Consensus recommendations for the use of novel antiretrovirals in persons with HIV who are heavily treatment-experienced and/or have multidrug-resistant HIV-1: Endorsed by the American Academy of HIV Medicine, American College of Clinical Pharmacy: An executive summary.

Treatment options are currently limited for persons with HIV-1 (PWH) who are heavily treatment-experienced and/or have multidrug-resistant HIV-1. Three agents have been approved by the U.S. Food and Drug Administration (FDA) since 2018, representing a significant advancement for this population: ibalizumab, fostemsavir, and lenacapavir. However, there is a paucity of recommendations endorsed by national and international guidelines describing the optimal use (e.g., selection and monitoring after initiation) of these novel antiretrovirals in this population. To address this gap, a modified Delphi technique was used to develop these consensus recommendations that establish a framework for initiating and managing ibalizumab, fostemsavir, or lenacapavir in PWH who are heavily treatment-experienced and/or have multidrug-resistant HIV-1. In addition, future areas of research are also identified and discussed in the main document.

Consensus recommendations for the use of novel antiretrovirals in persons with HIV who are heavily treatment-experienced and/or have multidrug-resistant HIV-1: Endorsed by the American Academy of HIV Medicine, American College of Clinical Pharmacy.

Treatment options are currently limited for persons with HIV-1 (PWH) who are heavily treatment-experienced and/or have multidrug-resistant HIV-1. Three agents have been approved by the U.S. Food and Drug Administration (FDA) since 2018, representing a significant advancement for this population: ibalizumab, fostemsavir, and lenacapavir. However, there is a paucity of recommendations endorsed by national and international guidelines describing the optimal use (e.g., selection and monitoring after initiation) of these novel antiretrovirals in this population. To address this gap, a modified Delphi technique was used to develop these consensus recommendations that establish a framework for initiating and managing ibalizumab, fostemsavir, or lenacapavir in PWH who are heavily treatment-experienced and/or have multidrug-resistant HIV-1. In addition, future areas of research are also identified and discussed.

Impact of time to treatment in first occurrence, non-severe Clostridioides difficile infection for elderly patients: are we waiting too long to treat?

Objective: Data evaluating timeliness of antibiotic therapy in Clostridioides difficile infections (CDI) are not well established. The study's purpose was to evaluate the impact of time-to-CDI treatment on disease progression. Methods: A case-control study was performed among hospitalized patients with CDI from 1/2018 to 2/2022. Inclusion criteria were age ≥65 years, first occurrence, non-severe CDI at symptom onset, and CDI treatment for ≥72 hours. Cases included patients who progressed to severe or fulminant CDI; controls were patients without CDI progression. Time to CDI treatment was evaluated in three ways: a classification and regression tree (CART)-defined threshold, time as a continuous variable, and time as a categorical variable. Results: 272 patients were included; 136 with CDI progression, 136 patients without. The median (IQR) age was 74 (69-81) years, 167 (61%) were women, and 108 (40%) were immunosuppressed. CDI progression patients more commonly were toxin positive (66 [49%] vs 52 [38%], P = .087) with hospital-acquired disease (57 [42%] vs 29 [21%], P < 0.001). A CART-derived breakpoint for optimal time-to-CDI treatment of 64 hours established early (184, 68%) and delayed treatment (88, 32%). When accounting for confounding variables, delayed CDI treatment was associated with disease progression (adjOR, 4.6; 95%CI, 2.6-8.2); this was observed regardless of how time-to-CDI-active therapy was evaluated (continuous adjOR, 1.02; categorical adjOR, 2.11). Conclusion: Delayed CDI treatment was associated with disease progression and could represent an important antimicrobial stewardship measure with future evaluation.

No observed bidirectional effect between tenofovir diphosphate concentrations and gender-affirming hormone concentrations among transgender persons switching from tenofovir disoproxil fumarate/emtricitabine to tenofovir alafenamide/emtricitabine for HIV pre-exposure prophylaxis.

