Empirical Choice Research Articles

Exploring the Prevalence, Predictors, and Impact of Bacterial Infections to Guide Empiric Antimicrobial Decisions in Cirrhosis (EPIC-AD)

BackgroundThis study delved into cirrhosis-related infections to unveil their epidemiology, risk factors, and implications for antimicrobial decisions. MethodsWe analyzed acutely decompensated cirrhosis patients (n=971) from North India between 2013-2023 at a tertiary center. Microbiological and clinical features based on infection sites (EASL criteria) and patient outcomes were assessed. ResultsMedian age was 45 years; 87% were males with 47% having alcoholic hepatitis. Of these, 675 (69.5%) had infections; 305 (45%) were culture-confirmed. Notably, 71% of confirmed cases were MDRO-related, chiefly carbapenem-resistant (48%). MDRO prevalence was highest in pulmonary (80.5%) and skin-soft-tissue infections (76.5%). Site-specific distribution and antimicrobials were suggested.Predictive models identified prior hospitalization [OR:2.23 (CI:1.58-3.14)], norfloxacin prophylaxis [OR:2.26 (CI:1.44-3.55)], prior broad-spectrum antibiotic exposure [OR:1.61 (CI:1.12-2.30)], presence of SIRS [OR:1.75 (CI: 1.23-2.47)], procalcitonin [OR:4.64 (CI:3.36-6.40)], and HE grade [OR:1.41 (CI:1.04-1.90)], with an AUC of 0.891 for infection prediction. For MDRO infection prediction, second infection [OR: 7.19 (CI: 4.11-12.56)], norfloxacin prophylaxis [OR: 2.76 (CI: 1.84-4.13)], CLIF-C OF [OR: 1.10 (CI: 1.01-1.20)], prior broad-spectrum antibiotic exposure [OR: 1.66 (CI: 1.07-2.55)], rifaximin [OR: 040 (0.22-0.74)] multisite [OR: 3.67 (CI: 1.07-12.56)], and polymicrobial infection [OR: 4.55 (CI: 1.45-14.17)] yielded an AUC of 0.779 and 93% specificity. Norfloxacin prophylaxis, multisite infection, mechanical ventilation, prior broad-spectrum antibiotic exposure, and infection as acute precipitant predicted carbapenem-resistant infection (AUC: 0.821).Infections (culture-proven or probable), MDROs, carbapenem/pan-drug resistance, and second infections independently linked with mortality (p<0.001), adjusted for age, leucocytosis, and organ failures. A model incorporating age [HR:1.02 (CI: 1.01-1.03), infection [HR:1.52 (CI: 1.05-2.20)], prior hospitalization [HR:5.33 (CI: 3.75-7.57)], norfloxacin [HR:1.29 (CI: 1.01-1.65)], multisite infection [HR:1.47 (CI:1.06-2.04)], and CLIF-C OF [HR:1.17 (CI: 1.11-1.23)] predicted mortality with C-statistics of 0.782 (p<0.05). ConclusionHigh MDRO burden, especially carbapenem-resistant, necessitates urgent control measures in cirrhosis. Site-specific epidemiology and risk models can guide empirical antimicrobial choices in cirrhosis management. Lay summaryOur study delved into infections among hospitalized cirrhosis patients, investigating their occurrence, distribution, risks, and consequences. Notably, infections affected almost 70% of patients, with nearly half of them being confirmed through culture. Most concerning was the identification of multidrug-resistant organisms (MDROs) in 71% of culture-proven cases, particularly carbapenem-resistant bacteria (48%). Pulmonary and skin-soft-tissue infections were the hardest hit. We developed predictive models to foresee infections and particularly drug-resistant and carbapenem-resistant bacterial infections and their mortality. Thus, highlighting the urgent need for measures to counter the substantial impact of MDRO infections in cirrhosis patients. Our findings underscore the importance of targeted antimicrobial therapy guided by site-specific epidemiological insights.

