Determinants of antibiotic prescribing in primary care in Vietnam: a qualitative study using the Theoretical Domains Framework.

BACKGROUND: To formulate effective strategies for antimicrobial stewardship (AMS) in primary care, it is crucial to gain a thorough understanding of factors influencing prescribers' behavior within the context. This qualitative study utilizes the Theoretical Domains Framework (TDF) to uncover these influential factors. METHODS: We conducted a qualitative study using in-depth interviews and focus group discussions with primary care workers in two provinces in rural Vietnam. Data analysis employed a combined inductive and deductive approach, with the deductive aspect grounded in the TDF. RESULTS: Thirty-eight doctors, doctor associates, and pharmacists participated in twenty-two interviews and two focus group discussions. We identified sixteen themes, directly mapping onto seven TDF domains: knowledge, skills, behavioral regulation, environmental context and resources, social influences, social/professional role and identity, and optimism. Factors driving unnecessary prescription of antibiotics include low awareness of antimicrobial resistance (AMR), diagnostic uncertainty, prescription-based reimbursement policy, inadequate medication supplies, insufficient financing, patients' perception of health insurance medication as an entitlement, and maintaining doctor-patient relationships. Potential factors facilitating AMS activities include time availability for in-person patient consultation, experience in health communication, and willingness to take action against AMR. CONCLUSION: Utilizing the TDF to systematically analyze and present behavioral determinants offers a structured foundation for designing impactful AMS interventions in primary care. The findings underscore the importance of not only enhancing knowledge and skills but also implementing environmental restructuring, regulation, and enablement measures to effectively tackle unnecessary antibiotic prescribing in this context.

Current state of data stewardship tools in life science.

In today's data-centric landscape, effective data stewardship is critical for facilitating scientific research and innovation. This article provides an overview of essential tools and frameworks for modern data stewardship practices. Over 300 tools were analyzed in this study, assessing their utility, relevance to data stewardship, and applicability within the life sciences domain.

Effectiveness of caregiver educational materials for paediatric community-acquired pneumonia in the emergency department: a qualitative study.

OBJECTIVES: The objective of this study was to better understand caregiver perspectives on educational materials relating to paediatric community-acquired pneumonia and antibiotic stewardship in the emergency department setting. METHODS: This was a phenomenologically informed qualitative study. Caregivers of young children in Hamilton, Ontario were presented with four educational materials (animated video, physician led lecture-style video, caregiver led testimony-style video, and a printed brochure) providing information relating to treatment strategies for community-acquired pneumonia. Caregivers were then asked open-ended questions about how they felt about the effectiveness of the media used. The principles of conventional content analysis guided the coding and synthesis of the transcribed interviews. RESULTS: Eleven caregivers were interviewed. Most caregivers preferred the animated video and brochure to the lecture-style physician video and caregiver testimonial video. Common themes for effective educational materials included visually attention-grabbing graphics, accessible language, and formats they could reference following their visit (e.g. brochure). CONCLUSIONS: The busy nature of the emergency department setting can impede effective communication between clinicians and parents. Employing educational materials may allow for more informed parent-provider communication on care decision making. Caregivers in our study prioritized the simplest information formats for education around community-acquired pneumonia and antimicrobial stewardship which could be referenced following discharge. This was best accomplished by short, animated videos and brochures. Results from this study can inform development of future educational materials used in paediatric emergency department settings to optimize caregiver education and corresponding care plan adherence.

