Barrett, Kemar O.

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.

Background: Candidemia is a serious complication after gastrointestinal (GI) perforation and/or ischemia, yet most evidence pools candidemia with intra-abdominal candidiasis (IAC). We sought candidemia-specific risk factors after GI perforation and/or ischemia and evaluated associated outcomes. Methods: We conducted a single-center, retrospective matched case–control study of adults undergoing emergency surgical procedure for GI perforation and/or ischemia and admitted to a surgical intensive care unit. Cases with candidemia during index admission were matched 4:1 to controls by age, Charlson Comorbidity Index, and surgical procedure year. Conditional logistic regression assessed pre-specified risk factors, and exploratory outcomes included mortality, length of stay, and days on invasive ventilation. Results: Twenty-four cases were matched to 99 controls. Factors identified to be independently associated with candidemia include the presence of IAC (adjusted OR [aOR]: 5.51, 95% CI: 1.61, 18.89; p = 0.007), upper GI injury (aOR: 4.28, 95% CI: 1.52–12.08; p = 0.006), and diffuse intra-abdominal contamination, compared with contained/none (aOR: 3.21, 95% CI: 1.06–9.74; p = 0.040). Among candidemia cases, species distribution was Candida albicans 41.7%, C. glabrata 33.3%, C. parapsilosis 12.5%, with single cases of C. tropicalis, C. krusei , and C. dubliniensis . Candidemia was associated with a longer hospital length of stay (+13.97 d; 95% CI: 0.90–27.04; p = 0.036), without significant differences in ICU stay, duration of invasive ventilation, or mortality. Conclusions: After GI perforation and/or ischemia, the risk of candidemia is highest in patients with upper GI injury and diffuse contamination, independent of IAC. These readily identifiable operative features may guide targeted surveillance and selective early antifungal strategies. Prospective validation is warranted.

Abstract Background Candidemia can occur as a consequence of gastrointestinal (GI) injury. The mortality of candidemia is high, ranging 30-60%, even with treatment with antifungal agents. In this retrospective matched case-control study, we aimed to elucidate the medical and surgical risk factors of developing candidemia in patients who received emergency surgery for GI ischemia and/or perforation, and compare clinical outcomes in these patients with or without candidemia. Methods All patients ≥ 18 years of age who had emergency GI surgery at Mayo Clinic Rochester, MN, for the indication of GI ischemia and/or perforation between 01/01/2018 to 07/31/2024 were included. Cases were defined as patients who developed candidemia during index admission and had no alternative sources of candidemia. Controls and cases were matched 4:1 on age (± 5 years), Charlson Comorbidity Index (± 3), and year of surgery (± 2 years). The relationships between risk factors of interest and case/control were assessed using conditional logistic regression. Results Among medical risk factors, any shock requiring vasopressor (OR = 3.44, 95% CI 1.00, 11.97) or respiratory failure (OR = 8.20, 95% CI 1.04, 64.53) during hospitalization were associated with increased risk of candidemia. Among surgical risk factors, perforation in the upper GI tract was strongly associated with development of candidemia (OR = 16.99, 95% CI 2.11, 136.95) and perforation in the lower GI tract were less likely to lead to candidemia (OR = 0.06, 95% CI 0.01, 0.44). The patients who had diffuse intraabdominal contamination were more likely to develop candidemia compared to those who had no contamination or contained contamination (OR = 3.87, 95% CI 1.33, 11.25). The patients with candidemia showed signal towards higher in-hospital and 30-day mortality, and had significantly longer stay in the hospital. Conclusion Candidemia was more frequently identified in patients with shock, respiratory failure, upper GI perforation, and intra-abdominal contamination, and contributed to significant morbidity and mortality. Further analysis will include building a multivariate logistic regression model to implement prospective trial for early initiation of antifungal therapy for high-risk population. 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