Invasive fungal infection is associated with antibiotic exposure in preterm infants: a multi-centre prospective case-control study

J Hosp Infect. 2023 Apr:134:43-49. doi: 10.1016/j.jhin.2023.01.002. Epub 2023 Jan 14.

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.

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

Publication types

  • Multicenter Study

MeSH terms

  • Anti-Bacterial Agents / adverse effects
  • Carbapenems
  • Case-Control Studies
  • Cephalosporins
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Premature*
  • Invasive Fungal Infections* / drug therapy
  • Invasive Fungal Infections* / epidemiology
  • Retrospective Studies

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • Cephalosporins