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.
Keywords: Antibiotic use rate; Invasive fungal infection; Preterm infants.
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