.gov number, NCT06590207.).

BACKGROUND:Staphylococcus aureus bacteremia is associated with high mortality. Whether cefazolin or an antistaphylococcal penicillin should be preferred for the treatment of methicillin-susceptible S. aureus bacteremia is unclear. METHODS:In an ongoing international Bayesian adaptive platform trial, we conducted an open-label, randomized comparison of cefazolin with an antistaphylococcal penicillin (flucloxacillin or cloxacillin) in adult patients with penicillin-resistant, methicillin-susceptible S. aureus bacteremia. The primary outcome, which was evaluated with a hierarchical Bayesian logistic-regression model, was death from any cause within 90 days after enrollment in the platform. We assessed the posterior probability of the noninferiority of cefazolin to flucloxacillin or cloxacillin (with the criterion for noninferiority prespecified as an adjusted odds ratio of <1.2, which approximates an absolute difference in mortality of <2.5 percentage points if mortality in the antistaphylococcal-penicillin group is 15%), as well as the posterior probability of superiority (with the criterion of an adjusted odds ratio of <1.0). Secondary safety outcomes included the development of acute kidney injury within 14 days. RESULTS:This domain of the ongoing trial was conducted between February 17, 2022, and August 7, 2024, by which time the criterion for noninferiority had been met. Mortality at 90 days among adults who could be evaluated was 15.0% (97 deaths among 645 patients) in the cefazolin group and 17.0% (109 deaths among 642 patients) in the antistaphylococcal-penicillin group (adjusted odds ratio, 0.81; 95% credible interval, 0.59 to 1.12; probability of noninferiority, 99.2%; probability of superiority, 89.8%). Acute kidney injury occurred in 92 of 660 patients (13.9%) in the cefazolin group, as compared with 127 of 648 (19.6%) in the antistaphylococcal-penicillin group (adjusted odds ratio, 0.67; 95% credible interval, 0.50 to 0.89; probability of superiority, 99.7%). CONCLUSIONS:In patients with methicillin-susceptible S. aureus bacteremia, cefazolin was noninferior to flucloxacillin or cloxacillin with respect to 90-day mortality and was associated with a lower incidence of acute kidney injury. (Funded by the National Health and Medical Research Council and others; SNAP ClinicalTrials.gov number, NCT05137119.).

OBJECTIVES:To characterize the microbiological profile of post-cesarean surgical site infection (SSI) wound cultures, examine associations between specific pathogens and clinical or surgical characteristics, and delineate institutional wound culture collection practices. METHODS:A retrospective cohort study including women with positive wound cultures from clinically diagnosed post-cesarean SSIs between 2012 and 2024. Microorganisms were categorized into designated pathogen groups based on taxonomic classification and clinical relevance. Each microorganism group was compared with all remaining cases. Demographic, obstetric, surgical, laboratory, and outcome variables were analyzed using appropriate univariate statistical tests. RESULTS:A total of 207 positive wound cultures were analyzed. The most frequently isolated organisms were Enterobacterales (30.4 %), Staphylococcus aureus and β-hemolytic streptococci (27.1 %), and coagulase-negative staphylococci (20.3 %). Enterobacterales infections were significantly associated with obesity (BMI >35), meconium-stained amniotic fluid, and longer intervals from rupture of membranes to labor onset. Non-fermenting Gram-negative organisms were strongly associated with subcutaneous tissue approximation and intradermal skin closure. Coagulase-negative staphylococci were associated with fewer established risk factors, suggesting possible contamination or colonization. Only Enterobacterales infections demonstrated a statistically significant, though clinically modest, increase in peak white blood cell count. No significant differences were observed in other severity markers or clinical outcomes. CONCLUSIONS:Routine wound cultures in post-cesarean SSIs provide limited information regarding disease severity. However, specific pathogen profiles are associated with distinct obstetric and surgical characteristics, suggesting that selective culture use may be informative in high-risk clinical contexts. These findings may help improve institutional wound-culture practices and inform future studies on culture-guided management strategies.

