Late-Onset Sepsis in Very Low Birth Weight Neonates: The Experience of the NICHD Neonatal Research Network
* Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
Research Triangle Institute, Research Triangle Park, North Carolina
Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio
|| National Institute of Child Health and Human Development, Bethesda, Maryland
¶ Department of Pediatrics, University of Alabama, Birmingham, Alabama
# Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut
** Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana
Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio
Joint Program in Neonatology, Harvard University, Children’s Hospital, Boston, Massachusetts
|||| Center for Clinical Research and Evidence Based Medicine, University of Texas Health Science Center at Houston Medical School, Houston, Texas
¶¶ Department of Pediatrics, Brown University, Providence, Rhode Island
## Department of Pediatrics, University of Miami, Miami, Florida
*** The Newborn Center, University of Tennessee-Memphis, Memphis, Tennessee
Division of Neonatal and Perinatal Medicine, Wayne State University, Detroit, Michigan
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
|||||| Division of Neonatology, Stanford University Medical Center, Palo Alto, California
¶¶¶ Department of Pediatrics, University of New Mexico School of Medicine, Albuquerque, New Mexico
Objective. Late-onset sepsis (occurring after 3 days of age) is an important problem in very low birth weight (VLBW) infants. To determine the current incidence of late-onset sepsis, risk factors for disease, and the impact of late-onset sepsis on subsequent hospital course, we evaluated a cohort of 6956 VLBW (401–1500 g) neonates admitted to the clinical centers of the National Institute of Child Health and Human Development Neonatal Research Network over a 2-year period (1998–2000).
Methods. The National Institute of Child Health and Human Development Neonatal Research Network maintains a prospective registry of all VLBW neonates admitted to participating centers within 14 days of birth. Expanded infection surveillance was added in 1998.
Results. Of 6215 infants who survived beyond 3 days, 1313 (21%) had 1 or more episodes of blood culture-proven late-onset sepsis. The vast majority of infections (70%) were caused by Gram-positive organisms, with coagulase-negative staphylococci accounting for 48% of infections. Rate of infection was inversely related to birth weight and gestational age. Complications of prematurity associated with an increased rate of late-onset sepsis included patent ductus arteriosus, prolonged ventilation, prolonged intravascular access, bronchopulmonary dysplasia, and necrotizing enterocolitis. Infants who developed late-onset sepsis had a significantly prolonged hospital stay (mean length of stay: 79 vs 60 days). They were significantly more likely to die than those who were uninfected (18% vs 7%), especially if they were infected with Gram-negative organisms (36%) or fungi (32%).
Conclusions. Late-onset sepsis remains an important risk factor for death among VLBW preterm infants and for prolonged hospital stay among VLBW survivors. Strategies to reduce late-onset sepsis and its medical, social, and economic toll need to be addressed urgently.
Key Words: sepsis • infant • newborn infant • very low birth weight infant • premature
Abbreviations: VLBW, very low birth weight • NICHD, National Institute of Child Health and Human Development • CRP, C-reactive protein • CONS, coagulase-negative staphylococci • GA, gestational age • IVH, intraventricular hemorrhage • NEC, necrotizing enterocolitis • RDS, respiratory distress syndrome • BPD, bronchopulmonary dysplasia • NS, not significant • OR, odds ratio • PICC, percutaneously inserted central catheter • PAL, peripheral arterial line • CVL, surgically placed central venous line • UAC, umbilical arterial catheter • UVC, umbilical venous catheter • NICU, neonatal intensive care unit
Received for publication Sep 25, 2001; Accepted Feb 8, 2002.
