438: SAFETY AND EFFICACY OF CEFEPIME INTRAVENOUS PUSH VERSUS PIGGYBACK IN GRAM-NEGATIVE BACTEREMIA

Introduction: Gram-negative infections including bacteremia are a major cause of inpatient mortality. Optimizing management is key to improving outcomes. Beta-lactams exhibit optimal antibacterial effects based on the time free concentrations exceed an organism’s minimum inhibitory concentration. Limited data exists assessing outcomes using beta-lactams as intravenous push (IVP) compared to intravenous piggyback (IVPB) in serious infections. This study’s purpose was to compare safety and efficacy of cefepime administered IVP versus IVPB in gram-negative bacteremia. Methods: This was an IRB-approved, retrospective cohort of patients hospitalized January 2014 to December 2021 and administered cefepime for \u3e48 hours for gram-negative bacteremia involving Pseudomonas aeruginosa or AmpC beta-lactamase producing bacteria. Two groups were included: one of patients who received cefepime IVPB and the second of patients who received cefepime IVP. The primary outcome was a desirability of outcome ranking (DOOR) on a five-point ordinal scale including clinical cure (no recurrent bacteremia of initial pathogen, antibiotic escalation, or 30-day in-hospital mortality) and neurologic adverse effects during cefepime treatment up to 30 days inpatient or at discharge. Secondary outcomes included antibiotic escalation, time to defervescence, vasopressor use, and in-hospital mortality. A sample of 127 patients per group provided 80% power. Data was analyzed using measures of central tendency and variability, chi-square, student’s T test, and Mann-Whitney U. Results: A total 254 patients were included with 127 per group. DOOR with clinical cure was similar between the IVPB and IVP groups (105 (82.7%) vs. 104 (81.9%); P=0.656). Escalation of therapy was the most common reason for clinical failure in both the IVPB and IVP groups (17 (13.4%) vs. 18 (14.2%); P=0.856). More patients in the IVP group required vasopressors (13 (10.2%) vs. 28 (22.0%); P=0.011). No difference was found in time to defervescence or in-hospital mortality. Conclusions: When compared to cefepime IVPB in gram-negative bacteremia, treatment with IVP showed no significant difference in instances of clinical cure or adverse effects. Further research in a more severely ill population is needed to evaluate safety and efficacy of cefepime IVPB versus IVP

Respiratory culture nudge improves antibiotic prescribing for Moraxella catarrhalis and Haemophilus influenzae lower respiratory tract infections

We compared optimal antibiotic prescribing before and after implementing an interpretive β-lactamase microbiology comment for Haemophilus influenzae and Moraxella catarrhalis in lower respiratory-tract infections. The postintervention group was associated with 5-fold increased odds of optimal de-escalation (adjusted odds ratio, 5.03; 95% confidence interval, 2.57-9.87)

High-dose Cefepime vs Carbapenems for Bacteremia Caused by Enterobacterales With Moderate to High Risk of Clinically Significant AmpC β-lactamase Production

BACKGROUND: Limited data suggest that serious infections caused by Enterobacterales with a moderate to high risk of clinically significant AmpC production can be successfully treated with cefepime if the cefepime minimum inhibitory concentration (MIC) is ≤2 µg/mL. However, isolates with a cefepime-susceptible dose-dependent (SDD) MIC of 4-8 µg/mL should receive a carbapenem due to target attainment and extended-spectrum β-lactamase (ESBL) concerns. METHODS: This was a retrospective cohort study of hospitalized patients with RESULTS: Of the 315 patients included, 169 received cefepime and 146 received a carbapenem (ertapenem n = 90, meropenem n = 56). Cefepime was not associated with an increased risk of 30-day mortality compared with carbapenem therapy (adjusted hazard ratio [aHR], 1.45; 95% CI, 0.79-2.14), which was consistent for patients with cefepime SDD isolates (aHR, 1.19; 95% CI, 0.52-1.77). Multivariable weighted Cox models identified Pitt bacteremia score \u3e4 (aHR, 1.41; 95% CI, 1.04-1.92), deep infection (aHR, 2.27; 95% CI, 1.21-4.32), and ceftriaxone-resistant AmpC-E (aHR, 1.32; 95% CI, 1.03-1.59) to be independent predictors associated with increased mortality risk, while receipt of prolonged-infusion β-lactam was protective (aHR, 0.67; 95% CI, 0.40-0.89). CONCLUSIONS: Among patients with bacteremia caused by Enterobacterales with moderate to high risk of clinically significant AmpC production, these data demonstrate similar risk of 30-day mortality for high-dose cefepime or a carbapenem as definitive β-lactam therapy