RéSUMé: OBJECTIFS: L'objectif de cette étude était de mieux comprendre les perspectives des soignants sur le matériel éducatif relatif à la pneumonie acquise dans la communauté pédiatrique et à la gérance des antibiotiques dans le milieu du service d'urgence. MéTHODES: Il s'agissait d'une étude qualitative à base de données phénoménologiques. Les aidants naturels de jeunes enfants à Hamilton, en Ontario, ont reçu quatre documents éducatifs (vidéo animée, vidéo de présentation par le médecin, vidéo de témoignage par le soignant et brochure imprimée) qui fournissent des renseignements sur les stratégies de traitement pour la communauté pneumonie acquise. On a ensuite posé aux aidants des questions ouvertes sur leur opinion au sujet de l'efficacité du média utilisé. Les principes de l'analyse conventionnelle du contenu ont guidé le codage et la synthèse des entrevues transcrites. RéSULTATS: Onze aidants naturels ont été interrogés. La plupart des aidants préfèrent la vidéo animée et la brochure à la vidéo de présentation du médecin et à la vidéo de témoignage de l'aidant. Les thèmes communs pour un matériel pédagogique efficace comprenaient des graphiques visuellement accrocheurs, un langage accessible et des formats auxquels ils pourraient se référer après leur visite (p. ex., brochure). CONCLUSIONS: La nature occupée du service d'urgence peut entraver une communication efficace entre les cliniciens et les parents. L'utilisation de matériel éducatif peut permettre une communication plus éclairée entre les parents et le fournisseur de soins sur la prise de décisions en matière de soins. Les soignants de notre étude ont donné la priorité aux formats d'information les plus simples pour l'éducation sur la pneumonie communautaire et la gérance des antimicrobiens qui pourraient être référencés après le congé. Le meilleur moyen d'y parvenir était de présenter des vidéos et des brochures courtes et animées. Les résultats de cette étude peuvent éclairer le développement du matériel pédagogique futur utilisé dans les services d'urgence pédiatriques pour optimiser l'éducation des soignants et l'adhésion aux plans de soins correspondants.

Implementing the Infectious Diseases Society of America Antimicrobial Stewardship Core Curriculum: Survey Results and Real-World Strategies to Guide Fellowship Programs.

Background: The Infectious Diseases Society of America (IDSA) developed the Core Antimicrobial Stewardship (AS) Curriculum to meet the increasing demand for infectious diseases (ID) providers with AS expertise. Notable diversity in implementation approaches has been observed among ID fellowship programs using the curriculum. We sought to describe individual approaches and develop a curriculum implementation roadmap. Methods: We surveyed ID fellowship programs that had previously implemented the IDSA Core AS curriculum. The survey included questions regarding program characteristics, curriculum participants and presentation format, resources and barriers, and implementation strategies. Commonly reported program features were summarized in the context of the self-reported implementation strategies. Implementation guides were developed based on the most common characteristics observed. Results: Of 159 programs that had purchased the curriculum, 37 responded, and 34 (21%) were included in the analysis. The curriculum was primarily taught by AS physicians (85%) and AS pharmacists (47%). The most common conference structure was a longitudinal conference series (32%), and eLearning was the most common presentation format. Limited AS faculty time (76%) and limited first-year fellow availability (62%) were frequently reported as barriers, and dedicated AS curricular time was a resource available to most programs (67%); implementation guides were created for these 3 program features. Conclusions: Programs reported a variety of implementation barriers and resources, with several common themes emerging, allowing for the development of tailored curriculum planners for 3 commonly observed program characteristics. This work will equip fellowship programs with curriculum implementation strategies and guide future enhancements of the IDSA Core and Advanced AS curricula.

Introducing new antibiotics for multidrug-resistant bacteria: obstacles and the way forward.

BACKGROUND: Following intense efforts to revive the dry antibiotic research and development pipeline, a few highly awaited antibiotics with activity against multidrug-resistant (MDR) bacteria were recently approved. OBJECTIVES: We aim to highlight gaps in the evidence generated for new antibiotics by the time of their approval and to review the consequent limitations of treatment guidelines for priority MDR bacteria. We also report on availability of the new antibiotics, reimbursement strategies allowing use of these antibiotics in hospitals and antibiotic stewardship efforts. SOURCES: We searched PubMed for phase 3 randomized controlled trials that assessed antibiotics approved for use against MDR bacteria between 2013-2023. Other sources included governmental and professional documents regarding policies for reimbursement and use of the new antibiotics. CONTENT: Several gaps in the evidence available regarding the new antibiotics are described related to the trials' target populations, comparators, management algorithm within the trial, non-inferiority hypotheses and assessment of resistance development within the studies. We highlight the risk of current guidelines to increase usage of new antibiotics and consequently accelerate resistance development. Updated mapping of antibiotic availability reveals critical inequality in access to the new antibiotics. Finally, strategies used nationally in Europe to provide access to the new antibiotics are not sufficiently balanced by antibiotic stewardship efforts to calibrate judicious use of the new antibiotics. IMPLICATIONS: Antibiotic resistance is an immediate threat. The present review highlights areas where more systematic and uniform strategies across countries and geographical regions are warranted to improve evidence, availability and use of new broad-spectrum antibiotics.