AIMS: Many transgender and gender diverse (TGD) individuals have expressed concerns about the potential for oral pre-exposure prophylaxis to affect hormonal concentrations achieved from taking gender-affirming hormone therapy (GAHT). The purpose of this study was to understand the bidirectional effects between hormone and intraerythrocytic tenofovir diphosphate concentrations when switching from tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) to tenofovir alafenamide/emtricitabine (TAF/FTC) in TGD users/nonusers of GAHT. METHODS: The study evaluated stored blood samples and dried blood spot cards from TGD adults without HIV who took ≥12 weeks of TDF/FTC and then switched to ≥12 weeks of TAF/FTC for pre-exposure prophylaxis. RESULTS: Thirty-nine individuals met the study inclusion criteria. Regardless of sex assigned at birth and the use of GAHT, there were no significant differences in hormone concentrations when individuals taking GAHT were taking TDF/FTC and then switched to TAF/FTC. Further, there was no significant difference in intraerythrocytic tenofovir diphosphate concentrations between users and nonusers of GAHT. CONCLUSION: There are no bidirectional effects between hormone and intraerythocytic tenofovir diphosphate concentrations when switching from TDF/FTC to TAF/FTC in TGD users/nonusers of GAHT.

Relationship between publication of a postgraduate year 1 residency research project and subsequent career type at a large academic medical center.

PURPOSE: The study objectives were to (1) quantify the overall incidence of residency publications of postgraduate year 1 (PGY1) residency alumni; (2) evaluate annual fluctuations in publications over time; and (3) compare the career types of residency alumni who published their PGY1 residency research projects to those for alumni who did not. METHODS: A retrospective cohort study was performed among individuals who completed a PGY1 acute/ambulatory care residency between 2010 and 2021. A list of residency alumni was obtained along with the corresponding titles of their research projects. Each resident's name was entered into PubMed and Google Scholar to find the corresponding publication. LinkedIn and other publicly available resources were used to determine the career types of residents immediately after residency as well as their current career types. RESULTS: In total, 178 residency alumni completed an acute/ambulatory care PGY1 residency, of whom 16.7% (30/178) published their residency research project. Publication was associated with career type among those who pursued a postgraduate year 2 residency but was not associated with career type immediately after the PGY1 residency or current career type. The presence of an academic preceptor was associated with a higher probability of publishing compared to residents who did not have an academic preceptor (31.5% vs 10.5%; P < 0.01). CONCLUSION: The frequency of publications was within the range reported elsewhere, with fluctuations over time. Presence of an academic preceptor improved the probability of publication.

Fluoroquinolone-associated adverse events of interest among hospitalized veterans affairs patients with community-acquired pneumonia who were treated with a fluoroquinolone: A focus on tendonitis, Clostridioides difficile infection, and aortic aneurysm.

STUDY OBJECTIVE: The objectives of this study were to (i) quantify the incidence of three concerning fluoroquinolone adverse events of interest (FQAEI, i.e., adverse tendon event (TE), clostridioides difficile infection (CDI), and aortic aneurysm/dissection (AAD)), (ii) identify the patient-level factors that predict these events, and (iii) develop clinical risk scores to estimate the predicted probabilities of each FQAEI based on patient-level covariates available on clinical presentation. DESIGN: Retrospective cohort study. SETTING: Upstate New York Veterans' Healthcare Administration from 2011 to 2016. PATIENTS: Hospitalized patients with community-acquired pneumonia receiving care in the Upstate New York Veterans' Healthcare Administration from 2011 to 2016. INTERVENTION: N/A. MEASUREMENTS: The outcomes of interest for this study were the occurrence of TE, CDI, and AAD. We also evaluated a composite of these three outcomes, FQAEI. MAIN RESULTS: The study population consisted of 1071 patients. The overall incidence of FQAEI, TE, AAD, and CDI was 6.5%, 1.8%, 4.5%, and 0.3%, respectively. For each outcome evaluated, the probability of the event of interest was predicted by the presence of certain comorbidities, previous healthcare exposure, choice of specific FQ antibiotic, or therapy duration. Concomitant steroids, pneumonia in preceding 180 days, and creatinine clearance <30 mL/min predicted FQAEI. CONCLUSIONS: Individual frequencies of three important FQAEIs were quantified, and risk scores were developed to estimate the probabilities of experiencing these events to help clinicians individualize treatment decisions for patients and reduce the potential risks of select FQAEIs.

