BACKGROUND: Hospitalised neonates are vulnerable to infection and have high rates of antibiotic utilisation.
METHODS: Fourteen South African neonatal units (seven public, seven private sector) assembled multidisciplinary teams involving neonatologists, microbiologists, pharmacists, and nurses to implement prospective audit and feedback neonatal antimicrobial stewardship (NeoAMS) interventions. The teams attended seven online training sessions. Pharmacists conducted weekday antibiotic prescription reviews in the neonatal intensive care unit and/or neonatal wards providing feedback to the clinical teams. Anonymised demographic and NeoAMS interventions data were aggregated for descriptive purposes and statistical analysis.
RESULTS: During the 20-week NeoAMS intervention in 2022, 565 neonates were enrolled. Pharmacists evaluated seven hundred antibiotic prescription episodes; rule-out sepsis (180; 26%) and culture-negative sepsis (138; 20%) were the most frequent indications for antibiotic prescription. For infection episodes with an identified pathogen, only 51% (116/229) of empiric treatments provided adequate antimicrobial coverage. Pharmacists recommended 437 NeoAMS interventions (0·6 per antibiotic prescription episode), with antibiotic discontinuation (42%), therapeutic drug monitoring (17%), and dosing (15%) recommendations most frequent. Neonatal clinicians\' acceptance rates for AMS recommendations were high (338; 77%). Mean antibiotic length of therapy decreased by 24% from 9·1 to 6·9 days (0·1 day decrease per intervention week; p=0·001), with the greatest decline in length of therapy for culture-negative sepsis (8·2 days (95%CI 5·7-11·7) to 5·9 days (95% CI 4·6-7·5); p=0·032).
CONCLUSIONS: This neonatal AMS programme was successfully implemented in heterogenous and resource-limited settings. Pharmacist-recommended AMS interventions had high rates of clinician acceptance. The NeoAMS intervention significantly reduced neonatal antibiotic use, particularly for culture-negative sepsis.
BACKGROUND: A grant from Merck provided partial support.

BACKGROUND:  \"Direct-to-consumer (DTC) telemedicine\" is increasing worldwide and changing the map of primary health care (PHC). Virtual care has increased in the last decade and with the ongoing COVID-19 pandemic, patients\' use of online care has increased even further. In Sweden, online consultations are a part of government-supported health care today, and there are several digital care providers on the Swedish market, which makes it possible to get in touch with a doctor within a few minutes. The fast expansion of this market has raised questions about the quality of primary care provided only in an online setting without any physical appointments. Antibiotic prescribing is a common treatment in PHC.
OBJECTIVE:  This study aimed to compare antibiotic prescribing between digital PHC providers (internet-PHC) and traditional physical PHC providers (physical-PHC) and to determine whether prescriptions for specific diagnoses differed between internet-PHC and physical-PHC appointments, adjusted for the effects of attained age at the time of appointment, gender, and time relative to the COVID-19 pandemic.
METHODS:  Antibiotic prescribing data based on Anatomical Therapeutic Chemical (ATC) codes were obtained for Region Sörmland residents from January 2020 until March 2021 from the Regional Administrative Office. In total, 160,238 appointments for 68,332 Sörmland residents were included (124,398 physical-PHC and 35,840 internet-PHC appointments). Prescriptions issued by internet-PHC or physical-PHC physicians were considered. Information on the appointment date, staff category serving the patient, ICD-10 (International Statistical Classification of Diseases, Tenth Revision) diagnosis codes, ATC codes of prescribed medicines, and patient-attained age and gender were used.
RESULTS:  A total of 160,238 health care appointments were registered, of which 18,433 led to an infection diagnosis. There were large differences in gender and attained age distributions among physical-PHC and internet-PHC appointments. Physical-PHC appointments peaked among patients aged 60-80 years while internet-PHC appointments peaked at 20-30 years of age for both genders. Antibiotics with the ATC codes J01A-J01X were prescribed in 9.3% (11,609/124,398) of physical-PHC appointments as compared with 6.1% (2201/35,840) of internet-PHC appointments. In addition, 61.3% (6412/10,454) of physical-PHC infection appointments resulted in antibiotic prescriptions, as compared with only 25.8% (2057/7979) of internet-PHC appointments. Analyses of the prescribed antibiotics showed that internet-PHC followed regional recommendations for all diagnoses. Physical-PHC also followed the recommendations but used a wider spectrum of antibiotics. The odds ratio of receiving an antibiotic prescription (after adjustments for attained age at the time of appointment, patient gender, and whether the prescription was issued before or during the COVID-19 pandemic) during an internet-PHC appointment was 0.23-0.39 as compared with a physical-PHC appointment.
CONCLUSIONS:  Internet-PHC appointments resulted in a significantly lower number of antibiotics prescriptions than physical-PHC appointments, adjusted for the large differences in the characteristics of patients who consult internet-PHC and physical-PHC. Internet-PHC prescribers showed appropriate prescribing according to guidelines.

