The neurosteroid allopregnanolone (ALLO) is a potent positive modulator of g -aminobutyric acid A (GABA A ) receptors. Earlier work indicates that sensitivity to the anticonvulsant effect of ALLO was enhanced during ethanol (EtOH) withdrawal in rats and in C57BL/6 mice, an inbred strain with mild EtOH withdrawal. In contrast, ALLO sensitivity was reduced during EtOH withdrawal in DBA/2 mice, an inbred strain with severe EtOH withdrawal. Thus, the present studies examined ALLO sensitivity during EtOH withdrawal in another animal model of EtOH withdrawal severity, the Withdrawal SeizureProne (WSP) and Withdrawal Seizure-Resistant (WSR) selected lines. Male mice were exposed to EtOH vapor or air for 72 h. During peak withdrawal, animals were injected with ALLO [0, 3.2, 5, 10 or 17 mg/kg, intraperitoneally (i.p.)] and tested for their sensitivity to the anticonvulsant effect. In separate studies, potentiation of GABA-stimulated chloride uptake by ALLO (10 nM to 10 mM) was assessed in microsacs prepared from mouse brain mice during peak withdrawal. Notably, WSP mice were cross-tolerant to the anticonvulsant effect of ALLO during EtOH withdrawal (i.e. significant decrease in the efficacy of ALLO) when compared with values in airexposed mice. In contrast, sensitivity to the anticonvulsant effect of ALLO was unchanged during EtOH withdrawal in the WSR line. Functional sensitivity of GABA A receptors to ALLO was significantly decreased during EtOH withdrawal in WSP mice in a manner consistent with the change in behavioral sensitivity to ALLO. These findings suggest that mice selectively bred for differences in EtOH withdrawal severity are differentially sensitive to ALLO during EtOH withdrawal.
BackgroundOutpatient parenteral antimicrobial therapy (OPAT), widely used for serious infections, has high failure rates in people with substances use disorders (SUD)1–2. At our institution, completing therapy in the hospital was previously the best option for high-risk patients; but long hospital stays are often unacceptable to patients and costly. To improve outcomes, our Infectious Diseases division, OPAT program, and Improving Addiction Care Team (IMPACT) developed and implemented a novel multidisciplinary conference (OPTIONS-DC) for inpatients with SUD requiring prolonged antibiotics. This study describes the conference development, tool, and initial experience.MethodsFrom June 2017 to June 2018, diverse stakeholders collaboratively created and implemented a structured conference to discuss treatment options that balance medical efficacy, patient preferences, and feasibility using harm-reduction principles. After 10 months of hospital-wide implementation, we elicited provider feedback and performed a content analysis of OPTIONS-DC notes and patient records to evaluate the impact.ResultsThe goal of conference development was prioritizing patient preferences and engaging multidisciplinary input. One RN facilitates the conference using the tool (Figure 1) to elicit input from the relevant providers. The tool systematically addresses components that may predict treatment success (i.e., working phone) while emphasizing patient preference and harm reduction. The IMPACT social work PICC safety assessment informs risks for IV access. Antibiotic recommendations are not a binary of optimal/suboptimal choices for the infection but options that best fit patient context. The average conference length was 28 minutes (IQR 21). Preliminary data shows good clinical outcomes and savings to inpatient days and cost. Initial feedback suggests the model was positively experienced by medical providers (Figure 2) and supported patient preferences.ConclusionA multidisciplinary patient-centered conference that prioritizes patient preference and uses harm-reduction principles for this high-risk population is practical, effective, and positively experienced by providers. This model may serve as a roadmap for other institutions. Disclosures All authors: No reported disclosures.
Background The use of dalbavancin (DAL) enhances the management of serious gram-positive infections in people with substance use disorder (SUD) by eliminating the need for central lines, weekly lab monitoring, and may decrease length of hospitalizations. Though administered weekly, care coordination for DAL is often complex, due to variable access to resources, insurance variation and treatment settings. Our institution uses OPTIONS-DC, a multi-disciplinary discharge planning conference facilitated by an outpatient parenteral antimicrobial therapy (OPAT) registered nurse (RN) to determine safe treatment plans while emphasizing patient preference for hospitalized patients with SUD and serious infections. When DAL is selected for treatment, patients are enrolled in the RN-led OPAT program for coordination and monitoring. DAL has been shown to result in monetary savings but these estimates have yet to incorporate the true cost of coordination. Methods We conducted a retrospective chart review of OPAT staff interventions required to coordinate DAL doses for patients with SUD (identified via ICD-10 code or chart notes). Additionally, we recorded in real time, the amount of time spent per intervention over a one month period for 7 additional patients. Results 53 courses of DAL in patients with SUD were included with a variety of dosing regimens and treatment settings (Table 1). 41 (77%) patients endorsed IV substance use. 68% of patients received DAL for osteomyelitis or endocarditis. The majority were insured by Oregon Medicaid (70%). The number of RN interventions per course averaged 3.35 with the most common being coordinating with patients and vendors (Table 2). The average time spent per patient course during a one-month sample was 39.4 minutes (range 15 – 58 minutes). The most time-consuming interventions were conducting the OPTIONS-DC conferences and attempting to reach patients after hospital discharge. Readmission for adverse effects or infection occurred for 4 (8%) patients. Conclusion The OPAT-RN time required to coordinate outpatient DAL for patients with SUD is substantial. This enhanced coordination allows for potential cost savings to health systems. Disclosures Amber C. Streifel, PharmD, BCPS, Melinta (Advisor or Review Panel member) Monica K. Sikka, MD, FG2 (Scientific Research Study Investigator)
