Annals of Pharmacotherapy最新文献

Adverse events and medication-related errors are common with anticoagulants. Heparin infusions are frequently associated with administration errors or challenges potentially leading to undesired events. Solving these challenges is multi-faceted given related complexities associated with the process, numerous variabilities related to heparin itself, heparin resistance, factors impacting assays to measure the intensity of anticoagulation, ineffective education processes, and limited data even on describing optimal target ranges to hard outcomes of thrombosis and bleeding. To overcome this, health care professionals have looked to technology as a potential solution. Some components of technology, such as smart pumps, and timing lab slips for ordering assays at a selected time to avoid incorrect information, have been means of improving management; however, gaps are still recognized. One component of treatment post a venous thromboembolism is achieving target goals within 24 hours. However, incorrect timing of assay draws related to the bolus and the related changes in order of elimination can work against achieving it unless the situation is understood and adapted during management. Machine learning is being explored to do this; however, it is not yet ready for prime time. Moving forward, clinicians need to stay engaged and be aware of the variables present. This includes an understanding of all assumptions, limitations and verification of what is intended does occur. The process should include validation of hard outcomes with the management approach.

Background: Oral step-down therapy for the treatment of gram-negative blood stream infections (GNBSIs) has been shown to be noninferior to full courses of intravenous (IV) therapy. Studies comparing oral fluoroquinolones, sulfamethoxazole-trimethoprim (SMX-TMP), and beta-lactams have reported similar treatment outcomes, but beta-lactam groups have been small, and efficacy has been questioned given lower oral bioavailability.

Objective: This study aims to evaluate the safety and efficacy of oral cephalosporins compared with penicillins for step-down therapy for the treatment of GNBSI.

Methods: This was a retrospective study in adult patients admitted for Enterobacterales GNBSI that were transitioned from IV antibiotics to an oral beta-lactam. The primary outcome was treatment failure. Secondary outcomes included components of the primary outcome, microbiological failure, antibiotic-associated adverse drug events (ADEs), and Clostridioides difficile infection (CDI).

Results: Overall, 280 patients with GNBSI with step-down to an oral penicillin (n = 140) or cephalosporin (n = 140) were included. More patients in the cephalosporin group had a urinary source of infection (87.9% vs 62.1%, P < 0.001) and urinary abnormalities (40% vs 28.6%, P = 0.044). Treatment failure with oral cephalosporins was noninferior to penicillins (7.1% vs 7.1%; 95% confidence interval [-6.4, 6.4], P = 0.002). No significant differences were found for microbiological failure, antibiotic-associated ADEs, or CDI.

Conclusion and relevance: Oral cephalosporins were noninferior to oral penicillins as step-down therapy for Enterobacterales GNBSI. This represents the first comparison of oral beta-lactams for the treatment of GNBSI.

Background: Antifungal resistance among Candida species has become increasingly prevalent in recent years.

Objectives: This study aims to identify independent predictors for poor outcomes associated with serious clinical infections caused by fluconazole non-susceptible Candida sp. across the Veterans Health Administration.

Methods: This retrospective, observational, nationwide analysis included adults admitted to any Veterans Affairs Medical Center (VAMC) between January 1, 2009, and September 30, 2024, with positive cultures (or rapid diagnostic test) for Candida sp. from otherwise-sterile sites. Multivariate logistic regression assessed associations with the 30-day mortality in patients with these Candida sp. infections, regardless of fluconazole susceptibility.

Results: Eligible cases were found from 1613 patients with 1651 culture episodes from otherwise-sterile sites detecting Candida sp. with available fluconazole susceptibility data. Non-susceptible Candida sp. was discovered in 261 of these episodes. Independent variables associated with 30-day mortality in fluconazole non-susceptible infection included reduced serum bicarbonate, thrombocytopenia, recent exposure to the macrolide/tetracycline/clindamycin antibiotics, elevated blood urea nitrogen, and lack of recent outpatient surgery. In the propensity-matched comparison, 30-day mortality between the 2 groups was not statistically significant: 26.6% for episodes with susceptible fluconazole isolates vs 24.9% for non-susceptible episodes (139/522 vs 65/251; P = 0.60).

Conclusion and relevance: Several host-derived physiological markers and recent exposure to protein synthesis inhibitor antibiotics were independent variables associated with 30-day mortality in patients with non-susceptible serious Candida sp.

Infections: This information may guide clinicians toward strategies to improve the clinical outcomes of these patients.

Objective: To review the efficacy and safety of elinzanetant for the management of vasomotor symptoms (VMS) associated with menopause.