OBJECTIVE:West Nile virus (WNV) is a mosquito-borne pathogen of growing public health concern that is endemic in Israel and has been responsible for intermittent outbreaks. The seroprevalence and durability of functional antibody responses in asymptomatic WNV-infected populations remain unclear. METHODS:We screened a large cohort of asymptomatic healthcare workers (HCWs) for WNV IgG and neutralizing antibody titers. Predictors of seropositivity and neutralization levels were assessed using multivariable regression. Among seropositive individuals, longitudinal samples, collected up to 44 months prior to the final blood sampling, were analyzed to evaluate neutralizing antibody kinetics. RESULTS:Of 2365 HCWs screened (median age 47 years; 66.6% females), 14.8% (n = 301) were WNV IgG seropositive, and 94.0% of these demonstrated detectable neutralizing efficacy. Age was independently associated with IgG seropositivity (adjusted OR 1.33 per 10 years; 95% CI: 1.23-1.45). Neutralizing efficacy was high (Geometric-Mean-Titer 6171, 95% CI: 4361-8723), and IgG and neutralizing antibody titers were correlated (R² = 0.17). Over 44 months, a 23% annual decrease in neutralizing titers was observed. CONCLUSION:WNV seropositivity increases with age, indicating cumulative exposure. Correlation between IgG and neutralizing efficacy suggests durable protection among seropositive individuals. Despite waning antibody levels, high neutralizing capacity likely confers extended protection.

Using a cohort of 893 adults who underwent medical check-ups with rich data collection across diet, lifestyle, clinical labs, cardiac stress testing, and microbiome profiling, we show that a gut microbial health index (MHI), originally defined using a large meta-analysis of various human disease cohorts, is also substantially associated with lifestyle and diet. This association persists across the overall cohort, disease-free subsets, and individuals with common medical conditions such as hypertension and dyslipidemia. The gut MHI was positively correlated with factors such as variation in cardiac stress test fitness, fiber intake, and well-being, and negatively correlated with exposure to ultra-processed foods and markers of subclinical inflammation (WBC and CRP mostly within normal limits). Lipidomics profiling of a subcohort revealed that triglycerides correlate positively with ultraprocessed foods, and negatively with unsaturated fats, olive oil, and nuts, linking diet, MHI, and lipid profile. Estimating the contribution of modifiable dietary and lifestyle factors to the MHI uncovers actionable ways to improve or worsen the personal MHI. Analyses of previously published intervention studies showed that the MHI responds quickly to dietary changes, within the predicted range. Our findings emphasize the potential of using microbiomes, and specifically the MHI, as a reporter of overall health.

BACKGROUND Campylobacter is one of the leading causes of gastrointestinal disease. AIM We aimed to investigate trends in the incidence rate of campylobacteriosis in Israel. METHODS We collected data on laboratory-confirmed cases of campylobacteriosis reported to the Israel Sentinel Laboratory-Based Surveillance Network (ISLBSN) in 2013–2022. Trends in the incidence rates of campylobacteriosis were evaluated using the Joinpoint software to calculate annual percent change (APC) and by time series analysis auto-regressive integrated moving average model. RESULTS Between 2013 and 2022, 43,334 cases of campylobacteriosis were reported to the ISLBSN. The highest incidence rate of campylobacteriosis was observed in children aged 0-4 years (327.8/100,000) and overall, the incidence rate was higher among Jews and others (98.7/100,000) than among Arabs (85.9/100,000). However, the incidence rate among Arabs aged 0-4 years was higher (546.3/100,000) than among Jews and others (316.9/100,000). The incidence rate decreased significantly from 101.7 per 100,000 in 2013 to 79.4 per 100,000 in 2020 (APC = −2.7%) and then increased to 109.5 per 100,000 in 2022 (APC = 13.9%). We identified consistent peaks in incidence rate in April–May, specifically among Jews and others, with no corresponding increase among Arabs. Passover weeks were associated with a significantly higher risk of campylobacteriosis (incidence rate ratio (IRR) = 1.18; 95% CI: 1.12 to 1.23; p < 0.0001) compared with non-Passover weeks. CONCLUSION Campylobacteriosis incidence rate in Israel is high, particularly among young children. Collaboration between veterinary and public health authorities and timely public awareness campaigns, especially before holidays, are essential to reduce zoonotic transmission and prevent future peaks.