Testing serum C-reactive protein (CRP) levels can help determine whether there is a need for antibiotics and can limit prescribing of antibiotics for illnesses that are likely viral or non-infectious in origin. Using Health Search, an Italian primary care database, we identified all patients, aged 15 years or older, being registered in the period between 1 January 2000 and 31 December 2019 and newly diagnosed with upper respiratory tract infections (URTIs) or COPD- or asthma-related exacerbations. From the date of these diagnoses, patients were followed up until occurrence of antibiotic prescription (for these indications) up to 31 December 2019. The association between the CRP testing and the outcome was investigated using a nested case-control analysis. In a cohort of 469 684 patients being diagnosed for URTI (83%), COPD- (11%) and asthma (7%)-related exacerbations, 28 688 (6.11%) were prescribed with antibiotics because of the aforementioned indications. Of note, 98% of cases, nominally those prescribed with antibiotics, were not tested with CRP. However, those receiving antibiotics were more likely to have been previously tested for CRP than controls who did not receive antibiotics (833/28 601 [3%] and 4128/277 968 [1.5%]; OR 2.0 [95% CI: 1.8-2.1]). Our findings indicate that most of the antibiotic prescriptions for the investigated conditions were given without any prior CRP testing. A small minority of GPs did properly use CRP to determine whether antibiotics were needed. Further guidance is needed in Italy on the use of CRP in guiding antibiotic prescribing in primary care.

BACKGROUND: Antimicrobial resistance (AMR) is an important global public health concern in adults and children. Laryngotracheobronchitis (croup) is a common acute respiratory infection (ARI) among children, most often caused by a virus, and should not be treated with antibiotics. Reducing the usage of unnecessary antibiotics in ARI using an antimicrobial stewardship program (ASP) is an effective measure against AMR in children. This study investigates the antibiotic prescription pattern in pediatric patients with laryngotracheobronchitis in Korea. Our results will be useful to improve the ASP.
METHODS: The data were obtained from the government agency Health Insurance Review and Assessment Service. We analyzed outpatient prescriptions issued to children ≤ 5 years of age with a first-listed diagnosis code for laryngotracheobronchitis, i.e., International Classification of Disease, 10th Revision, code J050 (croup), J040 (laryngitis), or J041 (tracheitis), during 2017-2020. For each prescription, demographic information and information about medical facilities visited (type of hospital, specialty of physician, location of hospital) were extracted. The overall antibiotic prescription rate was subsequently estimated, and multivariable analysis was conducted to determine the associated factors of antibiotic prescription. Prescribed antibiotics were described and classified into extended-spectrum penicillins, cephalosporin, and macrolides.
RESULTS: Of 2,358,194 prescriptions reviewed, 829,172 (35.2%) contained antibiotics. In the multivariable analysis, management in a hospital was the strongest factor associated with antibiotic prescription (adjusted odds ratio [aOR], 22.33; 95% confidence interval [CI], 20.87-23.89; P < 0.001), followed by management in a clinic (aOR, 12.66; 95% CI, 11.83-13.54; P < 0.001) and management in a general hospital (aOR, 8.96; 95% CI, 8.37-9.59; P < 0.001). Antibiotic prescription was also significantly associated with patients who were ≤ 2 years of age, managed by a pediatric specialist, and treated at a hospital located in a non-metropolitan region. Overall, extended-spectrum penicillins were the most frequently prescribed (18.6%) antibiotics, followed by cephalosporins (9.4%) and macrolides (8.5%).
CONCLUSIONS: The results of our study suggest that ASPs need to focus on physicians in hospitals, clinics, general hospitals, and pediatric specialties. Providing education programs to these groups to increase awareness of AMR and appropriate antibiotics use could be effective ASP policy and may help to reduce unnecessary prescriptions of antibiotics for laryngotracheobronchitis among pediatric patients and therefore potentially AMR in children in Korea.