Can employees' trust their supervisor? The role of high-performance work systems and stewardship climate on employee voice.

The focus of this research is to investigate the factors that influence employee voice behaviour by examining the integration of high-performance work systems, stewardship climate, and trust in supervisor. Drawing on social exchange theory and leader-member exchange, this study investigates the positive relationship between trust in supervisor, high-performance work systems, stewardship climate and employee voice. Data were collected in three stages from 376 Nigerian telecommunications customer-contact employees. Partial Least Squares-Structural Equation Modelling was used to test the dataset. The findings indicate that high-performance work systems have a favourable association with employee voice, while stewardship climate has an adverse correlation with employee voice. Moreover, trust in supervisor is found to mediate and enhance the favourable relationship between high-performance work systems, stewardship climate, and employee voice. The relevance of this study to service industries, management research, and its practical implications is discussed.

Changes in factors associated with inhaled antibiotic prescriptions for people with cystic fibrosis over time in the U.S.

RATIONALE: CF care guidelines recommend chronic inhaled antibiotics for chronic Pseudomonas aeruginosa (Pa) lung infection. These medications are costly, time consuming and prescription needs may change with improved outcomes. OBJECTIVES: We determined the proportion of pwCF with chronic, intermittent or negative Pa infection categories, their clinical and demographic characteristics, factors associated with inhaled antibiotic prescription and changes between 2011 and 2019. METHODS: This cohort study using the U.S. CF Foundation patient registry for pwCF >2 years, no prior lung transplant, and with ≥3 respiratory cultures/year determined chronic inhaled antibiotics (≥3 months per calendar year) and Pa infection status from encounter level data. Outcomes and odds of prescription for relevant clinical factors were evaluated using generalized estimating equation models with additional interaction between the predictor and the calendar year to examine changes of predictors over time. RESULTS: Proportion of pwCF with chronic and intermittent Pa decreased and antibiotic prescription rates increased for these groups and decreased for Pa negative pwCF. Hispanic ethnicity, female sex, pancreatic insufficiency, CF diabetes, and ivacaftor/lumacaftor were associated with higher antibiotic prescriptions for each Pa status. Among Pa-negative pwCF prescriptions were higher with Burkholderia spp. (1.17, (CI95 1.03,1.34)) or MRSA (OR 1.45, (1.26,1.68)) but decreased between 2011 and 2019. For Aspergillus OR increased to 1.6,(1.3,1.8) in 2019. Prescriptions for pwCF on ivacaftor decreased, becoming lower in 2019 for chronic (OR 0.7, (0.5,0.8)) and Pa-negative pwCF (OR 0.7, (0.5,0.8)). CONCLUSIONS: Factors predicting inhaled antibiotic prescription differed between 2011 and 2019 indicating changes in health and care for pwCF even prior to triple-modulators.

Insights Into Antimicrobial Resistance From Dental Students in the Asia-Pacific Region.

