Antibiotic stewardship in the emergency department setting: Focus on oral antibiotic selection for adults with skin and soft tissue infections.

PURPOSE: An advisory panel of experts was convened by the ASHP Foundation as a part of its Medication-Use Evaluation Resources initiative to provide commentary on an approach to antibiotic stewardship in the treatment of skin and soft tissue infections (SSTIs), with a focus on oral antibiotics in the emergency department (ED) setting for patients who will be treated as outpatients. Considerations include a need to update existing guidelines to reflect new antibiotics and susceptibility patterns, patient-specific criteria impacting antibiotic selection, and logistics unique to the ED setting. SUMMARY: While national guidelines serve as the gold standard on which to base SSTI treatment decisions, our advisory panel stressed that institutional guidelines must be regularly updated and grounded in local antimicrobial resistance patterns, patient-specific factors, and logistical considerations. Convening a team of experts locally to establish institution-specific guidelines as part of a comprehensive antibiotic stewardship program can ensure patients receive the most appropriate oral therapy for the outpatient treatment of SSTIs in patients visiting the ED. CONCLUSION: SSTI treatment considerations for antibiotic selection in the ED supported by current, evidence-based guidelines, including guidance on optimal oral antibiotic selection for patients discharged for outpatient treatment, are a useful tool to improve the quality and efficiency of care, enhance patient-centric outcomes and satisfaction, decrease healthcare costs, and reduce overuse of antibiotics.

Using symbiotic empirical ethics to explore the significance of relationships to clinical ethics: findings from the Reset Ethics research project.

BACKGROUND: At the beginning of the coronavirus (Covid-19) pandemic, many non-Covid healthcare services were suspended. In April 2020, the Department of Health in England mandated that non-Covid services should resume, alongside the continuing pandemic response. This 'resetting' of healthcare services created a unique context in which it became critical to consider how ethical considerations did (and should) underpin decisions about integrating infection control measures into routine healthcare practices. We draw on data collected as part of the 'NHS Reset Ethics' project, which explored the everyday ethical challenges of resetting England's NHS maternity and paediatrics services during the pandemic. METHODS: Healthcare professionals and members of the public participated in interviews and focus group discussions. The qualitative methods are reported in detail elsewhere. The focus of this article is our use of Frith's symbiotic empirical ethics methodology to work from our empirical findings towards the normative suggestion that clinical ethics should explicitly attend to the importance of relationships in clinical practice. This methodology uses a five-step approach to refine and develop ethical theory based on a naturalist account of ethics that sees practice and theory as symbiotically related. RESULTS: The Reset project data showed that changed working practices caused ethical challenges for healthcare professionals, and that infection prevention and control measures represented harmful barriers to the experience of receiving and offering care. For healthcare professionals, offering care as part of a relational interaction was an ethically important dimension of healthcare delivery. CONCLUSIONS: Our findings suggest that foregrounding the importance of relationships across a hospital community will better promote the ethically important multi-directional expression of caring between healthcare professionals, patients, and their families. We offer two suggestions for making progress towards such a relational approach. First, that there is a change of emphasis in clinical ethics practice to explicitly acknowledge the importance of the relationships (including with their healthcare team) within which the patient is held. Second, that organisational decision-making should take into account the moral significance afforded to caring relationships by healthcare professionals, and the role such relationships can play in the negotiation of ethical challenges.

Pharmacokinetics and Optimal Dosing of Levofloxacin in Children for Drug-Resistant Tuberculosis: An Individual Patient Data Meta-Analysis.

