Antimicrobial Stewardship Research Articles

Pathogen-Directed Antimicrobial Stewardship Audit Rounds: Evaluation of an Objectively Planned, Clinical Microbiology-Driven Antimicrobial Stewardship Approach to Influence Antimicrobial Prescriptions of Prescribers.

Correct and prompt antimicrobial prescription modifications by the treating team based on the culture and antimicrobial susceptibility test (AST) reports are crucial. Pathogen-directed antimicrobial stewardship (PD-AMS) audit rounds are a clinical microbiology-driven approach to combine prompt appropriate patient management goals with goals of preventing irrational and improper use of antimicrobials. The study was a prospective before-after interventional study to evaluate the effectiveness of PD-AMS audit rounds in modifying antimicrobial usage by prescribers on an individual patient basis. It is divided into a two-month pre-intervention phase (no active advice is given with passive monitoring) and an intervention phase for four months, with antimicrobial therapy-related advice during PD-AMS rounds taken as "Intervention."Antimicrobial advice was objectively classified into various categories. The PD-AMS audit round was conducted for all inpatients with a culture-proven bloodstream infection with a pathogen, and objectively classified antimicrobial advice was given through bedside rounds, telephonically, and/or written advice forms. Compliance with the advice was monitored on the next day (or at the end of 24 hours) of the PD-AMS round. The compliance with culture AST report regarding antimicrobial prescription modifications improved significantly in the intervention phase compared to the pre-intervention phase as follows: overall (83.8% (612/730) vs. 56.7% (242/427)); medicine alliance (87.4% (263/301) vs. 57.8% (115/199)); surgery alliance (87.2% (170/195) vs. 54.0% (87/161)); pediatric alliance (87.3% (138/158) vs. 66.7% (26/39)); oncology alliance (53.9% (41/76) vs. 28.6% (8/28)); critical care locations (82.0% (260/317) vs. 62.7% (89/142)); and in-patient departments (85.2% (352/413) vs. 53.7% (153/285)). The clinical microbiology team should mandatorily conduct an objectively planned PD-AMS audit round to improve patient care and management and antimicrobial prescriptions through a mutual discussion with prescribers and to help address their doubts.

The impact of the COVID-19 pandemic on antibiotic prescription rates in out-of-hours primary care – a register-based study in Denmark

Background Antibiotic prescription rates can be affected by pandemic measures such as lockdowns, social distancing, and remote consultations in general practice. Therefore, such emergency states may negatively affect antimicrobial stewardship, specifically in out-of-hours (OOH) primary care. As contact patterns changed in the COVID-19 pandemic, it would be relevant to explore the impact on antimicrobial stewardship. Aim To study the impact of the pandemic on antibiotic prescription rates in OOH primary care, overall and per age group. Methods This cross-sectional register-based study used routine data from OOH primary care in the Central Denmark Region. We included all patient contacts in two equivalent time periods: pre-pandemic and pandemic period. The main outcome measure was defined as the number of antibiotic prescriptions per contact (antibiotic prescription rate). Results The overall antibiotic prescription rate decreased during the first year of the pandemic compared to the pre-pandemic period (RR = 0.97, 95%CI: 0.96–0.98). Likewise, the rate decreased for clinic consultations (RR = 0.63, 95%CI: 0.62–0.64). However, an increase was seen for telephone consultations (RR = 1.73, 95%CI: 1.70–1.76). The decline in clinic consultations was largest for consultations involving children aged 0–10 years (RR = 0.53, 95%CI: 0.51–0.56). Conclusion Antibiotic prescription rates in Danish OOH primary care decreased during the first year of the COVID-19 pandemic, especially for young children. Prescription rates decreased in clinic consultations, whereas the rates increased in telephone consultations. Further research should explore if antibiotic prescription rates have returned to pre-pandemic levels, and if the introduction of video consultations has affected antibiotic prescription patterns in OOH primary care.