Importance:Clostridioides difficile is a leading cause of health care-associated infections. Understanding the association among C difficile carriage, antibiotic use, and infection hazard is essential for infection prevention. Objective:To evaluate the hazard of C difficile infection (CDI) among asymptomatic carriers vs noncarriers of C difficile and whether it is associated with antibiotic exposure. Design, Setting, and Participants:This retrospective cohort study conducted between June 18, 2017, and June 21, 2023, analyzed hospitalizations from Sheba Medical Center in Ramat Gan, Israel, which routinely screens for C difficile in high-risk patients admitted to internal medicine. Adult patients (aged >18 years) without active CDI at admission were included. Exposure:Antibiotic exposure during hospitalization, including specific classes. Main Outcomes and Measures:The primary outcome was the development of CDI, as confirmed by laboratory testing for C difficile. Antibiotic exposure was assessed as a time-varying variable. Results:The study included 33 756 hospitalizations among 23 001 patients (median [IQR] age, 78 [68-87] years; 52.8% men). C difficile infection occurred in 67 of 1624 hospitalizations (4.1%) with positive screening results and in 47 of 32 132 hospitalizations (0.1%) with negative screening results. A positive C difficile screening result at admission was associated with a high hazard of infection (hazard ratio [HR], 27.5; 95% CI, 18.7-40.3). Antibiotic exposure was associated with an increased hazard for CDI (HR, 1.98; 95% CI, 1.24-3.16). Piperacillin and tazobactam showed the most pronounced hazard for CDI (HR, 2.18; 95% CI, 1.41-3.36). Among asymptomatic carriers, antibiotic exposure was not significantly associated with a further increase in CDI hazard (HR, 1.07; 95% CI, 0.73-1.58). Conclusions and Relevance:In this cohort study, carriers of C difficile had a substantially higher baseline hazard for hospital-onset CDI. Antibiotic exposure was associated with an increased hazard among noncarriers but was not significantly associated with additional hazard among carriers. These findings suggest that while antibiotic stewardship may reduce CDI risk in noncarriers, additional strategies may be needed for carriers given their elevated baseline risk.

Cardiovascular allografts are essential for patients with severe cardiovascular diseases. Yet, microbial contamination of the grafts poses a life-threatening risk to recipients. Tissue banks utilize various decontamination methods during cardiovascular tissue processing, often involving antibiotic solutions. This study compares the efficacy of an in-house prepared antibiotic cocktail (tissue bank cocktail) and a commercially available solution (BASE.128) in decontaminating cardiovascular tissues. For this study, the efficacy of the two antibiotic cocktails was compared through quantitative comparisons against challenge microorganisms, and retrospective analysis of routine sterility tests. Both solutions demonstrated comparable decontamination efficiency against challenge strains, achieving significant reductions in bacterial load. However, retrospective sterility tests revealed that while both antibiotic solutions were highly effective in decontaminating cardiovascular allografts, the use of BASE.128 followed a tenfold increase in contamination rates compared to the tissue bank cocktail, primarily due to a slow-growing non-tuberculous mycobacteria strain. These findings highlight the importance of tailored decontamination protocols that consider prevalent microbial contaminants while preserving tissue quality.

BACKGROUND:The high prevalence of asymptomatic Mycoplasma genitalium (MG) infection, combined with limited treatment options due to emerging antimicrobial resistance, raises important questions about the necessity of routine screening and treatment, particularly among men who have sex with men (MSM). This study aimed to determine the prevalence of macrolide and quinolone resistance in MG among HIV-positive MSM and assess its clinical relevance. METHODS:HIV-positive MSM were screened for sexually transmitted infections at the HIV clinic in Sheba Medical Center over a 43-month period, with demographic and clinical parameters recorded upon each visit. A subset of the patients underwent genetic resistance testing for macrolides and quinolones using real-time polymerase chain reaction assays. RESULTS:A total of 317 patients were screened during the study period. MG was detected in 80 (25.2%) patients, covering 150 episodes, at least once during follow-up. In 15 of these episodes (10.0%), patients reported symptoms that might be explained by MG infection. Among the 35 patients who were tested for resistance, 28 (82.3%) harbored macrolide resistance-associated mutations, whereas 11 of 33 (33.3%) exhibited quinolone resistance-associated mutations. CONCLUSIONS:The findings highlight a high prevalence of macrolide-resistant MG infections among HIV-positive MSM, with a notable proportion also exhibiting macrolide quinolone resistance. Given the asymptomatic nature of many MG infections and the increasing challenge of antimicrobial resistance, routine screening for MG in this population may provide limited clinical benefits.

