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.

  • Review Article
  • Published:

Neonatal sepsis and the skin microbiome

Journal of Perinatology volume 42, pages 1429–1433 (2022)Cite this article

Subjects

Abstract

Neonatal sepsis is a major cause of morbidity and mortality in preterm infants. Preterm and very low birth weight infants are particularly susceptible to sepsis due to their immature skin barrier, naive immune system, exposure to broad-spectrum antibiotics, and insertion of medical devices. Neonatal intestinal dysbiosis has been linked to neonatal sepsis; however, the cutaneous microbiome likely plays a role as well, as common sepsis pathogens also dominate the skin flora. This review summarizes our current understanding of the infant skin microbiome and common causative pathogens in neonatal sepsis, as well as the relationship between the two. A better understanding of the role of the skin microbiome in the pathogenesis of neonatal sepsis may guide future prophylaxis and treatment.

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

Similar content being viewed by others

References

  1. Gbd 2016 disease and injury incidence and prevalence collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: A systematic analysis for the global burden of disease study 2016. Lancet. 2017;390:1211–59.

    Article  Google Scholar 

  2. Fleischmann C, Reichert F, Cassini A, Horner R, Harder T, Markwart R, et al. Global incidence and mortality of neonatal sepsis: A systematic review and meta-analysis. Arch Dis Child. 2021;106:745–52.

  3. Shane AL, Sanchez PJ, Stoll BJ. Neonatal sepsis. Lancet. 2017;390:1770–80.

    Article  PubMed  Google Scholar 

  4. Madan JC, Salari RC, Saxena D, Davidson L, O’Toole GA, Moore JH, et al. Gut microbial colonisation in premature neonates predicts neonatal sepsis. Arch Dis Child Fetal Neonatal Ed. 2012;97:456–62.

    Article  Google Scholar 

  5. Masi AC, Stewart CJ. The role of the preterm intestinal microbiome in sepsis and necrotising enterocolitis. Early Hum Dev. 2019;138:104854.

    Article  PubMed  Google Scholar 

  6. 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  PubMed  PubMed Central  Google Scholar 

  7. 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 

  8. Schoch JJ, Monir RL, Satcher KG, Harris J, Triplett E, Neu J. The infantile cutaneous microbiome: A review. Pediatr Dermatol. 2019;36:574–80.

    Article  PubMed  Google Scholar 

  9. Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, et al. Late-onset sepsis in very low birth weight neonates: The experience of the nichd neonatal research network. Pediatrics. 2002;110:285–91.

    Article  PubMed  Google Scholar 

  10. Younge NE, Araujo-Perez F, Brandon D, Seed PC. Early-life skin microbiota in hospitalized preterm and full-term infants. Microbiome. 2018;6:98.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Bolognia JL, Schaffer JV, Lorenzo C. Dermatology. 4 ed. Elsevier: China, 2018.

  12. Hardman MJ, Moore L, Ferguson MW, Byrne C. Barrier formation in the human fetus is patterned. J Invest Dermatol. 1999;113:1106–13.

    Article  CAS  PubMed  Google Scholar 

  13. Narendran V, Visscher MO, Abril I, Hendrix SW, Hoath SB. Biomarkers of epidermal innate immunity in premature and full-term infants. Pediatr Res. 2010;67:382–6.

    Article  CAS  PubMed  Google Scholar 

  14. Nishijima K, Yoneda M, Hirai T, Takakuwa K, Enomoto T. Biology of the vernix caseosa: A review. J Obstet Gynaecol Res. 2019;45:2145–9.

    Article  PubMed  Google Scholar 

  15. Chu DM, Ma J, Prince AL, Antony KM, Seferovic MD, Aagaard KM. Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery. Nat Med. 2017;23:314–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci USA. 2010;107:11971–5.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Paul AA, Hoffman KL, Hagan JL, Sampath V, Petrosino JF, Pammi M. Fungal cutaneous microbiome and host determinants in preterm and term neonates. Pediatr Res. 2020;88:225–33.