The coronavirus disease (COVID-19) pandemic affects the healthcare system worldwide and challenges many governments and institutions. Antimicrobial stewardship program advocating the wise use of antimicrobial agents. Its metrics include antimicrobial use measures, process, and outcome performance indications. We will conduct a retrospective observational study with the main hypothesis that the COVID-19 pandemic does not affect the antimicrobial stewardship program and its metrics. We will compare antimicrobial stewardship metrics (process, outcome, utilization) and antibiotic resistance two years before (2018-2019) (Group A) & two years with the COVID-19 pandemic (2020-2021) (Group B). The study will be conducted in Saqr Hospital, a secondary care hospital in the emirate of Ras Al Khaimah in the United Arab Emirates. Data will be analyzed using SPSS version 22. Numerical data will be presented as mean (SD) or median (IQR). Chi-square or Fisher\'s exact test will be used to analyze categorical data. The t-test or Mann-Whitney U test will be used to compare the difference of numerical variables. p < 0.05 will be considered statistically significant. Multivariate logistic regression will be used to investigate the relation between different variables with (1) cost and (2) antibiotic resistance.

Coccidia of the genus Eimeria are specialized intracellular parasitic protozoa that cause severe coccidiosis when they infect their hosts. Animals infected with Eimeria develop clinical symptoms, such as anorexia, diarrhea, and hematochezia, which can even cause death. Although the current preferred regimen for the treatment of coccidiosis is antibiotics, this treatment strategy is limited by the ban on antibiotics and the growing problem of drug resistance. Therefore, the exploration of alternative methods for controlling coccidiosis has attracted much attention. Lactobacillus plantarum has been shown to have many beneficial effects. In this study, L. plantarum M2 was used as a research object to investigate the effect of L. plantarum on intestinal inflammation induced by infection with Eimeria falciformis in mice by detecting indicators, such as oocyst output, serum cytokines, and the intestinal microbiota. Compared with that in the infection group, the percent weight loss of the mice that were administered with L. plantarum M2 was significantly reduced (P < 0.05). Supplemented L. plantarum M2 and probiotics combined with diclazuril can reduce the total oocyst output significantly (P < 0.05, P < 0.001). L. plantarum M2 had outstanding performance in maintaining intestinal barrier function, and the levels of the mucin MUC1 and the tight junction protein E-cadherin were significantly elevated (P < 0.01, P < 0.05). Studies have shown that probiotic supplementation can alleviate adverse reactions after infection and significantly improve intestinal barrier function. In addition, probiotics combined with diclazuril could optimize the partial efficacy of diclazuril, which not only enhanced the effect of antibiotics but also alleviated their adverse effects. This study expands the application of probiotics, provides new ideas for alternative strategies for coccidia control, and suggests a basis for related research on lactobacilli antagonizing intracellular pathogen infection.IMPORTANCECoccidia of the genus Eimeria are specialized intracellular parasitic protozoa, and the current preferred regimen for the treatment of coccidiosis is antibiotics. However, due to antibiotic bans and drug resistance, the exploration of alternative methods for controlling coccidiosis has attracted much attention. In this work, we focused on Lactobacillus plantarum M2 and found that probiotic supplementation can alleviate adverse reactions after infection and improve intestinal barrier function. This study proposes the possibility of using lactic acid bacteria to control coccidiosis, and its potential mechanism needs further exploration.

