Characterizing Day 1 Area Under the Curve Following Vancomycin Loading Dose Administration in Adult Hospitalized Patients Using Non-Trapezoidal Linear Pharmacokinetic Equations: A Retrospective Observational Study.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) infections are a serious threat to public health. Vancomycin (VAN) remains the primary treatment for these infections, and achieving the recommended area under the curve (AUC) target has been linked to improved clinical outcomes. The current VAN therapeutic monitoring guidelines recommend a loading dose (LD) of 20-35 mg/kg to rapidly attain targeted VAN exposures within 24 h of therapy. However, there is a paucity of data describing the impact of VAN LD on day 1 area under the curve (AUC0-24). This study aims to employ pharmacokinetic (PK) equations to calculate and describe the AUC0-24 following a VAN LD of 20 mg/kg. METHODS: This was a retrospective study of adult patients who were loaded with VAN 20 mg/kg, received ≥ 48 h of treatment, and had two consecutive serum VAN levels collected within 24 h. Linear, non-trapezoidal PK equations and two post-infusion VAN levels were used to calculate AUC0-24. Therapeutic AUC0-24 was defined as 400-600 mg/l*h. RESULTS: Among 123 included patients, the median age was 46 years (IQR 36, 62), 54% (67/123) of the patients had a body mass index (BMI) ≥ 30 kg/m2 and 27% (33/123) were admitted to the intensive care unit (ICU). Following a LD of 20 mg/kg, 50% (61/123) of the patients met the therapeutic AUC0-24, while 22% (27/123) of the patients were subtherapeutic, and 28% (35/123) were supratherapeutic. Compared with patients who achieved therapeutic AUC0-24, patients with subtherapeutic AUC0-24 were more likely to be younger (44 vs. 37 years old) and have a BMI ≥ 30 kg/m2 (67 vs. 52%). In contrast, patients with supratherapeutic AUC0-24 were more likely to be older (64 vs. 44 years old) and to have chronic kidney disease diagnosis (23 vs. 7%) when compared to patients who achieved a therapeutic AUC0-24. CONCLUSIONS: Only 50% of patients achieve the target AUC0-24 following a VAN 20 mg/kg LD, with younger, heavier patients underexposed and older patients with renal impairment overexposed, suggesting that different dosing strategies are needed for these populations.

Prioritizing Equity in Antimicrobial Stewardship Efforts (EASE): a framework for infectious diseases clinicians.

Health equity gaps persist across minoritized groups due to systems of oppression affecting health-related social needs such as access to transportation, education and literacy, or food and housing security. Consequently, disparities in the prevalence of multidrug-resistant infections, infectious disease outcomes, and inappropriate antimicrobial use have been reported across minoritized populations. The Joint Commission and Centers for Medicare and Medicaid Services (CMS) have formally acknowledged the importance of integrating health equity-focused initiatives into existing hospital quality improvement (QI) programs. Here, we review documented disparities in antimicrobial stewardship and offer a framework, derived from components of existing health equity and QI tools, to guide clinicians in prioritizing equity in antimicrobial stewardship efforts (EASE).

Determining Susceptibility and Potential Mediators of Resistance for the Novel Polymyxin Derivative, SPR206, in Acinetobacter baumannii.

With the increase in carbapenem-resistant A. baumannii (CRAB) infections, there has been a resurgence in the use of polymyxins, specifically colistin (COL). Since the reintroduction of COL-based regimens in treating CRAB infections, several COL-resistant A. baumannii isolates have been identified, with the mechanism of resistance heavily linked with the loss of the lipopolysaccharide (LPS) layer of the bacterial outer membrane through mutations in lpxACD genes or the pmrCAB operon. SPR206, a novel polymyxin derivative, has exhibited robust activity against multidrug-resistant (MDR) A. baumannii. However, there is a dearth of knowledge regarding its efficacy in comparison with other A. baumannii-active therapeutics and whether traditional polymyxin (COL) mediators of A. baumannii resistance also translate to reduced SPR206 activity. Here, we conducted susceptibility testing using broth microdilution on 30 A. baumannii isolates (17 COL-resistant and 27 CRAB), selected 14 COL-resistant isolates for genomic sequencing analysis, and performed time-kill analyses on four COL-resistant isolates. In susceptibility testing, SPR206 demonstrated a lower range of minimum inhibitory concentrations (MICs) compared with COL, with a four-fold difference observed in MIC50 values. Mutations in lpxACD and/or pmrA and pmrB genes were detected in each of the 14 COL-resistant isolates; however, SPR206 maintained MICs ≤ 2 mg/L for 9/14 (64%) of the isolates. Finally, SPR206-based combination regimens exhibited increased synergistic and bactericidal activity compared with COL-based combination regimens irrespective of the multiple resistance genes detected. The results of this study highlight the potential utility of SPR206 in the treatment of COL-resistant A. baumannii infections.

