Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Higher intake of coagulase-negative staphylococci from maternal milk promotes gut colonization with mecA-negative Staphylococcus epidermidis in preterm neonates

Journal of Perinatology volume 38, pages 1344–1352 (2018)Cite this article

Subjects

Abstract

Objective

We aimed to determine factors associated with gut colonization of preterm neonates with coagulase-negative staphylococci (CoNS) from maternal milk (MM).

Study Design

CoNS isolated from weekly collected stool and MM of hospitalized preterm (n = 49) and healthy term neonates (n = 20) were genotyped. Colonization-related factors were determined by Cox proportional hazards regression.

Result

Gut colonization with mecA-negative Staphylococcus epidermidis from MM was less prevalent (40.8% vs. 95%) and delayed (median age 15.5 vs. 2 days) in preterm compared with term neonates. Enhanced colonization was associated with higher intake of CoNS from MM (hazard ratio (95% confidence interval) 1.006 (1.00–1.01) for 106 colony-forming units), lower proportion of mecA-positive predominant NICU strains in gut (0.09 (0.01–0.49) for 1%) and lower incidence of late-onset CoNS sepsis (5% vs. 34% in those without colonization).

Conclusion

Enteral feeding with larger proportion of unpasteurized MM and limiting spread of predominant strains may promote colonization with CoNS from MM.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Dong H, Cao H, Zheng H. Pathogenic bacteria distributions and drug resistance analysis in 96 cases of neonatal sepsis. BMC Pediatr. 2017;17:44.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Salgueiro VC, Azevedo MB, Iorio NL, Amorim EeL, dos Santos KR. Staphylococcal cassette chromosome mec elements in methicillin-resistant coagulase-negative staphylococci from a Brazilian neonatal care unit. Pediatr Infect Dis J. 2014;33:1089–90.

    Article  PubMed  Google Scholar 

  3. Kaplan HC, Lannon C, Walsh MC, Donovan EF. Ohio Perinatal Quality Collaborative. Ohio statewide quality-improvement collaborative to reduce late-onset sepsis in preterm infants. Pediatrics. 2011;127:427–35.

    Article  PubMed  Google Scholar 

  4. Soeorg H, Huik K, Parm Ü, Ilmoja ML, Metsvaht T, Lutsar I. Molecular epidemiology of Staphylococcus epidermidis in neonatal intensive care units. APMIS. 2017;125:63–73.

    Article  CAS  PubMed  Google Scholar 

  5. Soeorg H, Metsvaht T, Eelmäe I, Merila M, Treumuth S, Huik K, et al. The role of breast milk in the colonization of neonatal gut and skin with coagulase-negative staphylococci. Pediatr Res. 2017;82:759–67.

    Article  PubMed  Google Scholar 

  6. Soeorg H, Metsvaht HK, Keränen EE, Eelmäe I, Merila M, Treumuth S, et al. Genetic relatedness of Staphylococcus haemolyticus in gut and skin of preterm neonates and breast milk of their mothers. Pediatr Infect Dis J. 2018. https://doi.org/10.1097/INF.0000000000002056.

  7. Soeorg H, Huik K, Parm U, Ilmoja ML, Metelskaja N, Metsvaht T, et al. Genetic relatedness of coagulase-negative staphylococci from gastrointestinal tract and blood of preterm neonates with late-onset sepsis. Pediatr Infect Dis J. 2013;32:389–93.

    Article  PubMed  Google Scholar 

  8. Qin L, Da F, Fisher EL, Tan DC, Nguyen TH, Fu CL, et al. Toxin mediates sepsis caused by methicillin-resistant Staphylococcus epidermidis. PLoS Pathog. 2017;13:e1006153.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Tolo I, Thomas JC, Fischer RS, Brown EL, Gray BM, Robinson DA. Do Staphylococcus epidermidis genetic clusters predict isolation sources? J Clin Microbiol. 2016;54:1711–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Soeorg H, Metsvaht T, Eelmäe I, Metsvaht HK, Treumuth S, Merila M, et al. Coagulase-negative Staphylococci in human milk from mothers of preterm compared with term neonates. J Hum Lact. 2017;33:329–40.

    Article  PubMed  Google Scholar 

  11. Jiménez E, Delgado S, Maldonado A, Arroyo R, Albújar M, García N, et al. Staphylococcus epidermidis: a differential trait of the fecal microbiota of breast-fed infants. BMC Microbiol. 2008;8:143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Martín V, Maldonado-Barragán A, Moles L, Rodriguez-Baños M, Campo RD, Fernández L, et al. Sharing of bacterial strains between breast milk and infant feces. J Hum Lact. 2012;28:36–44.

