Pharmacotherapy最新文献

Introduction: The optimal dosing and monitoring of vancomycin in pediatrics is still unknown but has evolved to emphasize area under the curve over 24 h (AUC_0-24) over minimum concentration (C_min) monitoring. Real-world data supporting the feasibility of two-concentration kinetics with first-order equations for the estimation of vancomycin AUC_0-24 in pediatric patients are lacking.

Objectives: To describe the interplay of vancomycin dose, AUC_0-24, and C_min using first-order equations within four pediatric age groups.

Methods: This is a single-center, retrospective cohort study analyzing pediatric patients (<18 years) receiving intravenous vancomycin between 2020 and 2022. Included patients received at least 24 h of intravenous vancomycin with two concentrations obtained within 96 h of therapy initiation. Patients with baseline renal dysfunction were excluded. Patients were divided into four age categories: neonates (≤28 days), infants (29 days to <1 year), children (1-12 years), and adolescents (13-17 years). First-order equations were utilized to estimate pharmacokinetic parameters and AUC_0-24.

Results: Overall, 219 patients (median age of 6 years [IQR 1-12]) met inclusion criteria. The median vancomycin daily dose was 30 mg/kg in neonates, 70 mg/kg in infants and children, and 52 mg/kg in adolescents. Median C_min and AUC_0-24 values among all age groups were 8.68 mg/L and 505 mg * h/L, respectively. For AUC_0-24 values outside of the therapeutic range (400-600 mg * h/L), more values were SUPRAtherapeutic (>600 mg * h/L) than SUBtherapeutic (<400 mg * h/L). The overall trend within our data showed suboptimal correlation between C_min and AUC_0-24. However, 71% of patients with C_min values of 5-10 mg/L had an AUC_0-24 within the therapeutic range of 400-600 mg * h/L, whereas 23 patients (92%) with a SUPRAtherapeutic AUC_0-24 had a C_min value ≥15 mg/L. Approximately 10% of patients experienced acute kidney injury.

Conclusions: Our data describe the relationship between vancomycin dose, C_min, and AUC_0-24 in pediatric patients. We demonstrated the feasibility of using first-order equations to estimate AUC_0-24, using two concentrations obtained at steady state to monitor efficacy and safety in pediatric patients receiving intravenous vancomycin. Our data showed suboptimal correlation between AUC_0-24 and C_min, which indicates that C_min should not be used as a surrogate marker for a therapeutic AUC_0-24 in pediatric patients. In alignment with the 2020 vancomycin consensus guidelines, we suggest utilizing AUC_0-24 for efficacy and safety monitoring.

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia is associated with poor clinical outcomes and increased mortality. Clinical data regarding the optimal treatment of CRAB is limited, and combination therapy is often preferred. Eravacycline has demonstrated in-vitro activity against A. baumannii and has been considered for the treatment of pulmonary infections caused by CRAB.

Objective: The objective of this case series was to describe clinical outcomes associated with eravacycline when utilized as part of a combination regimen for the treatment of CRAB pneumonia at a county hospital.

Methods: A retrospective chart review was conducted from April 1, 2020, to October 1, 2020, which included hospitalized patients ≥18 years of age, diagnosed with coronavirus disease 2019 (COVID-19), with a sputum culture positive for CRAB, and receipt of at least one dose of eravacycline. The primary outcome studied was clinical resolution of CRAB pneumonia. A key secondary outcome was microbiological resolution.

Results: A total of 24 patients received combination eravacycline therapy for a median of 10.5 days. Overall, 17 (71%) patients demonstrated clinical resolution of CRAB pneumonia. Repeat sputum cultures post-treatment were collected in 17 (71%) patients, of which 12 (71%) achieved microbiological resolution. No adverse events attributable to eravacycline were identified.

Conclusion: With limited viable salvage treatment options, combination eravacycline therapy showed favorable microbiological and clinical outcomes in patients with CRAB pneumonia. In light of this, eravacycline could be considered as a potential treatment option when designing CRAB pneumonia salvage therapy regimens.

