Pediatr Gastroenterol Hepatol Nutr.  2012 Mar;15(1):29-37.

Monitoring of Clostridium difficile Colonization in Preterm Infants in Neonatal Intensive Care Units

Affiliations
  • 1Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea. jkseo@snu.ac.kr
  • 2Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.
  • 3Seoul Metropolitan Government, Seoul National University Boramae Medical Center, Seoul, Korea.
  • 4Department of Pediatrics, Kwandong Univesity College of Medicine, Incheon, Korea.

Abstract

PURPOSE
To examine the prevalence of Clostridium difficile (C. difficile) colonization (CDC) and potential neonatal determinants of CDC in hospitalized preterm infants.
METHODS
Fecal samples were serially collected within 72 h after birth and at 1, 2, and 4-6 weeks of age from preterm infants in the neonatal intensive care units (NICUs) of two different university hospitals. Total bacterial DNA was extracted from each fecal sample from 49 infants, and polymerase chain reaction (PCR) was performed with primers for the 16S gene of C. difficile and the toxin A and toxin B genes. The correlation between the results of C. difficile PCR assays and the clinical characteristics of the infants was analyzed.
RESULTS
The prevalence rates of CDC were 34.7, 37.2, 41.3, and 53.1% within 72 h after birth and at 1, 2, and 4-6 weeks of age, respectively. The toxin positivity rate was significantly higher in the infants with persistent CDC than in those with transient CDC (8/12 [66.7%] vs. 6/25 [24.5%] (p=0.001). Among the various neonatal factors, only the feeding method during the first week after birth was significantly associated with persistent CDC. Exclusive breast-milk feeding (EBMF) significantly decreased the risk of persistent CDC compared to formula or mixed feeding (adjusted odds ratio: 0.133, 95% confidence interval: 0.02-0.898, p=0.038).
CONCLUSION
The prevalence of CDC increased with the duration of hospitalization in preterm infants in the NICU. EBMF during the first week after birth in hospitalized preterm infants may protect against persistent CDC.

Keyword

Clostridium difficile; Preterm infants; Breast-milk feeding; NICU

MeSH Terms

Centers for Disease Control and Prevention (U.S.)
Clostridium
Clostridium difficile
Colon
DNA, Bacterial
Feeding Methods
Hospitalization
Hospitals, University
Humans
Infant
Infant, Newborn
Infant, Premature
Intensive Care Units, Neonatal
Intensive Care, Neonatal
Parturition
Polymerase Chain Reaction
Prevalence
DNA, Bacterial