BACKGROUND: Dentists, as prominent prescribers, are key stakeholders in addressing the antimicrobial resistance (AMR) crisis. Dental students' perceptions about the topic have been underexplored in the Asia-Pacific region, a key location for the development and spread of AMR. Thus, the aim of this study was to evaluate the awareness and confidence to prescribe antimicrobials amongst dental students studying in the region. METHODS: Students from 15 dental schools in 4 countries were invited to participate in a cross-sectional online survey during 2022-2023. A previously validated and standardised 14-item instrument was utilised. RESULTS: In all, 1413 responses were collected from Australia (n = 165), Sri Lanka (n = 112), Japan (n = 173), and Vietnam (n = 963). Of those, 201 were from final-year students (14.2%). On a scale from 1 to 10, awareness on AMR was placed at a mean (SEM) priority of 8.09 (0.05). With regards to target areas to address for mitigation of the AMR crisis, participants placed general public awareness at the top (mean [SEM] 8.53 [0.05]). Final-year students presented a mean (SEM) level of confidence to prescribe antibiotics of 6.01 (0.14) on a scale from 1 to 10, whilst 59.7% and 56.8% indicated feeling pressured to prescribe by patients or when lacking time, respectively. Final-year students participating in research activities assigned a higher priority to AMR compared to their peers not involved in research (mean [SEM] 8.6 [0.19] vs 7.81 [0.16]; P = .01). CONCLUSIONS: This study highlights a need for increased awareness and confidence to prescribe amongst dental students in the Asia-Pacific region, an understudied population thus far. To mitigate this issue, the implementation (followed by assessment) of local educational and antibiotic stewardship initiatives is warranted.

Development of an Electronic Clinical Surveillance Measure for Unnecessary Rapid Antibiotic Administration in Suspected Sepsis.

BACKGROUND: Substantial efforts focus on monitoring and reducing delays in antibiotic treatment for sepsis, but little has been done to characterize the balancing measure of sepsis overtreatment. We aimed to establish preliminary validity and usefulness of electronic health record (EHR) data-derived criteria for sepsis overtreatment surveillance (SEP-OS). METHODS: We evaluated adults with potential sepsis (≥2 Systemic Inflammatory Response Syndrome criteria within 6 hours of arrival) presenting to the emergency department of 12 hospitals, excluding patients with shock. We defined SEP-OS as the proportion of patients receiving rapid IV antibiotics (≤3 hours) who did not ultimately meet the Centers for Disease Control Adult Sepsis Event "true sepsis" definition. We evaluated the frequency and characteristics of patients meeting overtreatment criteria and outcomes associated with sepsis overtreatment. RESULTS: Of 113 764 eligible patients, the prevalence of sepsis overtreatment was 22.5%. The measure met prespecified criteria for reliability, content, construct, and criterion validity. Patients classified by the SEP-OS overtreatment criteria had higher median antibiotic days (4 days [IQR, 2-5] vs 1 day [1-2]; P < .01), longer median length of stay (4 days [2-6] vs 3 days [2-5]; P < .01), higher hospital mortality (2.4% vs 2.1%; P = .01), and higher frequency of Clostridium difficile infection within 6 months of hospital discharge (P < .01) compared with "true negative" cases. CONCLUSIONS: We developed a novel, valid EHR metric for clinical surveillance of sepsis overtreatment. Applying this metric to a large cohort of potential sepsis patients revealed a high rate of overtreatment and provides a useful tool to inform sepsis quality-improvement targets.

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

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

A randomized controlled non-inferiority trial of placebo versus macrolide antibiotics for Mycoplasma pneumoniae infection in children with community-acquired pneumonia: trial protocol for the MYTHIC Study.