Drug-resistant tuberculosis (TB) is a major public health concern and contributes to high morbidity and mortality. New evidence supports the use of shorter duration, all-oral regimens, which represent an encouraging treatment strategy for drug-resistant TB. As a result, the landscape of drug-resistant TB pharmacotherapy has drastically evolved regarding treatment principles and preferred agents. This narrative review focuses on the key updates of drug-resistant TB treatment, including the use of short-duration all-oral regimens, while calling attention to current gaps in knowledge that may be addressed in future observational studies.

Background: Vascular endothelial growth factor inhibitors, including tyrosine kinase inhibitors (TKIs) and anti-angiogenics, are first-line therapies for advanced and metastatic hepatocellular carcinoma. Although TKIs have a greater potential for off-target adverse effects compared with bevacizumab (anti-angiogenics), a direct comparison of the risk of cardiovascular adverse events between these two types of therapies has not been performed.

Objective: To compare the incidence of and characterize cardiovascular adverse events in patients with hepatocellular carcinoma receiving TKIs versus bevacizumab.

Methods: This cohort study included adult patients with hepatocellular carcinoma who received first-line TKIs (sorafenib or lenvatinib) or bevacizumab at two academic medical centers and one community cancer center from September 2018 to August 2021. The primary outcome was risk of cardiovascular adverse events. Major secondary outcomes included the incidence of individual types of cardiovascular adverse events and risk factors associated with major adverse cardiovascular events (MACE).

Results: The study included 221 patients (159 TKI patients; 62 bevacizumab patients). At a median follow-up of 5 months, the probability of cardiovascular adverse events was not significantly different between the two groups (hazard ratio [HR]: 0.85; 95% confidence interval [95% CI]: 0.58-1.24; p = 0.390). The cumulative incidence of cardiovascular events was highest in patients receiving lenvatinib (sub-distribution hazard ratio [SHR]: 1.53; 95% CI: 1.02-2.30) compared with those receiving sorafenib (reference) or bevacizumab (SHR: 1.05; 95% CI: 0.68-1.64) after adjustment for comorbidities, liver transplant status, and presence of portal vein thrombosis at baseline. Cardiovascular adverse events were observed in 151 (68%) patients, and MACE were observed in 27 (12%) patients. Risk factors associated with MACE were hypertension (SHR: 3.5; 95% CI: 0.9087-15.83; p = 0.086), prior history of MACE (SHR: 2.01; 95% CI: 0.83-4.87; p = 0.124), and tobacco use (SHR: 2.85; 95% CI: 0.90-8.97; p = 0.074).

Conclusions: Cardiovascular risk was not significantly different between TKIs and bevacizumab. Lenvatinib appears to have the highest risk of cardiovascular adverse events among these first-line VEGF inhibitors.

Introduction: The introduction of the highly effective modulator therapy elexacaftor-tezacaftor-ivacaftor (ETI) has revolutionized the care of persons with cystic fibrosis (PwCF) with major improvements seen in lung function and body mass index. The effects of ETI therapy in real-world cohorts on other parameters such as cholesterol levels are largely unknown.

Methods: A single-center, retrospective chart review study was conducted to assess the change in lipid panels before and after ETI initiation. The study investigated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride levels using both a univariate and multivariate mixed-effects model to evaluate the change after initiation of ETI in a cohort of PwCF.

Results: There were 128 adult PwCF included in the analysis. Statistically significant changes were seen in both univariate and multivariate analyses for TC, LDL-C, and HDL-C. On multivariate analysis, TC increased by an average of 15.0 mg/dL after ETI initiation (p < 0.0001), LDL-C increased by an average of 9.3 mg/dL (p < 0.001), and HDL-C increased by an average of 3.8 mg/dL (p < 0.001) after ETI initiation.