    Article  PubMed  Google Scholar 

  18. Capone KA, Dowd SE, Stamatas GN, Nikolovski J. Diversity of the human skin microbiome early in life. J Invest Dermatol. 2011;131:2026–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Dominguez-Bello MG, De Jesus-Laboy KM, Shen N, Cox LM, Amir A, Gonzalez A, et al. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nat Med. 2016;22:250–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Pammi M, O’Brien JL, Ajami NJ, Wong MC, Versalovic J, Petrosino JF. Development of the cutaneous microbiome in the preterm infant: A prospective longitudinal study. PLoS One. 2017;12:e0176669.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Cogen AL, Nizet V, Gallo RL. Skin microbiota: A source of disease or defence? Br J Dermatol. 2008;158:442–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Costello EK, Carlisle EM, Bik EM, Morowitz MJ, Relman DA. Microbiome assembly across multiple body sites in low-birthweight infants. mBio. 2013;4:e00782–13.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Stoll BJ, Puopolo KM, Hansen NI, Sanchez PJ, Bell EF, Carlo WA, et al. Early-onset neonatal sepsis 2015 to 2017, the rise of escherichia coli, and the need for novel prevention strategies. JAMA Pediatr. 2020;174:e200593.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Giannoni E, Agyeman PKA, Stocker M, Posfay-Barbe KM, Heininger U, Spycher BD, et al. Neonatal sepsis of early onset, and hospital-acquired and community-acquired late onset: A prospective population-based cohort study. J Pediatr. 2018;201:106–14.

    Article  PubMed  Google Scholar 

  25. Köstlin-Gille N, Härtel C, Haug C, Göpel W, Zemlin M, Müller A, et al. Epidemiology of early and late onset neonatal sepsis in very low birthweight infants: Data from the german neonatal network. Pediatr Infect Dis J. 2021;40:255–9.

    Article  PubMed  Google Scholar 

  26. Dong Y, Glaser K, Speer CP. Late-onset sepsis caused by gram-negative bacteria in very low birth weight infants: A systematic review. Expert Rev Anti Infect Ther. 2019;17:177–88.

    Article  CAS  PubMed  Google Scholar 

  27. Greenberg RG, Kandefer S, Do BT, Smith PB, Stoll BJ, Bell EF, et al. Late-onset sepsis in extremely premature infants: 2000-2011. Pediatr Infect Dis J. 2017;36:774–9.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Golińska E, Strus M, Tomusiak-Plebanek A, Więcek G, Kozień Ł, Lauterbach R, et al. Coagulase-negative staphylococci contained in gut microbiota as a primary source of sepsis in low- and very low birth weight neonates. J Clin Med. 2020;9:2517.

    Article  PubMed Central  Google Scholar 

  29. Bizzarro MJ, Shabanova V, Baltimore RS, Dembry LM, Ehrenkranz RA, Gallagher PG. Neonatal sepsis 2004-2013: The rise and fall of coagulase-negative staphylococci. J Pediatr. 2015;166:1193–9.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Healy CM, Baker CJ, Palazzi DL, Campbell JR, Edwards MS. Distinguishing true coagulase-negative staphylococcus infections from contaminants in the neonatal intensive care unit. J Perinatol. 2013;33:52–8.

    Article  CAS  PubMed  Google Scholar 

  31. Bradford R, Manan RA, Garland SM, Daley AJ, Deighton MA. Coagulase-negative staphylococci in low birth weight infants: Environmental factors affecting biofilm production in staphylococcus epidermidis. Curr Microbiol. 2011;62:850–4.

    Article  CAS  PubMed  Google Scholar 

  32. Pammi M, Liang R, Hicks J, Mistretta TA, Versalovic J. Biofilm extracellular DNA enhances mixed species biofilms of staphylococcus epidermidis and candida albicans. BMC Microbiol. 2013;13:257.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Salava A, Aho V, Lybeck E, Pereira P, Paulin L, Nupponen I, et al. Loss of cutaneous microbial diversity during first 3 weeks of life in very low birthweight infants. Exp Dermatol. 2017;26:861–7.

    Article  CAS  PubMed  Google Scholar 

  34. Soeorg H, Metsvaht HK, Keränen EE, Eelmäe I, Merila M, Ilmoja ML, et al. Genetic relatedness of staphylococcus haemolyticus in gut and skin of preterm neonates and breast milk of their mothers. Pediatr Infect Dis J. 2019;38:308–13.

    Article  PubMed  Google Scholar 

  35. Nagata R, Nagano H, Ogishima D, Nakamura Y, Hiruma M, Sugita T. Transmission of the major skin microbiota, malassezia, from mother to neonate. Pediatr Int. 2012;54:350–5.