BACKGROUND: Mycoplasma pneumoniae is a major cause of community-acquired pneumonia (CAP) in school-aged children. Macrolides are the first-line treatment for this infection. However, it is unclear whether macrolides are effective in treating M. pneumoniae CAP, mainly due to limitations in microbiological diagnosis of previous studies. The extensive global use of macrolides has led to increasing antimicrobial resistance. The overall objective of this trial is to produce efficacy data for macrolide treatment in children with M. pneumoniae CAP. METHODS: The MYTHIC Study is a randomized, double-blind, placebo-controlled, multicenter, non-inferiority trial in 13 Swiss pediatric centers. Previously healthy ambulatory and hospitalized children aged 3-17 years with clinically diagnosed CAP will be screened with a sensitive and commercially available M. pneumoniae-specific IgM lateral flow assay from capillary blood. Mycoplasma pneumoniae infection in screened patients will be verified retrospectively by respiratory PCR (reference test) and IgM antibody-secreting cell enzyme-linked immunospot (ELISpot) assay (confirmatory test for distinguishing between carriage and infection). Patients will be randomized 1:1 to receive a 5-day treatment of macrolides (azithromycin) or placebo. The co-primary endpoints are (1) time to normalization of all vital signs, including body temperature, respiratory rate, heart rate, and saturation of peripheral oxygen (efficacy), and (2) CAP-related change in patient care status (i.e., admission, re-admission, or intensive care unit transfer) within 28 days (safety). Secondary outcomes include adverse events (AEs), as well as antimicrobial and anti-inflammatory effects. For both co-primary endpoints, we aim to show non-inferiority of placebo compared to macrolide treatment. We expect no macrolide effect (hazard ratio of 1, absolute risk difference of 0) and set the corresponding non-inferiority margins to 0.7 and -7.5%. The "at least one" success criterion is used to handle multiplicity with the two co-primary endpoints. With a power of 80% to reject at least one null hypothesis at a one-sided significance level of 1.25%, 376 patients will be required. DISCUSSION: This trial will produce efficacy data for macrolide treatment in children with M. pneumoniae CAP that might help to reduce the prescription of antibiotics and therefore contribute to the global efforts toward reducing antimicrobial resistance. TRIAL REGISTRATION: ClinicalTrials.gov, NCT06325293. Registered on 24 April 2024.

Early treatment for Clostridioides difficile infection: retrospective cohort study.

INTRODUCTION: Clostridioides difficile (CDI) is a common cause of infectious diarrhea. The current recommendation is to initiate empirical antibiotic treatment for suspected CDI who have an anticipated delay of confirmatory results or fulminant colitis. This is based on limited clinical trials. The study aims to examine the impact of early treatment on mortality and clinical outcomes. METHODS: This retrospective cohort study included adult patients with CDI. Early treatment was defined as the initiation of an anti-Clostridioides medication within the first 24 h following stool sampling. Outcomes were 30 and 90 day mortality, length of hospital stay (LOS), recurrence, and colectomy rate. To address potential bias, propensity score matching followed by logistic regression was performed, P value less than 5% was considered statistically significant. RESULTS: Study cohort consisted of 796 patients; clinical characteristics were balanced following matching. There was no difference, in favor of early treatment, between the groups regarding 30 day mortality and 90 day mortality with HR of 0.91 (95% CI 0.56-1.47) and 0.7 (95% CI 0.45-1.08), respectively. No statistically significant difference in recurrence rate, ICU admission or colectomy rate was observed. The LOS was shorter in the early-treatment group with 6 days vs. 8 days. CONCLUSION: Early treatment for CDI had shortened hospital stay. However, it did not affect clinical outcomes in adult patients.

How, why and when are delayed (back-up) antibiotic prescriptions used in primary care? A realist review integrating concepts of uncertainty in healthcare.

BACKGROUND: Antimicrobial resistance is a global patient safety priority and inappropriate antimicrobial use is a key contributing factor. Evidence have shown that delayed (back-up) antibiotic prescriptions (DP) are an effective and safe strategy for reducing unnecessary antibiotic consumption but its use is controversial. METHODS: We conducted a realist review to ask why, how, and in what contexts general practitioners (GPs) use DP. We searched five electronic databases for relevant articles and included DP-related data from interviews with healthcare professionals in a related study. Data were analysed using a realist theory-driven approach - theorising which context(s) influenced (mechanisms) resultant outcome(s) (context-mechanism-outcome-configurations: CMOCs). RESULTS: Data were included from 76 articles and 41 interviews to develop a program theory comprising nine key and 56 related CMOCs. These explain the reasons for GPs' tolerance of risk to different uncertainties and how these may interact with GPs' work environment, self-efficacy and perceived patient concordance to make using DP as a safety-net or social tool more or less likely, at a given time-point. For example, when a GP uses clinical scores or diagnostic tests: a clearly high or low score/test result may mitigate scientific uncertainty and lead to an immediate or no antibiotic decision; an intermediary result may provoke hermeneutic (interpretation-related) uncertainty and lead to DP becoming preferred and used as a safety net. Our program theory explains how DP can be used to mitigate some uncertainties but also provoke or exacerbate others. CONCLUSION: This review explains how, why and in what contexts GPs are more or less likely to use DP, as well as various uncertainties GPs face which DP may mitigate or provoke. We recommend that efforts to plan and implement interventions to optimise antibiotic prescribing in primary care consider these uncertainties and the contexts when DP may be (dis)preferred over other interventions to reduce antibiotic prescribing. We also recommend the following and have included example activities for: (i) reducing demand for immediate antibiotics; (ii) framing DP as an 'active' prescribing option; (iii) documenting the decision-making process around DP; and (iv) facilitating social and system support.