Vaccine response after pneumococcal vaccination in allogeneic hematopoietic stem cell transplant recipients.

Current guidelines for vaccination in allogeneic hematopoietic stem cell transplant (HCT) recipients recommend initiation of pneumococcal vaccination series three to six months post-HCT, with most data supporting initiation at six months due to a more robust immune response. This single-center, retrospective, observational chart review aimed to evaluate the impact of initiating the pneumococcal vaccine series at three months post-HCT compared to six months post-HCT. The primary endpoints were defined as a percentage of patients with a serologic response of >1 and >1.3 µg/mL for over 50% of the defined serotypes. Outcomes showed no difference in immunologic response between the two groups.

Predictors of Post-switch Viremia in People With HIV on Injectable Cabotegravir/Rilpivirine.

BACKGROUND: Predictors of virologic failure in those receiving long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) have been evaluated; however, factors associated with low-level viremia, including blips and persistent low-level viremia (pLLV), are not well-described. METHODS: A retrospective cohort study was performed using data from April 2021 through December 2022. Inclusion criteria included treatment with CAB/RPV for at least 3 months, availability of pre- and postswitch HIV RNA values, HIV RNA value of <200 copies/mL (cpm) at the time of switch to CAB/RPV, and at least 1 postswitch HIV RNA collected >21 days after the start of CAB/RPV. Outcomes included incidence of HIV RNA ≥20, ≥50, and ≥200 cpm after switch and factors associated with detectable HIV RNA after switch. RESULTS: The median duration of follow-up among 144 participants was 287 days. After switching to CAB/RPV, occurrences of at least 1 HIV RNA ≥20, ≥50, and ≥200 cpm after switch were 34.7%, 15.3%, and 2.8%, respectively. Those with pLLV before switch were significantly more likely to have detectable HIV RNA after switch [hazard ratio 24.39 (8.71-68.34)], and 44.4% of those with pLLV before switch continued with pLLV after switch to LAI CAB/RPV. Body mass index, late injection, and monthly versus every two-month dosing were not associated with detectable viremia after switch. CONCLUSIONS: Despite virologic suppression at the time of switch and the perceived adherence benefits, participants still experienced blips or pLLV after switch to LAI CAB/RPV. Having detectable HIV RNA on oral therapy before switch was associated with detectable HIV RNA after switching.

Role of independent versus chain pharmacies in providing pharmacy access: a nationwide, individual-level geographic information systems analysis.

Pharmacy accessibility is critical for equity in medication access and is jeopardized by pharmacy closures, which disproportionately affect independent pharmacies. We conducted a geographic information systems analysis to quantify how many individuals across the US do not have optimal pharmacy access or solely rely on independent pharmacies for access. We generated service areas of pharmacies using OpenStreetMap data. For each individual in a 30% random sample of the 2020 RTI US Household Synthetic Population™ (n=90,778,132), we defined optimal pharmacy access as having a driving distance to the closest pharmacy ≤2 miles in urban counties, ≤5 miles in suburban counties, and ≤10 miles in rural counties. Individuals were then categorized according to their access to chain and independent pharmacies. Five percent of the sample or ~15.1 million individuals nationwide relied on independent pharmacies for optimal access. Individuals relying on independent pharmacies for optimal access were more likely to live in rural areas, be 65 years or older, and belong to low-income households. Another 19.5% of individuals in the sample did not have optimal pharmacy access, which corresponds to 59.0 million individuals nationwide. Our findings demonstrate that independent pharmacies play a critical role in ensuring equity in pharmacy access.

Evaluation of direct oral anticoagulants versus low molecular weight heparins for venous thromboembolism treatment in patients with gastrointestinal malignancies.

