The effect of carbapenem-resistant versus carbapenem-susceptible infections on patient outcomes at an academic medical center.

Objective: We sought to compare patient outcomes between carbapenem-resistant (CRE) and carbapenem-susceptible (CSE) infections at our academic medical center.

Design: We conducted a retrospective cohort study of adult patients with a positive culture of E. coli, E.

Comparing the activity of broad-spectrum beta-lactams in combination with aminoglycosides against VIM-producing .

Metallo-beta-lactamase (MBL)-producing carbapenem-resistant (CRE) infections continue to pose a serious threat to healthcare. Due to their unique active site, MBLs evade the activity of many novel beta-lactam/beta-lactamase inhibitor combinations, which have been specifically targeted toward those carbapenemases with serine active sites. Furthermore, resistance to most, if not all, other clinically relevant antimicrobial classes leaves few reliable therapeutic options.

Fixed dose daptomycin: An opportunity for pharmacokinetic/pharmacodynamic optimization in Staphylococcus aureus infections.

Background: Daptomycin is a high-use intravenous antimicrobial agent affording the convenience of once-daily dosing. Prior studies suggest an opportunity to use a more operationally convenient fixed rather than weight-based dosing but this approach has not been studied prospectively.

Methods: This study quantified the probability of toxicity and efficacy end points by prospectively testing a fixed dose regimen of daptomycin (750 mg) in obese and non-obese adults.

Performance of ePlex® blood culture identification panels in clinical isolates and characterization of antimicrobial stewardship opportunities.

We assessed the performance of GenMark's ePlex® Blood Culture Identification (BCID) Panels for overall agreement of organism identification and resistance mechanism detection with standard microbiologic methods. This study included patients with a positive blood culture from May 2020 to January 2021. The primary outcomes were to assess concordance of ePlex® organism identification with standard identification methods and concordance of ePlex® genotypic resistance mechanism detection with standard phenotypic susceptibility testing.

Vancomycin AUC estimation using first-order pharmacokinetic methods in pediatric patients.

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) over minimum concentration (C) monitoring. Real-world data supporting the feasibility of two-concentration kinetics with first-order equations for the estimation of vancomycin AUC in pediatric patients are lacking.

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

Daptomycin Dose Optimization in Pediatric Staphylococcus aureus Bacteremia: A Pharmacokinetic/Pharmacodynamic Investigation.

Daptomycin is an antibiotic with Gram-positive activity, including methicillin-resistant Staphylococcus aureus, for which optimal pediatric dosing is unknown. This study aimed to evaluate daptomycin exposures achieved with package label dosing and to identify dosing regimens necessary to enhance efficacy and minimize toxicity in children with S. aureus bacteremia.

Association of vancomycin-induced acute kidney injury with trough versus AUC monitoring in patients receiving extended durations of therapy.

Objective: Vancomycin therapy is associated with an increased risk of acute kidney injury (AKI). Previous studies suggest that area under the curve (AUC) monitoring reduces the risk of AKI, but literature is lacking to support this in patients receiving longer durations of vancomycin therapy.

Design: Retrospective cohort study.

Appropriateness of antibiotic use in patients with and without altered mental status diagnosed with a urinary tract infection.

Objective: The objective of this study was to determine antibiotic appropriateness based on Loeb minimum criteria (LMC) in patients with and without altered mental status (AMS).

Design: Retrospective, quasi-experimental study assessing pooled data from 3 periods pertaining to the implementation of a UTI management guideline.

Setting: Academic medical center in Lexington, Kentucky.

Changing times: The impact of gram-negative breakpoint changes over the previous decade.

We assessed breakpoint changes of 13,101 Enterobacterales and isolates from the past decade. All β-lactams and fluoroquinolones demonstrated decreased susceptibilities following breakpoint changes. experienced the largest average decrease in susceptibility amongst the Enterobacterales at 5.

Comparison of Bayesian-derived and first-order analytic equations for calculation of vancomycin area under the curve.

