Gajic, O

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 Critical care education has been identified as a global priority to improve the early identification and management of common syndromes, including sepsis and respiratory failure. International practice varies widely, and frontline clinical team perspectives remain poorly defined. The CERTAIN (Checklist for Early Recognition and Treatment of Acute Illness and iNjury) program provides a structured, checklist-based approach shown to improve the delivery of best practices and patient-centered outcomes worldwide. Over the past decade we have performed a needs assessment at the start of each international CERTAIN program. We performed a retrospective analysis of these data to examine the critical care domains prioritized by frontline interprofessional teams to inform global training priorities. MethodsWe developed an anonymous online survey consisting of 20 previously defined activities essential to the practice of critical care. Participants ranked these activities using Q-sort methodology on a forced distribution scale from -4 (lowest priority) to + 4 (highest priority). Individual rankings were summed across all participants to generate aggregate scores for each activity, with higher values reflecting greater collective prioritization. Aggregate scores were calculated for the entire cohort and each site and summarized with bar plots to illustrate prioritization patterns across critical care domains. ResultsA total of 213 intensivists, emergency medicine physicians, nurses, and pharmacists from hospitals in China (75), Cambodia (70), Croatia (31), Japan (24) and India (13) completed the survey. The distribution of priorities across content domains is illustrated in Figure. Management of shock, sepsis, mechanical ventilation, and respiratory failure received the highest aggregate scores. Interprofessional critical care coordination was the only process of care activity identified as high priority, and transitions of care, patient centered communication, and shared decision making were consistently ranked lowest. While minor variation existed across individual sites, resuscitation and the acute management of high-risk clinical conditions were consistently prioritized over processes of care and patient-centered care domains. ConclusionThis multicenter analysis demonstrates consistent interprofessional clinician prioritization of acute clinical management topics for training. These insights inform both areas of emphasis and highlight challenges that CERTAIN and other programs face to improve global patient care delivery. Variation in care processes has been consistently identified as the largest modifiable factor to improve patient outcomes, and cultural differences may present barriers to engagement on the best approaches to patient centered care. Figure. Distribution of aggregate Q-sort scores across 20 critical care activities. Scores represent summed participant rankings (n=213) from -4 (lowest priority) to +4 (highest priority). This abstract is funded by: None