(265) Long-Term Clinical Outcomes Associated with Antimicrobial Allergies Using Mixed-Effect Survival Models

Publication Number: 596

Background: Patients with β-lactam allergies incur higher rates of resistant infections, acute kidney injury (AKI), and long-term mortality compared to non-β-lactam-allergic comparators. It is unknown whether patients with other antimicrobial allergies share the same risks as the long-term outcomes of other antimicrobial allergies have not been evaluated.

Objectives: Compare the long-term clinical outcomes of patients with differing antimicrobial allergies, including both β-lactam and non-β-lactam allergies.

Methods: A cohort of patients (N=22074) from UPMC, a regional health system in western Pennsylvania, were identified with an index encounter with a diagnosis of sepsis, pneumonia, or urinary tract infection between 2007-2008. Electronic health records data for the years 2007–2018 was analyzed. Four mutually exclusive allergy groups were defined: no antimicrobial allergy (NAA), β-lactam allergy (BL), non-β-lactam-allergy (NBL), and both β-lactam and non-β-lactam allergies (BL-NBL). The primary outcome was all-cause mortality. Secondary outcomes included first occurrence of methicillin-resistant staphylococcus aureus (MRSA) or clostridium difficile (C.diff). Control variables included age, sex, race and baseline estimated glomerular filtration rate. Time-varying controls included Elixhauser comorbidity score, and length of stay. Multi-level mixed-effect survival models were used to conduct a time-to-event analysis of clinical outcomes using individual patients as a cluster variable. Estimates were calculated as population-average treatment effects expressed as hazard ratios.

Results: Among patients with NAA (N=16432), BL (N= 3611), NBL (N= 1083), and BL-NBL (N=948), death occurred in 59% (N=9617), 61% (N=2200), 57% (N=617), and 63% (N=599) patients, respectively. MRSA occurred in 17% (N=2821), 21% (N=757), 22% (N=235), and 21% (N=201) of patients, and C.diff in 2% (N=399), 3% (N=106), 3% (N=31), and 2% (N=23) of patients, respectively. Compared to patients with NAA, patients with BL allergies (HR=1.06; 95% CI=1.005 – 1.12) and BL-NBL allergies (1.20; 1.11 - 1.31) had higher rates of mortality, but NBL allergies alone were not associated with significant changes in mortality. BL allergies (1.28; 1.17 – 1.40), NBL allergies (1.16; 1.02 - 1.33), and BL-NBL allergies (1.30; 1.13 – 1.49) were all associated with increased rates of MRSA. Additionally, BL allergies (1.26; 1.02 - 1.57), NBL allergies (1.77; 1.33 – 2.36), and BL-NBL allergies (2.39; 1.74 - 3.27) were all also associated with higher rates of C.diff.

Conclusions: The detrimental effects of β-lactam allergies on clinical outcomes are well described; however, increased emphasis is needed on understanding and recognizing non β-lactam allergies as risk factors for long-term mortality and resistant infections, particularly in patients with multiple antimicrobial allergies.