Variational analysis and AI algorithm implementation of free energy landscapes of molecular system

Accurate description of the free energy landscape (FES) is the basis for understanding complex molecular systems, and for further realizing molecular design, manufacture and industrialization. Major challenges include multiple metastable states, which usually are separated by high potential barriers and are not linearly separable, and may exist at multiple levels of time and spatial scales. Consequently FES is not suitable for analytical analysis and brute force simulation. To address these challenges, many enhanced sampling methods have been developed. However, utility of them usually involves many empirical choices, which hinders research advancement, and also makes error control very unimportant. Although variational calculus has been widely applied and achieved great success in physics, engineering and statistics, its application in complex molecular systems has just begun with the development of neural networks. This brief review is to summarize the background, major developments, current limitations, and prospects of applying variation in this field. It is hoped to facilitate the AI algorithm development for complex molecular systems in general, and to promote the further methodological development in this line of research in particular.

Infections in Pregnancy

Abstract Infections in pregnant women tend to be more severe and pose unique treatment challenges. After all, the well-being of two individuals is at stake. Screening all pregnant women in early pregnancy for bacteriuria is recommended. Pyelonephritis and puerperal sepsis should be managed aggressively with appropriate empiric antibiotic choices. Increasing resistance in Enterobacterales is the complicating treatment of both these illnesses in the Indian setting. Influenza can lead to serious maternal and fetal outcomes; early empiric antiviral therapy and universal maternal vaccination are important. Dengue is an important cause of fever in pregnant women and can complicate vaginal and operative delivery due to thrombocytopenia. Falciparum malaria can now be treated with artemisinin-based combination therapy (ACT) in all trimesters. The drug of choice for scrub typhus is azithromycin; a combination of doxycycline and azithromycin can be considered in very severe disease. Treatment of both drug-sensitive and drug-resistant tuberculosis in pregnancy is similar to the nonpregnant. Safety data relating to bedaquiline and delamanid from animal models and cohort studies are reassuring.

Bayesian Approach to Estimate Distribution of Relaxation Times for Lithium-Ion Batteries

Electrochemical impedance spectroscopy (EIS) has emerged as a powerful tool for analyzing the state of lithium-ion batteries due to its ability to provide rich electrochemical information. Traditionally, equivalent circuit and physical models have been utilized for interpreting EIS data. However, these methods possess inherent drawbacks: equivalent circuit models are non-unique, while physical models can be challenging to implement. As an alternative, the distribution of relaxation times (DRT) has garnered increasing attention in recent years. The DRT method enables the analysis of EIS data without predefining a model's shape, allowing for the decomposition of internal characteristics in complex systems, such as lithium-ion batteries. Despite its advantages, DRT estimation is an ill-posed inverse problem that often requires regularization or fine-tuning based on empirical choices, which can lead to the misinterpretation of EIS data.To address these challenges, we propose a Bayesian approach that enables the estimation of DRT while considering uncertainties, even in the presence of observational errors in EIS data. Moreover, the proposed method can assist in estimating the state of health (SOH) of the battery, which provides valuable insights into the battery's overall performance, longevity, and safety. To validate the efficacy of our proposed method, we apply it to synthetic EIS data and compare its performance with existing DRT estimation methods. The results show that the proposed Bayesian approach offers a more robust and accurate estimation of DRT. We also demonstrate the practical applicability of the proposed method by applying it to real lithium-ion battery EIS experimental data, where it successfully extracts meaningful information about the battery's internal state and SOH. In summary, the proposed DRT-based Bayesian method has the potential to enable a robust diagnosis of the internal state and SOH of lithium-ion batteries through EIS measurements. By incorporating this approach, researchers and industry practitioners can gain a deeper understanding of battery performance, facilitating the development of improved diagnostic techniques and battery management strategies to enhance the performance and reliability of lithium-ion batteries. This, in turn, could contribute to the broader adoption of sustainable energy solutions, such as electric vehicles and renewable energy storage systems.This work was supported by the Korea Institute of Energy Technology Evaluation and Planning (KETEP) grants funded by the Ministry of Trade, Industry & Energy, Republic of Korea (No. 20214910100070). Figure 1