BACKGROUND: Direct oral anticoagulant (DOAC) use in cancer-associated venous thromboembolism (CA-VTE) has increased due to updates in recent guidelines and literature. However, select guidelines caution against DOAC use in patients with gastrointestinal (GI) malignancies due to reported increased bleeding events. The objective of this study was to compare the safety and effectiveness of DOACs versus low-molecular-weight heparins (LMWHs) for CA-VTE treatment in patients with GI malignancies. PATIENTS AND METHODS: This multicenter, retrospective cohort study included patients with primary GI malignancies who received therapeutic anticoagulation with a DOAC or LMWH for CA-VTE between January 1, 2018, and December 31, 2019. The primary outcome was the incidence rate of bleeding events (major, clinically relevant non-major, or minor bleeding events) within a 12-month period following the initiation of therapeutic anticoagulation. The secondary endpoint was the incidence rate of recurrent VTE events within a 12-month period following the start of therapeutic anticoagulation. RESULTS: After screening, 141 patients met inclusion criteria. The incidence rate of all bleeding events significantly differed between DOAC (4.98 events/100 person-months) and LWMH (10.2 events/100 person-months) recipients. The corresponding incidence rate ratio (IRR) with the DOAC group serving as the reference was 2.05 (p = 0.01), with the majority of bleeds in both groups presenting as minor bleeds. No difference was found between the incidence rate of recurrent VTE within a 12-month period of starting therapeutic anticoagulation between groups (IRR 3.08, p = 0.06). CONCLUSION: Our results suggest that DOACs do not pose an additional bleeding risk compared to LMWH in patients with certain GI malignancies. Careful selection of DOAC therapy with respect to bleeding risk is still warranted.

Management of Rare Open Patella Sagittal Plane Fracture with Associated Knee Joint Fractures: A Series of Three Cases.

Introduction: Open vertical patella fractures in combination with distal femoral or proximal tibial fractures are a rare combination of injuries that pose a challenge for adequate fixation and gaining favorable outcome. Case Report: Case 1 had an open fracture of sagittal fracture of patella with one half comminuted and a sagittal plane fracture of lateral femoral condyle with a 2 × 2 cm of articular bone loss. Case 2 had an open sagittal fracture of patella with ipsilateral lateral femoral condyle fracture and proximal tibia medial condyle fracture in sagittal plane. Case 3 had a closed comminuted fracture of patella with sagittal plane lateral femoral condyle fracture. Conclusion: Open vertical plane patella fractures with associated distal femoral or proximal tibial fracture when treated properly can restore knee function optimally.

Predictors of lenalidomide maintenance duration after autologous stem cell transplant in patients with multiple myeloma.

BACKGROUND: For patients with multiple myeloma (MM) who have undergone autologous stem cell transplant (auto-SCT), the immunomodulatory agent lenalidomide is a first-line option for maintenance therapy. Because longer durations of lenalidomide maintenance are associated with improved survival, identifying strategies to avoid premature cessation of maintenance is an important priority in the post-transplant setting. OBJECTIVES: The primary objective of this analysis was to identify specific clinical predictors of lenalidomide treatment duration that could guide optimal medication management. Key secondary objectives included predictors of intolerable toxicity, rationale for lenalidomide dose reduction/discontinuation, and characterization of dose adjustments. STUDY DESIGN: This retrospective, multi-center cohort study included adults with MM who underwent auto-SCT and initiated maintenance lenalidomide between 01/01/2012 and 02/28/2021. Variables assessed as potential predictors of maintenance duration or intolerable toxicity included age, body mass index (BMI), Eastern Cooperative Oncology Group (ECOG) performance status at time of auto-SCT, renal function, initial lenalidomide dose, use of combination maintenance therapy, and cytogenetic risk category. RESULTS: Among 299 patients included, the median age at time of auto-SCT was 62 years (range 30-77). The majority of patients had standard-risk cytogenetics (64%) and an ECOG performance status of 0 or 1 (72%). In the overall population, the median duration of maintenance was 1.3 years (range 0.3-8.6 years). The median initial dose of lenalidomide was 10 mg daily (range 2.5-25 mg). During the study period, 35% of patients had a dose reduction due to toxicity, 21% stopped lenalidomide due to disease progression, and 19% stopped due to toxicity. Multivariate linear regression analyses did not identify any significant predictors of lenalidomide duration or discontinuation due to intolerable toxicity. The most frequently reported toxicities leading to discontinuation were cytopenias, rash, and fatigue. CONCLUSION: This analysis did not identify any significant risk factors to predict the duration of lenalidomide maintenance or discontinuation for toxicity following auto-SCT in patients with MM. While limited by the retrospective design and relatively small sample size, our findings suggest that a priori lenalidomide dose reductions based on patient co-morbidities or performance status may not substantially affect the duration of lenalidomide maintenance.