Racial disparities among candidemic patients at a Southern California teaching hospital.

Racially and ethnically minoritized (REM) patients are disproportionately affected by infectious diseases, including candidemia. REM patients with candidemia were significantly younger, with trends toward more risk factors for candidemia and longer lengths of stay. Although Candida parapsilosis was more common in REM patients, there were no differences in mortality rates.

Examining racial and social vulnerability disparities in the outpatient treatment of uncomplicated cystitis at a Southern California Academic Hospital.

Racially and ethnically minoritized (REM) patients are disproportionately impacted by infectious diseases. In our study, REM patients were more likely to receive care for urinary tract infections in the emergency department or urgent care, were younger, and were more likely to have higher social vulnerability.

Identifying the potential impact of a multidisciplinary outpatient antimicrobial therapy program in an area of high social vulnerability.

Background: Outpatient parenteral antimicrobial therapy (OPAT) and complex outpatient antimicrobial therapy (COpAT) are common practice in the management of infectious diseases (IDs). However, providing OPAT/COpAT can pose significant challenges pre- and post-discharge, particularly in vulnerable patient populations. Objectives: The objective of this study is to assess outpatient complications related to OPAT/COpAT in patients discharged with a home health services referral and to identify pre- and post-discharge intervention opportunities and the associated cost-savings that could be achieved with a multidisciplinary ID team-run OPAT/COpAT program. Design/methods: This is a retrospective cohort study of patients who were discharged with OPAT/COpAT through home health services over a 3-month study period. Data on potential pre-discharge interventions and post-discharge complications were recorded. Results: Medication-related issues were the most common pre-discharge complications, accounting for more than 50% of identified intervention opportunities. More than half of the included patients experienced at least one documented outpatient complication post-discharge with peripherally inserted central catheter-line-related complication (20.7%) being the most common issue. Using previously published cost-estimates, the implementation of a designated pre- and post-discharge OPAT/COpAT program could have saved over $100,000 over the 3-month study period. Conclusion: A multidisciplinary OPAT/COpAT program located in a high social vulnerable area can help reduce complications related to a patient's antimicrobial therapy. Medication-related issues represent a major area for potential intervention. Our findings suggest that a multidisciplinary ID team will have ample opportunities to improve the transition of care, at both pre- and post-discharge, for patients requiring antimicrobial therapy.

Examining the impact of racial disparities on Clostridioides difficile infection outcomes at a Southern California academic teaching hospital.

Racial differences in Clostridioides difficile infection (CDI) outcomes have been reported. In this study, minoritized patients with CDIs had prolonged hospitalizations and increased intensive care unit admissions. Chronic kidney disease was shown to partially mediate the relationship between race or ethnicity and severe CDI. Our findings suggest potential areas for equitable interventions.

Characterizing Safety and Clinical Outcomes Associated with High-Dose Micafungin Utilization in Patients with Proven Invasive Candidiasis.

Micafungin is the empiric antifungal agent of choice for the treatment of invasive candidiasis (IC). Pathophysiologic changes that occur in obese and/or critically ill patients can alter micafungin serum concentrations and the probability of target attainment. Although high doses of micafungin have been shown to be safe, clinical outcomes have not been widely evaluated. We conducted a single-center, retrospective observational study evaluating safety and clinical outcomes among adult patients treated with ≥200 mg of micafungin for ≥3 days for proven IC from 1 September 2013 through 1 September 2021. Twenty-three unique encounters for 21 patients were evaluated. The median BMI and APACHE II scores were 37.1 (IQR 28.8-48.9) and 24 (IQR 17.7-31), respectively. The median average daily dose of micafungin was 300 mg (IQR 275-400). Patients were treated with high-dose (HD) micafungin for the entirety of their echinocandin course in 15 encounters (65.2%). Transaminases remained stable, while a trend towards increased alkaline phosphatase was observed. A total of four deaths occurred (17.4%). Patients that died were predominantly young, Hispanic males who were obese and/or critically ill. Future studies are needed to determine the necessity and appropriate placement of HD micafungin in obese and/or critically ill patients.