Using wafer scale ferroelectric domains of LiNbO3 to form permanent planar p–n junction in narrow band gap nanocrystals

p–n junctions based on nanocrystals now serve as fundamental components in optoelectronics. However, the process of designing these p–n junctions has largely relied on empirical choices, either for ligand exchange or for the selection of charge transport layers. Therefore, a systematic strategy is still lacking. In this study, we explore the utilization of ferroelectric domains as a general method for remotely inducing the formation of a p–n junction. To ensure compatibility with devices of various designs, we employ a commercially available periodically poled LiNbO3 (PPLN) substrate commonly used in nonlinear optics. We engineer a PPLN/graphene/HgTe heterostructure and demonstrate its planar photodiode behavior. Through x-ray photoemission microscopy, we confirm that the rectifying behavior stems from the influence of the ferroelectric domains, by ruling out the possibility of the formation of non-ohmic contacts at the electrode/semiconductor interfaces. This approach proves to be quite general and holds promise for the future design of high-speed nanocrystal-based photodiodes.

2951. Nursing home clinician characteristics associated with simulated urinary tract infection treatment decision-making

Abstract Background Antibiotic overuse and misuse are common in nursing homes (NHs). Urinary tract infection (UTI) is the most common indication for antibiotics in NHs. We conducted a clinical vignette experiment to identify clinician-level characteristics associated with suboptimal UTI treatment decision-making among a sample of NH clinicians. Methods Six clinical vignettes, two designed to assess clinicians’ treatment threshold and four designed to assess antibiotic choice decision-making, were created through an iterative process. NH clinicians were recruited nationally via professional organizations from December 2021 to April 2022. Clinical vignettes were shared using a web-based survey tool (Qualtrics) during which participants were asked if they would initiate antibiotics and which one. Participants provided demographic information, including degree, specialty training and NH experience. A multivariable logistic regression model with the decision to initiate antibiotic therapy (Yes/No) as the dependent variable and a multivariable ordinal regression model with number of vignettes for which a fluoroquinolone (FQ) was empirically chosen as the dependent variable were constructed in R. Results A total of 298 NH clinicians, whose characteristics are detailed in Table 1, responded to the survey. Despite national guidelines not recommending treatment for asymptomatic bacteriuiria (ASB), 10.4% of participants chose to initiate antibiotics when presented with the ASB vignette. Physicians (vs. APPs) and clinicians with ≥ 10 years NH experience were less likely to initiate antibiotics for ASB (Table 2). Empiric treatment was withheld for simple cystitis by 38.9% of clinicians, with APPs more likely to withhold antibiotics than physicians (Table 2). Across the four cases assessing empiric antibiotic choice, 38.3% of clinicians chose a FQ in at least one clinical case (Table 1). Clinicians with more years of NH-practice experience were more likely to prescribe a FQ (aOR 2.41, 95% CI 1.47-3.95, p&amp;lt; 0.01, Table 2). Respondent Characteristics Abbreviations: Advanced Practice Provider (APP); Asymptomatic bacteriuria (ASB); Fluoroquinolone (FQ), Nursing Home (NH). Effect of clinician credentials, training, and experience on antibiotic prescribing for urinary tract infection Abbreviations: * reference; Adjusted odds ratio (aOR); Confidence interval (CI); Asymptomatic bacteriuria (ASB); Advanced practitioner (APP) Conclusion Our results indicate that specific clinician characteristics are associated with suboptimal antibiotic prescribing. This suggests that tailoring stewardship interventions to clinician-specific factors may augment ongoing efforts to improve antibiotic use in NHs. Disclosures Lindsay Taylor, MD, MS, Merck: Grant/Research Support Robin Jump, MD, PhD, Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support

Assessing the impact of discordant antibiotic treatment on adverse outcomes in community-onset UTI: a retrospective cohort study.