“Don’t Label Them as Addicts!” Student Pharmacists’ Views on the Stigma Associated with Opioid use Disorder

Background: Student pharmacists represent an important potential population for targeted educational interventions focused on skill and confidence development in order to improve interactions with opioid users and to decrease stigma. The objective of this study was to understand student pharmacists’ perceptions of opioid users. Methods: Focus groups were conducted with student pharmacists across Tennessee over two months in 2020. Concepts from the Transtheoretical Mode, Social Cognitive Theory, stigma, and results from a survey sent to student pharmacists were used to develop the open-ended questions. Thematic analysis was conducted to inductively identify main themes. The recruitment of student pharmacists continued until thematic saturation was obtained. Results: Three focus groups were conducted with a total of 16 student pharmacists in second, third, and fourth professional years. Thematic analysis revealed two themes: Don’t label them as addicts, Student Insight into OUD-Associated Stigma and five sub-themes: developing a judgment-free environment; unconscious bias; a possible connection between physical appearance and addiction; socio-cultural factors, addiction, and isolation; and motivators to decrease stigma. This study not only presents the pharmacy students experiences and their significance, but also reports their recommendations for addressing the stigma associated with OUD in the pharmacy curriculum. Conclusions: These findings highlight the need to normalize appropriate language when describing patients with OUD and avoid negative labels such as “addict.” The findings also indicate where the roots of stigma lie and provide some of the tools to fight stigma on different fronts. Future research should explore and address potential implicit biases throughout pharmacy curriculum

Impact of Ceftolozane-Tazobactam vs. Best Alternative Therapy on Clinical Outcomes in Patients with Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Lower Respiratory Tract Infections

INTRODUCTION: Infections caused by multidrug-resistant (MDR), extensively drug-resistant (XDR), and difficult-to-treat (DTR) Pseudomonas aeruginosa are increasingly challenging to combat. Ceftolozane-tazobactam (C/T) is a novel β-lactam-β-lactamase inhibitor combination now commonly used to treat MDR and XDR P. aeruginosa. Lower respiratory tract infections (LRTIs) remain the most common source of infection caused by MDR/XDR P. aeruginosa. Comparative effectiveness studies to date have been limited by the type of comparator agents (i.e., aminoglycosides and polymyxins) and the inclusion of multiple infection sources (i.e., urinary tract, abdominal, skin and soft tissue, etc.). METHODS: We performed a multicenter, retrospective analysis of adults with LRTI caused by MDR or XDR P. aeruginosa admitted from January 2014 to December 2019. We aimed to compare clinical outcomes between patients who received C/T (n = 118) versus best alternative therapy (n = 88). The primary outcome was clinical failure, defined as 30-day mortality and/or an adverse drug reaction on antibiotic therapy. RESULTS: Two hundred and six patients met inclusion criteria. The C/T group had a significantly higher proportion of XDR P. aeruginosa and ventilator-associated bacterial pneumonia (VABP). After multivariable logistic regression, C/T treatment was independently associated with a 73.3% reduction in clinical failure compared to those who received best alternative therapy (P \u3c 0.001). The number needed to harm with best alternative therapy was 3. CONCLUSION: Our results suggest that C/T is a safe and effective therapeutic regimen for patients with MDR and XDR P. aeruginosa LRTI

A Multicenter Evaluation of Vancomycin-Associated Acute Kidney Injury in Hospitalized Patients with Acute Bacterial Skin and Skin Structure Infections