BACKGROUND: Each year 25 000-32 000 children develop rifampicin- or multidrug-resistant tuberculosis (RR/MDR-TB), and many more require preventive treatment. Levofloxacin is a key component of RR/MDR-TB treatment and prevention, but the existing pharmacokinetic data in children have not yet been comprehensively summarized. We aimed to characterize levofloxacin pharmacokinetics through an individual patient data meta-analysis of available studies and to determine optimal dosing in children. METHODS: Levofloxacin concentration and demographic data were pooled from 5 studies and analyzed using nonlinear mixed effects modeling. Simulations were performed using current World Health Organization (WHO)-recommended and model-informed optimized doses. Optimal levofloxacin doses were identified to target median adult area under the time-concentration curve (AUC)24 of 101 mg·h/L given current standard adult doses. RESULTS: Data from 242 children (2.8 years [0.2-16.8] was used). Apparent clearance was 3.16 L/h for a 13-kg child. Age affected clearance, reaching 50% maturation at birth and 90% maturation at 8 months. Nondispersible tablets had 29% lower apparent oral bioavailability compared to dispersible tablets. Median exposures at current WHO-recommended doses were below the AUC target for children weighing <24 kg and under <10 years, resulting in approximately half of the exposure in adults. Model-informed doses of 16-33 mg/kg for dispersible tablets or 16-50 mg/kg for nondispersible tablets were required to meet the AUC target without significantly exceeding the median adult Cmax. CONCLUSIONS: Revised weight-band dosing guidelines with doses of >20 mg/kg are required to ensure adequate exposure. Further studies are needed to determine safety and tolerability of these higher doses.

Delivering compassionate NHS healthcare: A qualitative study exploring the ethical implications of resetting NHS maternity and paediatric services following the acute phase of the COVID-19 pandemic.

A distinction can be drawn between healthcare, where compassion is evident, and the functional delivery of health services. Measures to curb the spread of COVID-19, such as personal protective equipment, telehealth, and visiting restrictions created barriers to service delivery and put pressure on healthcare. Through 37 qualitative interviews with NHS senior managers (n = 11), health professionals (n = 26), and 5 focus group discussions with members of the public (n = 26), we explored experiences of the everyday ethical tensions created as services were being re-established following the acute phase of the COVID-19 pandemic in England. Our analysis enriches an understanding of compassionate care as outlined in NHS operational documents - covering the emotional, moral, and relational components of healthcare beyond the functionalities of treatment. From this analysis, we consider the normative standards underpinning NHS healthcare, concluding that, wherever possible, offering compassionate healthcare to patients and their families should be facilitated, and health professionals should themselves be compassionately supported in the workplace. Our findings foreground the need to consider the consequences of the short-term adoption of a functional treatment approach, including strategies that support health professionals and inform the public, to avoid the long-term damage caused by the fracturing of compassionate healthcare.

Pharmacokinetics and cardiac safety of clofazimine in children with rifampicin-resistant tuberculosis.

Clofazimine is recommended for the treatment of rifampicin-resistant tuberculosis (RR-TB), but there is currently no verified dosing guideline for its use in children. There is only limited safety and no pharmacokinetic (PK) data available for children. We aimed to characterize clofazimine PK and its relationship with QT-interval prolongation in children. An observational cohort study of South African children <18 years old routinely treated for RR-TB with a clofazimine-containing regimen was analyzed. Clofazimine 100 mg gelatin capsules were given orally once daily (≥20 kg body weight), every second day (10 to <20 kg), or thrice weekly (<10 kg). PK sampling and electrocardiograms were completed pre-dose and at 1, 4, and 10 hours post-dose, and the population PK and Fridericia-corrected QT (QTcF) interval prolongation were characterized. Fifty-four children contributed both PK and QTcF data, with a median age (2.5th-97.5th centiles) of 3.3 (0.5-15.6) years; five children were living with HIV. Weekly area under the time-concentration curve at steady state was 79.1 (15.0-271) mg.h/L compared to an adult target of 60.9 (56.0-66.6) mg.h/L. Children living with HIV had four times higher clearance compared to those without. No child had a QTcF ≥500 ms. A linear concentration-QTcF relationship was found, with a drug effect of 0.05 (0.027, 0.075) ms/µg/L. In some of the first PK data in children, we found clofazimine exposure using an off-label dosing strategy was higher in children versus adults. Clofazimine concentrations were associated with an increase in QTcF, but severe prolongation was not observed. More data are required to inform dosing strategies in children.