Rivera, Christina G

Background: Itraconazole is the preferred antifungal agent for mild to moderate histoplasmosis and step-down therapy following amphotericin B treatment. Although hydroxy-itraconazole, a major metabolite of itraconazole, displays antifungal activity comparable with that of the parent compound, its role in therapeutic drug monitoring targets for histoplasmosis remains uncertain. Methods: The objective was to compare clinical outcomes and adverse events using itraconazole parent-compound concentrations alone versus combined itraconazole and hydroxy-itraconazole concentrations in patients treated for histoplasmosis. This retrospective cohort study included adults with probable or proven histoplasmosis who received itraconazole and had at least 1 documented serum concentration. The primary outcome was clinical response across 3 groups: (1) parent (itraconazole parent-compound concentration >1.0 mcg/mL), (2) combined (parent-compound concentration <1.0 mcg/mL with combined itraconazole plus hydroxy-itraconazole >1.0 mcg/mL), and (3) subtherapeutic (failure to reach either threshold). Treatment response and adverse events were analyzed using the Fisher exact test. Results: Among 108 patients (parent, n = 40; combined, n = 40; subtherapeutic, n = 28), response rates differed across groups (parent (95%); combined (90%); subtherapeutic (67.9%); P = 0.006). There was no difference between the parent and combined groups. Adverse events did not differ, although drug discontinuation occurred more frequently in the subtherapeutic group (parent (5%); combined (20%); subtherapeutic (25%); P = 0.04). Conclusions: Patients who failed to achieve either an itraconazole concentration >1 mcg/mL or a combined itraconazole plus hydroxy-itraconazole concentration >1 mcg/mL had lower response rates. Similar outcomes among patients achieving the itraconazole target alone and those achieving the combined target suggest that hydroxy-itraconazole concentrations may contribute to therapeutic drug monitoring targets in histoplasmosis.

Abstract We describe early experience with beta-lactam therapeutic drug monitoring (TDM) in a high-volume outpatient parenteral antimicrobial therapy program. In selected patients, TDM informed dose optimization and toxicity mitigation. Illustrative cases highlight feasibility and emerging lessons supporting beta-lactam TDM in outpatient care.

Abstract Objective: Outpatient parenteral antimicrobial therapy (OPAT) programs continue to evolve with increases in multidisciplinary teams, complex oral antibiotics, long-acting injectable antimicrobials, patients with substance use disorder (SUD) and telehealth. We sought to examine how OPAT programs are currently structured and identify barriers to safe care. Design: Cross-sectional survey. Participants: Physician, pharmacist, and advanced practice providers (APP) Emerging Infections Network (EIN) members. Methods: A survey was conducted between February and March 2025 to assess OPAT structure, expansion to complex outpatient antimicrobial therapy (COpAT), and barriers to safe OPAT care. Results: Of 1639 EIN members, 622 (38%) responded; 75% reported an active role in OPAT. Oversight of patients on COpAT was reported by 59%, and mandatory ID consultation for OPAT by 59%. Eighty-one percent reported >75% of OPAT patients were followed by ID. Most patients received OPAT at home (78%) followed by post-acute care facilities. Outpatient and inpatient ID physicians were responsible for laboratory test monitoring (75% and 30% respectively), while 37% reported a multidisciplinary OPAT team and 32% reported non-specialists. Respondents cited inadequate support in data analysis, administration, information technology and financial support for clinical staff. Common challenges were lack of leadership awareness (51%), difficulty managing patients with SUD (50%) and timely access to laboratory test results (48%). Conclusions: ID physicians were commonly involved in OPAT care, with many programs expanding to COpAT. Several barriers to the safe delivery of OPAT remain, including lack of institutional support, reimbursement and poor communication between stakeholders.

