Abstract
BACKGROUND: Clinical guidance, research, and burden estimates prioritize antibacterial resistant organisms. However, understanding the relative burden of deaths due to resistant vs susceptible organisms might tailor clinical and public health priorities. We therefore contrasted mortality rates against absolute death counts associated with resistant vs susceptible infections in U.S. hospitals. [Figure: see text] [Figure: see text] METHODS: In this retrospective cohort study, adult inpatients with bacterial infection (culture growth and receiving antibiotics for > 3 days) were identified in the PINC-AI database. Resistance was defined by 2024 WHO Priority Pathogen and ECDC multidrug resistance (MDR) lenses. Predictive margins were used to obtain risk-adjusted mortality rates while controlling for confounders. To compare infection- vs resistance-related mortality, adjusted odds ratio (aOR) for mortality in matched patients hospitalized for similar conditions with (vs without) hospital-onset infection were compared. [Figure: see text] For WHO priority pathogen lens, “susceptible” refers to susceptible to the tracer antibiotic. Sepsis, septic shock and COVID-19 defined using explicit ICD-10 coding. E-SOFA= Electronic Sequential Acute Organ Failure Score. BSI=bloodstream infection [Figure: see text] RESULTS: At 285 hospitals between 2018-2022, 739,404 inpatients had 911,966 bacterial infections (Fig.1) of whom 10.7% died. Patients with infections due to resistant (vs susceptible) pathogens had more critical illness and inadequate empiric therapy (Table). Risk-adjusted mortality was marginally higher for resistant (vs susceptible) infections (11.1 vs 10.1% for WHO priority pathogens and 10.0% vs 9.6% vs 9.7% vs 9.4% for resistance to 3+(MDR), 2, 1 and 0 antibiotic categories, respectively; Fig.2). Modeled absolute deaths across all pathogens (except E. faecium) and subgroups were higher for susceptible infections (Figures 2 and 3). Among patients hospitalized for other reasons, hospital-onset infection itself was associated with greater excess odds of mortality than resistance (aOR resistant vs no infection= 1.55(95% CI. 1.48-1.63); aOR susceptible vs no infection=1.41(95% CI. 1.37-1.45). CONCLUSION: In US hospitals, risk-adjusted mortality rates are slightly higher for patients with resistant vs susceptible infections, but susceptible infections are more common and thus account for 2-3-fold more deaths compared to resistant organisms. Both antibiotic susceptible and resistant bacterial infections should be prioritized for prevention, management and research. DISCLOSURES: All Authors: No reported disclosures