Appropriateness of antibiotic prescribing among patients treated for dental diseases in Mekelle city, Northern Ethiopia: a cross sectional study

BackgroundLocal operative treatments are generally preferred for most dental diseases, with antibiotics only recommended as an adjunct in specific cases. Misuse and overuse of antibiotics has been shown to significantly contribute to the development of resistant bacteria. However, the antibiotic prescribing practices of dentists in Ethiopia have not been thoroughly studied. This study aimed to assess the appropriateness of antibiotic prescribing for patients with dental diseases at dental clinics in Mekelle City, Northern Ethiopia.MethodsA cross sectional study was conducted in April and May 2020 among patients visiting dental clinics in Mekelle City. Data were collected through patient medical record reviews and dentist interviews. The appropriateness of antibiotic prescription was evaluated based on guidelines from the American Dental Association and the European Society of Endodontology. Data were analyzed using SPSS Statistics, version 29. Binary logistic regression analysis was performed, and the results were presented as odds ratios with 95% confidence intervals. A p value less than 0.05 was considered statistically significant.ResultsTwo hundred and thirty-one patients with dental diseases participated in the study. The mean age was 30.6 years with a standard deviation of 16.1. Most participants had dental pulp related disease. 89% of patients were prescribed antibiotics, with amoxicillin being the most common. Inappropriate antibiotic prescribing was identified in 175 (75.8%) of the study participants. The most common inappropriate prescribing was unnecessary antibiotic prescribing for dental conditions without systemic signs, assessed in 141 (80.1%) participants. Patients diagnosed with pulp related disease without systemic signs and those who had tooth extractions were significantly associated with inappropriate antibiotic prescription (p value < 0.001).ConclusionsThe study findings show that antibiotics are over-prescribed for dental conditions in this resource constrained setting, especially in patients who have had tooth extractions. Dentists need training on appropriate antibiotic use and antimicrobial stewardship interventions should be implemented in dental setting to reduce unnecessary antibiotic prescriptions and prevent antibiotic resistance development.

The Challenges of Treating a Helicobacter pylori Infection following the COVID-19 Pandemic in Croatia: A Review.

Background:Helicobacter pylori (H. pylori) is a prevalent bacterial pathogen implicated in different stomach and duodenal diseases, including chronic gastritis, gastric and duodenal ulcer, and stomach cancer. The COVID-19 pandemic has significantly influenced antibiotic prescription practices, potentially exacerbating antibiotic resistance in H. pylori. Objective: This study aims to investigate antibiotic prescription during the COVID-19 pandemic in Croatia and its possible impact on H. pylori antibiotic resistance, with a focus on Croatia. Methods: An extensive literature search was conducted to identify relevant studies from March 2020 to June 2024. The search strategy included terms related to COVID-19, antibiotic prescription, and Croatia. Studies were selected based on predefined eligibility criteria, focusing on observational research addressing antibiotic use during the pandemic. Results: The COVID-19 pandemic has led to significant fluctuations in community antibiotic consumption within the European Union/European Economic Area. In Croatia, antibiotic use in 2022 surpassed 2019 levels, driven by increased consumption of macrolides and other antibiotics. This surge, influenced by early pandemic treatment claims and penicillin shortages, contributed to rising antibiotic resistance in H. pylori. Resistance rates to clarithromycin and levofloxacin were notably high, driven by mutations in the 23S rRNA, gyrA, and gyrB genes. Discussion: The increased antibiotic use during the COVID-19 pandemic has highly likely complicated H. pylori eradication efforts, highlighting the necessity of judicious antibiotic use and robust antimicrobial stewardship. The pandemic underscored the need for new therapeutic strategies, optimized eradication regimens, and advanced diagnostic methods to manage bacterial infections effectively. Conclusions: The COVID-19 pandemic has significantly affected antibiotic use and resistance patterns, posing new challenges for H. pylori eradication. Addressing these challenges requires a multifaceted approach, including the development of new drugs and advanced diagnostics, coupled with sustained efforts in antimicrobial stewardship to combat emerging resistance threats.