To investigate the risk of adverse outcomes following discordant antibiotic treatment (urinary organism resistant) for culture-confirmed community-onset lower urinary tract infection (UTI). Cohort study using routinely collected linked primary care, secondary care and microbiology data from patients with culture-confirmed community-onset lower UTI (COLUTI). Antibiotic treatment within ±3 days was considered concordant if the urinary organism was sensitive and discordant if resistant.The primary outcome was the proportion of patients experiencing urinary infection-related hospital admission (UHA) within 30 days. Secondary outcomes were the proportion of patients experiencing reconsultation within 30 days, and the odds of UHA and reconsultation following discordant treatment, adjusting for sex, age, risk factors for complicated UTI, previous antibiotic treatment, recurrent UTI and comorbidities. A total of 11 963 UTI episodes in 8324 patients were included, and 1686 episodes (14.1%, 95% CI 13.5%-14.7%) were discordant. UHA occurred in 212/10 277 concordant episodes (2.1%, 95% CI 1.8%-2.4%) and 88/1686 discordant episodes (5.2%, 95% CI 4.2%-6.4%). Reconsultation occurred in 3961 concordant (38.5%, 95% CI 37.6%-39.5%) and 1472 discordant episodes (87.3%, 95% CI 85.6%-88.8%). Discordant treatment compared with concordant was associated with increased odds of UHA (adjusted OR 2.31, 95% CI 1.77-3.0, P < 0.001) and reconsultation (adjusted OR 11.25, 95% CI 9.66-13.11, P < 0.001) on multivariable analysis. Chronic kidney disease and diabetes mellitus were also independently associated with increased odds of UHA. One in seven COLUTI episodes in primary care were treated with discordant antibiotics. In higher risk patients requiring urine culture, empirical antibiotic choice optimization could meaningfully reduce adverse outcomes.

Association Between Common Empiric Antibiotic Regimens and Clostridioides Difficile Infection in Pediatric Appendicitis

BackgroundClostridioides Difficile Infection (CDI) is a serious antibiotic related complication that has been reported among children undergoing treatment of appendicitis. CDI likelihood amongst different empiric antibiotic regimens for appendicitis remains unclear but likely has important implications for antibiotic stewardship. MethodsA retrospective cohort study of the Pediatric Health Information System was used to examine patients ages 1 through 18 who received operative management of acute appendicitis. Common empiric antibiotic regimens 1) Ceftriaxone & Metronidazole (CM) 2) Piperacillin & Tazobactam (PT) and 3) Cefoxitin were compared. Study outcomes were CDI within 28 days post-appendectomy and 30-day post-appendectomy percutaneous drainage procedures. Subset analyses were repeated to only include hospitals that standardized empiric antibiotic choice. ResultsOf 105,911 patients, 220 (0.21 %) developed CDI. CDI was more common in patients that received CM (CM 0.29 % vs PT 0.15 % vs Cefoxitin 0.18 %; P < 0.01). On adjusted analysis, PT was associated with a lower likelihood of CDI (OR, 0.48; 95%CI, 0.31–0.74) compared to CM which was consistent in hospitals with standardized antibiotic choice. Exposure to more unique antibiotic regimens (OR, 1.70; 95 % CI, 1.50–1.93) and higher total antibiotic days (OR, 1.17; 95 % CI 1.13–1.21) were associated with an increased likelihood of CDI. There was no significant difference in the likelihood of post-appendectomy percutaneous drainage between antibiotic regimens. ConclusionsCDI is rare following appendectomy for pediatric appendicitis. While PT was associated with statistically lower rates of CDI compared to CM, antibiotic stewardship efforts to avoid mixed regimens and decrease overall antibiotic exposure warrant exploration. Level of EvidenceLevel III.

Investigation of etiology of community-acquired pneumonia in hospitalized patients in a tertiary hospital of São Paulo City, Brazil

BackgroundCommunity-Acquired Pneumonia (CAP) is the primary cause of hospitalization in the United States and the third leading cause of death in Brazil. The gold standard for diagnosing the etiology of CAP includes blood culture, Gram-stained sputum, and sputum culture. However, these methods have low sensitivity. No studies investigating the etiology of CAP have been conducted in Brazil in the last 20-years, and the empirical choice of antimicrobials is mainly based on the IDSA guidelines. This is the first national study with this aim, and as a result, there's potential for the Brazilian consensus to be impacted and possibly modify its guidelines rather than adhering strictly to the IDSA's recommendations. MethodsThe aim of this study is to identify the main microorganisms implicated in CAP by employing a multiplex Polymerase Chain Reaction (mPCR) at the foremost public hospital in Brazil. All patients who were admitted to the emergency department and diagnosed with severe CAP underwent an mPCR panel using nasopharyngeal and oropharyngeal swabs, with the aim of detecting 13 bacterial and 21 viral pathogens. ResultsA total of 169 patients were enrolled in the study. The mPCR panel identified an etiological agent in 61.5% of patients, with viruses being the most common (42.01%), led by Rhinovirus, followed by Influenza and Coronavirus (non-SARS-CoV-2). Bacterial agents were identified in 34.91% of patients, with S. pneumoniae being the most common, followed by H. influenzae, M. catarrhalis, and S. aureus. Additionally, we found that the prescription for 92.3% of patients could be modified, with most changes involving de-escalation of antibiotics and antiviral therapy. ConclusionOur study revealed different etiological causes of CAP than those suggested by the Brazilian guidelines. Using molecular diagnostic tests, we were able to optimize treatment by using fewer antibiotics.