Background Dalbavancin, a lipoglycopeptide antibiotic, has an extended half-life that allows for weekly dosing and is an alternative to daily intravenous (IV) antibiotics. The dosing interval has the potential to expand treatment options for more severe infections in patients with substance use disorder (SUD), houselessness, and other complex social determinants of health where treatment of severe infections with long courses of IV antibiotics can have a high risk of failure. Questions remain regarding clinical outcomes for this indication and patient population. Methods We conducted a retrospective review of dalbavancin use for any patient with documented SUD either by ICD-10 or in chart notes. We identified all patients > 18 years who received > 1 dose of dalbavancin via medication records. Results 53 patients with documented SUD received dalbavancin as part of their treatment regimen (Table 1). The most common indication was osteomyelitis, including 14 cases of vertebral osteomyelitis (Table 2). The most common causative organism was Staphylococcus aureus, 23 (43%) cases due to MRSA and 10 (18%) due to MSSA. The majority of patients (41,77%) had a documented history of IV drug use (IDU) and 19% had alcohol use disorder. A structured, RN-lead multi-disciplinary discharge planning conference to discuss antibiotic options, risk factors for outpatient parenteral antibiotic therapy, and PICC safety in the community was held for 17 (32%). Concern about outpatient PICC safety in patients with history of IDU, unsafe home environment, and prior non-adherence to outpatient antibiotics were common reasons for choosing dalbavancin. Ten (19%) patients were lost to follow-up. The 30 and 90-day readmission rates were 13% and 19% respectively but were due to relapse or recurrence of infection in only 3 (6%) at 30 days and 2 (4%) additional at 90 days. There was only one death at 90 days ant it was unrelated to infection. (Table 3) Table 2. Dalbavancin Use Conclusion Dalbavancin was well tolerated and = a viable alternative for patients with SUD who often have social factors and preferences that make continuation of outpatient IV therapy high risk or impractical. Further data on clinical outcomes in complex infections is needed. Disclosures All Authors: No reported disclosures
Background Vancomycin and daptomycin are commonly used in outpatient parenteral antimicrobial therapy (OPAT) for patients requiring lengthy courses of intravenous antimicrobials who are otherwise stable for discharge. Balancing the convenience and cost-savings of OPAT with the potential for adverse effects is challenging, this study compared the rates of complications and antimicrobial interventions for patients receiving vancomycin versus daptomycin across multiple OPAT settings. Methods We performed a retrospective chart review of adult OPAT patients who received >72 hours of vancomycin or daptomycin via home infusion, infusion center, or skilled nursing facility between January 2017 and August 2019. The outcomes evaluated included the rates of adverse drug reactions (ADRs), laboratory results above a defined threshold (vancomycin levels >20 mg/mL in the vancomycin arm and creatinine phosphokinase (CPK) levels >500 units/L in the daptomycin group), line complications, emergency department (ED) visits, and hospital readmissions. Other outcomes included additional phone calls and interventions required to coordinate care (additional labs, assessment of symptoms, additional test or antimicrobial-related dose changes) by the OPAT team. Results 180 patients were included; 130 received vancomycin and 50 received daptomycin. (Table 1) Patients in the vancomycin group had more supratherapeutic vancomycin troughs than elevated CPK for patients in the daptomycin group (rate ratio [RR] 0.16, 95% CI 0.05-0.50, p=0.0018). Rates of interventions (RR 0.37, 95% CI 0.26-0.52, p< 0.0001) and additional phone calls (RR 0.56, 95% CI 0.43-0.72, p< 0.0001) were also higher for patients in the vancomycin group. There were no statistically significant differences between groups in the rates of ADRs, line complications, ED visits, or hospital readmissions. (Table 2) Table 1. Baseline Characteristics Table 2. Outcomes Conclusion Vancomycin-treated patients had significantly more laboratory abnormalities and required significantly more time in patient care coordination by the OPAT team. The difference in healthcare utilization between these groups suggests a potential for significant cost-savings for OPAT patients and the healthcare system. Disclosures All Authors: No reported disclosures
Background: Serious infections in persons who use drugs (PWUD) are rising. Dalbavancin, due to its extended half-life, offers an alternative treatment for patients in whom standard of care antibiotics are not feasible or practical, allowing for reduced hospital days and the avoidance of central line placement or the use of complex oral regimens. Objectives: We aim to describe the time and effort required for coordination of dalbavancin courses by outpatient registered nurses (RNs) and other outpatient parenteral antimicrobial therapy (OPAT) staff. Design and methods: We conducted a retrospective review of adult patients with documented substance use who received at least one dose of dalbavancin and quantified the number of interventions required by our OPAT RNs and other OPAT staff for coordination of dalbavancin courses. Additionally, detailed data on time spent per intervention were prospectively collected for a 1-month period. Results: A total of 52 patients with 53 dalbavancin courses were included. Most substance use was intravenous. Infectious diagnoses included bone and joint infections (61%) and endocarditis (7%), in addition to skin and soft tissue infections (19%). Infections were most commonly caused by Staphylococcus aureus (62%). RN intervention was required in the coordination of 60% of all courses and in 77% of courses in which at least one outpatient dose was needed. Adverse reactions occurred in one patient (2%) and 90-day readmissions due to infectious complications occurred in two patients (4%). Detailed time analysis was performed for seven consecutive patients, with a total of 179 min spent by OPAT RNs on coordination. Conclusions: The ease of dalbavancin administration does not eliminate the need for extensive RN coordination for successful administration of doses in the outpatient setting for PWUD. This need should be accounted for in program staffing to help increase successful dalbavancin course completion.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.