Antiretroviral Stewardship: Top 10 Questions Encountered by Stewardship Teams and Solutions to Optimize Therapy.

PURPOSE: Infectious disease pharmacists and physicians overseeing antimicrobial stewardship programs possess expertise and often advanced certification in management of antiretrovirals to treat HIV. Stewardship programs are responsible for managing facility formularies and must stay up to date with the latest antiretrovirals, including once daily formulations and depot injectables. Furthermore, stewardship program members need to understand drug-interactions, short-, and long-term toxicities of these regimens, including dyslipidemia and cardiovascular effects. Patients receiving chronic antiretroviral therapy may present to the acute care, ambulatory care, and long-term care settings. Like other antimicrobials, audit-and-feedback, drug monitoring, and dose-optimization are often required to prevent antiretroviral associated medication errors and minimize resistance. METHODS: A narrative review was conducted on antiretroviral stewardship, addressing common clinical questions encountered by stewardship teams and best practices to optimize antiretroviral therapy and reduce the risk for treatment interruptions, resistance, drug interactions, long term toxicities, and other adverse effects. FINDINGS: People living with HIV are often hospitalized and treated by medical teams without formal HIV training. For this reason, these patients are at greater risk for medication errors during hospitalization and between transitions of care. Many opportunities are present for antiretroviral stewardship to mitigate these errors. Frequent updates to simplify HIV regimen, maintain select patients on fixed-dose combination tablets, and strategies to minimize drug interactions make it difficult for even the seasoned clinician to keep up regularly. IMPLICATIONS: Despite the availability of free online HIV resources and progress made in HIV management, significant opportunities for antiretroviral stewardship remain. Implementing electronic order entry updates, formulary upgrades, and formal pharmacy renal dose adjustments to optimize antiretroviral therapy will help clinicians harness these opportunities. Dedicated time and expertise for antiretroviral stewardship as part of local antimicrobial stewardship programs are needed.

Five steps to high quality antimicrobial stewardship research.

The escalating threat of antimicrobial resistance (AMR) necessitates impactful, reproducible, and scalable antimicrobial stewardship strategies. This review addresses the critical need to enhance the quality of antimicrobial stewardship intervention research. We propose five considerations for authors planning and evaluating antimicrobial stewardship initiatives. Antimicrobial stewards should consider the following mnemonic ABCDE: (A) plan Ahead using implementation science; (B) Be clear and thoroughly describe the intervention by using the TidIER checklist; (C) Use a Checklist to comprehensively report study components; (D) Select a study Design carefully; and (E) Assess Effectiveness and implementation by selecting meaningful outcomes. Incorporating these recommendations will help strengthen the evidence base of antimicrobial stewardship literature and support optimal implementation of strategies to mitigate AMR.

Dalbavancin as an alternative to traditional outpatient parenteral antimicrobial therapy for deep gram-positive infections - an observational, retrospective review.

Background: Treatment of invasive gram-positive infections in complex patient populations is challenging. Dalbavancin, approved for skin and soft tissue infections, offers advantages in this setting due to its long half-life and infrequent dosing. However, less is known about the outcomes of off-label dalbavancin for deeper infections. Objectives: The objective of this study is to examine the feasibility and outcomes of patients with complex gram-positive infections treated with dalbavancin as an alternative to standard outpatient parenteral antimicrobial therapy (OPAT). Methods: We conducted a multicenter, retrospective review of adult patients managed within an OPAT program with intravenous dalbavancin for off-label indications. Adult patients were included if they had treatment details and follow-up documented between January 2020 and June 2023. Details of dalbavancin use including indications for prescription were captured. Outcomes of interest included 90-day infection recurrence, prosthesis retention rates, 90-day mortality, and adverse medication events. Results: In all, 61 patients received dalbavancin, mostly as sequential therapy. Twenty-three percent received dalbavancin strictly in the outpatient setting. Dalbavancin was used primarily for hardware (fracture, spine, or joint), native bone or joint, and complicated soft tissue infections. The predominant pathogen was Staphylococcus aureus (61%). Dalbavancin was frequently prescribed as a two-dose 1500 mg regimen (49%) due to persistent infection (23%), difficult line access (30%), difficulty achieving therapeutic vancomycin levels (18%), or substance abuse history (18%). Overall, six patients (10%) had infection recurrence and no patients died during the follow-up period. Three of eight patients with hardware retention had infection recurrence. Adverse effects were minimal and mostly self-limiting. Conclusion: Dalbavancin is an efficacious and safe alternative to standard OPAT, especially in those with barriers to traditional long-term intravenous antibiotics. Improved outcomes may be achieved with hardware removal. Dalbavancin may facilitate early discharge or prevent hospitalizations. Comparative studies of standard OPAT regimens versus dalbavancin are needed.