Appropriateness of the Empirical Antibiotherapy Choices of Primary Care Physicians for the Treatment of Uncomplicated Cystitis

Appropriateness of the Empirical Antibiotherapy Choices of Primary Care Physicians for the Treatment of Uncomplicated Cystitis

61 Antibiotic Resistant Patterns of Bacterial Pathogens Causing Invasive Neonatal Infections in Northern Alberta

Abstract Background Antimicrobial resistance is one of the most serious global health threats facing the world today. The neonatal intensive care unit (NICU) is a clinical environment that houses newborn infants who are highly susceptible to overwhelming infection. Early and decisive treatment with powerful anti-microbials tends to be the preferred clinical choice for treating sick infants empirically. Prolonged exposure to antimicrobials can result in multi-drug resistant organisms (MDROs), which can be associated with mortality due to an increase in virulence, delay in appropriate treatment, and a lack of treatment options. An updated antibiogram is important for determining the optimal empirical antimicrobial choice for sepsis evaluations. There is currently a lack of antimicrobial susceptibility data for bacterial pathogens in the Northern Alberta region. Objectives The objective of this study is to understand the antibiotic resistance patterns among isolates responsible for bacteremia and meningitis in the NICUs in Northern Alberta through the standard antibiograms produced by microbiology laboratories. Design/Methods We conducted a retrospective study to analyze antimicrobial resistance patterns found in NICUs during 2013-2021 in Northern Alberta. Bacteria isolated from blood and cerebrospinal fluid according to commonly used antibiotics in NICUs were collated to create a provincial antibiogram. Results A total of 5562 isolates were included in this antibiogram. The most frequently isolated organisms were Escherichia coli (1521), Staphylococcus aureus (1157), members of coagulase-negative staphylococcus (534), Enterococcus faecalis (326), and Klebsiella pneumoniae (357) in neonatal populations. Among the 1157 S. aureus isolates, 24% were resistant to oxacillin (i.e., “methicillin-resistant S. aureus” or MRSA) and 1% were resistant to vancomycin (i.e., “vancomycin-resistant S. aureus” or VRSA). Of the 326 strains of Enterococcus spp., there were no vancomycin-resistant enterococci (VRE) identified. Among gram-negative isolates, 251 out of the 2690 (9.6%) were producing extended-spectrum beta-lactamase (ESBL), in which 52% and 94% were susceptible to gentamicin and amikacin respectively. Among the non-ESBL-producing isolates, E. coli (1521) and K. pneumoniae (357), 7% of the E. coli strains and 1% of the K. pneumoniae strains were resistant to gentamicin. Conclusion The provincial antibiogram is a useful clinical tool that can best inform clinicians on the appropriate choice of empirical antimicrobial agent based on commonly identified invasive pathogens in neonatal infections within Northern Alberta. Our findings on these resistant patterns can aid next steps for developing an antimicrobial stewardship program.

GLAcier Feature Tracking testkit (GLAFT): a statistically and physically based framework for evaluating glacier velocity products derived from optical satellite image feature tracking

Abstract. Glacier velocity measurements are essential to understand ice flow mechanics, monitor natural hazards, and make accurate projections of future sea-level rise. Despite these important applications, the method most commonly used to derive glacier velocity maps, feature tracking, relies on empirical parameter choices that rarely account for glacier physics or uncertainty. Here we test two statistics- and physics-based metrics to evaluate velocity maps derived from optical satellite images of Kaskawulsh Glacier, Yukon, Canada, using a range of existing feature-tracking workflows. Based on inter-comparisons with ground truth data, velocity maps with metrics falling within our recommended ranges contain fewer erroneous measurements and more spatially correlated noise than velocity maps with metrics that deviate from those ranges. Thus, these metric ranges are suitable for refining feature-tracking workflows and evaluating the resulting velocity products. We have released an open-source software package for computing and visualizing these metrics, the GLAcier Feature Tracking testkit (GLAFT).

