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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.

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.

Purpose of Review Cefiderocol has a potential role in the treatment of infections caused by increasingly resistant non-fermenting Gram-negative organisms. Recent Findings Non-fermenting Gram-negative organisms pose a unique threat to public health given their arsenal of inherent resistance mechanisms. High rates of intrinsic resistance to a wide array of agents, inducible adaptive resistance, and the ability to acquire resistance through horizontal transfer of resistance genes limit the utility of conventional antimicrobial treatment options against non-fermenting Gram-negative infections. Beta-lactams, one of the most reliable classes of antimicrobials, are often rendered inactive by the acquisition of beta-lactamases, with activity potentially restored by beta-lactamase inhibitors. Alteration of intrinsic mechanisms of resistance, porin channels, and efflux pumps reduce the ability of beta-lactamase inhibitors to protect the activity of beta-lactams. This multifactorial nature of resistance exhibited by non-fermenting Gram-negative organisms is difficult to overcome and novel agents are needed to combat this growing threat. Summary Cefiderocol is a novel siderophore cephalosporin that utilizes the active transport of ferric iron to gain access to the periplasmic space of Gram-negative organisms. Cefiderocol also has additional modifications that confer some stability in the presence of beta-lactamases, which can be particularly beneficial for infections caused by non-fermenters. Herein, we discuss the potential role of cefiderocol therapy in the management of infections caused by non-fermenting Gram-negative bacilli, with an intentional focus on carbapenem-resistant Acinetobacter baumannii (CRAB), Pseudomonas aeruginosa, and Stenotrophomonas spp.

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 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.

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.

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.

Antimicrobial resistance is a global public health threat due to its associated increase in mortality, and the most appropriate treatment algorithms for resistant and persistent Gram-positive and Gram-negative infections have yet to be elucidated. Whilst combination therapy has been touted as a viable method to overcome prominent resistant mechanisms represented amongst these microbes, the optimal agents to utilize remains controversial. Beta-lactams have a safe profile and are bactericidal against most Gram-positive and Gram-negative microorganisms. Thus, the use of dual beta-lactam therapy to overcome multidrug-resistant pathogens is of supreme interest. This article reviews the mechanisms of beta-lactam resistance in Gram-positive and Gram-negative bacteria, discusses the rationale for dual beta-lactam use against multidrug-resistant infections (and other scenarios in which this strategy may be most utilized in clinical practice), explores the available in vitro, in vivo and clinical data, and provides considerations for the use of dual beta-lactam therapy against Enterococcus faecalis, Listeria monocytogenes, Staphylococcus aureus, Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii pathogens.

Background Infectious diseases are the second leading contributor to racial disparities in healthcare. Clostridioides difficile infection (CDI) is a common community/hospital acquired infection that can cause life-threatening colitis. Despite the influence that socioeconomic factors, insurance status, and access to care can have on CDI outcomes, there is a dearth of literature that evaluates the impact of racial differences. The objective of this study was to identify racial disparities in CDI and describe clinical outcomes among hospitalized adults. Methods This is an IRB approved, retrospective study of adult patients (≥ 18 years) hospitalized with initial episodes of CDI between January 2020 to June 2021. Initial CDI episodes were identified by the ICD-10 code A04.72. Medical records were reviewed for demographics, comorbid conditions, insurance, total length of stay (LOS), and need for intensive care unit (ICU) admission. Patients were dichotomized by race/ethnicity into either the racially and ethnically minoritized (REM) group or the non-Hispanic White (n-REM) group. P value of ≤ 0.05 was defined as significant. Results In total 220 patients (61.8% REM, 136/220; 38.2% n-REM, 84/220) with an initial CDI episode were included. Majority of the REM patients were Hispanic (38.2%) followed by Black (13.6%), and Asian (5%). Compared to the n-REM group, the REM patients were younger (60 vs 69 years, p =0.016) and were more likely to have underlying comorbidities (diabetes mellitus 33% vs 9.5%; p < 0.001 and chronic kidney disease 48.5% vs 21.3%; p < 0.001). The REM patients were more likely to present with fulminant CDI (21.3% vs 11.9%; p =0.1). The REM patients were also more likely to be admitted to the ICU during their stay (41.9% vs 26.2%; p =0.021) and have a longer hospital length of stay (LOS) (12 vs 7 days; p =0.02). Lastly, the REM patients were more likely to be under-insured with 91 patients (66.9%) having Medi-Cal insurance compared to 34 patients (40.5%) in the n-REM group (p < 0.001). Conclusion Despite being younger, REM patients were more likely to require an ICU admission, have underlying comorbidities, have a longer LOS, and be under-insured. There is a need for further studies to understand disparities between REM and n-REM patients regarding CDI. Disclosures All Authors: No reported disclosures.

