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.

Background: There are limited oral treatment options available for resistant Gram-negative bacterial (GNB) infections. Minocycline, a second-generation tetracycline antibiotic, offers good bioavailability and broad-spectrum coverage that may be an option for GNB infections. Methods: We conducted a retrospective review of minocycline susceptibility testing performed on GNB isolates at the Mayo Clinic reference lab between 2013 and 2022. Minocycline susceptibility was evaluated with a focus on difficult-to-treat organisms and relevant anatomic source. Organisms included resistant isolates of Escherichia coli and Klebsiella pneumoniae ; high-risk ampC-derepressors, including Citrobacter freundii, Enterobacter cloacae, and K. aerogenes; and clinically challenging non-Enterobacterales, Acinetobacter species, Achromobacter species, and Stenotrophomonas maltophilia . Results: Of 217,206 GNB isolates, 18,148 Enterobacterales (EB) and 8,190 non- Enterobacter isolates were tested for minocycline susceptibility. Of these, 80% of all EB and 92% of non-EB isolates were susceptible. Among E. coli isolates with ceftriaxone, ciprofloxacin, meropenem, or multidrug resistance, minocycline susceptibility was 78%, 76%, 70%, and 70.9%, respectively. Among the K. pneumoniae isolates with ceftriaxone, ciprofloxacin, meropenem, or multidrug resistance, minocycline susceptibility was 46%, 38%, 37%, and 39.3%, respectively. 85% of C. freundii , 81% of E. cloacae, and 85% of K. aerogenes isolates were susceptible to Minocycline. 83.5% of Achromobacter species isolates, 66% of Acinetobacter species isolates, and 99.1% of S. maltophilia isolates were susceptible. Conclusions: Our study reports the largest collection of minocycline susceptibility findings in GNB. Minocycline showed in vitro activity against many difficult-to-treat GNB isolates, including ceftriaxone- and multidrug-resistant E. coli and some K. pneumoniae isolates, common Amp-C-producing species, and non-fermenting GNB, including Stenotrophomonas , Acinetobacter , and Achromobacter .

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 Purpose SARS-CoV-2 infection continues to impact global health, particularly among high-risk vulnerable individuals. With the loss of federal funding for SARS-CoV-2 management, hospitals will need to budget appropriately for antivirals like remdesivir, which has demonstrated effectiveness in reducing mortality. We evaluated the economic impact realized by hospitals for patients hospitalized for SARS-CoV-2 infection and initiated on remdesivir therapy. Methods We conducted a retrospective analysis using data compiled in the Premier Healthcare Database from January 2023 to February 2024. Propensity score matching was used to compare remdesivir-treated (RDV) and untreated (No RDV) groups. The mortality rate, hazard ratios associated with remdesivir use, and hospitalization costs were assessed overall and among the elderly (age ≥65 years). We also conducted a cost-effectiveness analysis to assess the economic value of remdesivir treatment. Results Among 25,498 hospitalized patients, the mortality rate in the RDV group was lower than in the No RDV group (6.2% versus 8.1%), with a greater reduction in the elderly (6.9% versus 9.0%). Remdesivir significantly reduced mortality risk by approximately 25% overall and among the elderly. Each life saved was realized at a minimal increase in average hospitalization costs ($18,329 in the RDV group versus $14,845 in the No RDV group). Remdesivir was a cost-effective treatment option at a willingness-to-pay threshold of $25,000 overall and among the elderly. Conclusions Our evaluation provides contemporaneous evidence of benefits and costs associated with management of individuals hospitalized for SARS-CoV-2 infection. Initiation of remdesivir was associated with minimal incremental hospitalization costs for lives saved as compared to not initiating remdesivir. Hospital pharmacy leadership can utilize this real-world evidence to appropriately budget for remdesivir treatment.

Abstract Purpose While randomized controlled trials remain the gold standard for assessing treatment efficacy, studies using real-world data (RWD) offer valuable insights into treatment effectiveness across broader, more diverse patient populations. This commentary explores the importance of using fit-for-purpose data and emphasizes the need for rigorous evaluation of RWD quality to support valid and actionable evidence generation. Summary The utility of RWD-based studies depends heavily on the fitness-for-purpose of the data source, which requires careful assessment of 5 key quality dimensions: relevance, extensiveness, timeliness, coherence, and reliability. Practical examples from coronavirus disease 2019 (COVID-19) comparative effectiveness research are used to illustrate each data quality domain. Conclusions As the need for RWD increases, especially for post–COVID-19 pandemic decision-making, ensuring high data quality and appropriate study design is critical. Proper evaluation of RWD sources enhances the credibility of findings and supports their use in meta-analyses, clinical guidelines, and healthcare policy.