Extended and expanded role of nurses in antimicrobial stewardship program: A review

Antimicrobial resistance is a significant healthcare concern in this century, marked by the emergence of multidrug-resistant microorganisms. An antimicrobial stewardship program, while an innovative approach to mitigating the global threat of antimicrobial resistance and its effects on public health, is also an absolute need of the hour. When implemented effectively, such a program, in conjunction with selecting the appropriate drug, determining the correct dosage and route of administration, and integrating with an infection control program, has proven to be an effective method for curbing the rapid emergence and transmission of antimicrobial-resistant pathogens. Partnerships with nurses to strengthen antimicrobial stewardship programs in healthcare have recently gained recognition, especially in the backdrop of increased antimicrobial resistance in developing countries. Traditionally, stewardship activities have involved only prescribers and pharmacists, but including nurses in these efforts has become increasingly important. Highlights of nurse-driven antimicrobial stewardship activities include effective assessment of allergies, meticulous sampling for blood and urine cultures, antibiotic de-escalation, and 24-hour monitoring of patient status. Antibiotic or general ward rounds provide unique opportunities for nurses to influence the indication and duration of antimicrobial treatment. Including nurses in antimicrobial stewardship programs will make the management of antimicrobial therapy robust and empower healthcare institutions to approach the prevention of AMR with truly multi-disciplinary strategies. Antimicrobial stewardship is often redundant and centered around doctors in tertiary care centers. However, active participation by nurses in both healthcare facilities and community settings is crucial for making Antimicrobial stewardship practice (AMSP) a reality. Scalable nursing involvement in antimicrobial stewardship is essential for developing and developed nations to combat AMR effectively.

Prescription of oral antibiotics and its appropriateness for outpatients in a tertiary care hospital in Korea

Antimicrobial stewardship programs (ASPs) have gained prominence with increased awareness regarding the importance of appropriate antibiotic use. However, ASP implementation for outpatient antibiotic prescriptions is uncommon, particularly in South Korea. This study aimed to analyse the patterns and appropriateness of outpatient antibiotic prescriptions at a tertiary care hospital in Korea. We analysed the patterns of oral antibiotic prescription from June 1, 2018 to May 31, 2023, at the outpatient department of Seoul National University Bundang Hospital. Appropriateness was assessed for prescriptions issued between May 15 and May 19, 2023. The assessment criteria included: indications for antibiotic use, antibiotic choice, duration, dose, and frequency. Pharmacists and infectious diseases specialists performed evaluations. A total of 7,282,407 outpatient visits were recorded within the 5-year duration. Of these, 243,967 (3.4%) were prescribed oral antibiotics. The frequency of antibiotic prescription was highest in dentistry, dermatology, and urology departments. The most commonly prescribed antibiotics were cephalosporins, penicillins, and sulphonamides. Of the 423 prescriptions evaluated, 289 (68.3%) and 134 (31.7%) were for treatment and prophylaxis, respectively. Inappropriate prescriptions were identified in 28.4% (82/289) and 70.9% (95/134) of the treatment and prophylaxis cases, respectively. The primary reason for inadequacy in both treatment and prophylaxis was inappropriate indications, accounting for 46.3% (38/82) of treatment prescriptions and 96.8% (92/95) of prophylaxis prescriptions. Antibiotics were administered in 3.4% of all outpatient visits, with 28.4% of treatment and 70.9% of prophylactic antibiotics prescribed inappropriately. Proactive and expansive ASP activities by pharmacists should be considered in outpatient settings.

Durations of Antibiotic Treatment for Acute Otitis Media and Variability in Prescribed Durations Across Two Large Academic Health Systems.

Acute otitis media (AOM) accounts for roughly 25% of antibiotics prescribed to children annually. Despite national guidelines that recommend short (5-7 days) durations of antibiotics for children 2 years and older with AOM, most receive long (10 day) courses. This study aims to evaluate antibiotic durations prescribed for children aged 2-17 years with uncomplicated AOM across two pediatric academic health systems, and to assess the variability in prescribed durations between and within each system. Electronic medical record data from 135 care locations at two health systems were retrospectively analyzed. Outpatient encounters for children aged 2-17 years with a diagnosis of AOM from 2019 to 2022 were included. The primary outcome was the percent of 5-day prescriptions. Secondary outcomes included the proportion of 7-day prescriptions, 10-day prescriptions, prescriptions for nonfirst-line antibiotics, cases associated with treatment failure, AOM recurrence, and adverse drug events. Among 73 198 AOM encounters for children 2 years and older, 61 612 (84%) encounters resulted in an antibiotic prescription. Most prescriptions were for 10 days (45 689; 75%), 20% were for 7 days (12 060), and only 5% were for 5 days (3144). Treatment failure, AOM recurrence, adverse drug events, hospitalizations, and office, emergency department or urgent-care visits for AOM within 30 days after the index visit were rare. Despite national guidelines that recommend shorter durations for children with uncomplicated AOM, 75% of our cohort received 10-day durations. Shortening durations of therapy for AOM could reduce antibiotic exposure and should be a priority of pediatric antibiotic stewardship programs.