Background Racial disparities in diagnosis and management of infectious diseases in the US healthcare system have been reported. Candidemia is a leading healthcare associated bloodstream infection and is associated with significant mortality. Further, global rates of azole-resistant C. parapsilosis have dramatically increased. Nonetheless, literature describing racial and ethnic differences among candidemic patients is limited. The objective of this study was to describe infection characteristics and outcomes among non-Hispanic White (n-REM) and racially and ethnically minoritized (REM) patients with candidemia. Methods Adult patients hospitalized with ≥ 1 positive blood culture growing Candida between 1/2020 and 12/2021 were included. Based on documented race and ethnicity, patients were dichotomized into the n-REM or REM group. Pertinent data was collected and then compared between groups using univariate analysis. Significance was defined as P ≤0.05. Results 86 unique episodes of candidemia were included. REM patients were significantly younger (mean age 54 vs 62 years; P = 0.017) and had more risk factors for candidemia (median 4 vs 3). REM patients were also more likely to present with sepsis/septic shock (87% vs 81%) and require an ICU stay (57% vs 53%). Time to detection of candidemia was shorter in the REM group (median 38.5 vs 43 hours); however, time to initiation of active antifungal therapy was longer (median 48 vs 44 hours). Additionally, hospital LOS was longer in the REM group (median 25.5 vs 19.5 days). Central line infection was the most common source of candidemia. Despite similar documented sources of infection, microbiological differences were noted. Candida glabrata was more often isolated in n-REM patients (50% vs 27%; P = 0.04), whereas C. parapsilosis was more often isolated in REM patients (17% vs 3%; P = 0.048). Conclusion Despite being younger, REM patients were at an increased risk for candidemia. Furthermore, C. parapsilosis, a globally growing species of concern due to azole resistance, was more frequently isolated among REM patients. Rapid detection and speciation of candidemia may be particularly important among REM patients to ensure early initiation of optimal therapy. Further research exploring racial differences among candidemic patients is needed. Disclosures All Authors: No reported disclosures.

The purpose of this narrative review is to bring together the most recent epidemiologic, preclinical, and clinical findings to offer our perspective on best practices for managing patients with A. baumannii infections with an emphasis on carbapenem-resistant A. baumannii (CRAB). To date, the preferred treatment for CRAB infections has not been defined. Traditional agents with retained in vitro activity (aminoglycosides, polymyxins, and tetracyclines) are limited by suboptimal pharmacokinetic characteristics, emergence of resistance, and/or toxicity. Recently developed and US Food and Drug Administration (FDA)-approved β-lactam/β-lactamase inhibitor agents do not provide enhanced activity against CRAB. On balance, cefiderocol and eravacycline demonstrate potent in vitro activity and are well tolerated, but clinical data for patients with CRAB infections do not yet support widespread use. Given that CRAB has the capacity to infect vulnerable patients and preferred regimens have not been identified, we advocate for combination therapy. Our preferred regimen for critically ill patients infected, or considered to be at high risk for CRAB, includes meropenem, polymyxin B, and ampicillin/sulbactam. Importantly, site of infection, severity of illness, and local epidemiology are essential factors to be considered in selecting combination therapies. Molecular mechanisms of resistance may unveil preferred combinations at individual centers; however, such data are often unavailable to treating clinicians and have not been linked to improved clinical outcomes. Combination strategies may also pose an increased risk for antibiotic toxicity and Clostridioides difficile infection, and should therefore be balanced by understanding patient goals of care and underlying health conditions. Promising therapies that are in clinical development and/or under investigation include durlobactam–sulbactam, cefiderocol combination regimens, and bacteriophage therapy, which may over time eliminate the need for the continued use of polymyxins. Future goals for CRAB management include pathogen-focused treatment paradigms that are based on molecular mechanisms of resistance, local susceptibility rates, and the availability of well-tolerated, effective treatment options.

