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Gram-negative Late-onset Sepsis in Extremely Low Birth Weight Infants Is Emerging in The Netherlands Despite Quality Improvement Programs and Antibiotic Stewardship!

Ran, Nicolien C. MD*; van den Hoogen, Agnes PhD; Hemels, Marieke A. C. MD, PhD*

The Pediatric Infectious Disease Journal: September 2019 - Volume 38 - Issue 9 - p 952–957
doi: 10.1097/INF.0000000000002408
Maternal-Neonatal Reports

Background: Late-onset sepsis (LOS) is still an important cause of morbidity and mortality in premature infants. Indwelling devices and lower birth weight (BW) are the most important risk factors. Quality improvement programmes are implemented to reduce incidence of LOS. An increasing number of extremely low BW infants (ELBWs) (≤1000 g) are treated in the Netherlands, including infants with gestational age (GA) 24 weeks since Dutch law changed in 2010. We evaluated the incidence and causative microorganisms of LOS in ELBWs over an 8-year period in 2 Dutch neonatal intensive care units (NICUs).

Methods: The first LOS episodes of all ELBWs admitted to the NICU of the Wilhelmina Children’s Hospital Utrecht and the Isala Hospital Zwolle were included retrospectively from January 2008 to December 2015. LOS was defined as clinical signs of sepsis >72 hours postpartum, combined with a positive blood culture and C-reactive protein of ≥10 mg/L.

Results: Two hundred fifty-five out of 923 ELBWs (27.6%) had an episode of LOS, and no decrease in incidence was seen over the years. ELBWs with LOS had lower GA and BW. The percentage of Gram-negative organisms increased from 0% in 2008 to 27% in 2015, mainly in infants with GA <26 weeks. The number of invasive fungal infections decreased to zero.

Conclusions: No significant decrease in incidence of LOS in ELBWs was seen, despite the introduction of quality improvement programmes and attention to antibiotic stewardship. Furthermore, an increase in Gram-negative LOS was observed, with an overrepresentation among the growing proportion of the NICU population at the lowest GA and weight. Prevention, including high compliance to hand hygiene policies, may be an impactful intervention.

From the *Department of Neonatology, Isala Women and Children’s Hospital Zwolle, Zwolle, The Netherlands

Department of Neonatology, Wilhelmina Children’s Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands.

Accepted for publication May 26, 2019.

The authors have no funding or conflicts of interest to disclose.

Address for correspondence: Marieke A. C. Hemels, MD, PhD, Department of Neonatology, Isala Women and Children’s Hospital, P.O. Box 10400, 8000 GK, Zwolle, The Netherlands. E-mail:

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