Developing an antibiogram for empiric antibiotic prescribing for adult non-spinal orthopaedic infections in a developing world setting

PurposeEmpiric antibiotic strategies in the treatment of fracture-related infections, chronic osteomyelitis, prosthetic joint infection, and septic arthritis should be based on local microbiological antibiograms. This study aims to describe the microbiology and review the antibiogram profiles of bacterial isolates from patients undergoing surgical treatment for non-spinal orthopaedic infections, to identify the most appropriate empiric antibiotic strategy.MethodsA retrospective review was performed of all cases of non-spinal orthopaedic infections treated surgically from 1 January 2018 to 31 December 2018. The National Health Laboratory Service microbiology database was used to identify all intra-operative microbiological specimens obtained from orthopaedic patients, and data were correlated with the orthopaedic surgical database. Cases were divided into fracture-related infections, chronic osteomyelitis, prosthetic joint infection, and septic arthritis. Antibiotic susceptibility data were used to predict the efficacy of different empiric antibiotic regimens.ResultsA total of 107 cases were included in the study; 184 organisms were cultured. Overall, the most common organism cultured was Staphylococcus aureus (25%) followed by Acinetobacter baumannii (9%), Enterococcus faecalis (7%) and Enterobacter cloacae (5%). Across all categories the oral antibiotic combination with the highest effectiveness (81%) would have been a combination of co-trimoxazole, ciprofloxacin and amoxicillin. The most effective intravenous antibiotic combination would have been either piperacillin–tazobactam, amikacin and vancomycin or meropenem and vancomycin; 90% of tested isolates were susceptible to either of these combinations.ConclusionAntibiogram profiles can serve to guide to empiric antibiotic choice in the management of different categories of non-spinal orthopaedic infections.

Microbiological Profile of Fracture Related Infection at a UK Major Trauma Centre.

Fracture Related Infection (FRI) represents one of the biggest challenges for Trauma and Orthopaedic surgery. A better understanding of the microbiological profile should assist with decision-making and optimising outcomes. Our primary aim was to report on the microbiological profile of FRI cases treated over a six-year period at one of Europe's busiest trauma centres. Secondarily, we sought to correlate our findings with existing anti-microbiological protocols and report on diagnostic techniques employed in our practice. All adult cases of FRI treated in our institution between 2016 and 2021 were identified, retrospectively. We recorded patient demographics, diagnostic strategies, causative organisms and antibiotic susceptibilities. There were 330 infection episodes in 294 patients. A total of 463 potentially pathogenic organisms (78 different species) were identified from cultures, of which 57.2% were gram-positive and 39.7% gram-negative. Polymicrobial cultures were found in 33.6% of cases and no causative organism was found in 17.5%. The most prevalent organisms were Staphylococcus aureus (24.4%), coagulase-negative Staphylococci (14%), Pseudomonas aeruginosa (8.2%), Enterobacter species (7.8%) and Escherichia coli (6.9%). Resistant gram-positive organisms (methicillin resistant Staphylococcus aureus or vancomycin-resistant Enterococci) were implicated in 3.3% of infection episodes and resistant gram-negatives (extended-spectrum beta-lactamase, ampC or carbapenemase-producing bacteria) in 13.6%. The organisms cultured in 96.3% of infection episodes would have been covered by our empirical systemic antibiotic choice of teicoplanin and meropenem. To our knowledge, this is the largest reported single-centre cohort of FRIs from a major trauma centre. Our results demonstrate patterns in microbiological profiles that should serve to inform the decision-making process regarding antibiotic choices for both prophylaxis and treatment.