The purpose of this study was to elucidate characteristics of vaccine-hesitant nurses at two large Southern California medical centers where rates of COVID-19 vaccination were lower than expected.This study is a secondary analysis of nurse participants in a cross-sectional study conducted at the two medical centers. Participants completed an online survey regarding their demographics; work setting and role characteristics; influenza vaccination history; COVID-19 knowledge and beliefs; and personal history of COVID-19 exposure, diagnosis, and disease impact (infection or death) on those closest to them.Of 869 nurse participants, most (78.6%) were vaccinated and 21.4% were unvaccinated; more than half of the unvaccinated participants reported being unwilling to be vaccinated ("vaccine hesitant"). The χ 2 comparisons revealed no significant differences between vaccinated and vaccine-hesitant nurses in terms of education, contact with COVID-19 patients, work environment, or having friends and family impacted by COVID-19. Binary logistic regression showed that nurses who had no history of recent influenza vaccination were 10 times more likely to be vaccine hesitant, those who had inaccurate knowledge about COVID-19 vaccines were seven times more likely to be vaccine hesitant, and younger nurses and those with a prior COVID-19 diagnosis were approximately three times more likely to be vaccine hesitant. Furthermore, 17.3% of all participants were unwilling to recommend COVID-19 vaccination to others.The findings offer a nuanced understanding of vaccine hesitancy among nurses and will be useful to the planning and development of policies, campaigns, and interventions aimed at increasing vaccination rates among nurses. Changing attitudes is essential, and particular attention must be paid to nurses who are unwilling to recommend vaccination to others. Effective interventions are needed.

Cefiderocol (CFDC), (formerly S-649266), is a novel injectable siderophore cephalosporin developed by Shionogi & Co., Ltd., with potent in vitro activity against Gram-negative pathogens including multidrug-resistant (MDR) Enterobacteriaceae and non-fermenting organisms, such as Pseudomonas aeruginosa, Acinetobacter baumannii, Burkholderia cepacia, and Stenotrophomonas maltophilia. Characterized by its siderophore catechol-moiety, CFDC uses a "trojan-horse approach" to navigate through the bacterial periplasmic space, thus evading various beta-lactam degrading enzymes and other mechanisms of resistance present in Gram-negative bacteria. More specifically in carbapenem-resistant Enterobacteriaceae, CFDC has been shown to have activity against extended spectrum beta-lactamases (ESBLs), such as CTX-type, SHV-type, and TEM-type, as well as the Ambler classes of beta-lactamases, including class A (KPC), class B (NDM, IMP, and VIM), class C (AmpC), and class D (OXA, OXA-24, OXA-48, and OXA-48-like). In addition to the strong activity that CFDC has been shown to have against MDR P. aeruginosa, it has also displayed activity against the OXA-23, OXA-24, and OXA-51, beta-lactamases commonly found in MDR A. baumannii. Cefiderocol was recently approved by the US Food and Drug Administration (FDA) for use in complicated urinary tract infections (cUTI), including pyelonephritis, for use in patients 18 years or older with limited or no alternative options for treatment, and is currently being evaluated in a phase III trial for use in nosocomial pneumonia caused by Gram-negative pathogens. The unique features and enhanced activity of CFDC suggest that it is likely to serve as a viable therapeutic option in the treatment of MDR Gram-negative infections. The purpose of this review is to provide an overview of previously published literature explaining CFDC's pharmacology, pharmacokinetic / pharmacodynamic (PK / PD) properties, microbiologic activity, resistance mechanisms, safety parameters, dosing and administration, clinical data, and potential place in therapy.

Black Americans are disproportionately represented among coronavirus disease 2019 (COVID-19)-related morbidities and mortalities. While the COVID-19 vaccines are positioned to change this disparity, vaccine hesitancy, attributed to decades of systemic racism and mistreatment by the United States health care system, heavily exists among this racially and ethnically minoritized group. In addition, social determinants of health within Black communities including the lack of health care access and inequitable COVID-19 vaccine allocation, further impacts vaccine uptake. Black pharmacists have worked to address the pandemic's deleterious effects that have been recognized within Black communities, as they are intimately aware of the structural and systematic limitations that contribute to lower vaccination rates in comparison to other racial and ethnic groups. Black pharmacists have been integral to promoting equity in COVID-19 uptake within Black communities by disseminating factual, trustworthy information in collaboration with community leaders, advocating for the equitable access to the immunizations into vulnerable areas, and creating, low-barrier, options to distribute the vaccines. Herein, we thoroughly explain these points and offer a framework that describes the role of Black pharmacists in narrowing vaccine equity gaps.

