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Multicenter Study
. 2022 Oct;181(10):3715-3724.
doi: 10.1007/s00431-022-04579-5. Epub 2022 Aug 4.

Association between duration of early empiric antibiotics and necrotizing enterocolitis and late-onset sepsis in preterm infants: a multicenter cohort study

Thomas H Dierikx #  1   2 , Nancy Deianova #  3   4 , Jip Groen  3   4 , Daniel C Vijlbrief  5 , Christian Hulzebos  6 , Willem P de Boode  7 , Esther J d'Haens  8 , Veerle Cossey  9 , Boris W Kramer  10 , Mirjam M van Weissenbruch  11   12 , Wouter J de Jonge  13 , Marc A Benninga  4   14 , Chris H van den Akker  11   12 , Anton H van Kaam  11   12 , Nanne K H de Boer  4   15 , Douwe H Visser  11   12 , Hendrik J Niemarkt  16 , Tim G J de Meij  3   4
Affiliations
Multicenter Study

Association between duration of early empiric antibiotics and necrotizing enterocolitis and late-onset sepsis in preterm infants: a multicenter cohort study

Thomas H Dierikx et al. Eur J Pediatr. 2022 Oct.

Abstract

The threshold to initiate empiric antibiotics for suspicion of early-onset sepsis (EOS) is low in preterm infants. Antibiotics' effects on short-term outcomes have recently been debated. We aimed at exploring the extent of early empiric antibiotic exposure (EEAE) in preterm infants and the association between the duration of EEAE with necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) within different EEAE groups. EEAE practice for suspicion of EOS was evaluated in all included infants (gestational age < 30 weeks) born in 9 centers in the Netherlands and Belgium between Oct. 2014 and Jan. 2019. EEAE association with NEC and LOS development was analyzed by multivariate regression. After excluding 56 EOS cases, 1259 infants were included. A total of 1122 infants (89.1%) were exposed to empirical antibiotics for the suspicion of EOS of whom 802 (63.7%) had short (≤ 72 h) and 320 (25.4%) prolonged EEAE (> 72 h). Infants with EEAE ≤ 72 h had a lower incidence of NEC compared to both infants without EEAE (adjusted odds ratio (aOR) 0.39; 95% confidence interval (CI) [0.19-0.80]; p = 0.01) and with prolonged EEAE (> 72 h) (aOR [95%CI]: 0.58 [0.35-0.96]; p = 0.03). With every additional day of EEAE, LOS incidence decreased (aOR [95%CI]: 0.90 [0.85-0.97]; p = 0.003).

Conclusion: Almost 90% of preterm infants who have negative blood culture results in the first 72 h of life are exposed to EEAE under suspicion of EOS. One-fourth has prolonged EEAE. Duration of EEAE was differently associated with NEC and LOS incidence. The effects of antibiotics, and potentially induced microbial dysbiosis related to development of NEC and LOS, should further be explored.

What is known: • Preterm infants often receive antibiotics empirically directly after birth for suspicion of early-onset sepsis. • The effects of the duration of early empirical antibiotic exposure on the risk for necrotizing enterocolitis and late-onset sepsis are debated.

What is new: • Almost 90% of preterm infants with a gestational age below 30 weeks are exposed to antibiotics empirically after birth despite negative culture results. In a quarter of these culture-negative infants, empirical antibiotics are prolonged. • A short course of empirical antibiotics (≤72h) is associated with decreased odds for necrotizing enterocolitis compared to both prolonged (>72h) or no empirical antibiotics after birth. Furthermore, every additional day of empirical antibiotic exposure is associated with decreased risk for late-onset sepsis in the first month of life.

Keywords: Empirical antibiotics; Late-onset sepsis; Necrotizing enterocolitis; Preterm infant.

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Conflict of interest statement

N. de Boer has served as a speaker for AbbVie, Takeda, and MSD. He has served as a consultant and principal investigator for Takeda and/or TEVA Pharma B.V. He has received research grants from Dr. Falk, MLDS, and Takeda. All outside the submitted work. All other authors declare not to have relevant financial or non-financial interests to disclose.

Figures

Fig. 1
Fig. 1
Flow chart of patient inclusions. EEAE: early empiric antibiotic exposure; GA: gestational age; h: hours
Fig. 2
Fig. 2
Stacked bar chart of incidence of (A) NEC and (B) LOS in the first 28 days of life, by EEAE category. EEAE, early empiric antibiotic exposure; LOS, late-onset sepsis, NEC, necrotizing enterocolitis
See this image and copyright information in PMC

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