Colonization pattern of coagulase-negative staphylococci in preterm neonates and the relation to bacteremia

  • M. BjörkqvistEmail author
  • M. Liljedahl
  • J. Zimmermann
  • J. Schollin
  • B. Söderquist


Coagulase-negative staphylococci (CoNS) are the major cause of sepsis in extreme preterm (EPT) newborns, but data on the CoNS colonization in EPT newborns prior to invasive infection are limited. Our aim was to describe the early establishment of the CoNS microflora in EPT newborns and to compare the colonization pattern in neonates with and without positive CoNS blood cultures. From a cohort of 46 EPT neonates, newborns with positive CoNS blood culture were identified (n = 10) and compared with matched controls. Samples for bacterial cultures were obtained repetitively from nares, perineum, and umbilicus. All CoNS isolates were characterized using the PhenePlate system for biochemical fingerprinting. Persistent CoNS strains were found on day 2–3 after delivery in 7/20 newborns, and there was a tendency for earlier colonization in nares than in the perineum or umbilicus. The CoNS blood strains were prevalent in superficial sites prior to positive blood culture (11/14 blood strains), but no single invasive pathway was identified. Most CoNS blood strains (9/14) persisted on superficial sites after antibiotic treatment. We hypothesize that the invasive pathways in neonatal CoNS sepsis are complex and that the colonization of mucosal membranes and umbilical catheters might be of equal importance.


Positive Blood Culture Colonization Pattern PFGE Pattern Preterm Newborn Blood Isolate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Coagulase-negative staphylococci


Extreme preterm


Pulsed-field gel electrophoresis


PhenePlate system


Minimum inhibitory concentration


Unweighted pair grouping by mathematical averaging


Diversity index



The authors wish to thank Bengt Hellmark for the rpoB sequencing. The study was supported by grants from the research committee of Örebro county.