    Article  CAS  PubMed  Google Scholar 

  36. Hannigan GD, Meisel JS, Tyldsley AS, Zheng Q, Hodkinson BP, SanMiguel AJ, et al. The human skin double-stranded DNA virome: Topographical and temporal diversity, genetic enrichment, and dynamic associations with the host microbiome. mBio. 2015;6:e01578–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hannigan GD, Zheng Q, Meisel JS, Minot SS, Bushman FD, Grice EA. Evolutionary and functional implications of hypervariable loci within the skin virome. PeerJ. 2017;5:e2959

    Article  PubMed  PubMed Central  Google Scholar 

  38. Glaser MA, Hughes LM, Jnah A, Newberry D. Neonatal sepsis: A review of pathophysiology and current management strategies. Adv Neonatal Care. 2021;21:49–60.

    Article  PubMed  Google Scholar 

  39. Kaufman DA, Coggins SA, Zanelli SA, Weitkamp JH. Congenital cutaneous candidiasis: Prompt systemic treatment is associated with improved outcomes in neonates. Clin Infect Dis. 2017;64:1387–95.

    Article  PubMed  Google Scholar 

  40. Tsai MH, Hsu JF, Chu SM, Lien R, Huang HR, Chiang MC, et al. Incidence, clinical characteristics and risk factors for adverse outcome in neonates with late-onset sepsis. Pediatr Infect Dis J. 2014;33:e7–13.

    Article  PubMed  Google Scholar 

  41. Caviness AC, Demmler GJ, Almendarez Y, Selwyn BJ. The prevalence of neonatal herpes simplex virus infection compared with serious bacterial illness in hospitalized neonates. J Pediatr. 2008;153:164–9.

    Article  PubMed  Google Scholar 

  42. Chuang YY, Huang YC. Enteroviral infection in neonates. J Microbiol Immunol Infect. 2019;52:851–7.

    Article  CAS  PubMed  Google Scholar 

  43. Kimberlin DW. Herpes simplex virus infections in neonates and early childhood. Semin Pediatr Infect Dis. 2005;16:271–81.

    Article  PubMed  Google Scholar 

  44. Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, Corey L. Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant. Jama. 2003;289:203–9.

    Article  PubMed  Google Scholar 

  45. Lin TY, Kao HT, Hsieh SH, Huang YC, Chiu CH, Chou YH, et al. Neonatal enterovirus infections: Emphasis on risk factors of severe and fatal infections. Pediatr Infect Dis J. 2003;22:889–94.

    Article  PubMed  Google Scholar 

  46. Scharschmidt TC. Establishing tolerance to commensal skin bacteria: Timing is everything. Dermatol Clin. 2017;35:1–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Pammi M, Suresh G. Enteral lactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev. 2020;3:CD007137.

    PubMed  Google Scholar 

  48. Heng X, Jiang Y, Chu W. Influence of fluconazole administration on gut microbiome, intestinal barrier, and immune response in mice. Antimicrob Agents Chemother. 2021;65:e02552–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Geuking MB, Cahenzli J, Lawson MA, Ng DC, Slack E, Hapfelmeier S, et al. Intestinal bacterial colonization induces mutualistic regulatory t cell responses. Immunity. 2011;34:794–806.

    Article  CAS  PubMed  Google Scholar 

  50. O’Neill CA, Monteleone G, McLaughlin JT, Paus R. The gut-skin axis in health and disease: A paradigm with therapeutic implications. Bioessays. 2016;38:1167–76.

    Article  PubMed  Google Scholar 

  51. França K. Topical probiotics in dermatological therapy and skincare: A concise review. Dermatol Ther (Heidelb). 2021;11:71–7.

    Article  Google Scholar 

  52. Yu Y, Dunaway S, Champer J, Kim J, Alikhan A. Changing our microbiome: Probiotics in dermatology. Br J Dermatol. 2020;182:39–46.

    Article  CAS  PubMed  Google Scholar 

  53. Hartz LE, Bradshaw W, Brandon DH. Potential nicu environmental influences on the neonate’s microbiome: A systematic review. Adv Neonatal Care. 2015;15:324–35.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Hourigan SK, Subramanian P, Hasan NA, Ta A, Klein E, Chettout N, et al. Comparison of infant gut and skin microbiota, resistome and virulome between neonatal intensive care unit (nicu) environments. Front Microbiol. 2018;9:1361.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Kusari A, Han AM, Virgen CA, Matiz C, Rasmussen M, Friedlander SF, et al. Evidence-based skin care in preterm infants. Pediatr Dermatol. 2019;36:16–23.

