Preclinical Detection of Non-catheter Related Late-onset Sepsis in Preterm Infants by Fecal Volatile Compounds Analysis: A Prospective, Multi-center Cohort Study

doi:10.1097/INF.0000000000002589

Multicenter Study

. 2020 Apr;39(4):330-335.

doi: 10.1097/INF.0000000000002589.

Preclinical Detection of Non-catheter Related Late-onset Sepsis in Preterm Infants by Fecal Volatile Compounds Analysis: A Prospective, Multi-center Cohort Study

Daniel J C Berkhout^{1

2}, Hendrik J Niemarkt³, Peter Andriessen^{3

4}, Daniel C Vijlbrief⁵, Marije K Bomers⁶, Veerle Cossey⁷, Christian V Hulzebos⁸, Anton H van Kaam⁹, Boris W Kramer⁴, Richard A van Lingen¹⁰, Alfian N Wicaksono¹¹, James A Covington¹¹, Mirjam M van Weissenbruch¹², Marc A Benninga², Nanne K H de Boer¹³, Tim G J de Meij¹

Affiliations

¹ From the Department of Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
² Department of Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
³ Neonatal Intensive Care Unit, Máxima Medical Centre, Veldhoven, the Netherlands.
⁴ Department of Pediatrics, Maastricht University Medical Centre, Maastricht, the Netherlands.
⁵ Neonatal Intensive Care Unit, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, the Netherlands.
⁶ Internal medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
⁷ Neonatal Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium.
⁸ Neonatal Intensive Care Unit, Beatrix Children's Hospital/ University Medical Centre Groningen, Groningen, the Netherlands.
⁹ Neonatal Intensive Care Unit, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
¹⁰ Neonatal Intensive Care Unit, Amalia Children's Centre/ Isala, Zwolle, the Netherlands.
¹¹ School of Engineering, University of Warwick, Warwick, United Kingdom.
¹² Neonatal Intensive Care Unit, Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
¹³ Department of Gastroenterology and Hepatology , Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

PMID: 32032172
DOI: 10.1097/INF.0000000000002589

Multicenter Study

Preclinical Detection of Non-catheter Related Late-onset Sepsis in Preterm Infants by Fecal Volatile Compounds Analysis: A Prospective, Multi-center Cohort Study

Daniel J C Berkhout et al. Pediatr Infect Dis J. 2020 Apr.

. 2020 Apr;39(4):330-335.

doi: 10.1097/INF.0000000000002589.

Authors

Affiliations

¹ From the Department of Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
² Department of Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
³ Neonatal Intensive Care Unit, Máxima Medical Centre, Veldhoven, the Netherlands.
⁴ Department of Pediatrics, Maastricht University Medical Centre, Maastricht, the Netherlands.
⁵ Neonatal Intensive Care Unit, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, the Netherlands.
⁶ Internal medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
⁷ Neonatal Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium.
⁸ Neonatal Intensive Care Unit, Beatrix Children's Hospital/ University Medical Centre Groningen, Groningen, the Netherlands.
⁹ Neonatal Intensive Care Unit, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
¹⁰ Neonatal Intensive Care Unit, Amalia Children's Centre/ Isala, Zwolle, the Netherlands.
¹¹ School of Engineering, University of Warwick, Warwick, United Kingdom.
¹² Neonatal Intensive Care Unit, Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
¹³ Department of Gastroenterology and Hepatology , Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

PMID: 32032172
DOI: 10.1097/INF.0000000000002589

Abstract

Background: Late onset sepsis (LOS) in preterm infants is preceded by fecal volatile organic compound (VOC) alterations, suggesting an etiologic role of gut microbiota in LOS rather than being primarily caused by central venous catheters (CVC). To increase our knowledge about the involvement of the gut microbiota in LOS, we analyzed fecal samples from septic infants without a CVC.

Methods: In this prospective multicenter study, fecal samples were collected daily from all infants born at ≤30 weeks gestation. Fecal VOC profiles up to 3 days prior to sepsis onset from infants with non-catheter-related LOS were compared with profiles from non-septic controls by means of High-Field Asymmetric Waveform Ion Mobility Spectrometry.

Results: In total, 104 fecal samples were analyzed. Fecal VOC profiles allowed for discrimination between non-catheter-related LOS cases (n = 24) and matched controls (n = 25). Discriminative accuracy increased after focusing on center of origin (area under the curve, sensitivity, specificity; 0.95, 100%, 83%) and after focusing on LOS cases caused by Staphylococcus epidermidis (0.95, 100%, 78%), the most cultured pathogen (n = 11).

Conclusions: Fecal VOC profiles of preterm LOS infants without a CVC differed from matched controls underlining the increasing notion that aberrations in gut microbiota composition and activity may play a role in LOS etiology.

