The implications of data aggregation on propagating racial and ethnic disparities within the health care landscape: Actionable recommendations and considerations for pharmacists.

As the U.S. population becomes more racially and ethnically diverse, it is increasingly important to characterize health inequities for targeted intervention. As it stands, demographic data regarding race and ethnicity for patients and pharmacy trainees alike are aggregated into heterogenous population groups, resulting in findings that may inaccurately reflect the experiences of smaller subgroups. Disaggregation of patient outcomes data can serve to better inform public health interventions for the most vulnerable populations. In pharmacy, disaggregation can allow for better identification of racial and ethnic subgroups who have been traditionally excluded from funding support among other opportunities. In this commentary, we provide historical context and actionable recommendations to better describe our patient and pharmacy trainee populations, with the objectives of improving pharmacist representation and health equity.

Infectious Inequity: How the Gut Microbiome and Social Determinants of Health May Contribute to Clostridioides difficile Infection Among Racial and Ethnic Minorities.

Infectious diseases are a leading contributor to death in the United States, and racial differences in clinical outcomes have been increasingly reported. Clostridioides difficile infection (CDI) is a growing public health concern, as it causes nearly half a million infections per year and considerable excess hospital costs. Concurrent with other infectious diseases, recent literature denotes racial disparities in CDI incidence rates, mortality, and associated morbidity. Of note, investigations into CDI and causative factors suggest that inequities in health-related social needs and other social determinants of health (SDoH) may cause disruption to the gut microbiome, thereby contributing to the observed deleterious outcomes in racially and ethnically minoritized individuals. Despite these discoveries, there is limited literature that provides context for the recognized racial disparities in CDI, particularly the influence of structural and systemic barriers. Here, we synthesize the available literature describing racial inequities in CDI outcomes and discuss the interrelationship of SDoH on microbiome dysregulation. Finally, we provide actionable considerations for infectious diseases professionals to aid in narrowing CDI equity gaps.

Evaluation of Omadacycline Alone and in Combination with Rifampin against Staphylococcus aureus and Staphylococcus epidermidis in an In Vitro Pharmacokinetic/Pharmacodynamic Biofilm Model.

Biofilm-associated infections lead to substantial morbidity. Omadacycline (OMC) is a novel aminomethylcycline with potent in vitro activity against Staphylococcus aureus and Staphylococcus epidermidis, but data surrounding its use in biofilm-associated infections are lacking. We investigated the activity of OMC alone and in combination with rifampin (RIF) against 20 clinical strains of staphylococci in multiple in vitro biofilm analyses, including an in vitro pharmacokinetic/pharmacodynamic (PK/PD) CDC biofilm reactor (CBR) model (simulating human exposures). The observed MICs for OMC demonstrated potent activity against the evaluated strains (0.125 to 1 mg/L), with an increase of MICs generally observed in the presence of biofilm (0.25 to >64 mg/L). Furthermore, RIF was shown to reduce OMC biofilm MICs (bMICs) in 90% of strains, and OMC plus RIF combination in biofilm time-kill analyses (TKAs) exhibited synergistic activity in most of the strains. Within the PK/PD CBR model, OMC monotherapy primarily displayed bacteriostatic activity, while RIF monotherapy generally exhibited initial bacterial eradication, followed by rapid regrowth likely due to the emergence of RIF resistance (RIF bMIC, >64 mg/L). However, the combination of OMC plus RIF produced rapid and sustained bactericidal activity in nearly all the strains (3.76 to 4.03 log10 CFU/cm2 reductions from starting inoculum in strains in which bactericidal activity was reached). Furthermore, OMC was shown to prevent the emergence of RIF resistance. Our data provide preliminary evidence that OMC in combination with RIF could be a viable option for biofilm-associated infections with S. aureus and S. epidermidis. Further research involving OMC in biofilm-associated infections is warranted.

Slowed progression: The utility of Test to Treat initiatives in improving the neglected inequities of COVID-19 among racially/ethnically minoritized groups.

