Cost analysis of one-time intravenous antibiotic doses in the emergency department.

BACKGROUND: Research shows that one-time doses of intravenous (IV) antibiotics do not improve resolution of infection. However, providers continue to use them-especially in the emergency department (ED). Very few studies have aimed to quantify the cost of this practice. OBJECTIVES: The primary objective was to evaluate the difference in average total cost of ED stay between patients who received a one-time dose of IV antibiotics in the ED before discharging on oral antibiotics and patients who were just discharged on oral antibiotics. Secondary objectives were to evaluate the differences in durations of stay between the 2 groups, as well as the differences in adverse drug effects and need for health care contact after discharge. METHODS: Chart review was conducted to identify patients who received and did not receive a one-time dose of IV antibiotics in the ED between April 30, 2020, and April 30, 2022. A microcosting approach was used to determine ED-associated costs per patient. Comparisons in primary and secondary outcomes were performed using statistical inferential tests. RESULTS: A total of 102 patients were analyzed in each group. Patients who received a one-time dose of IV antibiotics in the ED before being discharged on oral antibiotics had an average length of stay of 4.55 hours, as opposed to patients who did not receive a one-time dose of IV antibiotics before being discharged on oral antibiotics who had an average length of stay of 2.82 hours (absolute difference 1.73 hours, P < 0.001). One-time dosing of IV antibiotics in the ED incurred an additional cost of approximately $556 per patient, totaling to more than $56,000 in our study cohort. CONCLUSION: The use of one-time IV antibiotics in the ED did not confer any additional benefits to patients. The use of one-time doses resulted in statistically significant reduced throughput in the ED and statistically significant increased health care costs.

Implementation of a compulsory clinical pharmacist-led medication deprescribing intervention in high-risk seniors in the emergency department.

OBJECTIVES: The objective of this study was to assess the impact of an emergency department (ED) deprescribing intervention for geriatric adults. We hypothesized that pharmacist-led medication reconciliation for at-risk aging patients would increase the 60-day case rate of primary care provider (PCP) deprescribing of potentially inappropriate medications (PIMs). METHODS: This was a retrospective, before-and-after intervention pilot study conducted at an urban Veterans Affairs ED. In November 2020, a protocol utilizing pharmacists to perform medication reconciliations for patients 75 years or older who screened positive using an Identification of Seniors at Risk tool at triage was implemented. Reconciliations focused on identifying PIMs and providing deprescribing recommendations to patients' PCPs. A preintervention group was collected between October 2019 and October 2020, and a postintervention group was collected between February 2021 to February 2022. The primary outcome compared case rates of PIM deprescribing in the preintervention group to the postintervention group. Secondary outcomes include per-medication PIM deprescribing rate, 30-day PCP follow-up visits, 7- and 30-day ED visits, 7- and 30-day hospitalizations, and 60-day mortality. RESULTS: A total of 149 patients were analyzed in each group. Both groups were similar in age and sex, with an average age of 82 years and 98% male. The case rate of PIM deprescribing at 60 days was 11.1% preintervention compared to 57.1% postintervention (p < 0.001). Preintervention, 91% of PIMs remained unchanged at 60 days compared to 49% (p < 0.05) postintervention. Regardless of PIM identification, the 30-day primary care follow-up rate increased postintervention: 31.5% and 55.7% (p < 0.0001), respectively. There was no improvement in 7- or 30-day subsequent ED visits, hospitalization, or mortality. CONCLUSIONS: Pharmacist-led medication reconciliation in high-risk geriatric patients was associated with an increase both in the rate of PIM deprescribing and in post-ED primary care engagement.

Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide.

PURPOSE: Many tyrosine kinase inhibitors (TKI) undergo extensive hepatic metabolism, but mechanisms of their hepatocellular uptake remain poorly understood. We hypothesized that liver uptake of TKIs is mediated by the solute carriers OATP1B1 and OATP1B3. EXPERIMENTAL DESIGN: Transport of crizotinib, dasatinib, gefitinib, imatinib, nilotinib, pazopanib, sorafenib, sunitinib, vandetanib, and vemurafenib was studied in vitro using artificial membranes (PAMPA) and HEK293 cell lines stably transfected with OATP1B1, OATP1B3, or the ortholog mouse transporter, Oatp1b2. Pharmacokinetic studies were conducted with Oatp1b2-knockout mice and humanized OATP1B1- or OATP1B3-transgenic mice. RESULTS: All 10 TKIs were identified as substrates of OATP1B1, OATP1B3, or both. Transport of sorafenib was investigated further, as its diffusion was particularly low in the PAMPA assay (<4%) than other TKIs that were transported by both OATP1B1 and OATP1B3. Whereas Oatp1b2 deficiency in vivo had minimal influence on parent and active metabolite N-oxide drug exposure, plasma levels of the glucuronic acid metabolite of sorafenib (sorafenib-glucuronide) were increased more than 8-fold in Oatp1b2-knockout mice. This finding was unrelated to possible changes in intrinsic metabolic capacity for sorafenib-glucuronide formation in hepatic or intestinal microsomes ex vivo. Ensuing experiments revealed that sorafenib-glucuronide was itself a transported substrate of Oatp1b2 (17.5-fold vs. control), OATP1B1 (10.6-fold), and OATP1B3 (6.4-fold), and introduction of the human transporters in Oatp1b2-knockout mice provided partial restoration of function. CONCLUSIONS: These findings signify a unique role for OATP1B1 and OATP1B3 in the elimination of sorafenib-glucuronide and suggest a role for these transporters in the in vivo handling of glucuronic acid conjugates of drugs.

Ontogeny and sorafenib metabolism.

PURPOSE: To investigate the role of ontogeny in sorafenib metabolism to the equipotent active metabolite sorafenib N-oxide. EXPERIMENTAL DESIGN: Steady-state pharmacokinetic studies of sorafenib and metabolites were conducted in 30 children and young adults (17 males; median age, 9.5 years) receiving sorafenib 150 mg/m(2) or 200 mg/m(2) twice daily. Sorafenib metabolism was evaluated in vitro at 10 µmol/L using a panel of purified human cytochrome P450 (CYP) enzymes. Sorafenib metabolism and CYP3A4 expression was evaluated in 52 human liver samples from donors of ≤20 years old. The drug-drug interaction potential between sorafenib and azole antifungal agents was evaluated in vitro and in vivo. RESULTS: No age-related differences in sorafenib apparent oral clearance were observed. Mean sorafenib N-oxide metabolite ratio was 0.27 ± 0.14. In children of ≤10 years of age, boys had approximately 2-fold higher N-oxide ratios than girls (0.40 ± 0.15 vs. 0.22 ± 0.12, P = 0.026). Of the CYPs evaluated, sorafenib was exclusively metabolized to sorafenib N-oxide by CYP3A4. A trend for increased N-oxide formation in boys was observed in liver samples, which correlated with CYP3A4 mRNA expression. Posaconazole and voriconazole potently inhibited sorafenib N-oxide formation in vitro, and reduced sorafenib N-oxide formation in 3 children given sorafenib concurrent with azoles. CONCLUSION: We have identified several factors affecting interpatient variability in sorafenib metabolism to the active N-oxide metabolite including age, sex, and concurrent treatment with azole antifungals. This knowledge may provide important considerations for the clinical use of sorafenib in children and possibly other kinase inhibitors undergoing CYP3A4-mediated metabolism.