Detection of barely visible impact damage in composite plates using non-linear pump-probe technique

In the last decades, composite materials have been increasingly used in aircraft structures as a mean to reduce the weight. For safety reasons, periodic checks of impact-induced damage need to be performed. In that framework, ultrasound non destructive testing has proven its ability to detect macro-defects such as delamination. However, at early stages, Barely Visible Impact Damage (BVID) may not be detected via linear ultrasound techniques. In recent years, non-linear ultrasound has gained traction for the inspection of such defects. However, detection of the weak non-linear defect signature buried in ambient noise remains challenging, and depends on an empirical choice of excitation frequencies. This study focuses on the evaluation of a non-linear pump probe ultrasound inspection technique applied to BVID in multilayer carbon fibre reinforced composites used in aeronautics. In particular, the influence of various experimental parameters on the measured non-linear response is studied. A low frequency pump wave (via a shaker) and a high frequency wave (via a piezoelectric transducer) are transmitted to the medium while a second transducer records the ultrasonic response. Both pump and probe waves are sent in the form of a few secondslong frequency sweep, in the audible and ultrasonic range respectively. Appropriate post processing is then applied to the recorded signals to retrieve the non-linear response of the defect. The procedure is repeated on several composite plates with and without impact damages. The nonlinear response appears in the form of modulation sidebands in the frequency spectrum of the post-processed signals. The relative amplitudes of the side bands obtained for the various samples with various defect sizes and excitation amplitude or frequency content are studied. Optimal experimental parameters were obtained and led to a good detection of defects. The limits of the method are also discussed.

Modeling the Free Inclinations of the Classical Kuiper Belt with the von Mises–Fisher Distribution

The orientations of orbital planes of minor planets are directional random variables. Their free inclination is the deviation of the orbit plane from the plane forced by the major planets. We construct a model of the distribution of free inclinations of classical Kuiper Belt objects (CKBOs) based on the von Mises–Fisher (vMF) distribution function, the analog of the normal distribution for directional statistics. The CKBOs are known to have a “cold” component of orbit planes concentrated near the forced plane and a more widely dispersed “hot” component. Adopting a model with a linear combination of two vMF functions, we find that the cold and hot components account for 57% and 43%, characterized by widths of 1.°7 and 12.°9, respectively. This model improves upon previous models based on smaller observational samples and empirical choices of functional forms for inclination distributions.

Benefits and challenges of creating veterinary antibiograms for empiric antimicrobial selection in support of antimicrobial stewardship and advancement of one-health goals.

Antibiograms are important tools for antimicrobial stewardship that are often underutilized in veterinary medicine. Antibiograms summarize cumulative antimicrobial susceptibility testing (AST) data for specific pathogens over a defined time period; in veterinary medicine, they are often stratified by host species and site of infection. They can aid practitioners with empiric therapy choices and assessment of antimicrobial resistance trends within a population in support of one-health goals for antimicrobial stewardship. For optimal application, consideration must be given to the number of isolates used, the timeframe of sample collection, laboratory analytical methodology, and the patient population contributing to the data (eg, treatment history, geographic region, and production type). There are several limitations to veterinary antibiograms, including a lack of breakpoint availability for bacterial species, a lack of standardization of laboratory methodology and technology for culture and AST, and a lack of funding to staff veterinary diagnostic laboratories at a level that supports antibiogram development and education. It is vital that veterinarians who use antibiograms understand how to apply them in practice and receive relevant information pertaining to the data to utilize the most appropriate antibiogram for their patients. This paper explores the benefits and challenges of developing and using veterinary antibiograms and proposes strategies to enhance their applicability and accuracy. Further detail regarding the application of veterinary antibiograms by privately practicing clinicians is addressed in the companion Currents in One Health article by Lorenz et al (JAVMA, September 2023).

Elizabethkingia meningosepticum infections with varied presentations and different antimicrobial susceptibility - A case series.

We report three sporadic infections by Elizabethkingia meningosepticum from Government Medical College Kozhikode in Kerala state, South India over a period of three years. Two cases were commenced in the community in immunocompromised children beyond the newborn period, but both recovered promptly. Another was a hospital-acquired meningitis in a newborn baby who developed neurologic sequelae. In contrast to widespread antimicrobial resistance exhibited by this pathogen, there was good susceptibility to commonly used antimicrobials such as ampicillin, cefotaxime, piperacillin, ciprofloxacin, and vancomycin. Whilst ß lactam antibiotics are found effective in the treatment of Elizabethkingia septicaemia of children, piperacillin-tazobactam, vancomycin combination seems effective empiric choice of antibiotics for neonatal meningitis due to Elizabethkingia; there is a need for guidelines for the management of this infection, especially in neonatal meningitis.

