Invasive fungal infection is associated with antibiotic exposure in preterm infants: a multi-centre prospective case–control study
Senlin Hou, Xiaomeng Wang, Yonghui Yu, Hongyan Ji, Xiaoyu Dong, Jianfeng Li, Huan Li, Honglin He, Zaiwang Li, Zhuangqing Yang, Wen Chen, Gaiqi Yao, Yongfeng Zhang, Jian Zhang, M. Bi, S. Niu, Guoying Zhao, Runan Zhu, Gang Liu, Yi‐Jie Jia, Yanling Gao
Abstract
BACKGROUND: Previous antibiotic exposure is an important risk factor for invasive fungal infection (IFI). Antibiotic overexposure is common in lower-income countries; however, multi-centre studies concerning IFI in relation to antibiotic exposure are scarce. AIM: This prospective, multi-centre matched case-control study explored the correlation of IFI and antibiotic exposure in very preterm infants or very-low-birthweight infants admitted to 23 tertiary hospitals in China between 2018 and 2021. METHODS: Using a 1:2 matched design for gestational age, birth weight and early-onset sepsis (yes/no), the risk factors between infants diagnosed with IFI and infection-free controls were compared. The antibiotic use rate (AUR) was calculated using calendar days of antibiotic therapy in the 4 weeks preceding IFI onset divided by onset day of IFI. FINDINGS: In total, 6368 infants were included in the study, of which 90 (1.4%) were diagnosed with IFI. Median AUR, length of antibiotic therapy (LOT) and days of antibiotic therapy (DOT) within the 4 weeks preceding IFI onset were 0.90, 18 days and 30 days, respectively. Multi-variate analysis showed that a 10% increase in AUR, each additional day of DOT and LOT, and each additional day of third-generation cephalosporins and carbapenems were notably associated with IFI. CONCLUSION: Prolonged antibiotic therapy is common before the onset of IFI, and is an important risk factor, especially the use of third-generation cephalosporins and carbapenems. Antibiotic stewardship should be urgently developed and promoted for preterm infants in order to reduce IFI in lower-income countries such as China.