Otto, Ashley

Abstract Background Antimicrobial stewardship programs (ASP) commonly employ formulary restriction and prospective audit with feedback; however, frontline prescribers and other unit-based clinicians may enhance core ASP tactics as ASP extenders. We hypothesized that unit-based pharmacists act as ASP extenders and sought to characterize ASP interventions in their routine work.Top individual antimicrobial classes intervened on by unit-based pharmacistsUnit-based pharmacist antimicrobial intervention types Methods Retrospective, observational study of ASP interventions by unit-based pharmacists from July 2017 - April 2025 across the Mayo Clinic Enterprise. ASP interventions recorded using a standardized pharmacist documentation tool (Epic iVents [Software]) were collected retrospectively. Interventions on hospitalized, adult patients categorized as ‘ASP’ or linked with an antimicrobial were included; interventions by ASP dedicated staff were excluded. Secondary outcomes included: intervention subtypes and outcomes, location, and associated antimicrobial(s). Frequencies and percentages were used to summarize categorical data. Results A total of 104,055 interventions were included from 59,106 unique patients at 26 hospitals with the majority performed at the three destination sites. On average, 1,107 interventions were completed monthly by unit-based pharmacists. Frequently targeted antimicrobial classes were vancomycin and derivatives, penicillins, and 3rd/4th-generation cephalosporins (e.g., ceftriaxone and cefepime) (Figure 1); 20,111 (19.3%) interventions were on ≥ 1 antimicrobial. Of the 66,827 interventions with a documented subtype, ASP was the most common (77.8%), with the remainder classified as dose (17.3%), medication (3%), or duration changes (1%) (Figure 2). A minority (2.2%) were documented as conducted under pharmacist collaborative practice agreements. Documented prescriber intervention rejections were uncommon (6.6%). Reported outcomes, when available, included therapy optimization, cost savings and avoidance of adverse drug events. Conclusion Unit-based pharmacists acted frequently as ASP extenders. These findings support unit-based pharmacist and ASP collaborative efforts. Disclosures All Authors: No reported disclosures

AbstractPurposeProton pump inhibitors (PPIs) are widely prescribed medications. Various adverse clinical effects of PPIs have been reported in the literature, particularly over the past decade. The purpose of this article is to review published data primarily describing adverse effects associated with PPI use and to help clinicians determine which patients may still benefit from therapy despite safety concerns.SummaryAssociations between PPIs and the following have been described: bone fracture, acute and chronic kidney disease, gastrointestinal infections, deficiencies in vitamin B12 and magnesium, and coronavirus disease 2019 and respiratory infections. For inclusion in this review, studies must have evaluated potential adverse events associated with PPIs as a primary or secondary objective. Increased risks of bone fracture, acute and chronic kidney disease, gastrointestinal infections, and magnesium deficiency were consistently reported, albeit mostly in studies involving low-quality data (case-control and/or observational studies) and subject to bias. In the only pertinent randomized controlled trial to date, chronic pantoprazole use was associated with a greater risk of enteric infections relative to placebo use; there was no significant between-group difference in any other adverse event evaluated. PPIs continue to be recommended by the American College of Gastroenterology as a first-line treatment for management of gastroesophageal reflux disease and in the acute period following upper gastrointestinal and ulcer bleeding.ConclusionHigher-quality data is needed to better understand PPI-associated risks of the adverse effects listed above. Until then, clinicians may consider greater vigilance with PPI use; however, the data does not demonstrate a need for wide adoption of de-escalation strategies solely out of safety concerns.

Purpose of review To date, more than 30 antiretroviral drugs have been approved by the Food and Drug Administration for the treatment of HIV infection. As new drugs with better efficacy and safety profile become available for clinical practice, older drugs are either withdrawn from the market or become no longer actively prescribed. We review hepatotoxicity associated with contemporary antiretroviral drugs, with emphasis on data from the past 3 years. Recent findings Although less robust data exists for side effects of contemporary antiretroviral medications recently approved for the management of HIV (i.e., doravirine, ibalizumab, fostemsavir, cabotegravir), the risks of substantial hepatotoxicity appears to be minimal with these agents. Summary Although newer antiretroviral drugs are better tolerated than their earlier counterparts, they are not completely devoid of adverse drug reactions, including hepatotoxicity. Monitoring patients on antiretroviral therapy for treatment-emergent liver injury should continue to be part of routine clinical care.

Contemporary antiretroviral agents afford enhanced potency and safety for patients living with HIV. Newer antiretroviral drugs are often better tolerated than those initially approved in the early stages of the HIV epidemic. While the safety profile has improved, adverse drug reactions still occur. We have segregated the antiretroviral agents used in contemporary practice into class groupings based on their mechanism of antiviral activity (non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, integrase inhibitors, protease inhibitors, and entry inhibitors) while providing a review and discussion of the hepatoxicity seen in the most relevant clinical literature published to date. Clinical literature for individual agents is discussed and agent comparisons afforded within each group in tabular format. Our review will provide a summative overview of the incidence and medications associated with hepatic adverse reactions linked to the use of contemporary antiretroviral drugs.

Antiretroviral (ARV) therapy in people living with HIV (PLWH) and end-stage renal disease (ESRD) on hemodialysis (HD) is complicated, requiring renally adjusted nucleoside reverse transcriptase inhibitors (NRTIs) and daily administration of non-renally eliminated agents. Recent data in PLWH with ESRD on HD demonstrate maintenance of viral suppression (82% with viral loads (VLs) <50 copies/mL) and favorable safety/tolerability profiles after ARV simplification with a fixed dose combination single tablet [elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF)]. Extrapolation of these data to all F/TAF formulations would allow ARV simplification to most PLWH with ESRD receiving HD. The objective of this retrospective study was to identify if ARV-experienced PLWH with ESRD on HD receiving renally adjusted NRTIs may be simplified to once daily ARV formulations without adverse effects while maintaining viral suppression. This single-center retrospective analysis assessed virologic control (3–12 months) and ARV tolerability post-regimen simplification (primarily NRTI once-daily dose adjustment) in PLWH with ESRD on thrice weekly HD receiving human immunodeficiency virus (HIV) care in an ambulatory clinic. Seventeen PLWH with ESRD on HD were included after documented ARV simplification. At 12 months, 12 patients (71%) remained undetectable (HIV VL <50 copies/mL) with two additional maintaining viral suppression (<200 copies/mL). One patient remained undetectable at month eight but became non-adherent with viral rebound. Two patients did not complete the 6- and 12-month evaluation after documented nonadherence ( N = 1) and an adverse effect (pruritus) ( N = 1). At 12 months, virologic suppression and tolerability resulted after a simplified ARV regimen including once daily F/TAF was initiated in PLWH with ESRD on thrice weekly HD with a reduction in pill burden.