Reference

1. Kim BC, Yang HR, Jeong SJ, Lee KH, Kim JE, Ko JS, et al. Clostridium difficile colitis in childhood: associated antibiotics. Korean J Pediatr Gastroenterol Nutr. 2002. 5:143–149.
Article
2. Bolton RP, Tait SK, Dear PR, Losowsky MS. Asymptomatic neonatal colonisation by Clostridium difficile. Arch Dis Child. 1984. 59:466–472.
3. Enoch DA, Butler MJ, Pai S, Aliyu SH, Karas JA. Clostridium difficile in children: colonisation and disease. J Infect. 2011. 63:105–113.
4. Genta VM, Gilligan PH, McCarthy LR. Clostridium difficile peritonitis in a neonate. A case report. Arch Pathol Lab Med. 1984. 108:82–83.
5. Han VK, Sayed H, Chance GW, Brabyn DG, Shaheed WA. An outbreak of Clostridium difficile necrotizing enterocolitis: a case for oral vancomycin therapy? Pediatrics. 1983. 71:935–941.
Article
6. Cardines R, Luzzi I, Menichella G, Virgili Q, Mastrantonio P. Clostridium difficile in preterm neonates. Microbiologica. 1988. 11:259–261.
7. Enad D, Meishlich D, Brodsky NL, Hurt H. Is Clostridium difficile a pathogen in the newborn intensive csre unit? A prospective evalauation. J Perinatol. 1997. 17:355–359.
8. McFarland LV. Update on the changing epidemiology of Clostridium difficile-associated disease. Nat Clin Pract Gastroenterol Hepatol. 2008. 5:40–48.
Article
9. Hecker MT, Riggs MM, Hoyen CK, Lancioni C, Donskey CJ. Recurrent infection with epidemic Clostridium difficile in a peripartum woman whose infant was asymptomatically colonized with the same strain. Clin Infect Dis. 2008. 46:956–957.
Article
10. Rousseau C, Lemee L, Le Monnier A, Poilane I, Pons J, Collignon A. Prevalence and diversity of Clostidium difficile strains in infants. J Med Microbiol. 2011. 60:1112–1118.
11. Kalliomaki M, Collado MC, Salminen S, Isolauri E. Early differences in fecal microbiota composition in children may predict overweight. Am J Clin Nutr. 2008. 87:534–538.
Article
12. Fanaro S, Chierici R, Guerrini P, Vigi V. Intestinal microflora in early infancy:composition and development. Acta Paediatr Suppl. 2003. 91:48–55.
13. Penders J, Thijs C, Vink C, Stelma F, Smijders B, Kummeling I, et al. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics. 2006. 118:511–521.
Article
14. Cooperstock M, Riegle L, Woodruff CW, Onderdonk A. Influence of age, sex, and diet on asymptomatic colonization of infants with Clostridium difficile. J Clin Microbiol. 1983. 17:830–833.
Article
15. Gewolb IH, Schwalbe RS, Taciak VL, Harrison TS, Panigrahi P. Stool microflora in extremely low birthweight infants. Arch Dis Child Fetal Neonatal Ed. 1999. 80:F167–F173.
Article
16. Schwiertz A, Gruhl B, Lobnitz M, Michel P, Radke M, Blaut M. Development of the intestinal bacterial composition in hospitalized preterm infants in comparison with breast-fed, full-term infants. Pediatr Res. 2003. 54:393–399.
Article
17. Mshvildadze M, Neu J, Shuster J, Theriaque D, Li N, Mai V. Intestinal microbial ecology in premature infants assessed with non-culture-based techniques. J Pediatr. 2010. 156:20–25.
Article
18. Ferraris L, Butel MJ, Campeotto F, Vodovar M, Roze JC, Aires J. Clostridia in premature neonates'gut: incidence, antibiotic susceptibility, and perinatal determinants. PLoS One. 2012. 7:e30594.
19. el-Mohandes AE, Keiser JF, Refat M, Jackson BJ. Prevalence and toxigenicity of Clostridium difficile isolates in fecal microflora of preterm infants in the intensive care nursery. Biol Neonate. 1993. 63:225–229.
Article
20. Chang JY, Shin SM, Chun J, Lee JH, Seo JK. Pyrosequencing-based molecular monitoring of the intestinal bacterial colonization in preterm infants. J Pediatr Gastroenterol Nutr. 2011. 53:512–519.
Article
21. Li F, Hullar MA, Lampe JW. Optimization of terminal restriction fragment polymorphism (TRFLP) analysis of human gut microbiota. J Microbiol Methods. 2007. 68:303–311.
Article
22. Rinttila T, Kassinen A, Malinen E, Krogius L, Palva A. Development of an extensive set of 16S rDNA-targeted primers for quantification of pathogenic and indigenous bacteria in faecal samples by real-time PCR. J Appl Microbiol. 2004. 97:1166–1177.
Article
23. Kato H, Kato N, Watanabe K, Iwai N, Nakamura H, Yamamoto T, et al. Identification of toxin A-negative, toxin B-positive Clostridium difficile by PCR. J Clin Microbiol. 1998. 36:2178–2182.
Article
24. Shin BM, Yoo SJ, Oh HJ. Comparison of two enzyme immunoassay for detection of Clostridium difficile toxin A and toxin B. Korean J Lab Med. 2009. 29:122–126.
Article
25. Samie A, Obi CL, Franasiak J, Archbald-Pannone L, Bessong PO, Alcantara-Warren C. PCR detection of Clostridium difficile triose phosphate isomerase (tpi), toxin A(tcdA), toxinB (tcdB), binary toxin (cdtA, cdtB), and tcdC genes in Vhembe district, South Africa. Am J Trop Med Hyg. 2008. 78:577–585.
Article
26. Al-Jumaili IJ, Shibley M, Lishman AH, Record CO. Incidence and origin of Clostridium difficile in neonates. J Clin Microbiol. 1984. 19:77–78.
Article
27. Blakey JL, Lubitz L, Barnes GL, Bishop RF, Campbell NT, Gillam GL. Development of gut colonisation in pre-term neonates. J Med Microbiol. 1982. 15:519–529.
Article
28. Benno Y, Sawada K, Mitsuoka T. The intestinal microflora of infants: composition of fecal flora in breast-fed and bottle-fed infants. Microbiol Immunol. 1984. 28:975–986.
Article
29. Penders J, Vink C, Driessen C, London N, Thijs C, Stobberingh EE. Quantification of Bifidobacterium spp., Escherichia coli and Clostridium difficile in faecal samples of breast-fed and formula-fed infants by real-time PCR. FEMS Microbiol Lett. 2005. 243:141–147.
Article
30. Péchiné S, Janoir C, Boureau H, Gleizes A, Tsapis N, Hoys S, et al. Diminished intestinal colonization by Clostridium difficile and immune response in mice after mucosal immunization with surface proteins of Clostridium difficile. Vaccine. 2007. 25:3946–3954.
Article
31. Bourlioux P, Koletzko B, Guarner F, Braesco V. The intestine and its microflora are partners for the protection of the host: report on the Danone Symposium "The Intelligent Intestine," held in Paris, June 14, 2002. Am J Clin Nutr. 2003. 78:675–683.
Article
32. Magne F, Abely M, Boyer F, Morville P, Pochart P, Suau A. Low species diversity and high interindividual variability in faeces of preterm infants as revealed by sequences of 16S rRNA genes and PCR-temporal temperature gradient gel electrophoresis profiles. FEMS Microbiol Ecol. 2006. 57:128–138.
Article
33. Westerbeek EA, van den Berg A, Lafeber HN, Knol J, Fetter WP, van Elburg RM. The intestinal bacterial colonisation in preterm infants: a review of the literature. Clin Nutr. 2006. 25:361–368.
Article
34. Butel MJ, Roland N, Hibert A, Popot F, Favre A, Tessedre A, et al. Clostridial pathogenicity in experimental necrotising enterocolitis in gnotobiotic quails and protective role of bifidobacteria. Journal of Medical Microbiology. 1998. 47:391–399.
Article
35. Rousseau C, Levenez F, Fouqueray C, Dore J, Collignon A, Lepage P. Clostridium difficile Colonization in Early Infancy Is Accompanied by Changes in Intestinal Microbiota Composition. Journal of Clinical Microbiology. 2011. 49:858–865.
Article
36. Sjögren YM, Tomicic S, Lundberg A, Bbottcher M, Bjorksten B, Sverremark-Ekstrom E, et al. Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses. Clin Exp Allergy. 2009. 39:1842–1851.
Article
37. Morelli L. Postnatal development of intestinal microflora as influenced by infant nutrition. J Nutr. 2008. 138:1791S–1795S.
Article
38. Collignon A, Ticchi L, Depitre C, Gaudelus J, Delmee M, Corthier G. Heterogeneity of Clostridium-Difficile Isolates from Infants. Eur J Pediatr. 1993. 152:319–322.
Article
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