Antimicrobial Use Among Outpatients at Benjamin Mkapa Hospital in Dodoma Central Zone of Tanzania: A Prospective Descriptive Study.

Irrational antimicrobial use (AMU) has led to an exponential increase in antimicrobial resistance (AMR) in hospitals and communities, which creates challenges in treating infectious diseases caused by bacteria. This study aimed to evaluate antimicrobial prescriptions and usage patterns for treating bacterial infections among outpatients at Benjamin Mkapa Hospital (BMH). A prospective descriptive study design was used to evaluate the AMU trend. The data were collected from August 2022 to October 2022 from outpatient pharmacies at BMH using the World Health Organization/International Network of Rational Use of Drugs (WHO/INRUD) indicators. The simple random sampling method was employed to select the prescriptions. The WHO AWaRe (Access, Watch, and Reserve) classification was used to classify common antimicrobials. We analyzed the prevalence of outpatient AMU, including the types of antimicrobials, indications, and compliance with treatment guidelines. We also examined the number of antimicrobials per prescription and the adherence to drug use. We examined 1557 prescriptions, 406 (26.1%) (WHO recommendation 20.0-26.8%) of which included antimicrobials. All prescriptions with antimicrobials were written in generic names, drug utilization-90% (DU90%) was 100% (WHO recommendation 100%). The number of parenteral antimicrobials prescribed was 79 (19.5%) (WHO recommendation 13.4-24.1%). Furthermore, prescriptions with antimicrobials that complied with the current Standard Treatment Guidelines and National Essential Medicine List in Tanzania (STG/NEMLIT) were 369 (90.9%) (WHO recommendation 100%). Most antimicrobials were prescribed as monotherapy, accounting for 265 (65.3%). There were 1.4 (WHO recommendation 1.6-1.8) antimicrobials per prescription. Our study identified 21 commonly prescribed antimicrobials, whereby 9 (42.9%) (WHO recommendation >60%) antimicrobials were Access, 10 (47.6%) (WHO recommendation <20%) Watch, and 2 (9.5%) (WHO recommendation <1%) Reserved classes. Our study showed that BMH has optimal practices for prescribing and using antimicrobials for outpatients. It further underlined the need to expand and strengthen antimicrobial stewardship efforts to reinforce prescribing antimicrobials.

Label-free single-cell antimicrobial susceptibility testing in droplets with concentration gradient generation.

Bacterial communities exhibit significant heterogeneity, resulting in the emergence of specialized phenotypes that can withstand antibiotic exposure. Unfortunately, the existence of subpopulations resistant to antibiotics often goes unnoticed during treatment initiation. Thus, it is crucial to consider the concept of single-cell antibiotic susceptibility testing (AST) to tackle bacterial infections. Nevertheless, its practical application in clinical settings is hindered by its inability to conduct AST efficiently across a wide range of antibiotics and concentrations. This study introduces a droplet-based microfluidic platform designed for rapid single-cell AST by creating an antibiotic concentration gradient. The advantage of a microfluidic platform is achieved by executing bacteria and antibiotic mixing, cell encapsulation, incubation, and enumeration of bacteria in a seamless workflow, facilitating susceptibility testing of each antibiotic. Firstly, we demonstrate the rapid determination of minimum inhibitory concentration (MIC) of several antibiotics with Gram-negative E. coli and Gram-positive S. aureus, which enables us to bypass the time-consuming bacteria cultivation, speeding up the AST in 3 h from 1 to 2 days of conventional methods. Additionally, we assess 10 clinical isolates including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Staphylococcus aureus (MDRSA) against clinically important antibiotics for analyzing the MIC, compared to the gold standard AST method from the United States Clinical and Laboratory Standards Institute (CLSI), which becomes available only after 48 h. Furthermore, by monitoring single cells within individual droplets, we have found a spectrum of resistance levels among genetically identical cells, revealing phenotypic heterogeneity within isogenic populations. This discovery not only advances clinical diagnostics and treatment strategies but also significantly contributes to the field of antibiotic stewardship, underlining the importance of our approach in addressing bacterial resistance.