In the United States, coronavirus disease 2019 (COVID-19) has resulted in more than 95 million infections and 1 million deaths (as of September 2022), with individuals of racially/ethnically minoritized groups being disproportionately represented among these numbers. Despite the apparent pandemic fatigue in many communities, systemic and structural racism continue to place racially/ethnically minoritized groups at a disadvantage for overcoming the virus, especially as it relates to receiving vaccinations and COVID-19 targeted therapeutics. Test to Treat programs have the potential to mitigate these disparities by rapidly identifying the presence of a COVID-19 infection and readily offering treatment options. Nonetheless, Test to Treat programs must be optimized to adequately address the limitations to care within racially/ethnically minoritized communities.

Social Media: Flattening Hierarchies for Women and Black, Indigenous, People Of Color (BIPOC) to Enter the Room Where It Happens.

Social media platforms are widely used to connect people across multiple settings, including country of origin, profession, race/ethnicity, sexual orientation, gender identity, seniority, and training. Groups that have been marginalized or historically excluded from decision-making encounters may lack formal mentors/sponsors because of a lack of representation of women and Black, Indigenous, People Of Color (BIPOC) in senior leadership positions. This can serve as a barrier to professional advancement at all stages of career development. Identifying and connecting with these potential mentors/sponsors outside of one's institutional space can be challenging. For this reason, leveraging social media to develop these professional relationships through flattened hierarchies can allow for professional networking beyond traditional mechanisms. Here we aim to describe how individuals can connect through social media to advance their careers and scientific and clinical expertise, advocate for communities, and provide high-quality communication to the public.

Brighter horizons: The necessity of concentrated sponsorship targeted toward minoritized student pharmacists.

Due to the effects of structural racism, disproportionately lower numbers of Black, Hispanic or LatinX, American Indian, and Alaska Native students pursue a career in pharmacy and successfully matriculate into the profession. Despite these disparities being present for many years, little progress has been achieved in diversifying the pharmacy profession, resulting in a persistent lack of diversity within pharmacy leadership across employers and pharmacy organizations. Consistent with recent recommendations for improving diversity in pharmacy, the PharmGradWishlist (PGWL) initiative was created as a way for practicing pharmacists and organizations to provide direct financial sponsorship to racially and ethnically minoritized trainees to offset costs incurred during training and during the transition from student to practicing pharmacist. Many of these costs, such as residency and fellowship application fees, job interview travel costs, board exam and licensing fees, and moving expenses, are not typically subsidized by federal student funding. Offsetting these costs is an important way to reduce barriers to entering the profession and postgraduate training, the latter of which may be particularly important in trainees' pursuit of academic and leadership positions in pharmacy. The initial development and advertisement of the initiative occurred through social media and the grassroots efforts of the PGWL team, a group of 10 volunteer pharmacists from across the country, and resulted in generous donations from a small proportion of practicing pharmacists nationwide. It is now time for the profession as a whole to embrace the role of direct sponsorship in improving diversity in the profession. We call upon pharmacists and pharmacy organizations to advocate for and participate in financial sponsorship of racially and ethnically minoritized trainees and pharmacists as a way to increase diversity and promote health equity.

In Vitro Antibacterial Activity of Cefiderocol against Multidrug-Resistant Acinetobacter baumannii.

Cefiderocol (CFDC), a novel siderophore cephalosporin, demonstrates strong activity against multidrug-resistant (MDR) Acinetobacter baumannii. Limited studies have evaluated CFDC alone and in combination with other Gram-negative antibiotics against MDR A. baumannii isolates. Susceptibility testing revealed lower CFDC MIC values (87% of MICs ≤ 4mg/liter) than the comparator Gram-negative agents. Six isolates, with elevated CFDC MICs (16 to 32 mg/liter) were selected for further experiments. Time-kill analyses presented with synergistic activity and beta-lactamase inhibitors increased CFDC susceptibility in each of the isolates.

Exebacase in Addition to Daptomycin against MRSA.

