Schanz, Caitlin C.

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 Background Doxycycline is a frequently used alternative treatment for community-acquired pneumonia (CAP) in hospitalized patients; however, the evidence base is limited. We aimed to compare outcomes in CAP patients treated with doxycycline or azithromycin in combination with beta-lactams. Methods We evaluated patients with CAP admitted to Mayo Clinic hospitals from May 2018 to September 2022 and treated with either azithromycin or doxycycline in combination with a beta-lactam. Patients who received both antibiotics or were on either antibiotic as chronic therapy prior to admission were excluded. The primary outcome was mortality. Patients were 1-to-1 matched according to the presence of congestive heart failure, coronary artery disease, chronic obstructive pulmonary disease, human immunodeficiency virus infection, recent immunosuppressant use, and pneumonia severity index class. Results Among 8492 patients (5810 for azithromycin, 2682 for doxycycline), 2671 doxycycline-treated patients were matched with azithromycin-treated patients. In-hospital mortality was significantly lower in the azithromycin group than in the doxycycline group (odds ratio, 0.71; 95% confidence interval [CI], .56–.9), as was 90-day mortality (hazard ratio, 0.83; 95% CI, .73–.95). Patients on azithromycin also had significantly more hospital-free days (HFDs) than those on doxycycline (estimate, 1.37; 95% CI, .99–1.74). Conclusions Among hospitalized patients with CAP, azithromycin was associated with lower mortality and more HFDs compared with doxycycline in combination with beta-lactams. Randomized, controlled trials are needed to assess the effectiveness of each regimen and to compare their potential side effects.

Abstract Background Optimizing antimicrobial regimens for outpatients with community-acquired pneumonia (CAP) represents an area of opportunity for ambulatory antimicrobial stewardship programs. A pre-populated, antibiotic order panel for outpatient respiratory syndromes was implemented in the Mayo Clinic Enterprise on 1/4/2021. For CAP, it provides national guideline adherent regimens (i.e., selection, dosing, and durations) by patient comorbidity and beta-lactam allergy status. We aimed to assess impacts of panel use on antibiotic prescribing in outpatients with CAP. Methods This retrospective review included Mayo Clinic outpatient encounters from Minnesota in 2021 and 2022. Eligible encounters used a CAP-related primary ICD-10 code, conveyed intention to treat CAP in encounter notes, and were performed by primary care, emergency department, or urgent care clinicians who managed ≥1 CAP patient with the panel and ≥1 without the panel during the study period. Encounters were excluded if patients were already receiving antibiotics at the time of encounter. The primary outcome was adherence (drug and duration) to guideline recommendations. Secondary outcomes included utilization rate by agent and therapy duration. Outcomes were analyzed with Kruskal-Wallis rank sum and Pearson’s chi-squared tests (α level = 0.05). Results 352 encounters (134 panel vs. 218 non-panel) were included. Prescribing was guideline adherent in 61.9% and 29.4% (p< 0.01) of panel and non-panel encounters, respectively. The most common reason for guideline non-adherence during panel use was inappropriate drug selection (n = 45/51, 88.2%). This was predominantly driven by use of the incorrect section of the treatment panel based on patient comorbidity status (n = 30/45, 66.7%). Individual antibiotic utilization rates differed between panel and non-panel cohorts (Table 1), with higher rates of amoxicillin and amoxicillin/clavulanate use and lower rates of azithromycin and doxycycline use in the panel cohort. Durations >5 days were more common in the non-panel as compared to the panel cohort (34.4% vs. 7.5%, p < 0.01). Conclusion Use of a pre-populated antimicrobial order panel in outpatients with CAP resulted in greater adherence to national guideline recommendations. Disclosures Paschalis Vergidis, MD, MSc, AbbVie: Advisor/Consultant|Ansun: Grant/Research Support|Cidara: Grant/Research Support|Scynexis: Grant/Research Support