BACKGROUND:Available data on combat wound-related invasive mould infections (IMIs) are limited. OBJECTIVES:We aimed to describe the characteristics and outcomes of IMIs in casualties of a recent conflict. PATIENTS/METHODS:A retrospective study including hospitalised patients with combat-related injuries, fulfilling criteria for wound-related IMI based on Trauma Infectious Disease Outcomes Study definitions. Patient and injury characteristics, management and outcomes are described and compared to previous cohorts. Mould isolates and susceptibility testing results, including the novel agent manogepix, are reported. RESULTS:Overall, 31 patients (69 mould isolates) were included-resulting in an IMI incidence rate of 1.9%. Blast was the most common injury mechanism (71%), with limb amputations and abdominoperineal injuries in 35% and 45%, respectively. Mould cultures, obtained mostly from lower extremities wounds (62%), were positive in all patients. Most (68%) had poly-mould infections, with Aspergillus and Fusarium species predominating. Overall, non-susceptibility rates of > 50% to newer azoles and 38% to amphotericin B reflected the high proportion of Fusarium spp., A. terreus and A. flavus, with the lowest azole minimal inhibitory concentrations demonstrated with posaconazole. Manogepix displayed good in-vitro activity against all isolates, except for Mucorales species. Two patients (6.5%) died of disseminated IMIs and 19% required amputations. Patients with Mucorales had poorer outcomes (40% mortality/amputation vs. 19% for non-Mucorales). CONCLUSIONS:Combat wound-related IMIs are uncommon but carry significant morbidity and mortality. High susceptibility rates to manogepix were observed. Further studies are needed to evaluate optimal surgical approaches and the role of antifungal susceptibility testing in this setting.

BACKGROUND:Carbapenem-resistant Acinetobacter baumannii (CRAB) infections carry high case-fatality rates. Although the incidence of these infections is increasing and therapeutic options are limited, effective interventions to prevent the cross-transmission of CRAB have rarely been tested. AIM:To assess the impact of cohorting CRAB patients combined with intensified environmental cleaning on CRAB bloodstream infections (BSIs). METHODS:A quasi-experimental study at a tertiary hospital during January 2022 to June 2024. All patients with CRAB (either colonization or infection) hospitalized in the internal medicine departments were cohorted. Simultaneously, a twice-daily routine and a double terminal cleaning of all hospital rooms occupied by CRAB patients were performed. The monthly acquired CRAB BSI rates were calculated and the incidence rate ratio (IRR) estimated using Poisson regression discontinuity analysis with robust standard errors controlled for the influx of CRAB patients into the hospital. FINDINGS:During January 2022 to June 2024, 610 hospitalized patients with CRAB were identified, 350 (57%) of whom acquired the bacterium in hospital and 138 (39%) developed BSI. The average overall 30-day mortality rate was 61% and remained relatively similar throughout the study period. Cumulative BSI incidence decreased by 55%, from 1.43 per 10,000 hospitalization-days before the intervention to 0.65 afterwards. The slope of the BSI incidence rate decreased by 9% per month (adjusted IRR: 0.909; 95% CI: 0.834-0.990; P = 0.029). CONCLUSION:Cohorting CRAB patients in the internal medicine departments, combined with intensified cleaning throughout the hospital, significantly reduced the incidence of CRAB BSI across the entire institution.

