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Am J Perinatol 2015; 32(07): 675-682
DOI: 10.1055/s-0034-1393936
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Risk Factors and Outcomes of Late-Onset Bacterial Sepsis in Preterm Neonates Born at < 32 Weeks' Gestation

Jyotsna Shah
1   Department of Pediatrics, Mount Sinai Hospital, University of Toronto, Toronto, Canada
,
Ann L. Jefferies
1   Department of Pediatrics, Mount Sinai Hospital, University of Toronto, Toronto, Canada
,
Eugene W. Yoon
2   Maternal-Infant Care Research Centre, Mount Sinai Hospital, Toronto, Canada
,
Shoo K. Lee
1   Department of Pediatrics, Mount Sinai Hospital, University of Toronto, Toronto, Canada
2   Maternal-Infant Care Research Centre, Mount Sinai Hospital, Toronto, Canada
,
Prakesh S. Shah
1   Department of Pediatrics, Mount Sinai Hospital, University of Toronto, Toronto, Canada
2   Maternal-Infant Care Research Centre, Mount Sinai Hospital, Toronto, Canada
,
on behalf of the Canadian Neonatal Network › Author Affiliations
Further Information

Publication History

10 July 2014

28 August 2014

Publication Date:
08 December 2014 (online)

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Abstract

Objective This study aims to identify the incidence, risk factors, and outcomes of late-onset sepsis in preterm neonates in Canadian neonatal intensive care units (NICUs).

Study Design This retrospective analysis included preterm infants born at < 32 weeks' gestation and admitted to 29 NICUs in the Canadian Neonatal Network during the years 2010 and 2011. Infants were classified into three groups: no infection, gram-positive infection, and gram-negative infection. Late-onset sepsis was defined as positive blood and/or spinal fluid cultures after 3 days of birth. Risk factors and the primary outcome of mortality or bronchopulmonary dysplasia (BPD) were compared between the groups.

Results Out of the 7,509 neonates, 6,405 (85%) had no infection, 909 (12%) had gram-positive, and 195 (3%) had gram-negative infections. Lower gestation, higher Score for Neonatal Acute Physiology, version II scores, the presence of central catheters for > 4 days, parenteral nutrition for > 7 days, and prolonged duration of nothing by mouth were associated with late-onset sepsis. After controlling for confounders, the odds ratio (OR) of mortality/BPD were higher in infants who had gram-negative (OR 2.79, 95% confidence interval [CI] 1.96–3.97) and gram-positive (OR 1.44, 95% CI 1.21–1.71) sepsis as compared with no infection.

Conclusions Bacterial late-onset sepsis in very preterm neonates was associated with mortality and BPD. Neonates with gram-negative sepsis had the highest risk of adverse outcomes as compared with gram-positive sepsis or no sepsis.

Keywords

infant - premature - nosocomial infection - late-onset sepsis - mortality - bronchopulmonary dysplasia
 