Telemedicine-based antibiotic stewardship program in pediatrics: study protocol of a stepped wedge cluster randomized trial-the TeleKasper study.

BACKGROUND: Overuse and misuse of antibiotics is one of the driving factors of antimicrobial resistance, a growing global health threat. The use of antibiotics is particularly high in children. Even though the implementation of antibiotic stewardship programs (ASP) in pediatrics has been shown to reduce antibiotic use, this implementation has been limited to large university hospitals in Germany. Telemedicine applications might be an effective approach to implement ASP in non-university settings. METHODS: This protocol details the TeleKasper study (Telemedical Competence Network "Antibiotic Stewardship in Pediatrics"). Tele-Kasper is a stepped-wedge cluster-randomized trial that will be conducted across non-university children's hospitals in Germany. The intervention consists of a telemedical consultation service in the form of a network in different German areas, using an app as a communication tool. The primary outcome will be a 20% reduction in overall antibiotic consumption measured using defined daily doses per 100 patient days. DISCUSSION: The TeleKasper study aims to implement and evaluate a prototype for a nationwide antibiotic stewardship program by telemedical means in pediatric departments in non-university hospitals in Germany to promote rational antibiotic use and improve medical care for infections. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00028534. Registered on 22nd of April 2022.

Is self-medication with Antibiotics among the public a global concern: a Mixed-Methods Systematic Review.

BACKGROUND: Irrational use of antibiotics is a major driver of antimicrobial resistance. Self-medication with antibiotics (SMA) may exacerbate antimicrobial resistance in the community without professional diagnosis by physicians, due to the complexity of the pharmacological mechanisms. There is still a lack of assessment of the global prevalence of SMA. We have evaluated the global prevalence of SMA and its associated factors, which could provide more reliable data to support global action. METHODS: We searched PubMed, Embase, Web of Science, and EBSCO CINAHL Plus. Quantitative studies were combined using meta-analysis with random-effects models, and qualitative synthesis was performed using interpretive meta-ethnographic methods. RESULTS: A total of 242 studies were included in this study. The pooled prevalence of SMA was 27.7% (95%CI: 24.9%-30.5%). Quantitative studies indicate that high income level, having family members working in the healthcare system, storing antibiotics at home, and purchasing antibiotics without prescriptions were associated with a greater likelihood of SMA. Qualitative findings revealed the following four factors: individual characteristics, healthcare, pharmacy, and social networks. CONCLUSIONS: The prevalence of global SMA among the public remains high level. Multisectoral and community-based interventions are needed to reduce SMA, including targeted health education, improved access to healthcare, and regulation of antibiotics sales in pharmacies. REGISTRATION: PROSPERO (CRD42023402206).

Management of neonates at risk of early onset sepsis: a probability-based approach and recent literature appraisal : Update of the Swiss national guideline of the Swiss Society of Neonatology and the Pediatric Infectious Disease Group Switzerland.