Access to community pharmacies: A nationwide geographic information systems cross-sectional analysis.

BACKGROUND: Pharmacy accessibility is key for the emerging role of community pharmacists as providers of patient-centered, medication management services in addition to traditional dispensing roles. OBJECTIVE: To quantify population access to community pharmacies across the United States. METHODS: We obtained addresses for pharmacy locations in the United States from the National Council for Prescription Drug Programs and geocoded each. For a 1% sample of a U.S. synthetic population, we calculated the driving distance to the closest pharmacy using ArcGIS. We estimated the proportion of population living within 1, 2, 5, and 10 miles of a community pharmacy. We quantified the role of chain vs regional franchises or independently owned pharmacies in providing access across degrees of urbanicity. RESULTS: We identified 61,715 pharmacies, including 37,954 (61.5%) chains, 23,521 (38.1%) regional franchises or independently owned pharmacies, and 240 (0.4%) government pharmacies. In large metropolitan areas, 62.8% of the pharmacies were chains; however, in rural areas, 76.5% of pharmacies were franchises or independent pharmacies. Across the overall U.S. population, 48.1% lived within 1 mile of any pharmacy, 73.1% within 2 miles, 88.9% within 5 miles, and 96.5% within 10 miles. Across the United States, 8.3% of counties had at least 50% of residents with a distance greater than 10 miles. These low-access counties were concentrated in Alaska, South Dakota, North Dakota, and Montana. CONCLUSIONS: Community pharmacies may serve as accessible locations for patient-centered, medication management services that enhance the health and wellness of communities. Although chain pharmacies represent the majority of pharmacy locations across the country, access to community pharmacies in rural areas predominantly relies on regional franchises and independently owned pharmacies.

Prevalence and Predictors of Pseudomonas aeruginosa Among Hospitalized Patients With Diabetic Foot Infections.

Background: Diabetic foot infections (DFIs) are commonly associated with antibiotic overuse. Empiric DFI treatment often includes coverage for Pseudomonas aeruginosa (PsA), but the frequency of PsA DFIs is poorly understood. The study objectives were to quantify the prevalence of and determine predictors for PsA DFIs. Methods: This multicenter, retrospective cohort included hospitalized patients with DFI from 2013 through 2020 who were age ≥18 years; diabetes mellitus diagnosis; and DFI based on International Classification of Diseases, Tenth Revision coding, antibiotic treatment, and DFI culture with organism growth. Osteomyelitis was excluded. Patient characteristics were described and compared; the primary outcome was presence of PsA on DFI culture. Predictors of PsA DFI were identified using multivariable logistic regression. Results: Two hundred ninety-two patients were included. The median age was 61 (interquartile range [IQR], 53-69) years; the majority were men (201 [69%]) and White (163 [56%]). The most commonly isolated organisms were methicillin-susceptible Staphylococcus aureus (35%) and streptococci (32%); 147 (54%) cultures were polymicrobial. Two hundred fifty-seven (88%) patients received empiric antibiotics active against PsA, but only 27 (9%) patients had PsA DFI. Immunocompromised status (adjusted odds ratio [aOR], 4.6 [95% confidence interval {CI}, 1.3-16.7]) and previous outpatient DFI antibiotic treatment failure (aOR, 4.8 [95% CI, 1.9-11.9]) were associated with PsA DFI. Conclusions: PsA DFI is uncommon, but most patients receive empiric antipseudomonal antibiotics. Empiric broad-spectrum antibiotics are warranted given the frequency of mixed infections, but patient-specific risk factors should be considered before adding antipseudomonal coverage.

Characterisation of infections in patients with acute myeloid leukaemia receiving venetoclax and a hypomethylating agent.

