Meta-analysis on safety of standard vs. prolonged infusion of beta-lactams.

Background: Efficacy for prolonged infusion beta-lactam dosing schemes has been previously described, but there has been less focus on the safety of standard vs. prolonged infusion protocols of beta-lactams. This study explored differences in adverse drug reactions (ADRs) reported for beta-lactams between each of these infusion protocols.

Evolution of the Umbilical Cord Blood Proteome Across Gestational Development.

Neonatal health is dependent on early risk stratification, diagnosis, and timely management of potentially devastating conditions, particularly in the setting of prematurity. Many of these conditions are poorly predicted in real-time by clinical data and current diagnostics. Umbilical cord blood may represent a novel source of molecular signatures that provides a window into the state of the fetus at birth.

In-vitro and in-vivo assessment of nirmatrelvir penetration into CSF, central nervous system cells, tissues, and peripheral blood mononuclear cells.

Three years after SARS-CoV-2 emerged as a global infectious threat, the virus has become endemic. The neurological complications such as depression, anxiety, and other CNS complications after COVID-19 disease are increasing. The brain, and CSF have been shown as viral reservoirs for SARS-CoV-2, yielding a potential hypothesis for CNS effects.

Individual meropenem epithelial lining fluid and plasma PK/PD target attainment.

It is unclear whether plasma is a reliable surrogate for target attainment in the epithelial lining fluid (ELF). The objective of this study was to characterize meropenem target attainment in plasma and ELF using prospective samples. The first 24-hour T was evaluated vs 1xMIC and 4xMIC targets at the patient (i.

Making the case for precision dosing: visualizing the variability of cefepime exposures in critically ill adults.

Objective: To investigate and describe the variability in cefepime exposures among 'real-world', critically ill patients by using population pharmacokinetic modelling and simulations, and with translation of these findings to visualizations.

Methods: A cohort of adult medical ICU patients who received cefepime with therapeutic drug monitoring was studied. Two compartment models were developed to estimate cefepime clearance (Model 1) and simulate cefepime exposures among 1000 patients, each with identical creatinine clearance of 60 mL/min and receiving a regimen of cefepime 1 gram IV over 30 minutes, every 8 hours (Model 2).

Genomics of Aminoglycoside Resistance in Pseudomonas aeruginosa Bloodstream Infections at a United States Academic Hospital.

Pseudomonas aeruginosa frequently becomes resistant to aminoglycosides by the acquisition of aminoglycoside modifying enzyme (AME) genes and the occurrence of mutations in the and genes. We examined resistance to aminoglycosides in a collection of 227 P. aeruginosa bloodstream isolates collected over 2 decades from a single United States academic medical institution.

Iohexol-measured glomerular filtration rate and urinary biomarker changes between vancomycin and vancomycin plus piperacillin-tazobactam in a translational rat model.

Recent clinical studies have reported additive nephrotoxicity with the combination of vancomycin and piperacillin-tazobactam. However, preclinical models have failed to replicate this finding. This study assessed differences in iohexol-measured glomerular filtration rate (GFR) and urinary injury biomarkers among rats receiving this antibiotic combination.

Machine Learning To Stratify Methicillin-Resistant Staphylococcus aureus Risk among Hospitalized Patients with Community-Acquired Pneumonia.

Methicillin-resistant Staphylococcus aureus (MRSA) is an uncommon but serious cause of community-acquired pneumonia (CAP). A lack of validated MRSA CAP risk factors can result in overuse of empirical broad-spectrum antibiotics. We sought to develop robust models predicting the risk of MRSA CAP using machine learning using a population-based sample of hospitalized patients with CAP admitted to either a tertiary academic center or a community teaching hospital.

Use of therapeutic drug monitoring to characterize cefepime-related neurotoxicity.

Study Objectives: Data evaluating cefepime thresholds associated with neurotoxicity remain limited. The objectives of this study were to evaluate the incidence of cefepime-related neurotoxicity (CRN) in patients with plasma cefepime concentrations, assess the relationship between cefepime exposure and CRN, investigate clinical factors associated with CRN, and describe electroencephalogram (EEG) abnormalities in CRN.

Design: This was a retrospective study of adult inpatients admitted between 2016 and 2018 who received cefepime therapeutic drug monitoring (TDM).

