O'Horo, John C

Introduction Community-acquired pneumonia (CAP) is common and remains the leading infectious cause of death worldwide. Antibiotics remain the mainstay of treatment, but organisms are often not identified, necessitating empirical treatment. Current treatment guidelines recommend combination therapy with beta-lactams and macrolides or monotherapy with fluoroquinolones for non-severe CAP. However, rising antibiotic resistance and safety concerns have led to increased doxycycline use, despite limited evidence supporting its efficacy. Our goal is to conduct a pragmatic, open-label, randomised clinical trial comparing the effectiveness of azithromycin with that of doxycycline in combination with beta-lactam therapy in adult patients hospitalised for CAP. Methods and analysis Patients presenting to the emergency department or directly referred to the hospital with a clinical presentation concerning for CAP and need for hospitalisation are eligible. We plan to enrol 1120 adults hospitalised at six hospitals across four states, including rural, suburban and urban settings and academic and community hospitals. Randomisation will be 1:1 using an electronic health record (EHR)-embedded screening and randomisation tool triggered by the treating clinician’s orders for azithromycin or doxycycline. Outcomes will be ascertained pragmatically via EHR-based data retrieval and will not require additional study visits. Our primary outcome is days alive and out of the hospital through day 28. Secondary outcomes include oxygen-free days; a composite of a need for advanced respiratory support or in-hospital mortality with analyses of each component separately; an ordinal measure of clinical deterioration defined by a prespecified severity scale; and 60-day and 180-day mortality. Safety outcomes are the incidence of Clostridioides difficile infection and QT prolongation. Analyses will follow an intention-to-treat framework, with per-protocol analyses for sensitivity. The primary endpoint will be compared between groups using a stratified van Elteren test, with supportive analyses using proportional odds regression and analysis of covariance adjusted for key covariates. Ethics and dissemination The Mayo Clinic Institutional Review Board reviewed and approved this protocol with a waiver of written consent, requiring verbal consent to be obtained by the clinician initiating the antibiotics (IRB# 24–0 06 503). Findings will be disseminated through peer-reviewed publications and international conference presentations. Trial registration number NCT07164131 .

Abstract Background We examined how the COVID-19 pandemic influenced influenza vaccination, healthcare engagement, and patient satisfaction. Methods We retrospectively analyzed influenza vaccination records and patient experience surveys of adult primary care patients in southeastern Minnesota during two 3-year phases: Prepandemic (1 January 2017–28 February 2020) and Pandemic-Plus (1 March 2020–31 December 2023). Vaccination status was defined as “always vaccinated” (AV), “never vaccinated” (NV), or “intermittently vaccinated” (IV) for seasonal influenza. Results During the Pandemic-Plus phase, 7.0% (n = 3556) of the Prepandemic AV and 48.7% (n = 16 710) of the Prepandemic IV patients never received another influenza vaccine. Compared to AV, IV and NV patients were more likely to reside in areas with greater socioeconomic deprivation (odds ratio [OR], 1.58 [95% confidence interval {CI}, 1.53–1.62] and 1.99 [1.94–2.05], respectively), have a high school education or less (2.86 [2.74–2.98] and 3.38 [3.23–3.53]), and report healthcare disengagement (1.59 [1.55–1.64] and 4.21 [4.09–4.33]). After adjusting for Area Deprivation Index and medical comorbidities, healthcare disengagement increased among the NV versus AV between phases (3.33 [3.24–3.41] and 4.23 [4.10–4.35]). In a subgroup analysis those with severe comorbidities were less likely AV (NV vs AV: 1.21 [1.14–1.27]) and more dissatisfied with care (NV vs AV: 1.25 [1.18–1.33]). Conclusions The COVID-19 pandemic altered vaccination behaviors and healthcare satisfaction, especially among those at high risk of developing influenza-related complications. Medical providers and public health officials should be aware of factors associated with vaccine refusal to better target interventions.