Conclusion: In this real-world cohort of PwCF, cholesterol parameters increased after initiation with ETI therapy. Further consideration may need to be given for PwCF in regards to screening for cardiometabolic risk factors as PwCF age as well as the potential need for cholesterol-lowering therapies.

Study objective: Studies have demonstrated sodium-glucose cotransporter-2 (SGLT2) inhibitors are kidney protective; however, their ability to cause hemodynamic changes may predispose patients to acute kidney injury (AKI). An FDA warning recommends evaluating for factors that predispose patients to AKI before initiating a SGLT2 inhibitor. The primary objective of this study is to identify risk factors that may predispose persons with diabetes to AKI when initiating SGLT2 inhibitor therapy.

Design: Multicenter retrospective cohort chart review.

Data source: Study patients were identified through an electronic medical record generated report if they had type 2 diabetes and were prescribed a SGLT2 inhibitor from January 2013 to September 2019.

Patients: Patients were included if they were receiving care at Advocate Medical Group and were confirmed to have taken one of the four SGLT2 inhibitors available at the time of study approval, canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin, for at least 7 days. Patients were excluded if they did not have a basic metabolic panel or comprehensive metabolic panel recorded 1 year prior to or 6 months after SGLT2 inhibitor therapy initiation.

Results: Data extraction from the electronic medical record identified 6425 patients receiving a SGLT2 inhibitor, of which 1962 met inclusion criteria and were included for analysis. Thirty-five (1.8%) patients experienced an AKI after SGLT2 inhibitor therapy initiation. There was no statistically significant difference between groups based on background medication use (p = 0.325). At baseline, patients experiencing an AKI after SGLT2 inhibitor initiation were more likely to be older in age (p = 0.010), have a higher serum potassium (p < 0.001), blood glucose (p = 0.018), SCr (p = 0.009) and UACR (p < 0.001), and a lower eGFR (p = 0.028) compared to those who did not experience AKI.

Conclusions: The transient eGFR decline with SGLT2 inhibitor initiation should be expected and is generally not an indication to discontinue therapy. Future initiatives should be directed at increasing knowledge of monitoring recommendations for these agents.

Study objective: Enoxaparin is standard of care for venous thromboembolism (VTE) prophylaxis in adult trauma patients, but fixed-dose protocols are suboptimal. Dosing based on body mass index (BMI) or total body weight (TBW) improves target prophylactic anti-Xa level attainment and reduces VTE rates. A novel strategy using estimated blood volume (EBV) may be more effective based on results of a single-center study. This study compared BMI-, TBW-, EBV-based, and hybrid enoxaparin dosing strategies at achieving target prophylactic anti-Factor Xa (anti-Xa) levels in trauma patients.

Design: Multicenter, retrospective review.

Data source: Electronic health records from participating institutions.

Patients: Adult trauma patients who received enoxaparin twice daily for VTE prophylaxis and had at least one appropriately timed anti-Xa level (collected 3 to 6 hours after the previous dose after three consecutive doses) from January 2017 through December 2020. Patients were excluded if the hospital-specific dosing protocol was not followed or if they had thermal burns with > 20% body surface area involvement.

Intervention: Dosing strategy used to determine initial prophylactic dose of enoxaparin.

Measurements: The primary end point was percentage of patients with peak anti-Xa levels within the target prophylactic range (0.2-0.4 units/mL).

Main results: Nine hospitals enrolled 742 unique patients. The most common dosing strategy was based on BMI (43.0%), followed by EBV (29.0%). Patients dosed using EBV had the highest percentage of target anti-Xa levels (72.1%). Multiple logistic regression demonstrated EBV-based dosing was significantly more likely to yield anti-Xa levels at or above target compared to BMI-based dosing (adjusted odds ratio (aOR) 3.59, 95% confidence interval (CI) 2.29-5.62, p < 0.001). EBV-based dosing was also more likely than hybrid dosing to yield an anti-Xa level at or above target (aOR 2.30, 95% CI 1.33-3.98, p = 0.003). Other pairwise comparisons between dosing strategy groups were nonsignificant.

