Schulte, P

Abstract Rationale Community-acquired pneumonia (CAP) remains a leading cause of morbidity and mortality worldwide; current guidelines recommend either the use of β-lactam therapy with a macrolide (azithromycin; AZM) or monotherapy with a fluoroquinolone for treatment. Limited evidence exists on their comparative effectiveness. To address this gap, we examined the differences in outcomes among CAP patients treated with β-lactam therapy plus AZM or fluoroquinolone monotherapymethods: We emulated a randomized clinical trial that hypothetically assigned patients to β-lactam therapy plus AZM or fluoroquinolone. Eligible patients were all adults hospitalized for nonsevere community-acquired pneumonia (CAP) based on ATS/IDSA criteria; at Mayo Clinic hospitals (3 academic and 16 community) between May 2018 and September 2022 and received one of the two treatments within 12 hours of admission. Ensemble machine learning with augmented inverse probability weighting (AIPW) was used to evaluate “intention to treat” effects on hospital-free days (HFDs), 180-day mortality, use of advanced respiratory support, in-hospital mortality, and the composite of advanced respiratory support and/or in-hospital mortality. We used the E-value and post-discharge systolic blood pressure (SBP) (negative outcome) to evaluate effects of potential unmeasured confounding and alternative “doubly robust” inverse probably weighting with regression adjustment (IPWRA) to evaluate robustness of the findings. Results 2,451 patients (2,142 β-lactam therapy plus AZM and 309 fluoroquinolone) were eligible and included in the analyses: 53.9% were female, 86.8% were White, and mean age was 58.4 years (SD: 17.02). Compared with β-lactam therapy plus AZM, the fluoroquinolone group experienced significantly higher HFD (1.50 days; 95% CI: 1.08, 1.91), lower use of advanced respiratory support (RR: 0.32; 95% CI: 0.09, 0.54), lower in-hospital mortality (RR: 0.14; 95% CI: 0.00, 0.40), and composite of advanced respiratory support and/or in-hospital mortality (RR: 0.29; 95% CI: 0.08, 0.49). Moderate to large e-values (ranging from 3.50 to 4.74) and use of negative outcomes (post-discharge SBP) suggested that unmeasured confounding is unlikely to change the findings. Sensitivity analysis using IPWRA showed very similar results. Conclusion Among hospitalized patients with non-severe CAP, treatment with fluoroquinolone monotherapy was associated with more hospital-free days, lower in-hospital mortality, and reduced need for advanced respiratory support compared with AZM and β-lactam combination. The findings highlight the role of fluoroquinolone as a beneficial alternative CAP patients. However, further studies are needed to explore the underlying mechanisms driving these differences and assess whether specific patient subgroups may benefit most from quinolone-based therapy. This abstract is funded by: none

Abstract Rationale Inflammatory bowel disease (IBD) is increasingly recognized as a systemic disorder, with extraintestinal manifestations (EIMs) involving multiple organ systems. Pulmonary involvement, particularly interstitial lung disease (ILD), remains an underrecognized manifestation of IBD. Its prevalence, clinical characteristics, and risk factors in IBD remain poorly defined. Methods We conducted a retrospective study of adults (≥18 years) with IBD who had at least one encounter in our health system between January 1, 2013 and December 31, 2023. IBD, and ILD cases were identified using ICD-9/ICD-10 codes, with ILD diagnoses confirmed by thoracic radiologists. Demographic, clinical, pulmonary, smoking, medication, and surgical data were abstracted. Associations between patient characteristics and ILD were evaluated using both a cohort design and a matched case-control design (1:3 ratio). Mortality was assessed using a Cox proportional hazards model with ILD as a time-dependent covariate. Results Among 875 patients with IBD, 109 (12%) had ILD. Radiographic patterns included nonspecific interstitial pneumonia (NSIP, 27%), indeterminate (26%), definite/probable UIP (24%), hypersensitivity pneumonitis (15%), and organizing pneumonia (8%). Pulmonary function testing demonstrated predominantly restrictive physiology and impaired diffusion capacity. In multivariable analysis, higher BMI (OR 1.04), bronchiectasis (OR 2.65), ex-smoking (OR 2.15), and use of adalimumab (OR 2.04) or infliximab (OR 2.14) were independently associated with ILD. The matched case-control design confirmed these findings and also identified older age (OR 1.04) as a significant factor. ILD was strongly associated with mortality (HR, 3.78; 95% CI, 2.50-5.72; p < 0.001). Conclusions ILD occurs in a meaningful subset of patients with IBD and is associated with older age, higher BMI, prior smoking, bronchiectasis, and TNF inhibitor use. ILD confers a markedly increased risk of death, highlighting the importance of early recognition and close monitoring in this population. This abstract is funded by: None