Itraconazole is the recommended first-line antifungal agent in blastomycosis treatment. However, pharmacokinetic limitations and adverse drug events may necessitate the use of alternative antifungal agents. The primary objective of the study was to retrospectively describe a cohort of patients with blastomycosis who received voriconazole (as partial or complete therapy), for complete or partial treatment, compared to those who received itraconazole alone. Secondary objectives included rationale for voriconazole selection, treatment response, mortality, and adverse drug events. This retrospective multicenter cohort study included adult patients with proven/probable blastomycosis who received itraconazole or voriconazole. Treatment response was evaluated at one year or end of therapy, whichever came first. Mortality outcomes were assessed within 7 days of the last documented azole dose. Propensity score weighting and subgroup analysis were utilized to control confounding variables between cohorts. A total of 119 patients receiving itraconazole and 25 receiving voriconazole as complete or partial treatment were included. Voriconazole was often selected for CNS involvement or after intolerance to alternative azoles. After propensity score weighting, no significant difference in complete or partial treatment response was observed. Rates of all-cause mortality and blastomycosis-related mortality were numerically higher in the voriconazole cohort. Adverse drug event rates were similar between cohorts; however, discontinuation due to adverse events was more common in the voriconazole cohort. Voriconazole was most utilized for the treatment of blastomycosis in cases with CNS involvement or intolerance to other azoles. A statistically significant difference in response rate was not identified between voriconazole-containing or itraconazole-treated patients; however, given limited sample sizes, further data is needed to assess the equivalency of these agents in the treatment of blastomycosis.

ABSTRACT Hospital‐at‐Home (HaH) programs provide acute care in patients' homes, reducing hospitalization and improving patient experience. While crucial in traditional settings, antimicrobial stewardship (AMS) in HaH programs remains understudied. This manuscript explores the potential benefits of AMS in HaH and the role of infectious diseases (ID) pharmacists in optimizing antimicrobial therapy. Key challenges in implementing AMS in HaH include medication delivery logistics, treatment regimen adjustments, and unique administration techniques. ID pharmacists can address these challenges by providing expertise in antimicrobial selection, dosing, and duration, as well as identifying opportunities for de‐escalation and intravenous (IV) to oral conversions. By integrating AMS into HaH programs, health care systems can improve patient outcomes, reduce antimicrobial resistance, and optimize resource utilization. Further research and training programs are needed to fully realize the potential of AMS in this emerging model of care.

Abstract Background With progressive accumulation of knowledge on SARS-CoV-2 infection clinical management, treatment guidelines recommended several options including remdesivir, a broad-spectrum antiviral. Given the evolving nature of coronavirus disease 2019, capturing the totality of scientific evidence from clinical trials and observational studies is critical to inform clinical decision making. We conducted a systematic literature review with meta-analysis to summarize the effectiveness of remdesivir among hospitalized adults. Methods We systematically searched MEDLINE, Embase and Cochrane Library databases for interventional and observational studies examining remdesivir efficacy. A rigorous double-reviewer approach was used for source identification, screening, data extraction and risk of bias assessment. A hierarchical random-effects model meta-analysis was used, with subgroup analyses for randomized controlled trials (RCTs) and real-world (RW) studies. Results From January 2019 to December 2023 &gt;18 000 sources were screened, and 122 unique studies were identified, reporting on 25 174 participants in RCTs and 1 279 859 in RW studies. Remdesivir significantly increased survival in the overall population (odds ratio, 0.69 [95% confidence interval, .55–.86]; P = .001] across SARS-CoV-2 variants and disease severity levels: no supplemental oxygen (0.81 [.75–.88]), low-flow oxygen (0.71 [.64–.79]), high-flow oxygen (0.87 [.83–.91]), and invasive mechanical ventilation (0.78 [.68–.90]). Rehospitalization risk was significantly reduced in patients receiving remdesivir (odds ratio, 0.72 [95% confidence interval, .64–.81]). Conclusions Our comprehensive systematic literature review, capturing the totality of evidence, showed a significant survival benefit among patients hospitalized for SARS-CoV-2 infection and receiving remdesivir, across all disease severity levels. To assure that healthcare providers are aware of and deploy evidence-based optimal care, recommendations should rely on both RCT and RW data.

