Inpatient Insights
APhA Staff
Levetiracetam may be as effective as valproic acid for poststroke seizure
Poststroke seizures are common after a cerebrovascular stroke, and understanding the optimal antiseizure medication regimen for patients with poststroke seizures is crucial to improving the prognosis for these patients.
Both levetiracetam (a newer-generation antiseizure medication) and valproic acid (an older-generation medication) are currently used as treatment for poststroke seizures, but evidence supporting the use of levetiracetam is limited. Researchers from Harvard Medical School and the National Taiwan University assessed the risk of seizure rehospitalization between levetiracetam and valproic acid in patients with poststroke seizures.
Using data from Taiwan’s National Health Insurance Research Database, the researchers conducted an observational retrospective cohort study to emulate a hypothetical randomized trial estimating the effectiveness of levetiracetam for poststroke seizure management. Patients who were hospitalized for their first seizure event between 2012 and 2020 and were newly prescribed levetiracetam (740 patients) or valproic acid (786 patients) before discharge were included in the study, which was published in the November 25, 2025, issue of Neurology.
The researchers found that levetiracetam use was associated with a lower risk of seizure rehospitalization compared with valproic acid with no significant differences in all-cause mortality or the composite of seizure rehospitalization and all-cause mortality. ■
Is cefiderocol better than standard therapy for Gram-negative bacterial bloodstream infections?
Bloodstream infections caused by carbapenem-resistant bacteria are associated with high mortality, and while cefiderocol, a fifth-generation cephalosporin, has broad in vitro activity against Gram-negative bacilli, it is unclear whether it is as effective as standard-of-care antibiotics in preventing mortality in patients with bloodstream infection caused by carbapenem-resistant Gram-negative bacilli.
In a study published online in The Lancet Infectious Diseases on October 7, 2025, researchers from Australia, Malaysia, Singapore, Taiwan, Thailand, and Türkiye conducted an open-label, parallel-group, randomized clinical trial to determine the effectiveness of cefiderocol in treating health care–associated or hospital-acquired Gram-negative bloodstream infections.
More than 500 patients with positive Gram-negative bacilli blood cultures were recruited from 17 tertiary hospitals. Participants were randomly assigned in a 1:1 ratio to cefiderocol (2 g intravenously every 8 hours) or standard of care (chosen by the patient’s clinical team) using an online randomization tool with strata defined by severity of comorbidities and region. The primary outcome was all-cause mortality at 14 days after randomization. The non-inferiority margin was 10%, with superiority to be assessed if non-inferiority was shown and was evaluated in both the main analysis population and in patients with at least one carbapenem-resistant organism causing bloodstream infection.
Among patients with a health care–associated or hospital-acquired Gram-negative bloodstream infection, cefiderocol resulted in non-inferior 14-day mortality compared with standard of care. In both the main analysis population and the carbapenem-resistant subset, cefiderocol was not superior to standard of care treatment. The researchers suggested that this evidence shows that cefiderocol is efficacious in patients with health care–associated Gram-negative bloodstream infection who are at high risk of antibiotic resistance, but more evidence is required to define its efficacy when carbapenem-resistant organisms are the cause. ■
Should oral anticoagulant treatment be continued after initial treatment for unprovoked VTE?
Clinical guidelines recommend anticoagulation treatment for at least 3 to 6 months for patients with deep vein thrombosis provoked by transient venous thromboembolism (VTE) risk factors, such as major trauma, surgery, and pregnancy, and extended treatment beyond 3 months if the VTE is unprovoked. However, randomized controlled trials comparing continuation with discontinuation of oral anticoagulant (OAC) after initial anticoagulation of 3 to 6 months underrepresented the highly frail and complex patients seen in routine care. Researchers at Harvard Medical School conducted a target trial emulation to compare the effect on health outcomes of continuing or discontinuing OACs among patients with unprovoked VTE after initial treatment for at least 90 days.
The study used data from the Optum CDM (2009–2025) and Medicare fee-for-service claims (2009–2022) related to adults with VTE who initiated OACs (warfarin or direct OACs) within 30 days of a first hospital admission with VTE without reversible provoking factors and who continued treatment for at least 90 days. Primary outcomes were hospital admission for recurrent VTE or major bleeding. Secondary outcomes were net clinical benefit (a composite of recurrent VTE and bleeding) and mortality.
Results of the study, published online on November 12, 2025, in The BMJ, showed that patients who continued treatment had markedly lower rates of recurrent VTE, higher rates of major bleeding, lower mortality rates, and greater net clinical benefit. The greater net clinical benefit was consistent across OAC types and length of initial OAC treatment. The authors concluded that these results reflect the average effect of continuing OACs and should help inform decisions on continuation of treatment, which should be individualized for each patient with an unprovoked VTE. ■
For alcohol withdrawal, phenobarbital shows promise
Benzodiazepines remain the primary pharmacological treatment for alcohol withdrawal syndrome (AWS), but the risk of respiratory depression and concerns in patients with hepatic impairment have led to interest in alternatives such as phenobarbital.
To evaluate whether phenobarbital monotherapy improves emergency department (ED) operational outcomes compared to benzodiazepines or combination therapy, researchers from the University of Tennessee and Wake Forest University conducted a single-center, retrospective cohort study of 1,178 adults at a regional academic medical center. Patients 18 years or older who were treated with I.V. phenobarbital, I.V. benzodiazepines, or both for AWS in the ED were included.
Results of the study, published online in Academic Emergency Medicine on October 28, 2025, indicated that hospital admission rates were highest (74.0%) for benzodiazepine-only encounters, followed by combination therapy (62.4%), and lowest for phenobarbital-only (52.1%). Among discharged patients, length of stay in the ED was shortest for the phenobarbital-only group at 5.8 hours, versus 7.6 hours for the benzodiazepine-only group and 10.3 hours for combination therapy. Logistic regression analysis revealed treatment with phenobarbital alone was independently associated with discharge, while increasing age, increasing heart rate, and treatment with benzodiazepines alone were independently associated with hospitalization.
The authors concluded that these findings support the use of phenobarbital as a potential alternative to benzodiazepines for managing AWS in the ED. They suggested that prospective, randomized trials are needed to confirm their results and guide best practice protocols. ■