Annals of Pharmacotherapy最新文献

Background: A protocol was established for ventilator-associated tracheitis or pneumonia using inhaled tobramycin 300 mg every 12 hours in mechanically ventilated children via a vibrating mesh nebulizer, 30 cm from the endotracheal tube in the inspiratory loop of the mechanical ventilator.

Objectives: The primary objective was to determine the incidence of detectable tobramycin trough concentrations >0.5 µg/mL. Secondary objectives included a comparison of clinical characteristics between those with and without detectable concentrations and identification of patients with acute kidney injury (AKI) as defined by the Kidney Diseases Improving Global Outcomes (KDIGO) criteria.

Methods: This was a single-center retrospective study of critically ill children <18 years without cystic fibrosis receiving inhaled tobramycin between July 1, 2016, and August 31, 2021. Data collection included demographics, tobramycin regimen, and renal function. Analysis was performed using SAS 9.4, with a P-value <0.05, and a multivariable regression model was performed to identify factors for detectable concentrations and AKI.

Results: Forty-four patients (66 courses) were included, with an overall age of 0.83 years. Thirty (68%) patients had detectable concentrations and 9 (20.5%) developed AKI. No significant differences in demographics, diagnosis, mechanical ventilation settings, and number of nephrotoxins were noted between those with and without detectable concentrations or AKI. Multivariable regressions did not identify factors associated with detectable concentrations or AKI.

Conclusion and relevance: Detectable concentrations occurred with the majority of courses, with AKI associated with approximately one-fourth of courses. Clinicians should consider utilizing trough monitoring for all mechanically ventilated critically ill children receiving inhaled tobramycin.

Objective: To describe and analyze the pharmacodynamic and pharmacokinetic properties and clinical evidence supporting the efficacy and use of cefepime-enmetazobactam (FEP-EMT).

Data sources: A literature search was conducted using MEDLINE and EMBASE databases (January 2015 to May 2024). Search terms included: "cefepime-enmetazobactam" or "cefepime" or "enmetazobactam" or "cefepime" or "novel beta-lactamase inhibitor" and "complicated urinary tract infection" or "cUTI." Conference abstracts, bibliographies, clinical trials, and drug monographs were included for review.

Study selection and data extraction: Relevant studies in English and clinical trials conducted in humans were reviewed.

Data synthesis: In February 2024, the Food and Drug Administration (FDA) approved the combination beta-lactam/beta-lactamase inhibitor (BL/BLI) FEP-EMT for the treatment of complicated urinary tract infections (cUTIs) and acute pyelonephritis following the completion of the Phase III ALLIUM trial comparing it to piperacillin-tazobactam (TZP). The trial resulted in 79.1% of the FEP-EMT group versus 58.9% of the TZP group meeting the primary outcome of clinical cure and microbiological eradication (95% CI 21.2 [14.3 to 27.9]).

Relevance to patient care and clinical practice in comparison to existing agents: This review describes the use of FEP-EMT for the treatment of cUTI and compares its use to other novel BL/BLI combinations including utility in drug-resistant infections.

Conclusions: FEP-EMT provides an antimicrobial option to reduce overuse of carbapenems for extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae. However, unlike other novel BL/BLI combinations, its limited spectrum of antibacterial effect for more difficult-to-treat pathogens and cost may also impact its overall utilization.

Background: Patients admitted with acute myocardial infarction (AMI) are at high risk for morbidity and rehospitalizations. Pharmacists can play a vital role in secondary prevention by providing services such as medication reconciliation and patient education upon discharge. Objective: The purpose of this study was to evaluate the impact of a pharmacist-led transitions of care (TOC) service on readmissions in patients hospitalized with AMI. Methods: This single center, pre-post observational cohort study evaluated adults with AMI who received pharmacist TOC services compared with a historical cohort who did not. Patients were excluded if they underwent cardiac surgery during admission. The primary outcome was the difference in 90-day cardiovascular (CV)-related readmissions. Secondary outcomes included 30- and 90-day all-cause readmissions, 30-day CV-related readmissions, and patients discharged on defect-free guideline-directed medical therapy (GDMT) for AMI. Results: There were 252 patients in each cohort included. No difference was found in 90-day CV readmissions, with a rate of 10.7% in the pre-TOC group versus 9.9% in the post-TOC group (OR 0.937, 95% CI [0.493, 1.769]; P = 0.842). Patients discharged on defect-free GDMT significantly increased from 61.5% pre-TOC to 87.7% post-TOC (OR 5.424, 95% CI [3.204, 9.468]; P < 0.001). There were no significant differences found in other key secondary outcomes. Conclusion and relevance: This study did not find a significant difference in hospital readmissions after implementation of a pharmacist-led TOC service. However, the service was associated with a significant increase in patients discharged on defect-free GDMT. Further studies are needed to confirm the impact of increased GDMT on clinical outcomes.

Background: Evidence is inconclusive if early administration of subcutaneous (SQ) long-acting insulin (LAI) in management of diabetic ketoacidosis (DKA) improves outcomes.

Objective: This study compares early versus late administration of SQ LAI in time to DKA resolution.

Methods: This single-center, retrospective study included patients with DKA who received ≥12 hours of continuous intravenous insulin (CIVI) with LAI overlap. Patients were compared based on LAI administration time to CIVI initiation: Early (<12 hours) versus Late (≥12 hours). The DKA resolution is defined as blood glucose < 200 mg/dL and 2 of the following: anion gap < 12 mEq/L, pH > 7.35, or serum carbon dioxide >15 mEq/L. Outcomes included time to DKA resolution, length of stay (LOS), CIVI duration, and adverse events.

Results: A total of 27 patients were included in each group. Baseline characteristics were similar between both groups. There was no difference in time to DKA resolution, Early = 17.6 (13.9-26.8) hours versus Late = 19.2 (17.1-32.1) hours, P = 0.16. The Early group had shorter CIVI duration (Early = 19.5 ± 10.3 hours vs Late = 25.6 ± 8.4 hours, P = 0.02) and received less intravenous (IV) fluids in the first 36 hours (Early = 4.04 ± 2.12 L vs Late = 5.85 ± 2.24 L, P = 0.004). No differences were identified with adverse events, including hypoglycemia, or LOS.

Conclusion and relevance: Administration of SQ LAI < 12 hours did not decrease time to DKA resolution or LOS. Patients in the Early group had received a lower dose of LAI, shorter duration of CIVI infusion, and required less IV fluids within 36 hours of admission. This study supports the need for further research to determine the potential benefits of administering SQ insulin early in managing DKA.