44. Cost Effectiveness and Clinical Outcomes of Long Acting Lipoglycopeptides Used in Transitions of Care for Deep-Seated Infections

Background Dalbavancin and oritavancin are long-acting lipoglycopeptides (LaLGPs) FDA-approved for one-time only dosing for skin and skin structure infections. The use of these agents in serious, deep-seated infections requiring protracted antibiotic courses is of increasing interest. The purpose of this study is to evaluate the economic and clinical utility of LaLGPs in patients requiring protracted antibiotic courses who are not ideal candidates for oral transition or outpatient parenteral antibiotic therapy (OPAT). Methods This is a retrospective, observational, matched cohort study of adult patients who received a LaLGP. Patients who received a LaLGP were matched 1:1 to those who received standard of care (SOC) therapy by age (+/- 10 years), infection type, microorganism, and socioeconomic factor (e.g. persons who inject drugs, homelessness). Cost effectiveness was evaluated as total healthcare-related costs between groups. Clinical failure was a composite endpoint of mortality, recurrence, or need for extended antibiotics beyond planned course within 90 days of initial infection. Secondary outcomes included hospital length of stay and proportion of patients who left against medical advice (AMA). Results A total of 46 patients were included (23 per group). The most frequent indication was endovascular infection and the most common organism methicillin-resistant Staphylococcus aureus. The average length of stay was 22.9 days vs. 31.9 days in the LaLGP and SOC cohorts, respectively (p=0.153). The average total healthcare-related cost of care was USD &295,589 in the LaLGP cohort compared to &326,089 in the SOC cohort (p=0.282). LaLGPs were associated with a mean savings of &30,500 - &55,831 per patient (cumulative cost savings of &701,510). There was no difference in clinical failure between the two cohorts (22% vs. 30%; p=0.491). Nearly 26% of patients in the SOC cohort left AMA compared to 0% in the LaLGP cohort (p=0.022). Conclusion Receipt of LaLGPs may be a beneficial treatment option for patients with socioeconomic factors and deep-seated infections who are not candidates for oral transition or OPAT. Disclosures Julie Ann Justo, PharmD, MS, BCPS-AQ ID, bioMerieux (Speaker’s Bureau)Merck & Co. (Advisor or Review Panel member)Therapeutic Research Center (Speaker’s Bureau)Vaxart (Shareholder) P. Brandon Bookstaver, Pharm D, ALK Abello, Inc. (Grant/Research Support, Advisor or Review Panel member)Biomerieux (Speaker’s Bureau)Kedrion Biopharma (Grant/Research Support, Advisor or Review Panel member)

Short Courses of Antibiotics Are Safe in Necrotizing Soft Tissue Infections

Introduction Necrotizing soft tissue infections (NSTIs) carry high morbidity and mortality. While early aggressive surgical debridement is well-accepted treatment for NSTIs, the optimum duration of adjunct antibiotic therapy is unclear. An increasing focus on safety and evidence-based antimicrobial stewardship suggests a value in addressing this knowledge gap. Objective To determine whether shorter antibiotic courses have similar outcomes compared to longer courses in patients with NSTI following adequate source control. Population 142 consecutive patients with surgically managed NSTI were identified on retrospective chart review between December 2014 and December 2018 at two academic medical centers. Results Patients were predominately male (74%) with a median age of 52 and similar baseline characteristics. The median number of debridements to definitive source control was 2 (IQR 1-3) with the short course group undergoing a greater number of debridements control 2.57 ± 1.8 vs 1.9 ± 1.2, ( P = .01). Of 142 patients, 34.5% received a short course and the remaining 65.5% received a longer course of antibiotics. There was no significant difference in the incidence of bacteremia or wound culture positivity between groups. There was also no significant difference in in-hospital mortality, 8% vs 6, ( P = .74), incidence of C. difficile infection, median length of stay, or 30-day readmission. Conclusion Provided adequate surgical debridement, similar outcomes in morbidity and mortality suggest antibiotic courses of 7 days or less are equally safe compared to longer courses.