Introduction: Consensus guidelines recommend targeting a vancomycin area under the curve to minimum inhibitory concentration (AUC :MIC) ratio of 400-600 to improve therapeutic success and reduce nephrotoxicity. Although guidelines specify either Bayesian software or first-order equations may be used to estimate AUC , there are currently no large studies directly comparing these methods.

Objective: To compare calculated vancomycin AUC using first-order equations with two-drug concentrations at steady state to Bayesian two- and one-concentration estimations.

Acute Kidney Injury Associated with Area under the Curve versus Trough Monitoring of Vancomycin in Obese Patients.

Vancomycin is a first-line agent used in the treatment of methicillin-resistant Staphylococcus aureus; however, vancomycin is associated with acute kidney injury (AKI). Previous literature demonstrates decreased incidence of AKI using 24-h area under the concentration-time curve (AUC) monitoring, but its safety is unknown in obese populations. Patients ≥18 years, with body mass indices (BMI) ≥30 kg/m, admitted between August 2015 and July 2017 or October 2017 and September 2019, who received vancomycin for ≥72 h and had level(s) drawn within 96 h of initiation were included.

Time Above All Else: Pharmacodynamic Analysis of β-Lactams in Critically Ill Patients.

β-Lactams are the most commonly used antibiotics in intensive care units (ICUs). As critically ill patients often experience pharmacokinetic aberrations, and rates of antimicrobial resistance vary between hospital settings, reliance on tertiary sources or package labeling to guide empiric dosing often results in suboptimal β-lactam exposure. The primary objective was to identify β-lactam regimens capable of achieving ≥90% cumulative fraction of response (CFR) against 7 Gram-negative pathogens within 4 ICUs at our institution.

Efficacy and safety of vancomycin loading doses in critically ill patients with methicillin-resistant infection.

Background: While vancomycin loading doses may facilitate earlier pharmacokinetic-pharmacodynamic target attainment, the impact of loading doses on clinical outcomes remains understudied. Critically ill patients are at highest risk of morbidity and mortality from methicillin resistant (MRSA) infection and hypothesized to most likely benefit from a loading dose. We sought to determine the association between receipt of a vancomycin loading dose and clinical outcomes in a cohort of critically ill adults.

First-Dose Vancomycin Pharmacokinetics Versus Empiric Dosing on Area-Under-the-Curve Target Attainment in Critically Ill Patients.

Background: Early attainment of target area under the curve (AUC) to minimum inhibitory concentration (MIC) ratios have been associated with clinical success, as well as lower incidence of acute kidney injury (AKI), in patients receiving vancomycin for methicillin-resistant Staphylococcus aureus (MRSA). Critically ill patients are particularly vulnerable to poor outcomes from infection and face multiple risk factors for AKI, thus early precision dosing of vancomycin is vital in this population. We hypothesized that a personalized dosing approach, using vancomycin levels obtained after the first dose to guide further dosing, would be superior to empiric dosing in terms of AUC target attainment assessed at steady state (SS).

In vitro activity of eravacycline compared with tigecycline against carbapenem-resistant Enterobacteriaceae.

Eravacycline has been shown to have broad-spectrum activity against Gram-negative bacteria, including carbapenem-resistant Enterobacteriaceae (CRE). We compared the activity of eravacycline with that of tigecycline in CRE isolates cultured from patients at an academic medical centre. Eravacycline was more potent than tigecycline [mean minimum inhibitory concentration (MIC) ratio = 0.

Plazomicin: a new aminoglycoside in the fight against antimicrobial resistance.

Objective: To review the mechanism of action, mechanisms of resistance, activity, pharmacokinetics, pharmacodynamics, and clinical data for a novel aminoglycoside.

Data Sources: A PubMed search was performed from January 2006 to August 2019 using the following search terms: plazomicin and ACHN-490. Another search was conducted on clinicaltrials.

In vitro activity of plazomicin compared to other clinically relevant aminoglycosides in carbapenem-resistant Enterobacteriaceae.

We evaluated the in vitro activity of plazomicin against other aminoglycosides in 122 clinical carbapenem-resistant Enterobacteriaceae isolates using several clinical susceptibility breakpoints. Plazomicin had excellent in vitro activity with 98% overall susceptibility. Amikacin was the next most active with 86% overall susceptibility.