BACKGROUND: We sought to determine the real-world incidence of and risk factors for vancomycin-associated acute kidney injury (V-AKI) in hospitalized adults with acute bacterial skin and skin structure infections (ABSSSI). METHODS: Retrospective, observational, cohort study at ten U.S. medical centers between 2015 and 2019. Hospitalized patients treated with vancomycin (≥ 72 h) for ABSSSI and ≥ one baseline AKI risk factor were eligible. Patients with end-stage kidney disease, on renal replacement therapy or AKI at baseline, were excluded. The primary outcome was V-AKI by the vancomycin guidelines criteria. RESULTS: In total, 415 patients were included. V-AKI occurred in 39 (9.4%) patients. Independent risk factors for V-AKI were: chronic alcohol abuse (aOR 4.710, 95% CI 1.929-11.499), no medical insurance (aOR 3.451, 95% CI 1.310-9.090), ICU residence (aOR 4.398, 95% CI 1.676-11.541), Gram-negative coverage (aOR 2.926, 95% CI 1.158-7.392) and vancomycin duration (aOR 1.143, 95% CI 1.037-1.260). Based on infection severity and comorbidities, 34.7% of patients were candidates for oral antibiotics at baseline and 39.3% had non-purulent cellulitis which could have been more appropriately treated with a beta-lactam. Patients with V-AKI had significantly longer hospital lengths of stay (9 vs. 6 days, p = 0.001), higher 30-day readmission rates (30.8 vs. 9.0%, p \u3c 0.001) and increased all-cause 30-day mortality (5.1 vs. 0.3%, p = 0.024) CONCLUSIONS: V-AKI occurred in approximately one in ten ABSSSI patients and may be largely prevented by preferential use of oral antibiotics whenever possible, using beta-lactams for non-purulent cellulitis and limiting durations of vancomycin therapy

Real-world Multicenter Analysis of Clinical Outcomes and Safety of Meropenem-Vaborbactam in Patients Treated for Serious Gram-Negative Bacterial Infections

Fourty patients were treated with meropenem-vaborbactam (MEV) for serious Gram-negative bacterial (GNB) infections. Carbapenem-resistant Enterobacteriaceae (CRE) comprised 80.0% of all GNB infections. Clinical success occurred in 70.0% of patients. Mortality and recurrence at 30 days were 7.5% and 12.5%, respectively. One patient experienced a probable rash due to MEV

Preliminary, real-world, multicenter experience with omadacycline for Mycobacterium abscessus infections

Twelve patients were treated with omadacycline (OMC) as part of a multidrug regimen fo

Dalbavancin Sequential Therapy for Gram-Positive Bloodstream Infection: A Multicenter Observational Study

Introduction Long-acting lipoglycopeptides such as dalbavancin may have utility in patients with Gram-positive bloodstream infections (BSI), particularly in those with barriers to discharge or who require prolonged parenteral antibiotic courses. A retrospective cohort study was performed to provide further multicenter real-world evidence on dalbavancin use as a sequential therapy for Gram-positive BSI. Methods One hundred fifteen patients received dalbavancin with Gram-positive BSI, defined as any positive blood culture or diagnosed with infective endocarditis, from 13 centers geographically spread across the United States between July 2015 and July 2021. Results Patients had a mean (SD) age of 48.5 (17.5) years, the majority were male (54%), with many who injected drugs (40%). The most common infection sources (non-exclusive) were primary BSI (89%), skin and soft tissue infection (SSTI) (25%), infective endocarditis (19%), and bone and joint infection (17%). Staphylococcus aureus accounted for 72% of index cultures, coagulase-negative Staphylococcus accounted for 18%, and Streptococcus species in 16%. Dalbavancin started a median (Q1–Q3) of 10 (6–19) days after index culture collection. The most common regimen administered was dalbavancin 1500 mg as one dose for 50% of cases. The primary outcome of composite clinical failure occurred at 12.2%, with 90-day mortality at 7.0% and 90-day BSI recurrence at 3.5%. Conclusions Dalbavancin may serve as a useful tool in facilitating hospital discharge in patients with Gram-positive BSI. Randomized controlled trials are anticipated to validate dalbavancin as a surrogate to current treatment standards

Project #37: Management Guidelines for Patients with COVID-19: Rapid Cycle Improvement

Project’s purpose is to rapidly devise, continually improve, educate, and implement a live and changing COVID-19 management guideline based upon emerging best available evidence. This project also aims to optimize the care of patients with COVID-19 and improve patient outcomes.https://scholarlycommons.henryford.com/qualityexpo2022/1004/thumbnail.jp