The Impact of Antibiotic Misuse in Adult Patients: A Review of Contributing Factors, Consequences, and Strategies for Mitigation.

Antibiotic misuse, characterized by inappropriate use, over-prescription, and self-medication, is a severe threat to health in that it increases the rate at which antibiotic-resistant bacteria develop. This paper provides a review of antibiotic misuse concerning adult patients, an outline of factors that perpetuate it, the consequences, and the possible mitigation strategies. We discuss patient-related issues, such as lack of knowledge and non-compliance, problems with healthcare providers in terms of over-subscription and poor training, and system problems like poor stewardship programs and lack of regulatory efforts. In addition, the authors debate the environmental consequences of poor antibiotic stewardship coming from agriculture use and contamination. The consequences of misuse include the development of antibiotic-resistant pathogens and deleterious drug reactions, but also imply significant costs to the health system. The review calls for increased antibiotic stewardship, improved patient education, the development of new antimicrobial agents, and good policy infection control. This review is essence, a call to multifaceted efforts in the fight against the misuse of antibiotics and stresses that continuous research works are required to change policies. Antibiotic misuse is emerging as a global problem because addressing this problem not only ensures sustainability in the existing antibiotics but also assures that public health is protected.

Assessing antimicrobial resistance profiles of Salmonella enterica in the pork production system.

Introduction. Salmonella enterica is a significant enteric pathogen affecting human and livestock health. Pork production is a common source of Salmonella contamination, with emerging multidrug resistance (MDR) posing a global health threat.Gap statement. Salmonella contamination and antimicrobial resistance (AMR) profiles in the pig production chain are underreported.Aim. To investigate the prevalence of S. enterica in the pig production chain and characterise their AMR profiles.Methodology. We collected 485 samples from pig farms, a standard pig abattoir and retail markets in Patthalung and Songkhla provinces in southern Thailand. Antimicrobial susceptibility testing was performed on these samples, and AMR profiles were determined.Results. S. enterica was detected in 68.67% of farm samples, 45.95% of abattoir samples and 50.67% of retail market samples. Analysis of 264 isolates, representing 18 serotypes, identified S. enterica serotype Rissen as the most prevalent. The predominant resistance phenotypes included ampicillin (AMP, 91.29%), tetracycline (TET, 88.26%) and streptomycin (STR, 84.47%). Over 80% of isolates showed resistance to three or more antimicrobial classes, indicating MDR. The AMP-STR-TET resistance pattern was found in nearly 70% of all MDR isolates across the production chain.Conclusions. The high prevalence of MDR is consistent with extensive antimicrobial use in the livestock sector. The presence of extensively resistant S. enterica highlights the urgent need for antimicrobial stewardship. Strengthening preventive strategies and control measures is crucial to mitigate the risk of MDR Salmonella spreading from farm to fork.

ENOVAT: the European Network for Optimization of Veterinary Antimicrobial Treatment

The global antimicrobial resistance crisis has been the driver of several international strategies on antimicrobial stewardship. For their implementation at the field level, the veterinary sector encounters several specific challenges and in particular: (i) a shortage of experts in key disciplines related to antimicrobial stewardship, (ii) a lack of evidence-based antimicrobial treatment guidelines, and (iii) inferior diagnostic tests available compared to human medicine. The present white paper describes how the COST Action ENOVAT (the European Network for Optimization of Veterinary Antimicrobial Treatment, CA18217), comprising 332 persons from 51 countries, worked towards solutions to these challenges. Initially, surveys were conducted to explore the present state in Europe in terms of existing antimicrobial use guidelines and microbiology practices performed. Concurrently, various research activities were launched to optimize diagnostics, including development of epidemiological cut-offs, clinical breakpoints and matrix-assisted laser desorption ionization time of flight mass spectrometry interpretive criteria. Also, guidelines drafting groups working towards evidence-based antimicrobial treatment guidelines for six conditions in food-producing and companion animals were established. The processes and outcomes, also in terms of capacity building, are summarized in this white paper where emphasis is placed on sustainability of the activities. Although several ENOVAT initiatives and spin-off projects will continue beyond the Action, we recommend that a new European veterinary research agenda is launched focusing on research and funding leading to long-term impacts on veterinary antimicrobial use.