Exebacase is a lysin (cell wall hydrolase) with direct lytic activity against Staphylococcus aureus including methicillin-resistant S. aureus (MRSA). Time-kill analysis experiments illustrated bactericidal activity of exebacase-daptomycin against MRSA strains MW2 and 494. Furthermore, exebacase in addition to daptomycin (10, 6, and 4 mg/kg/day) in a two-compartment ex vivo pharmacokinetic/pharmacodynamic simulated endocardial vegetation model with humanized doses resulted in reductions of 6.01, 4.99, and 2.81 log10 CFU/g (from initial inoculum) against MRSA strain MW2.

Daptomycin Plus ß-Lactam Combination Therapy for Methicillin-resistant Staphylococcus aureus Bloodstream Infections: A Retrospective, Comparative Cohort Study.

BACKGROUND: Mounting evidence suggests the addition of a ß-lactam (BL) to daptomycin (DAP) results in synergistic in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA) and bolsters the innate immune response to infection. This study's objective was to provide clinical translation to these experimental data and determine if DAP+BL combination therapy results in improved clinical outcomes compared with treatment with DAP alone in patients with MRSA bloodstream infections (BSIs). METHODS: This was a retrospective, comparative cohort study conducted at 2 academic medical centers between 2008 and 2018. Adults with MRSA BSI treated with DAP for ≥72 hours and initiated ≤5 days of culture collection were included. Patients who received a BL for ≥24 hours and initiated ≤24 hours of DAP comprised the DAP+BL group. The primary outcome was composite clinical failure (60-day all-cause mortality and/or 60-day recurrence). Analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW). RESULTS: A total of 229 patients were included (72 DAP+BL and 157 DAP). In unadjusted and IPTW-adjusted analyses, DAP+BL was associated with significantly reduced odds of clinical failure (odds ratio [OR], 0.362; 95% confidence interval [CI], .164-.801; adjusted OR, 0.386; 95% CI, .175-.853). Adjusted analyses restricted to prespecified subgroups based on infection complexity and baseline health status were consistent with the main analysis. CONCLUSIONS: The addition of a BL to DAP was associated with improved clinical outcomes in patients with MRSA BSI. This study provides support to ongoing and future studies evaluating the impact of combination therapy for invasive MRSA infections.Patients treated with daptomycin plus a ß-lactam for MRSA bloodstream infection had lower odds of composite clinical failure defined as 60-day all-cause mortality and/or 60-day recurrence compared with patients treated with daptomycin monotherapy after adjusting for confounding variables using inverse probability of treatment weighting.

Bacteriophage-Antibiotic Combination Strategy: an Alternative against Methicillin-Resistant Phenotypes of Staphylococcus aureus.

Comparative time-kill experiments with Staphylococcus aureus bacteriophage (phage) Sb-1 alone and phage-antibiotic combinations (PACs) against two methicillin-resistant S. aureus (MRSA) strains have shown synergy with both daptomycin-phage and vancomycin-phage combinations. PACs prevented development of phage resistance and demonstrated bactericidal activity for all triple combinations. In addition, the extracellular membrane vesicle (MV) formation and the potential impact of phage on MV suppression were examined. Our results demonstrate the potential of PAC for combating MRSA infections.

Bacteriophage-Antibiotic Combinations for Enterococcus faecium with Varying Bacteriophage and Daptomycin Susceptibilities.

Concerns regarding increased prevalence of daptomycin (DAP)-resistant strains necessitate novel therapies for Enterococcus faecium infections. Obligately lytic bacteriophages are viruses that target, infect, and kill bacterial cells. Limited studies have evaluated phage-antibiotic combinations against E. faecium After an initial screen of eight E. faecium strains, three strains with varying DAP/phage susceptibilities were selected for further experiments. Phage-to-strain specificity contributed to synergy with antibiotics by time-kill analyses and was associated with lower development of phage resistance.

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.

Examining Antimicrobial Stewardship Program Implementation in Carceral Settings.

Antimicrobial resistance is a global threat that inequitably affects minoritized populations, including Black, Latinx, and Indigenous people-especially in carceral settings-and is largely driven by inappropriate antimicrobial prescribing practices. People whose identities are minoritized are more likely to be incarcerated, and people who are incarcerated experience higher disease risk than people who are not incarcerated. This article draws on a case of dental infection suffered by a woman who is incarcerated to consider key ethical and clinical complexities of antimicrobial prescribing in carceral settings.