    Article  PubMed  Google Scholar 

  13. Corpeleijn WE, Kouwenhoven SM, Paap MC, van Vliet I, Scheerder I, Muizer Y, et al. Intake of own mother’s milk during the first days of life is associated with decreased morbidity and mortality in very low birth weight infants during the first 60 days of life. Neonatology. 2012;102:276–81.

    Article  CAS  PubMed  Google Scholar 

  14. Johansson A, Koskiniemi S, Gottfridsson P, Wiström J, Monsen T. Multiple-locus variable-number tandem repeat analysis for typing of Staphylococcus epidermidis. J Clin Microbiol. 2006;44:260–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Cremniter J, Sivadon-Tardy V, Caulliez C, Bauer T, Porcher R, Lortat-Jacob A, et al. Genetic analysis of glycopeptide-resistant Staphylococcus epidermidis strains from bone and joint infections. J Clin Microbiol. 2013;51:1014–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cavanagh JP, Klingenberg C, Hanssen AM, Fredheim EA, Francois P, Schrenzel J, et al. Core genome conservation of Staphylococcus haemolyticus limits sequence based population structure analysis. J Microbiol Methods. 2012;89:159–66.

    Article  CAS  PubMed  Google Scholar 

  17. Zhang K, Sparling J, Chow BL, Elsayed S, Hussain Z, Church DL, et al. New quadriplex PCR assay for detection of methicillin and mupirocin resistance and simultaneous discrimination of Staphylococcus aureus from coagulase-negative staphylococci. J Clin Microbiol. 2004;42:4947–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kondo Y, Ito T, Ma XX, Watanabe S, Kreiswirth BN, Etienne J, et al. Combination of multiplex PCRs for staphylococcal cassette chromosome mec type assignment: rapid identification system for mec, ccr, and major differences in junkyard regions. Antimicrob Agents Chemother. 2007;51:264–74.

    Article  CAS  PubMed  Google Scholar 

  19. Milani C, Duranti S, Bottacini F, Casey E, Turroni F, Mahony J, et al. The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota. Microbiol Mol Biol Rev. 2017;81:e00036–17.

    Article  PubMed  Google Scholar 

  20. Cortese F, Scicchitano P, Gesualdo M, Filaninno A, De Giorgi E, Schettini F, et al. Early and late infections in newborns: where do we stand? A review. Pediatr Neonatol. 2016;57:265–73.

    Article  PubMed  Google Scholar 

  21. Cossey V, Vanhole C, Verhaegen J, Schuermans A. Intestinal colonization patterns of staphylococci in preterm infants in relation to type of enteral feeding and bacteremia. Breastfeed Med. 2014;9:79–85.

    Article  PubMed  Google Scholar 

  22. Shaw AG, Sim K, Randell P, Cox MJ, McClure ZE, Li MS, et al. Late-onset bloodstream infection and perturbed maturation of the gastrointestinal microbiota in premature infants. PLoS ONE. 2015;10:e0132923.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Korpela K, Blakstad EW, Moltu SJ, Strømmen K, Nakstad B, Rønnestad AE, et al. Intestinal microbiota development and gestational age in preterm neonates. Sci Rep. 2018;8:2453.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Gibson MK, Wang B, Ahmadi S, Burnham CA, Tarr PI, Warner BB, et al. Developmental dynamics of the preterm infant gut microbiota and antibiotic resistome. Nat Microbiol. 2016;1:16024.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Jiménez E, Delgado S, Fernández L, García N, Albújar M, Gómez A, et al. Assessment of the bacterial diversity of human colostrum and screening of staphylococcal and enterococcal populations for potential virulence factors. Res Microbiol. 2008;159:595–601.

    Article  PubMed  Google Scholar 

  26. Cailes B, Kortsalioudaki C, Buttery J, Pattnayak S, Greenough A, Matthes J, et al. Epidemiology of UK neonatal infections: the neonIN infection surveillance network. Arch Dis Child Fetal Neonatal Ed. 2017. https://doi.org/10.1136/archdischild-2017-313203.

  27. Rodrigues C, Severo M, Zeitlin J, Barros H. The type of feeding at discharge of very preterm infants: neonatal intensive care units policies and practices make a difference. Breastfeed Med. 2017. https://doi.org/10.1089/bfm.2017.0135.

    Article  PubMed  Google Scholar 

  28. Wilson E, Edstedt Bonamy AK, Bonet M, Toome L, Rodrigues C, Howell EA, et al. Room for improvement in breast milk feeding after very preterm birth in Europe: results from the EPICE cohort. Matern Child Nutr. 2018;14:e12485.

    Article  Google Scholar 

  29. Snyder R, Herdt A, Mejias-Cepeda N, Ladino J, Crowley K, Levy P. Early provision of oropharyngeal colostrum leads to sustained breast milk feedings in preterm infants. Pediatr Neonatol. 2017;58:534–40.