Isolation and characterization of pathogenic Klebsiella pneumoniae strains from lettuce: a potential source of antibiotic resistance and development of a mathematical model for ANOVA results.

This study aimed to evaluate the prevalence of Klebsiella pneumoniae contamination in raw lettuce from Risalpur, Pakistan, and to analyze the antibiotic susceptibility profiles of the isolated strains. The presence of foodborne pathogens such as K. pneumoniae poses significant public health risks, particularly in regions with suboptimal hygiene practices and improper food handling. Lettuce samples were collected from various sources in Risalpur and screened for K. pneumoniae. Antimicrobial susceptibility testing was performed to evaluate the effectiveness of various antibiotics against the isolated strains. Statistical analyses, including ANOVA and linear regression, were conducted to assess differences in inhibition zones and to predict antibiotic effectiveness based on concentration. The results revealed a significant prevalence of K. pneumoniae in the lettuce samples, highlighting the risks associated with poor hygiene, transportation, storage, and contaminated irrigation water. The isolated strains exhibited high susceptibility to gentamicin but demonstrated notable resistance to doxycycline, vancomycin, and ticarcillin. Multidrug-resistant (MDR) strains were identified. ANOVA showed significant differences in inhibition zones, and the linear regression model predicted a Zone of Inhibition based on antibiotic concentration (β0 = 10.6667, β1 = 0.4556). The identification of MDR strains of K. pneumoniae underscores the urgent need for enhanced antibiotic stewardship and food safety protocols to manage foodborne pathogens. Improved hygiene practices throughout the food production and supply chain are critical to mitigate health risks and address the challenge of growing antibiotic resistance.

Medical residents' knowledge, attitudes and practices regarding antibiotics, antimicrobial stewardship and multidrug-resistant bacteria: a cross-sectional study in a major university in Iran.

Antimicrobial resistance (AMR) is one of the biggest threats to global public health systems. This study aimed to assess the knowledge, attitudes and practice about AMR, antimicrobial stewardship programs (ASPs) and multidrug-resistant (MDR) bacteria. A web-based questionnaire survey was conducted among the residents of Isfahan University of Medical Sciences from May to November 2023. Data analysis was done using SPSS version 24.0 software. Overall, 400 out of 450 medical residents responded to the questionnaire, giving a response rate of 88.9%. The participants' ages ranged from 26 to 54 years, and the majority were female (227/400 56.8%). Average scores for knowledge, attitudes, and practices were 53.70 ± 15.88, 36.97 ± 5.89 and 24.69 ± 4.24, respectively. In terms of knowledge, only 26.8% had heard the term "ASPs" and knew what it was. Most incorrect answers appeared to the treatment of infection caused by MDR bacteria including ESBL-producing Escherichia coli (27.8%) and carbapenem-resistant Klebsiella pneumoniae (30.8%), as well as the atypical bacteria (45.5%). Approximately, 50 and 71.7% said they had received no specific training in the fields of microbiological sampling methods and the appropriate time to prescribe antibiotics, respectively. Surprisingly, regarding practice, 81.8% of the respondents stated that antibiotics are used to treat flu or the common cold. Residents considered their training on important issues including ASPs, MDR bacteria and the spectrum of antibiotics insufficient. This result highlights the need for targeted training interventions about antibiotic prescription in the curriculum at the university with more emphasis on ASPs to limit the development of resistance.