Carbapenem-resistant Enterobacterales susceptibility patterns to new antimicrobials: A single-center analysis

Background: Multidrug-resistant bacteria are of high concern, and empiric antimicrobial choice for infections caused by these pathogens, while awaiting susceptibilities, is increasingly encountered. We describe the susceptibility patterns of ceftazidime-avibactam (CZA), imipenem-rel-ebactam (I-R), meropenem-vaborbactam (MVB), cefiderocol (FDC), ceftolozone-tazobactam (C/T), minocycline (MIN), and tigecycline (TGC) for carbapenem-resistant Enterobacterales at an academic medical center. Methods: We performed a single-center analysis of Enterobacterales isolates from 110 hospitalized adult patients who had CZA, I-R, MVB, FDC, MIN, or TGC susceptibility testing performed between October 2020 and September 2022. The study included 1 isolate per patient per infection site per year. Isolates were divided into carbapenem susceptible and non susceptible categories. For carbapenem nonsusceptible isolates, phenotypic confirmatory testing of carbapenem nonsusceptibility was performed using disk diffusion, gradient diffusion, and/or broth microdilution. Interpretive categories were applied using CLSI- or FDA-approved break-points where applicable. Carbapenemase testing was also performed using the modified carbapenem inactivation method (mCIM) and, where applicable, this testing was confirmed at the Massachusetts State Public Health Laboratory using genotypic methods. Results: In total, 125 unique isolates were reviewed: 34 meropenem-susceptible and 91 meropenem-intermediate or resistant isolates. CZA, I-R, MVB, and FDC were active against all tested meropenem-susceptible isolates; however, 50% of tested isolates were susceptible to C/T. MIN and TGC, when tested, were active against 2 of 11 isolates (18%) and 14 of 16 isolates (86%), respectively. Of 91 meropenem-nonsusceptible isolates, most tested isolates were susceptible to MVB (59 of 72, 82%), followed by CZA (63 of 82, 77%), I-R (8 of 11, 73%), FDC (9 of 16, 56%), and C/T (1 of 12, 8%). TGC retained activity against 78 of 81 (96%) tested isolates. In contrast, MIN retained activity against 8 of 45 isolates (18%). Additionally, all (28 of 28, 100%) isolates that were nonsusceptible to at least 1 novel agent (CZA, I-R, MVB, FDC, or C/T) remained susceptible to TGC. State laboratory confirmatory testing was available for 75 isolates. Of 43 mCIM-positive isolates, all 28 KPC-producing isolates were susceptible to CZA, I-R, MVB, FDC and TGC. Conclusions: Among Enterobacterales, CZA, MVB, and I-R retained activity against most non-NDM CRE isolates in this local analysis, with comparable susceptibilities. TGC demonstrated excellent susceptibility for CRE and meropenem-susceptible isolates, offering an alternative for nonbloodstream infections. Choice of empiric agent with a newβ-lactam, β-lactam–β-lactamase inhibitors, or TGC appear to be reasonable empiric therapeutic options at our institution. CT and MIN warrant confirmatory testing prior to use due to low susceptibility rates among meropenem nonsusceptible isolates.Disclosures: None

A new partition method for DIRECT-type algorithm based on minimax design

This article presents a new DIRECT-type SCABALL (scattering balls) algorithm with a new partition method for derivation-free optimization problems. It does not focus on dividing the region of interest into specific geometric shapes, but rather scatters several balls to cover it. In SCABALL, several potential optimal regions are selected at each iteration, and they are covered by smaller balls sequentially. In this way, the SCABALL ensures the everywhere dense convergence. The center points and radii of the scattered balls significantly influence the efficiency of SCABALL; therefore, the minimax designs are used in the initial and sequential stages to obtain better coverage. The SCABALL parameters, including the number of balls and their radii, were analyzed by numerical investigation. We provided the empirical choices for those parameters and found that the balls’ radii can be contracted to balance efficiency and global convergence. Numerical experiments show that the SCABALL algorithm is locally biased and robust.