We investigated the incidence of invasive fungal infections (IFIs) and other infectious complications in patients receiving venetoclax and hypomethylating agent therapy for acute myeloid leukaemia (AML). This retrospective, multicentre cohort study included adult patients with AML who received at least one cycle of venetoclax and either azacitidine or decitabine between January 2016 and August 2020. The primary outcome was the incidence of probable or confirmed IFI. Secondary outcomes included antifungal prophylaxis prescribing patterns, incidence of bacterial infections, and incidence of neutropenic fever hospital admissions. Among 235 patients, the incidence of probable or confirmed IFI was 5.1%. IFI incidence did not differ significantly according to age, antifungal prophylaxis use, or disease status. In the subgroup of patients with probable or confirmed IFIs, six (50%) were receiving antifungal prophylaxis at the time of infection. The overall incidence of developing at least one bacterial infection was 33.6% and 127 (54%) patients had at least one hospital admission for febrile neutropenia. This study demonstrated an overall low risk of developing probable or confirmed IFI as well as a notable percentage of documented bacterial infections and hospital admissions due to neutropenic fever.

Method of Calculating Renal Function Estimates Could Inappropriately Exclude Transgender Patients Receiving Gender-Affirming Hormone Therapy from Pre-Exposure Prophylaxis Eligibility.

Purpose: Despite the importance of reliable renal function estimation among the growing transgender population, research describing the variability of existing equations is scarce. Study objectives were to (1) quantify the range of renal function estimates that would be observed if different gender coefficients are used in the estimating equations, (2) compare estimates of renal function (creatinine clearance [CLCR] or estimated glomerular filtration rate [GFR]) between users and nonusers of gender-affirming therapies, and (3) quantify the proportion of subjects who would be deemed ineligible for tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for pre-exposure prophylaxis (PrEP) based on the gender coefficient used. Methods: A retrospective analysis was performed among transgender PrEP users enrolled in a multicenter observational study between June 2017 and October 2021. The primary outcome was estimated kidney function, defined using calculated CLCR or GFR before initiating TDF/FTC for PrEP based on the three most commonly used estimating equations. Results: A total of 258 participants were evaluated. Median differences in renal function ranged from 13 to 25 mL/min based on which gender coefficient and equation was used. Regardless of the method used to compute renal function, there were significant differences between users and nonusers of gender-affirming therapy. There were 17 (6.6%) participants where at least one of the methods would potentially render them ineligible to receive TDF/FTC for PrEP. Conclusions: Renal function estimates vary considerably with different estimating equations in the transgender population and are modified by use of gender-affirming therapy. These variations could result in exclusion from drug therapies such as TDF/FTC for PrEP.

Overcoming Past Perceptions and a Profession-Wide Identity Crisis to Reflect Pharmacy's Future.

The profession of pharmacy has come to encompass myriad identities, including apothecary, dispenser, merchandiser, expert advisor, and health care provider. While these identities have changed over time, the responsibilities and scope of practice have not evolved to keep up with the goals of the profession and the level of education of practicing pharmacists in the United States. By assuming that the roles of the aforementioned identities involve both product-centric and patient-centric responsibilities, our true professional identity is unclear, which can be linked to the prevalence of the impostor phenomenon within the profession. For pharmacy to truly move forward, a unified definition for the profession is needed by either letting go of past identities or separating these identities from each other by altering standards within professional degree programs and practice models. Without substantial changes to the way we approach this challenge as a profession, the problems described will only persist and deepen.

US-Focused Conceptual Health Care Decision-Analytic Models Examining the Value of Pivmecillinam Relative to Current Standard-of-Care Agents Among Adult Patients With Uncomplicated Urinary Tract Infections due to Enterobacterales.