ABSTRACT A total of 1,925 Corynebacterium isolates were tested for antimicrobial susceptibility at the Mayo Clinic Microbiology laboratory (Rochester, Minnesota) from January 2012 to March 2023, with C. striatum (35.6%) and C. amycolatum (24.4%) identified as the predominant species. Species known to potentially carry diphtheria toxin were excluded. Common sources of isolation included skin and soft tissue (56.8%), bone and/or native joint synovial fluid (14.2%), urine (13.1%), sputum (6.1%), and blood (5.9%). For penicillin, susceptibility decreased from 47.5% (58 of 122) in 2012 to 20.6% (14 of 68) in 2023. Isolates also showed a decrease in susceptibility to erythromycin from 22.4% (26 of 116) in 2012 to 13.2% (9 of 68) in 2023. Susceptibility to trimethoprim-sulfamethoxazole averaged around 50% throughout the period. Notably, linezolid and vancomycin were universally effective in vitro against all species. The highest susceptibility rates among tested oral agents were to linezolid and doxycycline for non- C . striatum species. Daptomycin minimal inhibitory concentrations (MICs) of >256 µg/mL were observed for one C. amycolatum isolate, one C. tuberculostearicum isolate, and for seven C. striatum isolates, all from patients with prior daptomycin exposure. Daptomycin MICs of 2 µg/mL (nonsusceptible) were observed in one C. striatum isolate recovered from a daptomycin-naïve patient and in six C. jeikeium isolates, from both daptomycin-exposed and non-exposed patients. Significant variation in susceptibility profiles across different Corynebacterium species underscores the importance of performing antimicrobial susceptibility testing to guide effective treatment. Moreover, multidrug resistance observed in C. striatum poses substantial therapeutic challenges especially in patients requiring prolonged or chronic antibiotic suppression.

Abstract Outpatient parenteral antimicrobial therapy (OPAT) has become more common in infectious diseases practice settings. Similarly, OPAT-related publications have also increased. The objective of this article was to summarize clinically important OPAT-related publications from 2023. Eighty-one articles were found on initial search, with 52 meeting inclusion criteria. A survey containing the 19 articles that had at least 1 citation was sent to an email listserv of multidisciplinary clinicians with OPAT experience. This article summarizes the “top 10” 2023 OPAT articles from the survey results.

Abstract Objective This study aimed to conduct a scoping review of machine learning (ML) techniques in outpatient parenteral antimicrobial therapy (OPAT) for predicting adverse outcomes and to evaluate their validation, implementation and potential barriers to adoption. Materials and methods This scoping review included studies applying ML algorithms to adult OPAT patients, covering techniques from logistic regression to neural networks. Outcomes considered were medication intolerance, toxicity, catheter complications, hospital readmission and patient deterioration. A comprehensive search was conducted across databases including Cochrane Central, Cochrane Reviews, Embase, Ovid MEDLINE and Scopus, from 1 January 2000 to 1 January 2024. Results Thirty-two studies met the inclusion criteria, with the majority being single-centre experiences primarily from North America. Most studies focused on developing new ML models to predict outcomes such as hospital readmissions and medication-related complications. However, there was very little reporting on the performance characteristics of these models, such as specificity, sensitivity and C-statistics. There was a lack of multi-centre or cross-centre validation, limiting generalizability. Few studies advanced beyond traditional logistic regression models, and integration into clinical practice remains limited. Discussion ML shows promise for enhancing OPAT outcomes by predicting adverse events and enabling pre-emptive interventions. Despite this potential, significant gaps exist in development, validation and practical implementation. Barriers include the need for representative data sets and broadly applicable, validated models. Conclusion Future research should address these barriers to fully leverage ML’s potential in optimizing OPAT care and patient safety. Models must deliver timely, accurate and actionable insights to improve adverse event prediction and prevention in OPAT settings.

Abstract Nontuberculous mycobacteria (NTM) can cause a variety of infections, including serious pulmonary disease. Treatment encompasses polypharmacy, with a targeted regimen of 2–5 active medications, depending on site of infection, species, and clinical characteristics. Medications may include oral, intravenous, and inhalational routes. Medication acquisition can be challenging for numerous reasons, including investigational status, limited distribution models, and insurance prior authorization. Additionally, monitoring and managing adverse reactions and drug interactions is a unique skill set. While NTM is primarily medically managed, clinicians may not be familiar with the intricacies of medication selection, procurement, and monitoring. This review offers insights into the pharmacotherapeutic considerations of this highly complex disease state, including regimen design, medication acquisition, safety monitoring, relevant drug–drug interactions, and adverse drug reactions.