Conclusions: An EBV-based dosing strategy was associated with higher odds of achieving anti-Xa level within target range for enoxaparin VTE prophylaxis compared to BMI-based dosing and may be a preferred method for VTE prophylaxis in adult trauma patients.

Introduction: Falls are the leading cause of injury in older individuals, with intracranial hemorrhage (ICH) being a common complication. Anticoagulants, such as vitamin K antagonist and direct oral anticoagulants, are increasingly utilized, and clinicians may question the necessity of reversal in patients with minor ICH, especially in the setting of increased risk of adverse events. This study aimed to identify a population of patients with minor traumatic ICH at low risk for poor-neurologic status where anticoagulant reversal may not improve outcomes.

Methods: This retrospective cohort study utilized data accessed from 35 trauma centers from 2018 to 2021. Patients included had a preinjury anticoagulant regimen, ICH due to blunt trauma, Glasgow Coma Scale score of 15, an Abbreviated Injury Scale (AIS) head score from 2 to 4, and an AIS of ≤1 for non-head regions within 24 h of hospital arrival. Patients were excluded if they required an emergent neurosurgical procedure or were on a preinjury purinergic-P2 receptor-12 protein (P2Y12) inhibitor. The primary outcome was the rate of in-hospital mortality or hospice.

Results: There were 654 patients on preinjury anticoagulation who were included with a minor traumatic ICH without neurologic deficits. Overall, 263 patients were reversed and 391 were not reversed. Twelve (4.6%) patients with in-hospital mortality or hospice were reversed compared with 19 (4.91%) patients who were not reversed (p = 0.861). A composite of hospital complications occurred in 21 (8%) reversed patients and 34 (8.7%) not reversed patients (p = 0.748). The average intensive care unit length of stay was 1.4 ± 3.4 days in the reversed group and 1.1 ± 1.8 days in the not reversed group (p = 0.069).

Conclusion: This study found no difference in hospital outcomes between patients with minor traumatic ICH on oral anticoagulants who were neurologically intact that were reversed versus those who were not reversed. Further studies should continue to define the subset of traumatic ICH patients who may not require reversal of anticoagulation.

Study objective: Few data are available on the association between the use of oxycodone in patients with chronic kidney disease (CKD) and acute respiratory conditions. The aim of this study was to investigate whether oxycodone is associated with an increased risk of acute respiratory conditions in patients with cancer and CKD compared with other opioids.

Design and setting: The data were obtained from a claims database in Japan. Patients with cancer and CKD who had received sustained-release opioids, including oral oxycodone, oral morphine, or transdermal fentanyl, between April 2014 and May 2021 were selected. The primary outcome was defined as an acute respiratory condition. Data for age and sex, morphine equivalent daily dose, concomitant use of specified medications, comorbidities defined based on the modified Charlson comorbidity index, substance use disorder, and lung cancer or metastatic lung cancer were investigated as covariates. Distribution of acute respiratory conditions was compared among the three sustained-release opioid groups using the log-rank test. Estimates of the incidence of acute respiratory conditions were compared among the groups using a Cox proportional hazards model with time-varying variables.

Main results: A significant difference in the distribution of acute respiratory conditions was found among the three groups (p < 0.01). Cox regression analysis showed a significantly higher risk of acute respiratory conditions with morphine (hazard ratio [HR]: 3.04, 95% confidence interval [CI]: 1.07-8.65, p = 0.04) compared with oxycodone but no significant difference in risk with oxycodone (HR 0.67, 95% CI: 0.32-1.38, p = 0.27) compared with fentanyl.

Conclusions: The findings suggest that the risk of acute respiratory conditions may be lower in patients with CKD who use oxycodone for cancer pain than in those who use morphine. Additionally, no difference in the risk of acute respiratory conditions was found between oxycodone and fentanyl use.