Paradox of trimethylamine-N-oxide, the impact of malnutrition on microbiota-derived metabolites and septic patients

Background Trimethylamine N-oxide (TMAO) is a microbiota-derived metabolite, which is linked to vascular inflammation and atherosclerosis in cardiovascular (CV) diseases. But its effect in infectious diseases remains unclear. We conducted a single-center prospective study to investigate association of TMAO with in-hospital mortality in septic patients admitted to an intensive care unit (ICU). Methods Totally 95 septic, mechanically ventilated patients were enrolled. Blood samples were obtained within 24 h after ICU admission, and plasma TMAO concentrations were determined. Septic patients were grouped into tertiles according to TMAO concentration. The primary outcome was in-hospital death, which further classified as CV and non-CV death. Besides, we also compared the TMAO concentrations of septic patients with 129 non-septic patients who were admitted for elective coronary angiography (CAG). Results Septic patients had significantly lower plasma TMAO levels than did subjects admitted for CAG (1.0 vs. 3.0 μmol/L, p < 0.001). Septic patients in the lowest TMAO tertile (< 0.4 μmol/L) had poorer nutrition status and were given longer antibiotic courses before ICU admission. Circulating TMAO levels correlated positively with daily energy intake, the albumin and prealbumin concentration. Compared with those in the highest TMAO tertile, septic patients in the lowest TMAO tertile were at greater risk of non-CV death (hazard ratio 2.51, 95% confidence interval 1.21–5.24, p = 0.014). However, TMAO concentration was no longer an independent predictor for non-CV death after adjustment for disease severity and nutritional status. Conclusion Plasma TMAO concentration was inversely associated with non-CV death among extremely ill septic patients, which could be characterized as TMAO paradox. For septic patients, the impact of malnutrition reflected by circulating TMAO levels was greater than its pro-inflammatory nature.

Comparison of the Knowledge and Practices in Medicine Dispensing between Retail Medicine Shops and Model Pharmacies in Dhaka Metropolis

Model pharmacy has been adopted recently to upgrade the healthcare delivery system in Bangladesh. This study was aimed to analyze and compare the effectiveness of drug dispensing patterns, practices, and knowledge of both clients and dispensers of model pharmacies over traditional retail medicine shops. Two established methods, namely, client simulated method (CSM) and provider interview method (PIM), were employed to determine the practice differences in 90 retail medicine shops and 90 model pharmacies in and around Dhaka city. The results are represented primarily in comparison with corresponding percentages. The survey results did not fully support the findings obtained from the observations of the CSM as PIM contrasted these to some extent, and the differences are statistically significant ( p < 0.0001 ). According to CSM, the presence of A-grade pharmacists during working hours in retail medicine shops was 0%, and 63% in model pharmacies. As reported by PIM, in the retail medicine shops, 36% of clients were ignorant of visiting doctors before purchasing medicine. On the other hand, only 18% of clients could visit doctors. As per CSM, 40% of clients did not follow doctors' recommendations for completion of the full dose of antibiotics bought from retail medicine shops and 51% did not finish full antibiotic courses collected from model pharmacies. Additionally, CSM revealed that 28% of the clients administered leftover drugs following old and obsolete prescriptions of retail medicine shops and 21% of clients followed the same practices in terms of model pharmacies. The report of CSM revealed that 95% of dispensers of retail medicine shops sold medicine without prescription except over-the-counter (OTC), and in the model pharmacies, the percentage was 77%. The qualitative findings revealed substandard practices and dispensing pattern too. Model pharmacies were established to prevent aberrant medicine dispensing patterns and ensure proper medication dispensing practices and medicine intake. This research could not verify the situation that pharmacists or owners of model pharmacies were fully abiding by the guidelines set for them by the Directorate General of Drug Administration (DGDA).