In this study, we evaluated the status of and attitudes toward COVID-19 vaccination of healthcare workers in two major hospital systems (academic and private) in Southern California. Responses were collected via an anonymous and voluntary survey from a total of 2491 participants, including nurses, physicians, other allied health professionals, and administrators. Among the 2491 participants that had been offered the vaccine at the time of the study, 2103 (84%) were vaccinated. The bulk of the participants were middle-aged college-educated White (73%), non-Hispanic women (77%), and nursing was the most represented medical occupation (35%). Political affiliation, education level, and income were shown to be significant factors associated with vaccination status. Our data suggest that the current allocation of healthcare workers into dichotomous groups such as “anti-vaccine vs. pro-vaccine” may be inadequate in accurately tailoring vaccine uptake interventions. We found that healthcare workers that have yet to receive the COVID-19 vaccine likely belong to one of four categories: the misinformed, the undecided, the uninformed, or the unconcerned. This diversity in vaccine hesitancy among healthcare workers highlights the importance of targeted intervention to increase vaccine confidence. Regardless of governmental vaccine mandates, addressing the root causes contributing to vaccine hesitancy continues to be of utmost importance.

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 log(10) CFU/g (from initial inoculum) against MRSA strain MW2.

BackgroundMounting evidence suggests the addition of a β-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).MethodsThis 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).ResultsA 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.ConclusionsThe 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 β-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.

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 minimum inhibitory concentration (MIC) values than the comparator Gram-negative agents (87% of MICs ≤ 4mg/L). Six isolates, with elevated CFDC MICs (16-32 mg/L), were selected for further experiments. Time-kill analyses presented with synergistic activity and beta-lactamase inhibitors increased CFDC susceptibility in each of the isolates.

Acinetobacter baumannii is currently classified as one of six pathogens that contribute to increased patient mortality. Thus, exploratory studies navigating alternative treatment strategies are of supreme interest. Herein, we completed minimum inhibitory concentration (MIC) testing, and time-kill analyses (TKA) on 50 carbapenem-resistant Acinetobacterbaumannii isolates including 28 colistin-resistant isolates. Upon testing of MEM or TGC in the presence of sub-inhibitory COL against the 50 isolates, there was a median 2-fold reduction in MEM and TGC MICs. In the TKAs, the COL+MEM combination was synergistic in 45 (90%) isolates and bactericidal in 43 (86%) isolates at 24 hours, whereas the COL+TGC combination TKAs demonstrated synergy in 32 (64%) isolates and bactericidal activity was shown in 28 (56%) isolates. Additionally, sulbactam (SUL) and TGC were added to the COL+MEM dual therapy regimen to assess the possible utility of a triple therapy regimen against five non-responsive isolates. The COL+MEM+SUL and COL+MEM+TGC regimens effectively restored synergy in (5/5) 100% of the isolates. The results of this study demonstrate the potential utility of COL combinations in the treatment of carbapenem-resistant isolates.

During the coronavirus disease 2019 (COVID-19) pandemic, we have witnessed profound health inequities suffered by Black, Indigenous, and People of Color (BIPOC). These manifested as differential access to testing early in the pandemic, rates of severe disease and death 2–3 times higher than white Americans, and, now, significantly lower vaccine uptake compared with their share of the population affected by COVID-19. This article explores the impact of these COVID-19 inequities (and the underlying cause, structural racism) on vaccine acceptance in BIPOC populations, ways to establish trustworthiness of healthcare institutions, increase vaccine access for BIPOC communities, and inspire confidence in COVID-19 vaccines.

Methicillin-resistant Staphylococcus aureus (MRSA) is associated with substantial morbidity and mortality. Vancomycin (VAN) has been used as the gold standard treatment for invasive MRSA infections for decades but, unfortunately, the reliance of VAN as the primary treatment option against these infections has led to a reduction in VAN susceptibility in MRSA isolates. Although daptomycin (DAP) is another common treatment option against invasive MRSA infections, it has been shown that the development of VAN resistance can lead to DAP nonsusceptibility. VAN or DAP backbone regimens in combination with other antibiotics has been advocated as an alternative approach to improve patient outcomes in VAN/DAP-susceptible infections, enhance outcomes in infections caused by isolates with reduced VAN/DAP susceptibility, and/or prevent the emergence of VAN/DAP resistance or further resistance. A peer-reviewed literature search was conducted using Medline, Google Scholar and PubMed databases. The primary purpose of this review is to describe the mechanisms and epidemiology of MRSA isolates with a reduction in VAN and/or DAP susceptibility, evaluate in vitro and in vivo literature describing combination therapy (CT) against MRSA isolates with reduced VAN and/or DAP susceptibility and describe studies involving the clinical outcomes of patients treated with CT against invasive MRSA infections.

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.

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.