Using Day-Level Registry Data to Assess Heterogeneous and Time-Varying Medication Exposure Patterns in Patients Receiving Long-Term Outpatient Antibiotic Therapy, 2015-2022

Background: Patients receiving outpatient parenteral antimicrobial therapy (OPAT) are often medically complex and require carefully tailored treatments to address severe and often concomitant infections.

Objectives: To illustrate the heterogeneity in antimicrobials used for patients in OPAT, within and across infection diagnosis groups, and over the patient's treatment course.

Methods: We conducted a cohort study of patients enrolled in the University of North Carolina Medical Center OPAT program between March 2015 and December 2022 (2358 OPAT courses, 7 person-weeks per patient, among 2072 unique patients). We classified infection diagnoses into 10 hierarchical/mutually exclusive categories: (e.g., bacteremia only, diabetic foot infection (DFI) only). To account for 64 antimicrobial medications and 520 unique cocktails administered for at least 1 patient-day in our OPAT registry, we defined 18 hierarchical/mutually exclusive classifications of treatment (e.g., “daptomycin alone” or “daptomycin + any other antibiotic(s)”). We conducted two stratified analyses to describe the heterogeneity across infection diagnoses with respect to (1) medications used at OPAT initiation (patient as unit of analysis); (2) medications used throughout OPAT (person-time as unit of analysis, allowing for differential OPAT course to other treatment classifications during follow-up). We assess stacked bar charts and Sankey diagrams to visualize the intersection between infection diagnosis and time-varying treatment group.

Results: Among patients in the cohort, 44.5% had osteomyelitis and/or DFI, 4.8% had bacteremia, and 44.6% had multiple infections. The most common medications in initial OPAT regimens were vancomycin (30.8% of OPAT patients), ceftriaxone (15.0%), and daptomycin (10.9%). There was overall similarity between the distribution of treatment groups at initiation compared to cumulative person-time during the OPAT course. However, there was heterogeneity in medications by infection diagnosis; for example, vancomycin was used in 39% of osteomyelitis cases but only 14% of endocarditis cases. For several infection groups (e.g., osteomyelitis, DFI, multiple infections, “other” single infections), no treatment classification exceeded 20% use.

Conclusions: Day-level data on medication use in this monitored registry of patients provided evidence of heterogeneity in the types of medications used throughout treatment in OPAT, within and across infection diagnoses. These data highlight the need for multi-layered ascertainment of medication exposure in this medically complex patient population to inform surveillance for adverse effects and guide comparative effectiveness research for post-discharge antibiotic treatment.