BACKGROUND: Pivmecillinam is approved for the treatment of adults with uncomplicated urinary tract infection (uUTI) in Canada and Europe and is pending United States (US) Food and Drug Administration submission for consideration for approval. US-focused health care decision-analytics were developed to define the value of an agent like pivmecillinam relative to current standard-of-care (SOC) agents among adult patients with Enterobacterales uUTIs based on its improved microbiologic activity against common Enterobacterales. METHODS: The model population was 100 theoretical adult outpatients with Enterobacterales uUTIs under 4 different uUTI first-line empiric treatment scenarios (ie, pivmecillinam, nitrofurantoin, trimethoprim-sulfamethoxazole [SXT], or fluoroquinolones). The total mean uUTI-related 30-day costs, including inappropriate treatment costs, were calculated for each regimen. The range of pivmecillinam regimen costs that conferred cost savings relative to the current SOC agents based on its potentially improved microbiologic activity against common Enterobacterales was determined. RESULTS: The 30-day uUTI-related costs associated with nitrofurantoin, SXT, and fluoroquinolones were $655.61, $687.57, and $659.69, respectively. The pivmecillinam neutral regimen cost thresholds that resulted in the same uUTI-related 30-day per-patient costs for nitrofurantoin, SXT, and fluoroquinolones were $83.50, $115.45, and $87.58, respectively. The overall antimicrobial susceptibility improvement required with pivmecillinam fixed at $200/regimen, for it to be cost savings relative to SOC agents, was 28%. CONCLUSIONS: The analyses suggests that an agent like pivmecillinam, if approved in the US, has the potential to reduce the economic burden associated with inappropriate treatment of adult outpatients with uUTIs, especially in patients at high risk for an Enterobacterales uUTI that is resistant to SOC agents.

Potential Cost Savings Associated with Targeted Substitution of Current Guideline-Concordant Inpatient Agents with Omadacycline for the Treatment of Adult Hospitalized Patients with Community-Acquired Bacterial Pneumonia at High Risk for Clostridioides difficile Infections: Results of Healthcare-Decision Analytic Model from the United States Hospital Perspective.

INTRODUCTION: Approximately 3% of hospitalized patients with community-acquired bacterial pneumonia (CABP) develop healthcare-associated Clostridioides difficile infection (HCA-CDI). The validated Davis risk score (DRS) indicates that patients with a DRS ≥ 6 are at an increased risk of 30-day HCA-CDI. In the phase 3 OPTIC CABP study, 14% of CABP patients with DRS ≥ 6 who received moxifloxacin developed CDI vs. 0% for omadacycline. This study assessed the potential economic impact of substituting current guideline-concordant CABP inpatient treatments with omadacycline in hospitalized CABP patients with a DRS ≥ 6 across US hospitals. METHODS: A deterministic healthcare-decision analytic model was developed. The model population was hospitalized adult CABP patients with a DRS ≥ 6 across US hospitals (100,000 patients). In the guideline-concordant arm, 14% of CABP patients with DRS ≥ 6 were assumed to develop an HCA-CDI, each costing USD 20,100. In the omadacycline arm, 5 days of therapy was calculated for the entire model population. RESULTS: The use of omadacycline in place of guideline-concordant CABP inpatient treatments for CABP patients with DRS ≥ 6 was estimated to result in cost savings of USD 55.4 million annually across US hospitals. CONCLUSION: The findings of this simulated model suggest that prioritizing the use of omadacycline over current CABP treatments in hospitalized CABP with a DRS ≥ 6 may potentially reduce attributable HCA-CDI costs. The findings are not unique to omadacycline and could be applied to any antibiotic that confers a lower risk of HCA-CDI relative to current CABP inpatient treatments.

Early clinical trial data and real-world assessment of COVID-19 vaccines: Insights from the Society of Infectious Diseases Pharmacists.

As of August 2021, there were three COVID-19 vaccines available in the United States for the prevention of coronavirus 2019 (COVID-19). The purpose of this narrative review is to examine the early experience from the Emergency Use Authorization (EUA) of BNT162b2 (Pfizer, Inc./BioNTech), mRNA-1273 (Moderna, Inc.), and Ad26.COV2.S (Johnson and Johnson/Janssen Global Services, LLC) through July 2021. The EUA data from the clinical trials have largely been corroborated by real-world effectiveness investigations post-authorization. These studies indicate that immunity is obtained within 2 weeks post-vaccination and may endure for 6 months. The immunity conferred by the vaccines may also be effective against SARS-CoV-2 variants of concern. Additionally, populations not included in the emergency use authorization studies may also benefit from vaccination. This look back at the initial clinical experience can be used by the global community to inform and develop COVID-19 vaccine programs.