  • References

  • 1 Didier C, Streicher MP, Chognot D , et al. Late-onset neonatal infections: incidences and pathogens in the era of antenatal antibiotics. Eur J Pediatr 2012; 171 (4) 681-687
    Search in Google Scholar
  • 2 Escobar GJ, Li DK, Armstrong MA , et al. Neonatal sepsis workups in infants >/=2000 grams at birth: A population-based study. Pediatrics 2000; 106 (2 Pt 1) 256-263
    CrossrefPubMedSearch in Google Scholar
  • 3 Hornik CP, Fort P, Clark RH , et al. Early and late onset sepsis in very-low-birth-weight infants from a large group of neonatal intensive care units. Early Hum Dev 2012; 88 (Suppl. 02) S69-S74
    CrossrefPubMedSearch in Google Scholar
  • 4 Lim WH, Lien R, Huang YC , et al. Prevalence and pathogen distribution of neonatal sepsis among very-low-birth-weight infants. Pediatr Neonatol 2012; 53 (4) 228-234
    CrossrefPubMedSearch in Google Scholar
  • 5 Ozkan H, Cetinkaya M, Koksal N, Celebi S, Hacımustafaoglu M. Culture-proven neonatal sepsis in preterm infants in a neonatal intensive care unit over a 7 year period: coagulase-negative Staphylococcus as the predominant pathogen. Pediatr Int 2014; 56 (1) 60-66
    CrossrefPubMedSearch in Google Scholar
  • 6 Tsai MH, Hsu JF, Chu SM , et al. Incidence, clinical characteristics and risk factors for adverse outcome in neonates with late-onset sepsis. Pediatr Infect Dis J 2014; 33 (1) e7-e13
    CrossrefPubMedSearch in Google Scholar
  • 7 Stoll BJ, Hansen N. Infections in VLBW infants: studies from the NICHD Neonatal Research Network. Semin Perinatol 2003; 27 (4) 293-301
    CrossrefPubMedSearch in Google Scholar
  • 8 Bizzarro MJ, Raskind C, Baltimore RS, Gallagher PG. Seventy-five years of neonatal sepsis at Yale: 1928-2003. Pediatrics 2005; 116 (3) 595-602
    CrossrefPubMedSearch in Google Scholar
  • 9 Shane AL, Stoll BJ. Neonatal sepsis: progress towards improved outcomes. J Infect 2014; 68 (Suppl. 01) S24-S32
    CrossrefPubMedSearch in Google Scholar
  • 10 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
    CrossrefPubMedSearch in Google Scholar
  • 11 Levit O, Bhandari V, Li FY, Shabanova V, Gallagher PG, Bizzarro MJ. Clinical and laboratory factors that predict death in very low birth weight infants presenting with late-onset sepsis. Pediatr Infect Dis J 2014; 33 (2) 143-146
    CrossrefPubMedSearch in Google Scholar
  • 12 Shane AL, Stoll BJ. Recent developments and current issues in the epidemiology, diagnosis, and management of bacterial and fungal neonatal sepsis. Am J Perinatol 2013; 30 (2) 131-141
    Thieme ConnectPubMedSearch in Google Scholar
  • 13 Shah PS, Yoon W, Kalapesi Z, Bassil K, Dunn M, Lee SK. Seasonal variations in healthcare-associated infection in neonates in Canada. Arch Dis Child Fetal Neonatal Ed 2013; 98 (1) F65-F69
    CrossrefPubMedSearch in Google Scholar
  • 14 Higgins RD, Baker CJ, Raju TN. Executive summary of the workshop on infection in the high-risk infant. J Perinatol 2010; 30 (6) 379-383
    CrossrefPubMedSearch in Google Scholar
  • 15 Ehrenkranz RA, Das A, Wrage LA , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Early nutrition mediates the influence of severity of illness on extremely LBW infants. Pediatr Res 2011; 69 (6) 522-529
    CrossrefPubMedSearch in Google Scholar
  • 16 Perlman SE, Saiman L, Larson EL. Risk factors for late-onset health care-associated bloodstream infections in patients in neonatal intensive care units. Am J Infect Control 2007; 35 (3) 177-182
    CrossrefPubMedSearch in Google Scholar
  • 17 Samanta S, Farrer K, Breathnach A, Heath PT. Risk factors for late onset gram-negative infections: a case-control study. Arch Dis Child Fetal Neonatal Ed 2011; 96 (1) F15-F18
    CrossrefPubMedSearch in Google Scholar
  • 18 Downey LC, Smith PB, Benjamin Jr DK. Risk factors and prevention of late-onset sepsis in premature infants. Early Hum Dev 2010; 86 (Suppl. 01) 7-12
    PubMedSearch in Google Scholar
  • 19 Sarkar S, Bhagat I, DeCristofaro JD, Wiswell TE, Spitzer AR. A study of the role of multiple site blood cultures in the evaluation of neonatal sepsis. J Perinatol 2006; 26 (1) 18-22
    CrossrefPubMedSearch in Google Scholar
  • 20 Richardson DK, Gray JE, McCormick MC, Workman K, Goldmann DA. Score for Neonatal Acute Physiology: a physiologic severity index for neonatal intensive care. Pediatrics 1993; 91 (3) 617-623
    PubMedSearch in Google Scholar