  1. 1.
    Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, Lemons JA, Donovan EF, Stark AR, Tyson JE, Oh W, Bauer CR, Korones SB, Shankaran S, Laptook AR, Stevenson DK, Papile LA, Poole WK (2002) Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 110:285–291CrossRefPubMedGoogle Scholar
  2. 2.
    Fanaroff AA, Stoll BJ, Wright LL, Carlo WA, Ehrenkranz RA, Stark AR, Bauer CR, Donovan EF, Korones SB, Laptook AR, Lemons JA, Oh W, Papile LA, Shankaran S, Stevenson DK, Tyson JE, Poole WK; NICHD Neonatal Research Network (2007) Trends in neonatal morbidity and mortality for very low birthweight infants. Am J Obstet Gynecol 196:147.e1–147.e8CrossRefGoogle Scholar
  3. 3.
    Liljedahl M, Bodin L, Schollin J (2004) Coagulase-negative staphylococcal sepsis as a predictor of bronchopulmonary dysplasia. Acta Paediatr 93:211–215CrossRefPubMedGoogle Scholar
  4. 4.
    Speer CP (2003) Inflammation and bronchopulmonary dysplasia. Semin Neonatol 8:29–38CrossRefPubMedGoogle Scholar
  5. 5.
    Wilson-Costello D, Borawski E, Friedman H, Redline R, Fanaroff AA, Hack M (1998) Perinatal correlates of cerebral palsy and other neurologic impairment among very low birth weight children. Pediatrics 102:315–322CrossRefPubMedGoogle Scholar
  6. 6.
    Isaacs D (2003) A ten year, multicentre study of coagulase negative staphylococcal infections in Australasian neonatal units. Arch Dis Child Fetal Neonatal Ed 88:F89–F93CrossRefPubMedGoogle Scholar
  7. 7.
    Klingenberg C, Rønnestad A, Anderson AS, Abrahamsen TG, Zorman J, Villaruz A, Flægstad T, Otto M, Ericson Sollid JE (2007) Persistent strains of coagulase-negative staphylococci in a neonatal intensive care unit: virulence factors and invasiveness. Clin Microbiol Infect 13:1100–1111CrossRefPubMedGoogle Scholar
  8. 8.
    Villari P, Sarnataro C, Iacuzio L (2000) Molecular epidemiology of Staphylococcus epidermidis in a neonatal intensive care unit over a three-year period. J Clin Microbiol 38:1740–1746PubMedGoogle Scholar
  9. 9.
    Björkqvist M, Söderquist B, Törnqvist E, Sjöberg L, Fredlund H, Kühn I, Colque-Navarro P, Schollin J (2002) Phenotypic and genotypic characterisation of blood isolates of coagulase-negative staphylococci in the newborn. APMIS 110:332–339CrossRefPubMedGoogle Scholar
  10. 10.
    Vermont CL, Hartwig NG, Fleer A, de Man P, Verbrugh H, van den Anker J, de Groot R, van Belkum A (1998) Persistence of clones of coagulase-negative staphylococci among premature neonates in neonatal intensive care units: two-center study of bacterial genotyping and patient risk factors. J Clin Microbiol 36:2485–2490PubMedGoogle Scholar
  11. 11.
    Center KJ, Reboli AC, Hubler R, Rodgers GL, Long SS (2003) Decreased vancomycin susceptibility of coagulase-negative staphylococci in a neonatal intensive care unit: evidence of spread of Staphylococcus warneri. J Clin Microbiol 41:4660–4665CrossRefPubMedGoogle Scholar
  12. 12.
    Keyworth N, Millar MR, Holland KT (1992) Development of cutaneous microflora in premature neonates. Arch Dis Child 67:797–801CrossRefPubMedGoogle Scholar
  13. 13.
    Eastick K, Leeming JP, Bennett D, Millar MR (1996) Reservoirs of coagulase negative staphylococci in preterm infants. Arch Dis Child Fetal Neonatal Ed 74:F99–F104CrossRefPubMedGoogle Scholar
  14. 14.
    D’Angio CT, McGowan KL, Baumgart S, St Geme J, Harris MC (1989) Surface colonization with coagulase-negative staphylococci in premature neonates. J Pediatr 114:1029–1034CrossRefPubMedGoogle Scholar
  15. 15.
    Sloos JH, Dijkshoorn L, Vogel L, van Boven CPA (2000) Performance of phenotypic and genotypic methods to determine the clinical relevance of serial blood isolates of staphylococcus epidermidis in patients with septicemia. J Clin Microbiol 38:2488–2493PubMedGoogle Scholar
  16. 16.
    Spare MK, Tebbs SE, Lang S, Lambert PA, Worthington T, Lipkin GW, Elliott TS (2003) Genotypic and phenotypic properties of coagulase-negative staphylococci causing dialysis catheter-related sepsis. J Hosp Infect 54:272–278CrossRefPubMedGoogle Scholar
  17. 17.
    Nilsdotter-Augustinsson Å, Koskela A, Öhman L, Söderquist B (2007) Characterization of coagulase-negative staphylococci isolated from patients with infected hip prostheses: use of phenotypic and genotypic analyses, including tests for the presence of the ica operon. Eur J Clin Microbiol Infect Dis 26:255–265CrossRefPubMedGoogle Scholar
  18. 18.
    Hellmark B, Söderquist B, Unemo M (2009) Simultaneous species identification and detection of rifampicin resistance in staphylococci by sequencing of the rpoB gene. Eur J Clin Microbiol Infect Dis 28:183–190CrossRefPubMedGoogle Scholar
  19. 19.
    Jung K, Brauner A, Kühn I, Ransjö U, Hylander B, Flock JI, Möllby R (1995) Typing of coagulase-negative staphylococci from peritonitis in CAPD-patients by the PhP-CS system and REA. APMIS 103:679–685CrossRefPubMedGoogle Scholar
  20. 20.
    Tenover FC, Arbeit RD, Goering RV, Mickelsen PA, Murray BE, Persing DH, Swaminathan B (1995) Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol 33:2233–2239PubMedGoogle Scholar
  21. 21.
    Hall SL, Riddell SW, Barnes WG, Meng L, Hall RT (1990) Evaluation of coagulase-negative staphylococcal isolates from serial nasopharyngeal cultures of premature infants. Diagn Microbiol Infect Dis 13:17–23CrossRefPubMedGoogle Scholar
  22. 22.
    Costa SF, Miceli MH, Anaissie EJ (2004) Mucosa or skin as source of coagulase-negative staphylococcal bacteraemia? Lancet Infect Dis 4:278–286CrossRefPubMedGoogle Scholar
  23. 23.
    Vuong C, Otto M (2002) Staphylococcus epidermidis infections. Microbes Infect 4:481–489CrossRefPubMedGoogle Scholar
  24. 24.
    von Eiff C, Peters G, Heilmann C (2002) Pathogenesis of infections due to coagulase-negative staphylococci. Lancet Infect Dis 2:677–685CrossRefGoogle Scholar
  25. 25.
    de Silva GD, Kantzanou M, Justice A, Massey RC, Wilkinson AR, Day NP, Peacock SJ (2002) The ica operon and biofilm production in coagulase-negative Staphylococci associated with carriage and disease in a neonatal intensive care unit. J Clin Microbiol 40:382–388CrossRefPubMedGoogle Scholar
  26. 26.
    Bradford R, Abdul Manan R, Daley AJ, Pearce C, Ramalingam A, D’Mello D, Mueller Y, Uahwatanasakul W, Qu Y, Grando D, Garland S, Deighton M (2006) Coagulase-negative staphylococci in very-low-birth-weight infants: inability of genetic markers to distinguish invasive strains from blood culture contaminants. Eur J Clin Microbiol Infect Dis 25:283–290CrossRefPubMedGoogle Scholar
  27. 27.
    Tee WSN, Soh SY, Lin R, Loo LH (2003) Staphylococcus lugdunensis carrying the mecA gene causes catheter-associated bloodstream infection in premature neonate. J Clin Microbiol 41:519–520CrossRefPubMedGoogle Scholar
  28. 28.
    Frank KL, del Pozo JL, Patel R (2008) From clinical microbiology to infection pathogenesis: how daring to be different works for Staphylococcus lugdunensis. Clin Microbiol Rev 21:111–133CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • M. Björkqvist
    • 1
    Email author
  • M. Liljedahl
    • 1
  • J. Zimmermann
    • 2
  • J. Schollin
    • 1
  • B. Söderquist
    • 2
  1. 1.Department of PediatricsÖrebro University HospitalÖrebroSweden
  2. 2.Department of Clinical MicrobiologyÖrebro University HospitalÖrebroSweden

Personalised recommendations