Role of Therapeutic Drug Monitoring in the Treatment of Persistent Central Nervous System Infection: A Case Report and Review of the Literature.

A patient presenting with recurrent ventriculoperitoneal shunt infection was found to have growing from cerebrospinal fluid (CSF), which remained persistently positive. Therapeutic monitoring of clarithromycin, imipenem, and linezolid in CSF and plasma revealed lower than expected concentrations, prompting alternative therapy and culture clearance on hospital day 42.

Urinary Metabolomics From a Dose-Fractionated Polymyxin B Rat Model of Acute Kidney Injury.

Background: Polymyxin B treatment is limited by kidney injury. This study sought to identify Polymyxin B-related urinary metabolomic profile modifications for early detection of polymyxin-associated nephrotoxicity.

Methods: Samples were obtained from a previously conducted study.

Pharmacokinetic/Pharmacodynamic Considerations of Alternate Dosing Strategies of Tocilizumab in COVID-19.

Tocilizumab is one of few treatments that have been shown to improve mortality in patients with coronavirus disease 2019 (COVID-19), but increased demand has led to relative global shortages. Recently, it has been suggested that lower doses, or fixed doses, of tocilizumab could be a potential solution to conserve the limited global supply while conferring equivalent therapeutic benefit to the dosing regimens studied in major trials. The relationship between tocilizumab dose, exposure, and response in COVID-19 has not been adequately characterized.

Defining the Importance of Age-Related Changes in Drug Clearance to Optimizing Aminoglycoside Dosing Regimens for Adult Patients with Cystic Fibrosis.

Background And Objective: The number of adults living with cystic fibrosis (CF) has increased and will continue to do so with the approval of cystic fibrosis transmembrane conductance regulator (CFTR) modulators. Because systemic aminoglycosides are commonly administered for CF pulmonary exacerbations, we sought to define optimized dosing regimens using a population pharmacokinetic modeling and simulation approach.

Methods: Adult CF patients admitted for pulmonary exacerbation, receiving at least 72 h of systemic gentamicin, tobramycin, or amikacin, with measured concentrations were included.

Impact of early antimicrobial stewardship intervention in patients with positive blood cultures: results from a randomized comparative study.

Background: Antimicrobial stewardship intervention (ASI) appears to be necessary to realize the full benefits of rapid diagnostic technologies in clinical practice. This study aimed to compare clinical outcomes between early ASI paired with matrix-associated laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) compared with MALDI-TOF with standard of care (SOC) reporting in patients with positive blood cultures.

Methods: Adult patients with positive blood cultures and organism speciation via MALDI-TOF admitted between February 2015 and September 2015 were randomized to ASI or SOC in a 1:1 fashion.

Implementation of a clinical pharmacist-driven comprehensive medication management program in an outpatient wound healing center.

Background: The role of the pharmacist in wound healing management among patients with diabetic and nondiabetic foot ulcers (DFU) is unclear. We sought to implement and evaluate an integrated pharmacist-driven comprehensive medication management (CMM) program in a multidisciplinary podiatrist-led wound healing center (WHC).

Objectives: The objectives were to determine the role of the clinical pharmacist in a WHC and evaluate the impact of CMM interventions on prescribing rates and wound healing rates.

Characterizing Risk Factors for Clostridioides difficile Infection among Hospitalized Patients with Community-Acquired Pneumonia.

Hospitalized patients with community-acquired pneumonia (CAP) are at risk of developing Clostridioides difficile infection (CDI). We developed and tested clinical decision rules for identifying CDI risk in this patient population. The study was a single-center retrospective, case-control analysis of hospitalized adult patients empirically treated for CAP between 1 January 2014 and 3 March 2018.

Multicenter point prevalence evaluation of the utilization and safety of drug therapies for COVID-19 at the onset of the pandemic timeline in the United States.

Key Points: In a multicenter point-prevalence study, we found that the rate of supportive care was high; among those receiving COVID-19 drug therapies, adverse reactions occurred in 12% of patients.

Purpose: There are currently no FDA-approved medications for the treatment of coronavirus disease 2019 (COVID-19). At the onset of the pandemic, off-label medication use was supported by limited or no clinical data.