PubMed Disclaimer

Cited by

The Potential of Fecal Volatile Organic Compound Analysis for the Early Diagnosis of Late-Onset Sepsis in Preterm Infants: A Narrative Review.
de Kroon RR, Frerichs NM, Struys EA, de Boer NK, de Meij TGJ, Niemarkt HJ. de Kroon RR, et al. Sensors (Basel). 2024 May 16;24(10):3162. doi: 10.3390/s24103162. Sensors (Basel). 2024. PMID: 38794014 Free PMC article. Review.
Fecal Microbiota and Volatile Metabolome Pattern Alterations Precede Late-Onset Meningitis in Preterm Neonates.
Frerichs NM, Deianova N, El Manouni El Hassani S, Acharjee A, Quraishi MN, de Boode WP, Cossey V, Hulzebos CV, van Kaam AH, Kramer BW, d'Haens E, de Jonge WJ, Vijlbrief DC, van Weissenbruch MM, Daulton E, Wicaksono AN, Covington JA, Benninga MA, de Boer NKH, van Goudoever JB, Niemarkt HJ, de Meij TGJ. Frerichs NM, et al. J Infect Dis. 2025 Jul 11;231(6):1382-1391. doi: 10.1093/infdis/jiae265. J Infect Dis. 2025. PMID: 38781449 Free PMC article.
Fecal Volatile Metabolomics Predict Gram-Negative Late-Onset Sepsis in Preterm Infants: A Nationwide Case-Control Study.
Frerichs NM, El Manouni El Hassani S, Deianova N, van Weissenbruch MM, van Kaam AH, Vijlbrief DC, van Goudoever JB, Hulzebos CV, Kramer BW, d'Haens EJ, Cossey V, de Boode WP, de Jonge WJ, Wicaksono AN, Covington JA, Benninga MA, de Boer NKH, Niemarkt HJ, de Meij TGJ. Frerichs NM, et al. Microorganisms. 2023 Feb 24;11(3):572. doi: 10.3390/microorganisms11030572. Microorganisms. 2023. PMID: 36985146 Free PMC article.
Insight Into Neonatal Sepsis: An Overview.
Attia Hussein Mahmoud H, Parekh R, Dhandibhotla S, Sai T, Pradhan A, Alugula S, Cevallos-Cueva M, Hayes BK, Athanti S, Abdin Z, K B. Attia Hussein Mahmoud H, et al. Cureus. 2023 Sep 19;15(9):e45530. doi: 10.7759/cureus.45530. eCollection 2023 Sep. Cureus. 2023. PMID: 37868444 Free PMC article. Review.
Preterm infants at low risk for early-onset sepsis differ in early fecal microbiome assembly.
Mukhopadhyay S, Lee JJ, Hartman E, Woodford E, Dhudasia MB, Mattei LM, Daniel SG, Wade KC, Underwood MA, Bittinger K. Mukhopadhyay S, et al. Gut Microbes. 2022 Jan-Dec;14(1):2154091. doi: 10.1080/19490976.2022.2154091. Gut Microbes. 2022. PMID: 36474348 Free PMC article.

See all "Cited by" articles

References

1. Erdei C, McAvoy LL, Gupta M, et al. Is zero central line-associated bloodstream infection rate sustainable? A 5-year perspective. Pediatrics. 2015;135:e1485–e1493.
1. Stoll BJ, Hansen N, Fanaroff AA, et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics. 2002;110(2, pt 1):285–291.
1. Sherman MP. New concepts of microbial translocation in the neonatal intestine: mechanisms and prevention. Clin Perinatol. 2010;37:565–579.
1. Parm Ü, Metsvaht T, Sepp E, et al. Mucosal surveillance cultures in predicting Gram-negative late-onset sepsis in neonatal intensive care units. J Hosp Infect. 2011;78:327–332.
1. Madan JC, Salari RC, Saxena D, et al. Gut microbial colonisation in premature neonates predicts neonatal sepsis. Arch Dis Child Fetal Neonatal Ed. 2012;97:F456–F462.

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

LinkOut - more resources

Full Text Sources
- Ovid Technologies, Inc.
- Wolters Kluwer
Medical
- MedlinePlus Health Information

[1] Erdei C, McAvoy LL, Gupta M, et al. Is zero central line-associated bloodstream infection rate sustainable? A 5-year perspective. Pediatrics. 2015;135:e1485–e1493.

[2] Erdei C, McAvoy LL, Gupta M, et al. Is zero central line-associated bloodstream infection rate sustainable? A 5-year perspective. Pediatrics. 2015;135:e1485–e1493.

[3] Stoll BJ, Hansen N, Fanaroff AA, et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics. 2002;110(2, pt 1):285–291.

[4] Stoll BJ, Hansen N, Fanaroff AA, et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics. 2002;110(2, pt 1):285–291.

[5] Sherman MP. New concepts of microbial translocation in the neonatal intestine: mechanisms and prevention. Clin Perinatol. 2010;37:565–579.

[6] Sherman MP. New concepts of microbial translocation in the neonatal intestine: mechanisms and prevention. Clin Perinatol. 2010;37:565–579.

[7] Parm Ü, Metsvaht T, Sepp E, et al. Mucosal surveillance cultures in predicting Gram-negative late-onset sepsis in neonatal intensive care units. J Hosp Infect. 2011;78:327–332.

[8] Parm Ü, Metsvaht T, Sepp E, et al. Mucosal surveillance cultures in predicting Gram-negative late-onset sepsis in neonatal intensive care units. J Hosp Infect. 2011;78:327–332.

[9] Madan JC, Salari RC, Saxena D, et al. Gut microbial colonisation in premature neonates predicts neonatal sepsis. Arch Dis Child Fetal Neonatal Ed. 2012;97:F456–F462.

[10] Madan JC, Salari RC, Saxena D, et al. Gut microbial colonisation in premature neonates predicts neonatal sepsis. Arch Dis Child Fetal Neonatal Ed. 2012;97:F456–F462.

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Preclinical Detection of Non-catheter Related Late-onset Sepsis in Preterm Infants by Fecal Volatile Compounds Analysis: A Prospective, Multi-center Cohort Study

Affiliations

Preclinical Detection of Non-catheter Related Late-onset Sepsis in Preterm Infants by Fecal Volatile Compounds Analysis: A Prospective, Multi-center Cohort Study

Authors

Affiliations

Abstract

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Abstract

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

LinkOut - more resources

Full Text Sources

Medical