Purpose: Infection in general is a frequent and serious complication after hip fracture (HF) surgery. Multimorbidity in HF patients is associated with elevated infection risk. It remains unclear whether multimorbidity interacts with HF surgery to increase infection risk beyond their individual effects.

Methods: Using Danish registries, we identified 92,599 patients >= 65 years surgically treated for HF 2004 to 2018 and an age- and sex-matched comparison cohort from the background population without HF (n=462,993). Multimorbidity was defined using the Charlson Comorbidity Index in categories no, moderate, or severe. We computed incidence rates (IR) of any kind of hospital-treated infection within 1 month and 1 year with 95% confidence intervals and estimated the attributable proportion (in %) based on differences in IRs.

Results: The IR of infection within 1 month was 181 (176-186) per 100 person years in HF patients with no multimorbidity and 9 (95% CI 8-9) in the comparison cohort with no multimorbidity. The IRs were 240 (234-246) and 302 (291-313) in HF patients with moderate and severe multimorbidity compared with 17 (16-18) and 31 (30-33) in the comparison cohort with same multimorbidity level. The attributable proportion indicates that 21% and 33% of the IR among HF patients with moderate and severe multimorbidity, respectively, was explained by interaction. Similar interactions were observed within 1 year.

Conclusion: Multimorbidity and HF surgery interact synergistically, which substantially increases the infection risk. The interaction effect increased with multimorbidity level. Our findings highlight the potential benefits of implementing more targeted and personalized preventive initiatives for multimorbid patients.