Abstract Background Outpatient parenteral antimicrobial therapy (OPAT) has been shown to have numerous benefits including lower costs, increased patient satisfaction, and decreased healthcare associated infections. Patient education is a crucial part of the OPAT process, as lack of understanding may lead to adverse drug events, emergency department visits, or hospital re-admission. A baseline survey of OPAT clinicians at a large multi-state health system revealed low awareness of existing OPAT education resources and consensus that the materials needed improvement. We hypothesized that an OPAT education video would improve OPAT staff satisfaction with the educational offerings.Figure 1.OPAT Video Link Engagement (2024)Figure 2.Patient Electronic Chart Message Methods Adult patients ( &gt; 18 years of age) enrolled in OPAT programs at 4 sites within Mayo Clinic throughout Minnesota and Wisconsin from 5/1/23 - 8/1/24 were included. A standardized OPAT patient education video was developed using voice over PowerPoint slides. Video content included lab monitoring requirements, signs and symptoms of adverse effects including alarm symptoms, and intravenous catheter care. The video was available as a link for delivery via patient electronic chart message, to be played on clinic and hospital room computers, and accessed by patients via QR code on rack cards. We implemented inclusion rules built within our electronic health record which automated the delivery of these patient chart messages. The primary outcome was staff satisfaction with OPAT education materials. Secondary metrics included number of video patient accesses in hospital and clinic rooms, number of message deliveries, and frequency of message opening. Staff satisfaction with OPAT education was compared pre- and post-intervention using the Pearson chi-square test. Results The patient education video was accessed 73 times in hospital and clinic rooms and was delivered by automated patient chart message 157 times during the study period. Patient chart messages were opened 91.5% of the time. The percentage of staff who felt OPAT education materials needed improvement decreased from 90% pre-intervention to 38.1% post-intervention (p=0.05). Conclusion A standardized OPAT patient education video allowed for efficient electronic delivery of educational information to patients and improved OPAT staff satisfaction. Disclosures All Authors: No reported disclosures

Abstract Background Outpatient parenteral antimicrobial therapy (OPAT) is effective and cost-efficient, but 12%–63% of patients experience adverse events, requiring close monitoring. Therapeutic drug monitoring (TDM) is routinely used for vancomycin and aminoglycosides but is underutilized for beta-lactams (BLs) due to limited access, logistical barriers, and clinician inexperience. This study evaluated its use and clinical impact within a high-volume OPAT program. Methods This retrospective, single-center cohort included adult patients (≥18 years) enrolled in an OPAT program who received cefepime (CEF), piperacillin/tazobactam (TZP), or meropenem (MEN) and underwent BL TDM between April 2023 and April 2025. BL TDM was not protocolized within the OPAT program; however, institutional guidance supported its use in carefully selected patients. We aimed to describe TDM indications, lab trends, microbiological profiles, and the impact of TDM on treatment. Results During the study period, 25 OPAT patients underwent BL TDM. TDM was performed in patients receiving CEF (64%), TZP (20%), and MEN (16%). The most common indication for TDM was suspected beta-lactam toxicity (32%) (Figure 1). Post-TDM therapy adjustments were made in 52% (n = 13), including changes in dosing frequency (38.5%) and dosage strength (30.8%). Additional changes included infusion strategy modification or agent substitution (15.4% each). Subtherapeutic levels were the most common reason for adjustment (46.2%), followed by adverse effects, supratherapeutic levels, and changes in renal function (23.1% each). Skin, soft tissue, and musculoskeletal infections were most common (Figure 2). Positive cultures were present in 80%, with Pseudomonas spp most frequently isolated. Therapy was completed in 17 patients; 7 discontinued early, and 1 had treatment ongoing. Reasons for therapy discontinuation are detailed in Table 1. Conclusion BL TDM is contributing to a paradigm shift in OPAT practice by improving both efficacy and safety. While inpatient TDM typically targets efficacy, safety concerns more commonly motivate TDM in the OPAT setting. Although this review involved a small cohort, our experience adds to the growing body of evidence supporting BL TDM as a tool to enhance patient outcomes in the OPAT setting. Disclosures All Authors: No reported disclosures