Confronting the Disruption of the Infectious Diseases Workforce by Artificial Intelligence: What This Means for Us and What We Can Do About It.

With the rapid advancement of artificial intelligence (AI), the field of infectious diseases (ID) faces both innovation and disruption. AI and its subfields including machine learning, deep learning, and large language models can support ID clinicians' decision making and streamline their workflow. AI models may help ensure earlier detection of disease, more personalized empiric treatment recommendations, and allocation of human resources to support higher-yield antimicrobial stewardship and infection prevention strategies. AI is unlikely to replace the role of ID experts, but could instead augment it. However, its limitations will need to be carefully addressed and mitigated to ensure safe and effective implementation. ID experts can be engaged in AI implementation by participating in training and education, identifying use cases for AI to help improve patient care, designing, validating and evaluating algorithms, and continuing to advocate for their vital role in patient care.

Minimizing Low-Value, Uncompensated Work in Academic Infectious Diseases: A 6-Step Program.

Uncompensated work in academic infectious diseases (ID) may be high value (eg, important for academic promotion or necessary for advancement to leadership roles) or low value (eg, not aligning with or contributing to professional goals and aspirations). "Curbside" consultations, participation in hospital committees outside of professional interests, and other "citizenship" tasks are common examples of threats to our valuable time as ID providers. Herein, we define the scope of the problem of low-value uncompensated work in academic ID and outline a 6-step program to minimize these threats. Collaboration with professional sponsors, such as division chiefs, to align individual and team goals and use of a "value-versus-compensation" matrix to prioritize activities may help us establish our own agendas and reclaim our professional autonomy.

Nirmatrelvir/ritonavir and risk of long COVID symptoms: a retrospective cohort study.

We conducted a retrospective cohort study to assess whether treatment with nirmatrelvir/ritonavir was associated with a reduced risk of long COVID. We enrolled 500 adults with confirmed SARS-CoV-2 who were eligible for nirmatrelvir/ritonavir; 250 who took nirmatrelvir/ritonavir and 250 who did not. The primary outcome was the development of one or more of eleven prespecified long COVID symptoms, assessed through a structured telephone interview four months after the positive SARS-CoV-2 test. Multivariable logistic regression models controlled for age, sex, race/ethnicity, chronic conditions, and COVID-19 vaccination status. We found that participants who took nirmatrelvir/ritonavir were no less likely to develop long COVID symptoms, compared to those who did not take the medication (44% vs. 49.6%, p = 0.21). Taking nirmatrelvir/ritonavir was associated with a lower odds of two of the eleven long COVID symptoms, brain fog (OR 0.58, 95% CI 0.38-0.88) and chest pain/tightness (OR 0.51, 95% CI 0.28-0.91). Our finding that treatment with nirmatrelvir/ritonavir was not associated with a lower risk of developing long COVID is different from prior studies that obtained data only from electronic medical records.

What is the role of the clinical microbiology laboratory in the care of diagnostically challenging OPAT patients? Illustrative cases and literature review.

Optimal care of patients requiring long-term outpatient parenteral or oral antimicrobial therapy by infectious diseases (ID) specialists is facilitated by an accurate microbiologic diagnosis. Close collaboration between ID specialists and the clinical microbiology laboratory for routine or specialized molecular testing can result in more accurate diagnoses, streamlined antimicrobial regimens, and improved patient outcomes.