Reducing antibiotic prescribing by enhancing communication of general practitioners with their immigrant patients: protocol for a randomised controlled trial (PARCA study)

IntroductionAlthough antibiotic use and antimicrobial resistance in the Netherlands is comparatively low, inappropriate prescription of antibiotics is substantial, mainly for respiratory tract infections (RTIs). General practitioners (GPs) experience pressure from patients with an immigration background to prescribe antibiotics and have difficulty communicating in a culturally sensitive way. Multifaceted interventions including communication skills training for GPs are shown to be most effective in reducing antibiotic prescription. The PARCA study aims to reduce the number of antibiotic prescriptions for RTIs through implementing a culturally sensitive communication intervention for GPs and evaluate it in a randomised controlled trial (RCT).Methods and analysisA non-blinded RCT including 58 GPs (29 for each arm). The intervention consists of: (1) An E-learning with 4 modules of 10–15 min each; (2) A face-to-face training session in (intercultural) communication skills including role plays with a training actor and (3) Availability of informative patient-facing materials that use simple words (A2/B1 level) in multiple languages. The primary outcome measure is the number of dispensed antibiotic courses qualifying for RTIs in primary care, per 1000 registered patients. The secondary outcome measure is the number of all dispensed antibiotic courses, per 1000 registered patients. The intervention arm will receive the training in Autumn 2021, followed by an observation period of 6 winter months for which numbers of antibiotics will be collected for both trial arms. The GPs/practices in the control arm can attend the training after the observation period.Ethics and disseminationThe study protocol was approved by the Medical Ethics Review Committee of Erasmus MC, University Medical Center Rotterdam (MEC-2020-0142). The results of the trial will be published in international peer-reviewed scientific journals and will be disseminated through national and international congresses. The project is funded by The Netherlands Organisation for Health Research and Development (ZonMw).Trial registration numberNL9450.

Lack of regulation over antibiotic prescription and dispensation: A prospective cohort in a community setting

Background: The emergence of bacterial resistance caused health authorities to attempt to implement strict regulations for rational antibiotic prescription. However, supervision is often neglected in low- and middle-income countries, leading to inappropriate administration of antibiotics. The objective of our study is to highlight the lack of monitoring in the community setting of a middle-income country. Material and methods: We asked 68 patients presenting to an infectious diseases consultation office to report the antibiotic courses they had taken in the three months preceding their visit. We assessed for treatment indication, molecule choice, dosing and duration, as well as microbial cultures, demographics and specialty of the prescriber. Results: Among the 68 patients included in our study, we counted a total of 95 outpatient antibiotic courses, mostly composed of quinolones (36%), followed by amoxicillin-clavulanate (21%). The prescriber was most commonly a primary care physician, but we reported several cases of auto-medication and dispensation of antibiotics by pharmacists. Only 30% of cases had true indications for antibiotics. Conclusion: In sum, our results indicate an evident lack of regulation over the administration of antibiotics. This easy accessibility needs to be promptly addressed as we run the risk of inevitable bacterial resistance.

Evaluation of Antibiotic Initiation Tools in End-of-Life Care

Background: Hospice patients are frequently confronted with potentially infectious complications necessitating antibiotic consideration. Information regarding the appropriate use of antibiotics and their impact on symptom management in hospice patients are unknown. Objectives: This study aimed to evaluate and describe the use of an antibiotic initiation tool in patients admitted to outpatient hospice services. The primary outcome assessed the percentage of antibiotics that were appropriately initiated based on Loeb’s Minimum Criteria (LMC) for Antibiotic Initiation Tool. Secondary outcomes included the number of patients with documented symptom resolution following antibiotic completion, the number of antibiotic courses that were successfully completed, and treatment-related adverse events. Methods: This was a retrospective, multisite, descriptive analysis of hospice patients treated with antibiotics between April 2019 and September 2020. Results: Two hundred and thirty patients were assessed for inclusion, with 172 meeting eligibility criteria and receiving a total of 201 antibiotic courses. Based on LMC, 84 of the 201 (42%) antibiotics ordered were appropriate, with 60% of these LMC-approved courses resulting in symptom resolution. Out of 201 total courses, 99 (49%) resulted in symptom resolution. Overall, 160 (80%) antibiotic courses were successfully completed. Conclusion: In this study, antibiotic initiation in hospice patients frequently did not meet LMC. Less than half of the antibiotics prescribed led to symptom resolution despite antibiotic course completion in most patients. There is no consensus or guidelines directing appropriate antibiotic decision-making in hospice patients. The appropriate use of antibiotics in terminally ill patients warrants additional research.