    Article  PubMed  Google Scholar 

  56. Lund C, Kuller J, Durand DJ. Baby’s first bath: Changes in skin barrier function after bathing full-term newborns with water vs liquid baby cleanser. Pediatr Dermatol. 2020;37:115–9.

    Article  PubMed  Google Scholar 

  57. Chapman AK, Aucott SW, Milstone AM. Safety of chlorhexidine gluconate used for skin antisepsis in the preterm infant. J Perinatol. 2012;32:4–9.

    Article  CAS  PubMed  Google Scholar 

  58. Johnson J, Bracken R, Tamma PD, Aucott SW, Bearer C, Milstone AM. Trends in chlorhexidine use in us neonatal intensive care units: Results from a follow-up national survey. Infect Control Hosp Epidemiol. 2016;37:1116–8.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Johnson J, Suwantarat N, Colantuoni E, Ross TL, Aucott SW, Carroll KC, et al. The impact of chlorhexidine gluconate bathing on skin bacterial burden of neonates admitted to the neonatal intensive care unit. J Perinatol. 2019;39:63–71.

    Article  CAS  PubMed  Google Scholar 

  60. Dramowski A, Pillay S, Bekker A, Abrahams I, Cotton MF, Coffin SE, et al. Impact of 1% chlorhexidine gluconate bathing and emollient application on bacterial pathogen colonization dynamics in hospitalized preterm neonates - a pilot clinical trial. EClinicalMedicine. 2021;37:100946.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Darmstadt GL, Badrawi N, Law PA, Ahmed S, Bashir M, Iskander I, et al. Topically applied sunflower seed oil prevents invasive bacterial infections in preterm infants in egypt: A randomized, controlled clinical trial. Pediatr Infect Dis J. 2004;23:719–25.

    Article  PubMed  Google Scholar 

  62. Summers A, Visscher MO, Khatry SK, Sherchand JB, LeClerq SC, Katz J, et al. Impact of sunflower seed oil versus mustard seed oil on skin barrier function in newborns: A community-based, cluster-randomized trial. BMC Pediatr. 2019;19:512.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Pupala SS, Rao S, Strunk T, Patole S. Topical application of coconut oil to the skin of preterm infants: A systematic review. Eur J Pediatr. 2019;178:1317–24.

    Article  PubMed  Google Scholar 

  64. Campbell JR, Zaccaria E, Baker CJ. Systemic candidiasis in extremely low birth weight infants receiving topical petrolatum ointment for skin care: A case-control study. Pediatrics. 2000;105:1041–5.

    Article  CAS  PubMed  Google Scholar 

  65. AlKharfy T, Ba-Abbad R, Hadi A, AlFaleh K. Use of topical petroleum jelly for prevention of sepsis in very low-birthweight infants: A prospective, randomised controlled trial. Paediatr Int Child Health. 2014;34:194–7.

    Article  PubMed  Google Scholar 

  66. Edwards WH, Conner JM, Soll RF. The effect of prophylactic ointment therapy on nosocomial sepsis rates and skin integrity in infants with birth weights of 501 to 1000 g. Pediatrics. 2004;113:1195–203.

    Article  PubMed  Google Scholar 

  67. Cleminson J, McGuire W. Topical emollient for preventing infection in preterm infants. Cochrane Database Syst Rev. 2021;5:001150.

    Google Scholar 

  68. Erdemir A, Kahramaner Z, Yuksel Y, Cosar H, Turkoglu E, Sutcuoglu S, et al. The effect of topical ointment on neonatal sepsis in preterm infants. J Matern Fetal Neonatal Med. 2015;28:33–6.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Dermatology, University of Florida College of Medicine, Gainesville, USA

    Iris S. Harrison, Reesa L. Monir & Jennifer J. Schoch

  2. Departments of Pediatrics, University of Florida College of Medicine, Gainesville, USA

    Josef Neu & Jennifer J. Schoch

Authors
  1. Iris S. Harrison
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Reesa L. Monir
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Josef Neu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jennifer J. Schoch
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

IH, RM, JN, and JS: Conceived and/or designed the work that led to the submission, acquired data, and/or played an important role in interpreting the results, drafted or revised the manuscript, approved the final version and, agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Jennifer J. Schoch.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Harrison, I.S., Monir, R.L., Neu, J. et al. Neonatal sepsis and the skin microbiome. J Perinatol 42, 1429–1433 (2022). https://doi.org/10.1038/s41372-022-01451-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-022-01451-0

This article is cited by

Search

Advanced search

Quick links