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E. Capparelli, C. Hochwald, M. Rasmussen, A. Parham, J. Bradley, and F. Moya Population Pharmacokinetics of Cefepime in the Neonate Antimicrob. Agents Chemother., July 1, 2005; 49(7): 2760 - 2766. [Abstract] [Full Text] [PDF]
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E. Sarvikivi, O. Lyytikainen, D. R. Soll, C. Pujol, M. A. Pfaller, M. Richardson, P. Koukila-Kahkola, P. Luukkainen, and H. Saxen Emergence of Fluconazole Resistance in a Candida parapsilosis Strain That Caused Infections in a Neonatal Intensive Care Unit J. Clin. Microbiol., June 1, 2005; 43(6): 2729 - 2735. [Abstract] [Full Text] [PDF]
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H. Aly, V. Herson, A. Duncan, J. Herr, J. Bender, K. Patel, and A. A. E. El-Mohandes Is Bloodstream Infection Preventable Among Premature Infants? A Tale of Two Cities Pediatrics, June 1, 2005; 115(6): 1513 - 1518. [Abstract] [Full Text] [PDF]
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A. Ronnestad, T. G. Abrahamsen, S. Medbo, H. Reigstad, K. Lossius, P. I. Kaaresen, T. Egeland, I. E. Engelund, L. M. Irgens, and T. Markestad Late-Onset Septicemia in a Norwegian National Cohort of Extremely Premature Infants Receiving Very Early Full Human Milk Feeding Pediatrics, March 1, 2005; 115(3): e269 - e276. [Abstract] [Full Text] [PDF]
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 B. W. Kramer, M. Ikegami, T. J. M. Moss, I. Nitsos, J. P. Newnham, and A. H. Jobe Endotoxin-induced Chorioamnionitis Modulates Innate Immunity of Monocytes in Preterm Sheep Am. J. Respir. Crit. Care Med., January 1, 2005; 171(1): 73 - 77. [Abstract] [Full Text] [PDF]
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 Ch. Hartel, D. Finas, P. Ahrens, E. Kattner, Th. Schaible, D. Muller, H. Segerer, K. Albrecht, J. Moller, K. Diedrich, et al. Polymorphisms of genes involved in innate immunity: association with preterm delivery Mol. Hum. Reprod., December 1, 2004; 10(12): 911 - 915. [Abstract] [Full Text] [PDF]
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 W. McGuire, L. Clerihew, and P. W Fowlie Infection in the preterm infant BMJ, November 27, 2004; 329(7477): 1277 - 1280. [Full Text] [PDF]
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B. J. Stoll, N. I. Hansen, I. Adams-Chapman, A. A. Fanaroff, S. R. Hintz, B. Vohr, R. D. Higgins, and for the National Institute of Child Health and Hum Neurodevelopmental and Growth Impairment Among Extremely Low-Birth-Weight Infants With Neonatal Infection JAMA, November 17, 2004; 292(19): 2357 - 2365. [Abstract] [Full Text] [PDF]
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 Y. Liu, B. Ames, E. Gorovits, B. D. Prater, P. Syribeys, J. H. Vernachio, and J. M. Patti SdrX, a Serine-Aspartate Repeat Protein Expressed by Staphylococcus capitis with Collagen VI Binding Activity Infect. Immun., November 1, 2004; 72(11): 6237 - 6244. [Abstract] [Full Text] [PDF]
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 C. Klingenberg, A. Sundsfjord, A. Ronnestad, J. Mikalsen, P. Gaustad, and T. Flaegstad Phenotypic and genotypic aminoglycoside resistance in blood culture isolates of coagulase-negative staphylococci from a single neonatal intensive care unit, 1989-2000 J. Antimicrob. Chemother., November 1, 2004; 54(5): 889 - 896. [Abstract] [Full Text] [PDF]
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C. M. Healy, D. L. Palazzi, M. S. Edwards, J. R. Campbell, and C. J. Baker Features of Invasive Staphylococcal Disease in Neonates Pediatrics, October 1, 2004; 114(4): 953 - 961. [Abstract] [Full Text] [PDF]
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A. Jain, J. Agarwal, and S. Bansal Prevalence of methicillin-resistant, coagulase-negative staphylococci in neonatal intensive care units: findings from a tertiary care hospital in India J. Med. Microbiol., September 1, 2004; 53(9): 941 - 944. [Abstract] [Full Text] [PDF]