Demographic representation among speakers at the Society for Healthcare Epidemiology of America (SHEA) spring conferences.

BACKGROUND: The Society for Healthcare Epidemiology of America (SHEA) is a leading medical society for infection prevention and antibiotic stewardship. This descriptive study evaluated speaker demographics at the annual SHEA Spring conferences from 2019 to 2022. METHODS: This was a retrospective, descriptive analysis of the demographic composition of speakers at the annual SHEA Spring conferences between 2019 and 2022, excluding the cancelled 2020 conference. Self-reported demographics were available for gender, race, ethnicity, age, primary practice setting, and professional degrees in speaker and membership categories. RESULTS: In total, 447 speaker slots were filled by 305 unique speakers over 3 years. Average annual membership included 55.2% female, 44.8% male, 69.3% White, 21.4% Asian, 6.0% Hispanic/Latino, 2.9% Black, and 0.4% American Indian/Alaska Native or Native Hawaiian/Pacific Islander (AIAN/NHPI); 48.9% did not report a race or ethnicity. Speakers during the same period were 63.5% female, 36.5% male, 68.2% White, 13.3% Asian, 3.8% Black, 3.4% Hispanic/Latino, 0.8% AIAN/NHPI; 13.4% did not report race or ethnicity. In 2021, pharmacists represented 11.6% of speakers (and 2.9% of members) and members with nondoctoral degrees represented 11.6% of speakers (and 21.5% of members) (P < .0001). In each year, we detected underrepresentation of community and private-practice speakers relative to membership (eg, in 2022, 4.3% of speakers vs 15.7% of members; P < .05). CONCLUSIONS: The SHEA Spring conferences demonstrated an increase in pharmacist speakers over time, but speakers from community hospitals and with nondoctoral degrees remain underrepresented relative to membership. Racial and ethnic minoritized individuals remain underrepresented as members and speakers. Intentional interventions are needed to consistently achieve equitable speaker representation across multiple demographic groups.

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.

Striving for equity in academia: embracing the power of no in decision-making.

In academia, saying "yes" to opportunities and "no" to distractions is crucial for effective decision-making. Here, we emphasize the importance of carefully considering commitments and courageously declining those that may lead to overextension. We highlight that discernment is vital, particularly for junior faculty/scientists and those with marginalized identities, as overcommitment can hinder career advancement. The "Fame, Fortune, and Fun test" offers a practical heuristic for evaluating opportunities, enabling academics to make informed choices. Saying "no" effectively involves preserving personal and professional integrity by declining tasks that do not align with one's abilities or interests. However, challenges in saying "no" are multifaceted, including fear of missing career advancements, pressures to please superiors or peers, and perceived negative consequences. This decision can be even more complex for individuals with minoritized identities, as additional expectations and responsibilities may arise due to implicit biases. The article provides a scheme for academics when deciding whether to accept or decline opportunities. The "Fame, Fortune, and Fun test" is a simplified scheme based on the Japanese concept of Ikigai, which comes from two words that mean life's purpose. The concept allows an individual to determine their reason for being and aim to align their time spent with as many components that satisfy the following four categories: what one loves, what one is good at, what one can be paid for, and what the world needs. The more overlap, the more alignment with Ikigai, and the more compelling reason to say yes. Once one has determined that they can say no, effectively saying "no" involves clear and direct communication, offering alternatives, expressing gratitude, and considering a "not now" approach if unable to commit immediately. To promote inclusivity, we suggest recommending individuals from diverse backgrounds for opportunities. By amplifying underrepresented voices, we can foster a healthier academic environment. Saying "no" empowers academics to prioritize meaningful contributions and maintain work-life balance. Embracing the power of "no" is essential for maintaining integrity and well-being in academia. Junior faculty/scientists and individuals with marginalized identities may face additional challenges in their decision-making. By carefully evaluating commitments and effectively declining non-aligning opportunities, academics can focus on what truly matters, fostering a supportive and thriving academic environment.

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.