Our objectives were to compare the efficacy of ketoprofen or ceftiofur for treatment of metritis in dairy cows considering subsequent health, production, and reproduction. Cows from 2 commercial dairy farms in Ontario, Canada were examined with a Metricheck device 3 times per week from 2 to 14 d in milk (DIM). Cows with metritis (fetid vaginal discharge; n = 193) were blocked by parity and fever (rectal temperature ≥39.5°C or <39.5°C) and within each block per farm, randomly assigned to receive 3 mg/kg BW of ketoprofen (KET) or 2.2 mg/kg of ceftiofur hydrochloride (CEF), once a day for 3 d. Day of enrollment was considered study d 0. Rectal temperature and attitude were evaluated in cows with metritis on study d 0, 3, 4, 7, 10, and 13, and vaginal discharge was evaluated on study d 4, 7, 10, and 13. Body condition was scored at enrollment and 35 DIM, and serum concentration of haptoglobin was measured at d 0, 2, 4, and 7. Cows with rectal temperature ≥39.5°C or a depressed attitude on d 3 were classified as clinical failure and received treatment with ceftiofur for 3 d (KET), or 2 additional days (CEF), to a maximum of 5 d of treatment with ceftiofur. At 35 ± 3 DIM cows were examined for uterine involution by transrectal palpation, purulent vaginal discharge (PVD) by Metricheck, and endometritis by endometrial cytology. Time to onset of cyclicity was assessed by serum progesterone (P4) measurements at 28, 42, and 56 DIM. Contemporary cows from the same farms without metritis (NOMET; n = 1,043) were used for comparison. Data were analyzed with mixed linear or logistic regression or Cox\'s proportional hazard models, including herd as a random effect. The proportion of clinical resolution of metritis on d 3 (96% vs. 92%), of cows with fever (from d 3 to d 13 after enrollment) or fetid discharge (from d 4 to d 13 after enrollment), and the number of medical treatments (3.1 vs. 3.3) were not different between CEF and KET, respectively. Cows in KET received fewer antibiotic treatments than cows in CEF (0.3 vs. 3.1). Uterine involution, the prevalence of PVD (50% vs. 47%) and subclinical endometritis (6.6% vs. 4.3%), and the proportion of cyclic cows (82% vs. 86%) did not differ between CEF and KET. Cows in KET had greater serum haptoglobin concentration from d 2 to 7 after enrollment. The incidence of mastitis, lameness, or displaced abomasum to 60 DIM and subclinical ketosis to 21 DIM did not differ among CEF, KET, and NOMET. There were no differences in median days to first AI (CEF = 68 d; 95% CI: 65-70; KET = 69 d; 95% CI: 68-72; NOMET = 69 d; 95% CI: 68-70), and median days to pregnancy (CEF = 118 d; 95% CI: 92-145; KET = 113 d; 95% CI: 90-135; NOMET = 105 d; 95% CI: 101-109), pregnancy at first AI at 33 d after insemination (CEF = 42%; KET = 41%; NOMET = 41%), pregnancy loss after first AI (CEF = 8%; KET = 11%; NOMET = 8%), hazard of pregnancy or hazard of culling up to 300 DIM. Milk yield was not different between CEF and KET during the first 10 weeks, but lesser in KET at wk 2 and 4 and CEF at wk 2, 4, and 6 than in NOMET. In this pilot-scale study, given early detection, we did not detect differences in subsequent health, milk yield, or reproductive performance in cows with metritis initially treated for 3 d with CEF or KET. Additional, larger studies are warranted.

14 novel pleuromutilin derivatives were designed and synthesized as inhibitors against Staphylococcus aureus (S. aureus). The modification was focused on the C22 position of pleuromutilin. We conducted the characterization, in vitro and in vivo biological assessment of the compounds. Compound 18 exhibited the best antibacterial effect against MRSA (MIC = 0.015 μg/mL, MBC = 0.125 μg/mL). Compound 18 was further studied by time-kill kinetic and post-antibiotic effect (PAE) approaches. Besides, most compounds exhibited low cytotoxicity to RAW 264.7 cells. Compound 18 displayed decent bactericidal activity in vivo (-0.51 log10 CFU/mL). Molecular docking study indicated that compound 18 could be located stably at the ribosome (ΔGb = -7.30 kcal/mol). The results revealed that compound 18 might be further developed into a novel antibiotic.