Infections following chimeric antigen receptor T cell therapy: 2018–2022

AbstractBackgroundChimeric antigen receptor (CAR) T‐cell therapy is an emerging therapeutic modality for relapsed and refractory hematological malignancies. Infectious complications following CAR T‐cell therapy are not well defined.MethodsThis is a retrospective analysis of data on patients who received CAR T‐cell therapy between April 2018 and December 2022 at the Karmanos Cancer Center, Detroit. Patients’ data were collected up to their last known clinic or inpatient follow‐up visit. An infectious episode was defined as any microbiologically proven or clinically documented infection.ResultsSeventy‐six patients received therapy with FDA‐approved CAR T‐cell products. Thirty‐three patients (43.4%) had at least one infectious episode. There were 61 infectious episodes during a median follow‐up of 184 (96–340) days. Median duration for the onset of infection was 59 (22–209) days. Bacterial and viral infections occurred in 42.6% and 41% of the infectious episodes, respectively. COVID‐19 was the most common infectious complication (14.8%). Time‐to‐event analysis showed that most infections occurred within the first 100 days. Empirical antibiotic use during Cytokine Release Syndrome/Immune effector Cell‐Associated Neurotoxicity Syndrome (CRS/ICANS) in the absence of documented bacterial infection was reported in 85.7% of patients. Clostridioides difficile accounted for 11.5% of all infectious episodes. Five of six patients with C. difficile infection had CRS/ICANS and received antibiotics.ConclusionCOVID‐19 and C. difficile infection were the most common infections following CAR T‐cell therapy. Most infections occurred within the first 100 days. Empiric antibiotic use and C. difficile infection were common in patients with CRS/ICANS, in the absence of documented bacterial infection, thus providing an excellent opportunity for antimicrobial stewardship in this population. image

The Short-Term Impact of Educational Programs on Knowledge and Attitudes Regarding Antimicrobial Stewardship among Veterinary Students in Serbia.

Effective antimicrobial stewardship (AMS) is crucial for combating the rise of antimicrobial resistance (AMR), particularly in veterinary medicine. Educational programs targeting veterinary students can play a significant role in shaping their knowledge and attitudes toward antimicrobial use and stewardship. This study aimed to evaluate the impact of educational programs on the knowledge and attitudes regarding AMS among veterinary students in Serbia. A structured educational program on AMS was implemented for veterinary students at the Faculty of Agriculture, University of Novi Sad. Pre- and post-symposium assessments were conducted to measure changes in students' knowledge and attitudes. The study employed a mixed-methods approach, including surveys and focus groups, to gather quantitative and qualitative data. The study resulted in significant short-term improvements in students' knowledge of AMS principles and their attitudes toward responsible antimicrobial use. Participants demonstrated a better understanding of the mechanisms of resistance and the importance of adhering to stewardship guidelines. Qualitative feedback indicated increased awareness of the consequences of inappropriate antimicrobial use and a stronger commitment to applying stewardship practices in their future careers. The educational programs effectively enhanced immediate veterinary students' knowledge and attitudes regarding AMS. These findings underscore the importance of integrating targeted educational programs into veterinary curricula to promote responsible antimicrobial use and combat resistance in veterinary practice.

Defining age-specific reference intervals for biomarkers distinguishing bacterial from viral infection in paediatrics

Differentiating bacterial from viral infections in children is a common clinical challenge. Novel host immune biomarkers have the potential to aid thediagnosis of infection aetiology and identify children who require antibiotics. Data on novel infection biomarkers gender and age-specific correlations, and reference intervals in healthy paediatrics is lacking. This study reports the plasma levels of three novel biomarkers that can aid in the differentiation of bacterial and viral infection in a healthy group of paediatrics. The levels of (Interferon-Gamma Inducible Protein 10 kDa (IP-10), Lipocalin-2 (LCN2) and TNF-Related Apoptosis-Inducing Ligand (TRAIL) were quantified in 199 plasma samples from healthy paediatrics aged 2 to 16 years old from across the UK. Reference intervals (2.5th and 97.5th) were determined, and biomarker levels were examined for sex and age associations. Reference intervals for IP-10, LCN2 and TRAIL for ages 2–16 years were 36.7–168.1 pg/ml, 14.2–123.3 ng/ml, 57.4–71.4 pg/ml respectively. No biomarker showed an association with sex and IP-10 did not show any association with age. TRAIL levels had a weak continuous negative correlation with age and LCN2 levels had a continuous positive correlation with age. Specific cut-offs for LCN2 in two age categories were identified, while TRAIL did not require age partitions. This study provides age-appropriate reference intervals for three biomarkers of infection in healthy children. These findings have the potential to improve the impact of future research on these biomarkers, the accuracy of clinical decision-making in children with infection, paediatric patient care and outcomes, and antimicrobial stewardship.

An Overview of the Recent Advances in Antimicrobial Resistance.