Focusing the Lens on the CAMERA Concepts: Early Combination β-Lactam and Vancomycin Therapy in Methicillin-Resistant Staphylococcus aureus Bacteremia.

Methicillin-resistant (MRSA) has grown to become a major burden on health care systems. The cumulation of limited therapeutic options and worsened patient outcomes with persistent MRSA bacteremia has driven research in optimizing its initial management. The guidelines published by the Infectious Diseases Society of America currently recommend combination therapy for refractory MRSA bacteremia, but the utility of combining antibiotics from the start of therapy is under investigation.

Pharmacist Survey: Pharmacist Perception of Vancomycin Area Under the Curve Therapeutic Drug Monitoring.

Background: Evidence suggests the standard vancomycin trough goal of 15 to 20 mg/L for serious infections is associated with acute kidney injury, whereas appropriate monitoring of 24-hour area under the curve (AUC) may decrease nephrotoxicity. As a result, institutions have transitioned to AUC monitoring, the predictive pharmacokinetic/pharmacodynamic parameter of vancomycin to improve safety outcomes. However, this method may require increased pharmacist time and effort.

Impact of total body weight on rate of acute kidney injury in patients treated with piperacillin-tazobactam and vancomycin.

Purpose: Results of a study to determine whether obesity is associated with acute kidney injury (AKI) among patients receiving combination therapy with piperacillin-tazobactam and vancomycin are reported.

Methods: A retrospective, single-center cohort study of patients who received combination therapy for at least 48 hours was conducted using data from the University of Kentucky Center for Clinical and Translational Science's Enterprise Data Trust. Patients with chronic kidney disease, baseline creatinine clearance of less than 30 mL/min, cystic fibrosis, or missing height or weight information were excluded.

Imipenem/relebactam activity compared to other antimicrobials against non-MBL-producing carbapenem-resistant Enterobacteriaceae from an academic medical center.

Background: Carbapenem-resistant Enterobacteriaceae (CRE) cause significant mortality and are resistant to most antimicrobial agents. Imipenem/relebactam, a novel beta-lactam/beta-lactamase inhibitor combination, and 16 other antimicrobials were evaluated against non-metallo-beta-lactamase-producing carbapenem-resistant Enterobacteriaceae clinical isolates from a United States tertiary academic medical center.

Objectives: To evaluate imipenem/relebactam and other commonly utilised antimicrobial agents against carbapenem-resistant Enterobacteriaceae.

Evaluation of the BD Phoenix automated system for determining antimicrobial susceptibility against carbapenem-resistant Enterobacteriaceae compared with broth microdilution.

Purpose: Carbapenem-resistant Enterobacteriaceae (CRE) are increasingly widespread in the healthcare system, resulting in infections associated with mortality of up to 50%. Many laboratories use automated systems to identify CRE isolates and determine susceptibility. The aim of this study was to evaluate categorical agreement between the BD Phoenix automated system and the gold standard - broth microdilution - in determining minimum inhibitory concentrations of CRE.

Vancomycin Area Under the Curve Dosing and Monitoring at an Academic Medical Center: Transition Strategies and Lessons Learned.

Due to the inconsistent correlation of vancomycin trough concentrations with 24-hour area under the curve (AUC) and a desire to reduce rates of vancomycin-associated acute kidney injury, an institutional guideline was implemented by the Antimicrobial Stewardship Team in September 2017 to monitor vancomycin using AUC. Three stages were utilized to organize the process: preparation, implementation, and evaluation. The preparation stage was used to present literature to key stakeholders, and pharmacy meetings focused on the development of a dosing and monitoring guideline.

Amikacin target achievement in adult cystic fibrosis patients utilizing Monte Carlo simulation.

Aim: Pseudomonas aeruginosa (PsA) is a common pathogen in cystic fibrosis (CF). Management of an acute pulmonary exacerbation (APE) caused by PsA is dual anti-pseudomonal antibiotics, a beta-lactam plus aminoglycoside. Aminoglycoside dosing in CF differs from the general population due to altered pharmacokinetics.