BACKGROUND: The implementation of antibiotic intravenous-to-oral switch (IVOS) therapy in hospitals can slow down the development of drug resistance, reduce the occurrence of adverse reactions, and bring significant economic benefits. The aim of this study is to investigate the understanding of physicians at the Second Affiliated Hospital of Soochow University in Suzhou, China towards the antibiotic IVOS therapy.
METHODS: 15 physicians working in 9 different departments of the Second Affiliated Hospital of Soochow University participated in this study. A semi-structured face-to-face interview was conducted to collect interview information about the antibiotic IVOS therapy. NVivo12 software was used to organize the entire interview content, and the interview data was analyzed and summarized using the Colaizzi seven step method.
RESULTS: 60% of participants were not familiar with antibiotic IVOS therapy. Barriers of antibiotic IVOS therapy were included by three key issues: (i) Physicians\' potential cognition: \'Iv is always better than oral\'; (ii) Subjective infusion intention of patients; and (iii) Limitations of drug selection. 60% of participants expressed welcome for pharmacists to help them perform antibiotic IVOS treatment. And electronic recognition technology may be a feasible method for prompting IVOS conversion that recognized by all participants in the interview. Participants also provided some suggestions for pharmacists and IVOS computer reminders.
CONCLUSIONS: Physicians\' in China still have insufficient understanding of antibiotic IVOS therapy. The promotion of antibiotic IVOS therapy in China faces many challenges and obstacles. Strategies such as IVOS therapy computer reminders and clinical pharmacists\' medication guidance were worth studying to help physicians develop antibiotic IVOS treatment.

BACKGROUND: Up to 50% of antibiotic prescriptions for upper respiratory infections (URIs) are inappropriate. Clinical decision support (CDS) systems to mitigate unnecessary antibiotic prescriptions have been implemented into electronic health records, but their use by providers has been limited.
OBJECTIVE: As a delegation protocol, we adapted a validated electronic health record-integrated clinical prediction rule (iCPR) CDS-based intervention for registered nurses (RNs), consisting of triage to identify patients with low-acuity URI followed by CDS-guided RN visits. It was implemented in February 2022 as a randomized controlled stepped-wedge trial in 43 primary and urgent care practices within 4 academic health systems in New York, Wisconsin, and Utah. While issues were pragmatically addressed as they arose, a systematic assessment of the barriers to implementation is needed to better understand and address these barriers.
METHODS: We performed a retrospective case study, collecting quantitative and qualitative data regarding clinical workflows and triage-template use from expert interviews, study surveys, routine check-ins with practice personnel, and chart reviews over the first year of implementation of the iCPR intervention. Guided by the updated CFIR (Consolidated Framework for Implementation Research), we characterized the initial barriers to implementing a URI iCPR intervention for RNs in ambulatory care. CFIR constructs were coded as missing, neutral, weak, or strong implementation factors.
RESULTS: Barriers were identified within all implementation domains. The strongest barriers were found in the outer setting, with those factors trickling down to impact the inner setting. Local conditions driven by COVID-19 served as one of the strongest barriers, impacting attitudes among practice staff and ultimately contributing to a work infrastructure characterized by staff changes, RN shortages and turnover, and competing responsibilities. Policies and laws regarding scope of practice of RNs varied by state and institutional application of those laws, with some allowing more clinical autonomy for RNs. This necessitated different study procedures at each study site to meet practice requirements, increasing innovation complexity. Similarly, institutional policies led to varying levels of compatibility with existing triage, rooming, and documentation workflows. These workflow conflicts were compounded by limited available resources, as well as an implementation climate of optional participation, few participation incentives, and thus low relative priority compared to other clinical duties.
CONCLUSIONS: Both between and within health care systems, significant variability existed in workflows for patient intake and triage. Even in a relatively straightforward clinical workflow, workflow and cultural differences appreciably impacted intervention adoption. Takeaways from this study can be applied to other RN delegation protocol implementations of new and innovative CDS tools within existing workflows to support integration and improve uptake. When implementing a system-wide clinical care intervention, considerations must be made for variability in culture and workflows at the state, health system, practice, and individual levels.
BACKGROUND: ClinicalTrials.gov NCT04255303; https://clinicaltrials.gov/ct2/show/NCT04255303.