Background Electronic health records (EHRs) serve as a critical tool for clinical documentation, yet their complexity has raised concerns about readability and usability for healthcare providers and patients. Readability scores, such as the Flesch-Kincaid (FK) Grade Level, offer a quantitative method to assess documentation clarity. In this study, the authors evaluated the impact of an EHR transition on the readability of clinical notes across multiple medical specialties. Methods All clinical notes recorded between 2016 and 2019 at a large healthcare organization were evaluated across specialties. The organization transitioned EHR systems during the study period, in May 2018. FK Grade Level scores were calculated for each clinical consultation note and stratified by specialty and EHR. Results Across 10 medical specialties, 630,246 clinical notes were evaluated. The median FK grade levels from notes composed in the new EHR were similar to those composed in the previous EHR (8.228 vs 8.240; p=0.58). The variation in FK grade level as measured by standard deviation was lower in the new EHR compared with the old EHR (1.405 vs 1.764; p <0.01). Conclusions Calculation of FK grade level of clinical notes is a feasible method to assess clinical note readability. Study results showed that clinical documentation readability may not be strongly associated with underlying EHR. Migrating to a new EHR alone should not be expected to improve readability of clinical notes.

Abstract Objective: Patients with Opioid Use Disorder (OUD) are prone to Multidrug-Resistant Organism (MDRO) colonization and infections, thus at risk for worse outcomes during critical illness. Understanding the prevalence and predictors of MDRO infections is essential to optimize interventions and treatments. Design: Retrospective cohort study. Methods: The study evaluated the prevalence of MDRO isolation among adults with OUD admitted to an intensive care unit (ICU) between January 1, 2018, and July 31, 2023. It included adults admitted to an ICU with bacterial infections and positive cultures obtained within 48 hours of admission. Demographics, clinical traits, and MDRO isolation rates were analyzed using descriptive statistics, univariate methods, and Least Absolute Shrinkage and Selection Operator (LASSO) regression. Results: MDRO isolation occurred in 178 of 790 patients (22.5%), with methicillin-resistant Staphylococcus aureus as the most frequently isolated organism. LASSO regression identified housing insecurity (OR: 1.79, 95% CI 1.09–2.93, P = .022), no receipt of medications for OUD treatment (OR: 1.56, 95% CI 1.06–2.29, P = .023), positive hepatitis C virus (HCV) status (OR: 2.19, 95% CI 1.19–4.03, P = .012), and intravenous antibiotic use in the prior 90 days (OR: 1.04 per 24 h, 95% CI 1.01–1.07, P = .007) as significant predictors of MDRO isolation. Conclusions: The study highlights a high prevalence of MDRO isolation in critically ill OUD patients admitted for infection-related issues with positive cultures obtained within 48 hours of admission, influenced by factors like housing insecurity, no receipt of medications for OUD treatment, HCV status, and prior antibiotic use.

Abstract Background There remains a lack of consensus regarding the postoperative treatment regimen in patients with native valve Staphylococcus aureus infective endocarditis who undergo surgical valve replacement or repair. Methods We conducted a multicenter retrospective review of patients with S aureus native valve endocarditis who underwent surgical valve replacement or repair at Mayo Clinic Enterprise (Minnesota, Florida, Arizona, and Mayo Clinic Health Systems) between 1 January 2012 and 31 December 2022. Postoperative treatment regimens were classified as either monotherapy with a methicillin-sensitive or methicillin-resistant S aureus active agent or combination therapy that included rifampin and/or gentamicin with either active agent. Results Of the 339 patients diagnosed with S aureus native valve endocarditis, 61 underwent surgical valve replacement or repair within the initial 6 weeks of antimicrobial therapy. A total of 12 (20.2%) patients died during the 1-year follow-up period. Between patients postoperatively treated with monotherapy (n = 33) and combination therapy (n = 28), a propensity score–weighted analysis revealed that combination therapy was associated with increased risk of 1-year mortality (P = .039), 6-month relapse (P = .016), and treatment-related adverse events (P &lt; .001). Conclusions Among patients treated for native valve infective endocarditis caused by S aureus after valvular surgical intervention, all study outcomes—adverse events and drug-drug interactions, 6-month infective endocarditis relapse, and 1-year mortality—were higher in the combination therapy group than the monotherapy group.