In Switzerland and other high-income countries, one out of 3000 to 5000 term and late preterm neonates develops early onset sepsis (EOS) associated with a mortality of around 3%, while incidence and mortality of EOS in very preterm infants are substantially higher. Exposure to antibiotics for suspected EOS is disproportionally high compared to the incidence of EOS with consequences for future health and antimicrobial resistance (AMR). A safe reduction of unnecessary antibiotic treatment has to be a major goal of new management strategies and guidelines. Antibiotics should be administered immediately in situations with clinical signs of septic shock. Group B streptococcus (GBS) and Escherichia coli (E. coli) are the leading pathogens of EOS. Amoxicillin combined with an aminoglycoside remains the first choice for empirical treatment. Serial physical examinations are recommended for all neonates with risk factors for EOS. Neonates without any clinical signs suggestive of EOS should not be treated with antibiotics. In Switzerland, we do not recommend the use of the EOS calculator, a risk stratification tool, due to its unclear impact in a population with an observed antibiotic exposure below 3%. Not all neonates with respiratory distress should be empirically treated with antibiotics. Isolated tachypnea or respiratory distress starting immediately after delivery by elective caesarean section or a clearly assessed alternative explanation than EOS for clinical signs may point towards a low probability of sepsis. On the other hand, unexplained prematurity with risk factors has an inherent higher risk of EOS. Before the start of antibiotic therapy, blood cultures should be drawn with a minimum volume of 1 ml in a single aerobic blood culture bottle. This standard procedure allows antibiotics to be stopped after 24 to 36 h if no pathogen is detected in blood cultures. Current data do not support the use of PCR-based pathogen detection in blood as a standard method. Lumbar puncture is recommended in blood culture-proven EOS, critical illness, or in the presence of neurological symptoms such as seizures or altered consciousness. The accuracy of a single biomarker measurement to distinguish inflammation from infection is low in neonates. Therefore, biomarker guidance is not a standard part of decision-making regarding the start or stop of antibiotic therapy but may be used as part of an algorithm and after appropriate education of health care teams. Every newborn started on antibiotics should be assessed for organ dysfunction with prompt initiation of respiratory and hemodynamic support if needed. An elevated lactate may be a sign of poor perfusion and requires a comprehensive assessment of the clinical condition. Interventions to restore perfusion include fluid boli with crystalloids and catecholamines. Neonates in critical condition should be cared for in a specialized unit. In situations with a low probability of EOS, antibiotics should be stopped as early as possible within the first 24 h after the start of therapy. In cases with microbiologically proven EOS, reassessment and streamlining of antibiotic therapy in neonates is an important step to minimize AMR. CONCLUSION:  This guideline, developed through a critical review of the literature, facilitates a probability-based approach to the management of neonates at risk of early onset sepsis. WHAT IS KNOWN: • Neonatal exposure to antibiotics is disproportionally high compared with the incidence of early onset sepsis with implications for future health and antimicrobial resistance. WHAT IS NEW: • A probability-based approach may facilitate a more balanced management of neonatal sepsis and antibiotic stewardship.

Occurrence and predictors of laboratory abnormalities during outpatient parenteral antimicrobial therapy - A multicenter cohort study to inform laboratory test monitoring.

OBJECTIVES: Evidence on the optimal frequency of laboratory testing during outpatient parenteral antimicrobial therapy (OPAT) is lacking. Therefore, we investigated how often and when laboratory abnormalities occur during OPAT and which factors are associated with these abnormalities. METHODS: We performed a multicenter cohort study in four Dutch hospitals among adult patients receiving OPAT and collected routinely obtained laboratory test results. Incidence and incidence rates were calculated for various laboratory abnormalities. Survival analysis was performed to visualize the time to the first occurrence of laboratory abnormalities and Poisson regression analysis to compare the number of abnormalities in the first and second 30 OPAT days among patients receiving OPAT for ≥60 days. Predictors were identified using a multivariable Cox proportional hazard regression model. RESULTS: 45.1% of 1152 included patients developed laboratory abnormalities, but only 2% led to OPAT discontinuation. Hepatotoxicity was most common (33.9 events/1000 OPAT days), with a time-dependent decrease in the occurrence of the first hepatotoxic event, while hypokalemia was rare (1.7 events/1000 OPAT days). In the subgroup of patients receiving ≥60 days of OPAT, nephrotoxicity was more common in days 31-60. We observed partly toxicity-specific associations between antibiotic type, concomitant medication, baseline laboratory values, patient characteristics, and the occurrence of laboratory abnormalities. CONCLUSIONS: While laboratory abnormalities are frequently observed during OPAT, they rarely lead to discontinuation of OPAT. Specific patient, treatment and laboratory characteristics were associated with the occurrence of laboratory abnormalities. Based on our results, we recommend a more personalized laboratory monitoring policy with less blood sampling.