Abstract Background The recommendation to treat nocardiosis for long durations (usually 6-12 months) relies on small case series published decades ago. We implemented real-world data to assess the association between treatment duration and outcomes in nocardiosis.Table 1.Clinical characteristics and outcomes of individuals diagnosed with nocardiosis, according to treatment duration rangea Calculated for the three treatment groups using Chi-square test or Fisher’s exact test (⸙) and one-way ANOVA for categorical and continuous variables, respectively; b Average daily prednisone dosage (in milligrams), during the 90 days prior to presentation. Whenever dexamethasone was used, dosage was converted to the equivalent prednisone dosage; c Individuals with active malignancy, primary immune deficiency, autoimmune diseases, and chronic corticosteroid therapy (≥5 and <20 mg per day); d Solid organ transplant recipients, hematopoietic stem cell transplant recipients, and individuals with acquired immunodeficiency syndrome (AIDS) or on chronic corticosteroid therapy (≥20 mg per day); e Identification to the species level was available for 95/176 (54%) of the cohort. IV = intravenous; NA = not applicable; SMX-TMP = sulfamethoxazole-trimethoprim. Methods A multicenter retrospective cohort study comprising individuals with nocardiosis during 2007-2022, excluding those who died within 90 days from diagnosis. Patients were classified into three groups according to treatment duration: short (≤90 days), intermediate (91-180 days), and long ( >180 days). We compared overall mortality, relapse rates, and antibiotic-related adverse events at 1-year. Treatment duration was cross tabulated with immune status and nocardiosis syndrome, considering that clinical judgment has led physicians to deviate from recommended long durations in appropriate cases.Figure 1.Study flow diagram Results A total of 176 individuals were diagnosed with nocardiosis during the study period, 43 (24%) of whom died within 90 days and were excluded (Figure 1). Of the remaining 133 individuals, 45 (34%) were apparently immunocompetent, 26 (19%) and 62 (47%) had mild-moderate and substantial immune suppression, respectively. Patients received short (N=37, 28%), intermediate (N=40, 30%) and long (N=56, 42%) treatment durations. Longer treatment duration was positively associated with systemic corticosteroid use (p=0.009), immune suppression (p=0.014), and nocardiosis syndrome (longer durations for dissemination, p=0.001; Table, Figure 2). By 1-year, 20 (15%) individuals died and 2 (1.5%) relapsed. Treatment duration was not associated with mortality (p=0.977; Figure 3) or nocardiosis relapse (p=0.509). Of those with solitary pulmonary nocardiosis (N=73), none of the 20 immunocompetent individuals died by 1-year, while 5/16 (31%), and 6/37 (17%) of those with mild-moderate and substantial immune suppression, respectively, died, regardless of treatment duration. Adverse events rate did not differ significantly between duration groups.Figure 2.Distribution of treatment duration groups according to nocardiosis clinical syndrome and immune status For each color, shades signify immune status (apparently immunocompetent individuals, and those with mild-moderate or substantial immune suppression): darker shades signify diminished immunity. Conclusion With clinically guided case-by-case patient selection nocardiosis can be safely treated for durations significantly shorter than traditionally recommended.Figure 3.Survival curves of the entire cohort, according to treatment group The entire cohort is presented as a single curve up to 90 days, then divided into 3 treatment groups, according to the total treatment duration. p value calculated using Log-rank test. Disclosures All Authors: No reported disclosures

The ubiquitous bacterial pathogen Salmonella enterica is the causative agent of both enteric fever and gastroenteritis. Despite its significant global health burden, we lack an understanding of its genetic diversity during acute infection, with ramifications for treatment and prevention. Here, we investigated within-host infection diversity of acute salmonellosis using whole-genome sequencing of blood or stool isolates obtained from 23 different patients. We found that intestinal infections exhibited greater genetic variation than blood infections, including in their plasmid content. While same-patient isolates were separated by 10 single nucleotide polymorphisms or less, they often differed in the carriage of genes or alleles, including those associated with antibiotic resistance or virulence. Given the longstanding emphasis on single colony isolation in clinical and laboratory microbiology, these findings have implications for how we both study evolution and transmission and how we treat salmonellosis in an age of increasing antibiotic resistance.

Abstract Background Infections with extended‐spectrum beta‐lactamase‐producing Enterobacterales (ESBL‐PE) contribute to morbidity and mortality in human neonates. In foals, data are scarce. Objectives Determine the association between ESBL‐PE gastrointestinal colonization on hospital admission and infections in hospitalized neonates. Animals Sixty‐seven foals. Methods Prospective study of foals admitted to a veterinary hospital. Foals were screened for ESBL‐PE colonization and for infections. Risk factors and clinical outcomes were analyzed. Results Seventy‐six percent of foals suffered from at least 1 bacterial infection (n = 51/67). Sixty‐three non‐ESBL bacterial species and 19 ESBL‐PE species were isolated. Twenty foals (29.85%) had at least 1 hospital‐acquired infection (HAI) and 30 foals (44.8%) suffered from multidrug resistant infections. The prevalence rates of ESBL‐PE gastrointestinal colonization on admission and clinical ESBL HAIs were 47.8% (n = 32/67, 41 isolates) and 19.40% (n = 13/67, 19 isolates), respectively. On multivariable analysis, ESBL‐PE HAIs were associated with colonization on admission (P = .03, odds ratio [OR] = 4.60). In an outcome analysis, ESBL‐PE infection and HAIs were associated with surgery (ESBL‐PE infection: P = .04, OR = 4.70; HAI: P = .004, OR = 6.4) and HAI also was associated with increased duration of hospitalization (P < .001, OR = 9.13). The major colonizing and infecting bacterial species were Escherichia coli and Klebsiella spp. Concordant ESBL‐PE species were recovered from rectal screening and clinical samples in 7.46% (n = 5/67) of foals. Conclusions and Clinical Importance On‐admission ESBL‐PE rectal colonization was associated with ESBL‐PE HAI in neonatal foals. The ESBL‐PE infections were associated with surgery during hospitalization. These findings emphasize the importance of optimal infection control and treatment of clinical infections in equine neonatal intensive care units.