Abstract Objective: To retrospectively observe procalcitonin (PCT) and antibiotic ordering practices in patients hospitalized with community-acquired pneumonia (CAP). Design: Retrospective, exact matched, multicenter cohort study from October 1, 2018 – March 31, 2023. Setting: All hospitals across the Mayo Clinic Enterprise. Participants: Adult patients with CAP, identified using pneumonia diagnosis codes and receipt of systemic antibiotics with an indication of “respiratory tract infection” within 48 hours of hospitalization. Methods: PCT testing within the first 7 days of hospitalization was compared to non-PCT care (nPCT). The primary outcomes were treatment duration, antibiotic days of therapy (DOT), and length of stay (LOS). Results: 15364 patients met inclusion criteria. PCT testing occurred in 42.4% (6515/15364) of encounters, totaling 8214 PCT results. 12880 unique patient encounters were matched 1:1, 6440 in each group. Treatment duration was longer in the PCT group compared to the nPCT group (5.1 vs 4.6 days, respectively, P < 0.001). Patients in the PCT group also received more DOT (8.6 vs 7.6 DOT, P < 0.001) and had a longer LOS (6.8 vs 5.9 days, P < 0.001), respectively. There was no difference in 30-day all-cause mortality or C. difficile infection between groups. In a sensitivity analysis of nPCT patients compared to those with a peak value <0.25 ng/mL (i.e. normal result) there was no difference in treatment duration (4.6 days nPCT vs 4.7 days normal PCT, P = 0.104) or LOS (5.9 days nPCT vs 6.0 days normal PCT, P = 0.134). Conclusion: PCT testing in patients hospitalized with CAP was not associated with reduced antimicrobial utilization, LOS, or 30-day all-cause mortality.

Abstract Background The Grading Recommendations, Assessment, Development, and Evaluations (GRADE) framework is widely applied in clinical guidelines to facilitate transparent evidence evaluation. While developing Infectious Diseases Society of America (IDSA) guidelines on the management of patients with coronavirus disease 2019 (COVID-19), panel members suggested developing and implementing a visual aid to enable quicker identification of key information by providers at bedside seeking guidance. Methods We conducted a mixed-methods study evaluating the usability of a newly designed infographic/icon using a survey and focus groups. The survey incorporated a simulated COVID-19 IDSA guideline with and without the icon, followed by comprehension questions. Focus group discussions provided qualitative feedback on the GRADE methodology and icon usability. Results The survey was returned by 289 health care providers. There was no statistical difference in the correct response rates between icon-aided and non-icon-aided guideline questions (McNemar's chi-square test, P &gt; .1 for both questions). Interactions with the icon notably increased the time taken and number of clicks required to respond to the first question (Wilcoxon signed-rank test, P &lt; .01). In contrast, response time did not differ between versions for the second question (P = .38). Most subjects (85%) indicated that the icon improved the readability of the guidelines. A focus group follow-up suggested alternative designs for the icon. Conclusions This study highlights the promise of iconography in clinical guidelines, although the specific icons tested did not measurably improve usability metrics. Future research should focus on icon design and testing within a formal usability framework, considering the impact of GRADE language on user experience.

AbstractBackgroundPneumocystis pneumonia (PCP) is a growing concern as the immunocompromised population expands. Current laboratory approaches are limited. This systematic review aimed to evaluate metagenomic next-generation sequencing (MNGS) tests’ performance in detecting PCP.MethodsFive databases were searched through December 19, 2022, to identify original studies comparing MNGS with clinically diagnosed PCP. To assess the accuracy, symmetric hierarchical summary receiver operating characteristic models were used.ResultsEleven observational studies reporting 1442 patients (424 with PCP) were included. Six studies focused exclusively on recipients of biologic immunosuppression (none with HIV-associated immunosuppression). Six were exclusively on bronchoalveolar lavage, while 1 was on blood samples. The sensitivity of MGNS was 0.96 (95% CI, 0.90–0.99), and specificity was 0.96 (95% CI, 0.92–0.98), with negative and positive likelihood ratios of 0.02 (95% CI, 0.01–0.05) and 19.31 (95% CI, 10.26–36.36), respectively. A subgroup analysis of studies exclusively including bronchoalveolar lavage (BAL) and blood samples demonstrated a sensitivity of 0.94 (95% CI, 0.78–0.99) and 0.93 (95% CI, 0.80–0.98) and a specificity of 0.96 (95% CI, 0.88–0.99) and 0.98 (95% CI, 0.76–1.00), respectively. The sensitivity analysis on recipients of biologic immunosuppression showed a sensitivity and specificity of 0.96 (95% CI, 0.90–0.98) and 0.94 (95% CI, 0.84–0.98), respectively. The overall confidence in the estimates was low.ConclusionsDespite the low certainty of evidence, MNGS detects PCP with high sensitivity and specificity. This also applies to recipients of biologic immunosuppression and tests performed exclusively on blood samples without the need for BAL. Further studies are required in individuals with HIV-associated immunosuppression.