    Article  PubMed  Google Scholar 

  30. Dicky O, Ehlinger V, Montjaux N, Gremmo-Féger G, Sizun J, Rozé JC, et al. Policy of feeding very preterm infants with their mother’s own fresh expressed milk was associated with a reduced risk of bronchopulmonary dysplasia. Acta Paediatr. 2017;106:755–62.

    Article  PubMed  Google Scholar 

  31. Mense L, Rößler S, Hanusch R, Roßberg C, Rüdiger M. Bacterial contamination of mechanically extracted breast milk. Am J Perinatol. 2014;31:293–8.

    Article  PubMed  Google Scholar 

  32. Schanler RJ, Fraley JK, Lau C, Hurst NM, Horvath L, Rossmann SN. Breastmilk cultures and infection in extremely premature infants. J Perinatol. 2011;31:335–8.

    Article  CAS  PubMed  Google Scholar 

  33. Josephson CD, Caliendo AM, Easley KA, Knezevic A, Shenvi N, Hinkes MT, et al. Blood transfusion and breast milk transmission of cytomegalovirus in very low-birth-weight infants: a prospective cohort study. JAMA Pediatr. 2014;168:1054–62.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Kayıran PG, Can F, Kayıran SM, Ergonul O, Gürakan B. Transmission of methicillin-sensitive Staphylococcus aureus to a preterm infant through breast milk. J Matern Fetal Neonatal Med. 2014;27:527–9.

    Article  PubMed  Google Scholar 

  35. Weems MF, Dereddy NR, Arnold SR. Mother’s milk as a source of Enterobacter cloacae sepsis in a preterm infant. Breastfeed Med. 2015;10:503–4.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Brooks B, Olm MR, Firek BA, Baker R, Thomas BC, Morowitz MJ, et al. Strain-resolved analysis of hospital rooms and infants reveals overlap between the human and room microbiome. Nat Commun. 2017;8:1814.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. O’Connor C, Powell J, Finnegan C, O’Gorman A, Barrett S, Hopkins KL, et al. Incidence, management and outcomes of the first cfr-mediated linezolid-resistant Staphylococcus epidermidis outbreak in a tertiary referral centre in the Republic of Ireland. J Hosp Infect. 2015;90:316–21.

    Article  PubMed  Google Scholar 

  38. Asnicar F, Manara S, Zolfo M, Truong DT, Scholz M, Armanini F, et al. Studying Vertical microbiome transmission from mothers to infants by strain-level metagenomic profiling. mSystems. 2017;2:e00164–16.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Stewart CJ, Embleton ND, Marrs ECL, Smith DP, Fofanova T, Nelson A, et al. Longitudinal development of the gut microbiome and metabolome in preterm neonates with late onset sepsis and healthy controls. Microbiome. 2017;5:75.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank the study nurses Marika Zuihhina, Eve Kaur and Tuuli Tammekunn; clinical microbiologist Dr. Marika Jürna-Ellam; laboratory assistants Dagmar Hoidmets, Tiiu Rööp and Sandra Sokmann; and all the study participants.

Funding

This study was funded by Estonian Research Council (IUT34-24), European Regional Development Fund (Project SFOS WP1-NeuroAIDS), Archimedes Foundation (Project No. 3.2.1001.11-0032) and the European Society for Paediatric Infectious Diseases (ESPID Small Grant Award) and supported by Estonian Ministry of Education and Research (Grant No. KOGU-HUMB).

Author information

Authors and Affiliations

  1. Department of Microbiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia

    Hiie Soeorg, Sirli Treumuth, Hanna Kadri Metsvaht & Irja Lutsar

  2. Paediatric Intensive Care Unit, Clinic of Anaesthesiology and Intensive Care, Tartu University Hospital, Tartu, Estonia

    Imbi Eelmäe & Tuuli Metsvaht

  3. Neonatal Unit, Children’s Clinic, Tartu University Hospital, Tartu, Estonia

    Mirjam Merila

  4. Department of Anaesthesiology and Intensive Care, Tallinn Children’s Hospital, Tallinn, Estonia

    Mari-Liis Ilmoja

Authors
  1. Hiie Soeorg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sirli Treumuth
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hanna Kadri Metsvaht
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Imbi Eelmäe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mirjam Merila
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mari-Liis Ilmoja
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Irja Lutsar
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tuuli Metsvaht
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiie Soeorg.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Soeorg, H., Treumuth, S., Metsvaht, H.K. et al. Higher intake of coagulase-negative staphylococci from maternal milk promotes gut colonization with mecA-negative Staphylococcus epidermidis in preterm neonates. J Perinatol 38, 1344–1352 (2018). https://doi.org/10.1038/s41372-018-0183-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-018-0183-y

This article is cited by

Search

Advanced search

Quick links