Increasing Caudal Block Utilization to Promote Opioid Stewardship in the NICU Population: A Quality Improvement Project.

BACKGROUND: Regional anesthetic techniques are safe and effective in reducing pain and the need for opioid analgesia but may be underutilized in neonatal intensive care unit (NICU) patients. We developed an opioid stewardship pathway aimed at reducing the use of opioid analgesia in neonates by increasing caudal block utilization from a baseline of 50%-90% within 18 months. METHODS: We used control charts to track intra-operative opioid utilization in morphine milligram equivalents per kilogram (MME/kg) and immediate post-operative extubation rates. Unrelieved pain (defined as two consecutive Neonatal Pain, Agitation & Sedation Scale (NPASS) scores >/ = 4), post-operative opioid use, and reintubation within 24 h were tracked as balancing measures. We ran sample statistical analysis comparing the outcome and balancing measures in surgeries with and without caudal block. RESULTS: There were 125 surgeries in the pre-intervention and 48 in the post-intervention group. Caudal block utilization increased to 63%, while intra-operative opioid utilization decreased (0.230 vs 0.416 MME/kg), and extubation rates increased (75% vs 70%). There were no increases in unrelieved pain or post-operative opioid utilization. Caudal block was associated with decreased intra-operative opioid use (0.000 vs 0.366 MME/kg, p < 0.001) and increased extubation rates (83% vs. 59%, p < 0.001) with no increase in unrelieved pain (23% vs. 22%, p = 0.75) or post-operative opioid use (0.151 vs 0.000 MME/kg, p = 0.35). No patients required reintubation within 24 h. CONCLUSION: The modest increase in caudal block utilization is associated with a reduction in intraoperative opioid use and increased postoperative extubation rates without compromising pain control. LEVEL OF EVIDENCE: Level III.

Factors associated with the change of antimicrobial prescription before and after the national action plan on antimicrobial resistance: Additional analysis of a nationwide survey conducted by the Japanese Society of Chemotherapy and the Japanese Association for Infectious Diseases.

BACKGROUND: A nationwide survey conducted by the Japanese Society of Chemotherapy and the Japanese Association for Infectious Diseases in 2020 provided insights into antimicrobial prescription practices among clinic doctors. This study aimed to investigate factors influencing changes in antimicrobial prescriptions post-implementation of the National Action Plan on Antimicrobial Resistance (NAPAR) and doctors' inclination to prescribe antimicrobials for common cold cases. METHODS: In September 2020, randomly selected questionnaires were distributed to 3000 community-based medical clinics in Japan. The primary objective was to assess the reduction in antimicrobial prescriptions post-NAPAR implementation. Multivariate linear regression analysis was employed to identify associated factors. RESULTS: Analysis of 632 responses (response rate: 21.1 %) revealed determinants of decreased antimicrobial prescriptions, including familiarity with the Guide to Antimicrobial Stewardship (ß = .482, t = 3.177, p = 0.002) and awareness of NAPAR (ß = .270, t = 2.301, p = 0.022). CONCLUSION: Interventions such as the Guide to Antimicrobial Stewardship may have contributed to the reduction in antimicrobial prescriptions among Japanese physicians. However, targeted strategies are needed to address high-prescription groups. Enhancing awareness and education on appropriate antimicrobial use should be integral components of future initiatives to combat antimicrobial resistance effectively.