Antimicrobial resistance (AMR), frequently considered a major global public health threat, requires a comprehensive understanding of its emergence, mechanisms, advances, and implications. AMR's epidemiological landscape is characterized by its widespread prevalence and constantly evolving patterns, with multidrug-resistant organisms (MDROs) creating new challenges every day. The most common mechanisms underlying AMR (i.e., genetic mutations, horizontal gene transfer, and selective pressure) contribute to the emergence and dissemination of new resistant strains. Therefore, mitigation strategies (e.g., antibiotic stewardship programs-ASPs-and infection prevention and control strategies-IPCs) emphasize the importance of responsible antimicrobial use and surveillance. A One Health approach (i.e., the interconnectedness of human, animal, and environmental health) highlights the necessity for interdisciplinary collaboration and holistic strategies in combating AMR. Advancements in novel therapeutics (e.g., alternative antimicrobial agents and vaccines) offer promising avenues in addressing AMR challenges. Policy interventions at the international and national levels also promote ASPs aiming to regulate antimicrobial use. Despite all of the observed progress, AMR remains a pressing concern, demanding sustained efforts to address emerging threats and promote antimicrobial sustainability. Future research must prioritize innovative approaches and address the complex socioecological dynamics underlying AMR. This manuscript is a comprehensive resource for researchers, policymakers, and healthcare professionals seeking to navigate the complex AMR landscape and develop effective strategies for its mitigation.

Serum Procalcitonin, Hematology Parameters, and Cell Morphology in Multiple Clinical Conditions and Sepsis.

The clinical value of procalcitonin (PCT) in infection diagnosis and antibiotic stewardship is still unclear. This study aimed to investigate the association between serum PCT and different clinical conditions as well as other infectious/inflammatory parameters in different septic patients in order to elucidate the value of PCT detection in infection management. Chemiluminescence immunoassay was used for serum PCT analysis. Hematology analysis was used for complete blood cell count. Digital automated cell morphology analysis was used for blood cell morphology examination. Blood, urine, and stool cultures were performed according to routine clinical laboratory standard operating procedures. C-reactive protein (CRP) was analyzed by immunoturbidimetry. Erythrocyte sedimentation rate test was performed using natural sedimentation methods. Outpatients, ICU patients, and patients under 2 years of age with respiratory infections had higher serum PCT levels. Septic patients had the highest-serum PCT levels and other infection indexes. PCT levels in the blood, urine, and stool culture-positive patients were significantly higher than in culture-negative patients. The neutrophil granulation and reactive lymphocytes were observed together with the PCT-level increments in different septic patients, and these alterations were lessened after treatment. There was no significant change in monocyte morphology between pre- and posttreatment septic patients. Serum PCT is associated with neutrophil cytotoxicity and lymphocyte morphology changes in sepsis; thus, the combination of neutrophil and lymphocyte digital cell morphology evaluations with PCT detection may be a useful examination for guiding the clinical management of sepsis.

Impact of ESKAPE Pathogens on Bacteremia: A Three-Year Surveillance Study at a Major Hospital in Southern Italy.

ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pose a serious public health threat as they are resistant to multiple antimicrobial agents. Bloodstream infections (BSIs) caused by ESKAPE bacteria have high mortality rates due to the limited availability of effective antimicrobials. This study aimed to evaluate the prevalence and susceptibility of ESKAPE pathogens causing BSIs over three years in a large tertiary hospital in Salerno. Conducted at the Clinical Microbiology Laboratory of San Giovanni di Dio e ''Ruggi D'Aragona'' Hospital from January 2020 to December 2022, blood culture samples from different departments were incubated in the BD BACTEC™ system for 5 days. Species identification was performed using MALDI-TOF MS, and antimicrobial resistance patterns were determined by the VITEK2 system. Out of 3197 species isolated from positive blood cultures, 38.7% were ESKAPE bacteria. Of these, 59.9% were found in blood culture samples taken from men, and the most affected age group was those aged >60 years. (70.6%). Staphylococcus aureus was the main BSI pathogen (26.3%), followed by Klebsiella pneumoniae (15.8%). Significant resistance rates were found, including 35% of Staphylococcus aureus being resistant to oxacillin and over 90% of Acinetobacter baumannii being resistant to carbapenems. These results highlight the urgent need for antimicrobial stewardship programs to prevent incurable infections.