Effect of antibiotic combination on secondary invasive fungal infection in critically ill sepsis patients

BACKGROUND: Inappropriate use of antibiotics is a significant factor contributing to secondary invasive fungal infection (IFI) in patients with sepsis in the intensive care unit (ICU). Our study aimed to evaluate the relationship between the number of antibiotic types use and the risk of IFI in ICU sepsis patients. METHODS: This retrospective study included adult sepsis patients admitted to the ICU of a large tertiary hospital from 2014 to 2023. Multivariate logistic regression was used to measure the adjusted correlation between the number of types of antibiotics used and the risk of IFI, as well as the simultaneous combined use of antibiotics. RESULTS: Among the 768 patients ultimately included in the study, 165 (21.5%) developed IFI. After adjustment, for each additional type of antibiotic used in ICU sepsis patients, the risk of developing IFI increased by 58% (95% confidence interval (CI): 37–82; P < 0.001). When each additional antibiotic type was compared with the use of a single antibiotic, a dose-response relationship was observed between the number of antibiotics and the risk of IFI. Furthermore, when the number of types of antibiotics used was ≥ 3, the concurrent use of antibiotics was more likely to lead to IFI than the continuous use of a single antibiotic (adjusted odds ratio (OR): 2.31 (95% CI 1.27–4.20); P = 0.006), and the risk of IFI increased with the number of concurrent antibiotic types used. CONCLUSIONS: For ICU sepsis patients, the risk of IFI continues to increase as the number of different antibiotics used rises. Furthermore, combination use of different antibiotic types is more likely to lead to IFI than sequential use of a single antibiotic. Reducing unnecessary antibiotic changes or combination use of multiple antibiotics (> 3 types) may mitigate the occurrence of IFI and improve the adverse outcome of severe sepsis patients.