  • 21 Shennan AT, Dunn MS, Ohlsson A, Lennox K, Hoskins EM. Abnormal pulmonary outcomes in premature infants: prediction from oxygen requirement in the neonatal period. Pediatrics 1988; 82 (4) 527-532
    PubMedSearch in Google Scholar
  • 22 International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol 2005; 123 (7) 991-999
    CrossrefPubMedSearch in Google Scholar
  • 23 Bell MJ, Ternberg JL, Feigin RD , et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 1978; 187 (1) 1-7
    CrossrefPubMedSearch in Google Scholar
  • 24 Canadian Neonatal Network. Canadian Neonatal Network Abstractor's Manual. v 2.1.2, 1–94. 2014. Available at: www.canadianneonatalnetwork.org . Accessed 1 June, 2014
    PubMed
  • 25 Stoll BJ, Hansen NI, Bell EF , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 2010; 126 (3) 443-456
    CrossrefPubMedSearch in Google Scholar
  • 26 Gordon A, Isaacs D. Late onset neonatal Gram-negative bacillary infection in Australia and New Zealand: 1992-2002. Pediatr Infect Dis J 2006; 25 (1) 25-29
    CrossrefPubMedSearch in Google Scholar
  • 27 Vergnano S, Menson E, Kennea N , et al. Neonatal infections in England: the NeonIN surveillance network. Arch Dis Child Fetal Neonatal Ed 2011; 96 (1) F9-F14
    CrossrefPubMedSearch in Google Scholar
  • 28 Stewart CJ, Marrs EC, Magorrian S , et al. The preterm gut microbiota: changes associated with necrotizing enterocolitis and infection. Acta Paediatr 2012; 101 (11) 1121-1127
    CrossrefPubMedSearch in Google Scholar
  • 29 Bizzarro MJ. Health care-associated infections in the neonatal intensive care unit: barriers to continued success. Semin Perinatol 2012; 36 (6) 437-444
    CrossrefPubMedSearch in Google Scholar
  • 30 Sherman MP. New concepts of microbial translocation in the neonatal intestine: mechanisms and prevention. Clin Perinatol 2010; 37 (3) 565-579
    CrossrefPubMedSearch in Google Scholar
  • 31 Bizzarro MJ, Sabo B, Noonan M, Bonfiglio MP, Northrup V, Diefenbach K ; Central Venous Catheter Initiative Committee. A quality improvement initiative to reduce central line-associated bloodstream infections in a neonatal intensive care unit. Infect Control Hosp Epidemiol 2010; 31 (3) 241-248
    CrossrefPubMedSearch in Google Scholar
  • 32 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 (3) 427-435
    CrossrefPubMedSearch in Google Scholar
  • 33 Adams-Chapman I. Long-term impact of infection on the preterm neonate. Semin Perinatol 2012; 36 (6) 462-470
    CrossrefPubMedSearch in Google Scholar
  • 34 Kramer BW, Kramer S, Ikegami M, Jobe AH. Injury, inflammation, and remodeling in fetal sheep lung after intra-amniotic endotoxin. Am J Physiol Lung Cell Mol Physiol 2002; 283 (2) L452-L459
    CrossrefPubMedSearch in Google Scholar
  • 35 Pessoa-Silva CL, Miyasaki CH, de Almeida MF, Kopelman BI, Raggio RL, Wey SB. Neonatal late-onset bloodstream infection: attributable mortality, excess of length of stay and risk factors. Eur J Epidemiol 2001; 17 (8) 715-720
    CrossrefPubMedSearch in Google Scholar
  • 36 Johnson TJ, Patel AL, Jegier BJ, Engstrom JL, Meier PP. Cost of morbidities in very low birth weight infants. J Pediatr 2013; 162 (2) 243-249 , e1
    CrossrefPubMedSearch in Google Scholar
  • 37 Stoll BJ, Hansen NI, Adams-Chapman I , et al; National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA 2004; 292 (19) 2357-2365
    CrossrefPubMedSearch in Google Scholar
  • 38 Mitha A, Foix-L'Hélias L, Arnaud C , et al; EPIPAGE Study Group. Neonatal infection and 5-year neurodevelopmental outcome of very preterm infants. Pediatrics 2013; 132 (2) e372-e380
    CrossrefPubMedSearch in Google Scholar
  • 39 Schlapbach LJ, Aebischer M, Adams M , et al; Swiss Neonatal Network and Follow-Up Group. Impact of sepsis on neurodevelopmental outcome in a Swiss National Cohort of extremely premature infants. Pediatrics 2011; 128 (2) e348-e357
    CrossrefPubMedSearch in Google Scholar
  • 40 van der Ree M, Tanis JC, Van Braeckel KN, Bos AF, Roze E. Functional impairments at school age of preterm born children with late-onset sepsis. Early Hum Dev 2011; 87 (12) 821-826
    CrossrefPubMedSearch in Google Scholar
  • 41 Helwich E, Wójkowska-Mach J, Borszewska-Kornacka M , et al. [Epidemiology of infections in very low birth weight infants. Polish Neonatology Network research]. Med Wieku Rozwoj 2013; 17 (3) 224-231
    PubMedSearch in Google Scholar