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. 2026 Jan 3;26(1):237.
doi: 10.1186/s12879-025-12496-9.

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

Wenyi Jin #  1   2 , Yaqi Xu #  1 , Zhe Xu  3 , Jiaze Song  1 , Xiaoming Zhou  1   2 , Chen Liu  1   2 , Liang Wang  4 , Zhiyi Wang  5   6 , Jie Weng  7   8   9   10   11 , Ying Chen  12   13   14
Affiliations

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

Wenyi Jin et al. BMC Infect Dis. .

Abstract

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.

Supplementary Information: The online version contains supplementary material available at 10.1186/s12879-025-12496-9.

Keywords: Antibiotic use; Intensive care unit; Invasive fungal infection; Sepsis.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study protocol was approved by the Clinical Research Ethics Committee of the Second Affiliated Hospital of Wenzhou Medical University, complying with the ethical guidelines of the 1975 Declaration of Helsinki (2021-K-271-01). Due to the retrospective design, the exemption of informed consent was approved by the Clinical Research Ethics Committee of the Second Affiliated Hospital of Wenzhou Medical University. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Density plot of observed number of types of antibiotics used
Fig. 2
Fig. 2
Schematic diagram of the top three combinations of two and three types of antibiotics used concurrently in ICU sepsis patients with secondary IFI
Fig. 3
Fig. 3
Variation in the adjusted association of the number of types of antibiotics used and IFI risk in ICU patients with sepsis according to patient and clinical factors
See this image and copyright information in PMC

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