Abstract Background Antispike monoclonal antibodies are recommended for early treatment of high-risk persons with mild to moderate coronavirus disease 2019 (COVID-19). However, clinical outcomes of their use during the severe acute respiratory syndrome coronavirus 2 Omicron wave are limited. Methods This is a descriptive retrospective study of high-risk adult patients who received treatment with sotrovimab (January 1–March 20, 2022) or bebtelovimab (March 21–April 30, 2022). The primary outcome was the proportion of patients who progressed to severe outcome within 30 days after receiving antispike-neutralizing monoclonal antibody infusion. Results A total of 3872 high-risk patients (median age, 62.7 years; 41.1% male) with mild to moderate COVID-19 received sotrovimab (n = 2182) or bebtelovimab (n = 1690). Among sotrovimab-treated patients, the most common comorbidities were an immunosuppressed condition (46.7%), hypertension (38.2%), and diabetes (21.2%). The rates of severe outcome, intensive care unit (ICU) admission, and mortality were 2.2%, 1.0%, and 0.4%, respectively, after sotrovimab infusion. Among bebtelovimab-treated patients, the most common comorbidities were hypertension (42.7%), diabetes (17.1%), and an immunosuppressed condition (17.0%). The rates of severe disease, ICU admission, and mortality were 1.3%, 0.5%, and 0.2%, respectively, after bebtelovimab infusion. Older age, immunosuppressed status, and several comorbidities were associated with severe disease progression, while COVID-19 vaccination was associated with lower risk. No anaphylaxis was reported during monoclonal antibody infusion. Conclusions This real-world analysis of a large cohort of high-risk patients demonstrates low rates of severe disease after treatment with sotrovimab during the era dominated by Omicron B.1.1.529 and after treatment with bebtelovimab during the era dominated by BA.2 and Omicron subvariants.

Abstract Case reports of patients infected with COVID-19 and influenza virus (“flurona”) have raised questions around the prevalence and severity of coinfection. Using data from HHS Protect Public Data Hub, NCBI Virus, and CDC FluView, we analyzed trends in SARS-CoV-2 and influenza hospitalized coinfection cases and strain prevalences. We also characterized coinfection cases across the Mayo Clinic Enterprise from January 2020 to April 2022. We compared expected and observed coinfection case counts across different waves of the pandemic and assessed symptoms and outcomes of coinfection and COVID-19 monoinfection cases after propensity score matching on clinically relevant baseline characteristics. From both the Mayo Clinic and nationwide datasets, the observed coinfection rate for SARS-CoV-2 and influenza has been higher during the Omicron era (2021 December 14 to 2022 April 2) compared to previous waves, but no higher than expected assuming infection rates are independent. At the Mayo Clinic, only 120 coinfection cases were observed among 197,364 SARS-CoV-2 cases. Coinfected patients were relatively young (mean age: 26.7 years) and had fewer serious comorbidities compared to monoinfected patients. While there were no significant differences in 30-day hospitalization, ICU admission, or mortality rates between coinfected and matched COVID-19 monoinfection cases, coinfection cases reported higher rates of symptoms including congestion, cough, fever/chills, headache, myalgia/arthralgia, pharyngitis, and rhinitis. While most coinfection cases observed at the Mayo Clinic occurred among relatively healthy individuals, further observation is needed to assess outcomes among subpopulations with risk factors for severe COVID-19 such as older age, obesity, and immunocompromised status.