BACKGROUND:Urinary tract infection (UTI) is one of the most common bacterial infections in children. Early antibiotic treatment may prevent complications. Empirical treatment requires up-to-date knowledge of the local epidemiology. This study aims to describe trends in resistance rates in community-acquired UTI between 2017 and 2023, assess whether current recommendations for empirical treatment are valid and identify risk factors for resistance. METHODS:Data were collected retrospectively from the computerized system of Maccabi Health Services for all children under 18 years old diagnosed with a UTI in 2017, 2022 and 2023. Data was evaluated using chi-square tests and regression models to identify resistance trends and associated risk factors. RESULTS:A total of 24,592 urinary samples were included in the study. Escherichia coli was the most frequently isolated pathogen (76%-78%), with higher prevalence among females than males (78.3% vs. 59.3%, P < 0.001). Sensitivity to first-generation cephalosporins improved significantly (73% in 2017 to 82% in 2022, P < 0.001), while second- and third-generation cephalosporins showed minor fluctuations. Resistance to fluoroquinolones increased markedly, from 7% to 20% ( P < 0.001). Female gender, older age, prior antibiotic use and urinary tract abnormalities were significant risk factors for resistance. CONCLUSIONS:The increased resistance rate observed for most pathogens and antibiotics was statistically significant. Nevertheless, due to small absolute changes, the recommendations for empirical antibiotic treatment in Israel are still valid. Fluoroquinolones, which are not recommended as empirical treatment, should be avoided due to high levels of resistance.

Understanding how interpersonal interactions and immunological factors shape SARS-CoV-2 transmission in households is crucial for designing control measures. We developed a Bayesian data augmentation transmission model to evaluate the effects of isolation, parental care, and vaccine-induced immunity on Delta variant transmission from the follow-up of 1,093 Israeli households (July–August 2021). Among the 2883 household contacts, 1096 (38%) were infected. Children were 38% (CI: 7-81) more likely to be infected than adults. Isolation measures reduced transmission by 52% (CI: 46-57). Transmission was 39% (CI: 11-76) higher between children and adult females than males. Vaccine effectiveness was 78% (CI: 54-90), 85% (CI: 70-94), and 73% (CI: 49-88) for one, two, and three doses of recent vaccination (< 90 days), respectively but dropped to 18% (CI: (-6)-36) for two doses administered more than 90 days ago. Household member interactions significantly shaped transmission, and isolation measures effectively reduced transmission.

BACKGROUND:Chronic recalcitrant dermatophyte infection (CRDI) remains poorly understood, with limited research on its genetic, immunological and treatment aspects. OBJECTIVES:To investigate the genetic and immunological profiles, clinical characteristics and treatment outcomes in otherwise healthy patients with CRDI. METHODS:This was a prospective study of patients with isolated superficial dermatophyte infections persisting for > 5 years and refractory to at least three oral antifungal agents. Whole-exome sequencing, interleukin (IL)-17 quantification and lymphocyte subset analysis were performed. RESULTS:Of 5910 patients with superficial cutaneous fungal infections, 11 (10 men; 91%) with a mean (SD) disease duration of 26.4 (8.7) years were included in this study. All patients presented with extensive dermatophytosis, involving a mean (SD) of 5.6 (1.4) skin and nail sites. Immune alterations were identified in 55% (n = 6/11) of the patients, including three with monogenic immunodeficiency mutations (CARD9 and FOXN1), one with acquired immunodeficiency (Good syndrome) and two with isolated IL-17 deficiencies. Most patients (n = 10/11) showed a partial clinical response to continuous oral antifungal therapy, while only one patient remained a complete responder after discontinuing treatment. CONCLUSIONS:CRDI is a rare condition in patients with superficial cutaneous fungal infections. Genetic and immunological evaluation for immunodeficiency should be considered in patients with CRDI. Management may require prolonged or lifelong oral antifungal therapy.