Data sources: Literature was identified using PubMed (1966 to January 2026), EMBASE (1973 to January 2026), and clinicaltrials.gov. Search terms included elinzanetant, VMS, and menopause, limiting trials to those published in English.

Study selection and data extraction: Articles selected for inclusion included trials evaluating elinzanetant for the treatment of VMS.

Data synthesis: Elinzanetant was evaluated for reduction in frequency and severity of moderate-to-severe VMS associated with menopause in 3 phase 3 trials (OASIS 1, 2, and 3) and 1 phase 3 trial in patients receiving endocrine therapy for breast cancer (OASIS 4). All studies showed significant improvements in symptom frequency at week 12 compared to placebo (P < .001). Improvement in sleep disturbances and quality of life was also significant in OASIS 1, 2, and 4. Elinzanetant was well-tolerated, with headache, fatigue, dizziness, somnolence, abdominal pain, and rash reported as the most frequent drug-associated adverse effects.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:Elinzanetant is the first dual neurokinin-1 and neurokinin-3 receptor antagonist approved for moderate-to-severe VMS associated with menopause. Elinzanetant offers a nonhormonal treatment option with favorable tolerability, representing a promising alternative for patients who cannot or prefer not to use hormonal therapy.

Conclusion: The U.S. Food and Drug Administration approval of elinzanetant provides an additional nonhormonal option for managing moderate-to-severe VMS of menopause in patients for whom hormonal therapy is contraindicated or undesired.

Background: Atrial fibrillation (AF) is associated with an increased risk of stroke and heart failure (HF). Historically, rate control has been the preferred treatment strategy due to fewer adverse drug events, but emerging evidence suggests early rhythm control may offer mortality benefits. Despite this, a critical gap exists in understanding short-term outcomes of rhythm control.

Objectives: Assess the impact of early rhythm control strategy in patients with new-onset AF on mortality, hospitalizations, or emergency room (ER) visits compared to rate control strategy.

Methods: Retrospective observational study of patients at least 18 years of age diagnosed with new-onset AF cared for in a large United States healthcare system. Patients with identifiable triggers were excluded. The primary outcome was rates of all-cause mortality, hospitalization, or ER visit for AF, atrial flutter (AFL), or HF at 30 days.

Results: Four hundred sixty-three patients were included, 278 in the rate control group and 185 in the rhythm control group. The median follow-up duration across groups was 654.5 days. At 30 days post-diagnosis, the rate control group experienced a higher rate of the primary outcome (19.8% vs. 11.9%, P = 0.027). Cox proportional hazards model demonstrated that rhythm control was associated with a reduced risk of experiencing the secondary outcome (HR 0.759, 95% CI [0.582, 0.984], P = 0.042).

Conclusion and relevance: In patients with new-onset AF, early rhythm control was associated with a lower incidence of all-cause mortality, hospitalization, or ER visits. These findings underscore the importance of rhythm control in optimizing early AF management and improving patient outcomes.

Background: Antifungal-resistant Candida species have become increasingly prevalent in recent years, posing significant therapeutic challenges in the inpatient setting. Despite their clinical relevance, comprehensive data evaluating risk factors for the development of invasive infections caused by Candida sp. with antifungal resistance are limited.

Objective: This study aims to identify independent predictors for the development of invasive clinical infections caused by fluconazole-resistant or echinocandin-resistant Candida sp. in hospitalized veterans across the United States Veterans Health Administration.

Methods: This retrospective, observational, nationwide analysis included adults ≥18 years admitted to any Veterans Affairs Medical Center between January 1, 2009, and September 30, 2024, with culture-positive or rapid diagnostic test-confirmed invasive Candida sp. infection from otherwise-sterile sites. Data were gathered on baseline demographics, baseline laboratory data, comorbid conditions, and exposure to antibacterial agents, antifungal agents, β-Hydroxy β-methylglutaryl-CoA (HMG-CoA) reductase inhibitors, and immunosuppressant drug therapy. Univariate and multivariate logistic regression models were used to assess associations between clinical variables and the development of invasive fluconazole-resistant and echinocandin-resistant Candida sp.

Infections:

Results: Eligible cases were found from 25 Veterans Affairs Medical Center facilities; 1651 episodes had available fluconazole susceptibility data, and 1117 episodes had echinocandin susceptibility data. Fluconazole non-susceptibility was independently associated with at least 7 days of recent exposure to either fluconazole or an echinocandin, among a few other variables. Echinocandin resistance, while less common, was strongly linked to the receipt of dialysis, prolonged Gram-positive antibacterial exposure, and any prior antifungal use.

Conclusions and relevance: These findings can inform antifungal stewardship efforts to curb the rise of resistant Candida sp.