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P C Lindemann, I Foshaugen, and R Lindemann Characteristics of breast milk and serology of women donating breast milk to a milk bank Arch. Dis. Child. Fetal Neonatal Ed., September 1, 2004; 89(5): F440 - F441. [Abstract] [Full Text] [PDF]
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N. R. Payne, J. H. Carpenter, G. J. Badger, J. D. Horbar, and J. Rogowski Marginal Increase in Cost and Excess Length of Stay Associated With Nosocomial Bloodstream Infections in Surviving Very Low Birth Weight Infants Pediatrics, August 1, 2004; 114(2): 348 - 355. [Abstract] [Full Text] [PDF]
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D. Kaufman and K. D. Fairchild Clinical Microbiology of Bacterial and Fungal Sepsis in Very-Low-Birth-Weight Infants Clin. Microbiol. Rev., July 1, 2004; 17(3): 638 - 680. [Abstract] [Full Text] [PDF]
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P C Ng, H L Wong, D J Lyon, K W So, F Liu, R K Y Lam, E Wong, A F B Cheng, and T F Fok Combined use of alcohol hand rub and gloves reduces the incidence of late onset infection in very low birthweight infants Arch. Dis. Child. Fetal Neonatal Ed., July 1, 2004; 89(4): F336 - F340. [Abstract] [Full Text] [PDF]
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B. Holler, S. A. Omar, M. D. Farid, and M. J. Patterson Effects of Fluid and Electrolyte Management on Amphotericin B-Induced Nephrotoxicity Among Extremely Low Birth Weight Infants Pediatrics, June 1, 2004; 113(6): e608 - e616. [Abstract] [Full Text]
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B. J. Stoll, N. Hansen, A. A. Fanaroff, L. L. Wright, W. A. Carlo, R. A. Ehrenkranz, J. A. Lemons, E. F. Donovan, A. R. Stark, J. E. Tyson, et al. To Tap or Not to Tap: High Likelihood of Meningitis Without Sepsis Among Very Low Birth Weight Infants Pediatrics, May 1, 2004; 113(5): 1181 - 1186. [Abstract] [Full Text] [PDF]
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B. B. Poindexter, R. A. Ehrenkranz, B. J. Stoll, L. L. Wright, W. K. Poole, W. Oh, C. R. Bauer, L.-A. Papile, J. E. Tyson, W. A. Carlo, et al. Parenteral Glutamine Supplementation Does Not Reduce the Risk of Mortality or Late-Onset Sepsis in Extremely Low Birth Weight Infants Pediatrics, May 1, 2004; 113(5): 1209 - 1215. [Abstract] [Full Text] [PDF]
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P C Ng Diagnostic markers of infection in neonates Arch. Dis. Child. Fetal Neonatal Ed., May 1, 2004; 89(3): F229 - F235. [Abstract] [Full Text] [PDF]
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T. G. Krediet, E. M. Mascini, E. van Rooij, J. Vlooswijk, A. Paauw, L. J. Gerards, and A. Fleer Molecular Epidemiology of Coagulase-Negative Staphylococci Causing Sepsis in a Neonatal Intensive Care Unit over an 11-Year Period J. Clin. Microbiol., March 1, 2004; 42(3): 992 - 995. [Abstract] [Full Text] [PDF]
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K. B. Weatherstone, L. S. Franck, and N. J. Klein Are There Opportunities to Decrease Nosocomial Infection by Choice of Analgesic Regimen?: Evidence for Immunity and Pain Interactions Arch Pediatr Adolesc Med, November 1, 2003; 157(11): 1108 - 1114. [Abstract] [Full Text] [PDF]
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D. K. Benjamin Jr, C. Poole, W. J. Steinbach, J. L. Rowen, and T. J. Walsh Neonatal Candidemia and End-Organ Damage: A Critical Appraisal of the Literature Using Meta-analytic Techniques Pediatrics, September 1, 2003; 112(3): 634 - 640. [Abstract] [Full Text] [PDF]
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M Millar, M Wilks, and K Costeloe Probiotics for preterm infants? Arch. Dis. Child. Fetal Neonatal Ed., September 1, 2003; 88(5): F354 - F358. [Abstract] [Full Text] [PDF]
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R. A. Polin and L. Saiman Nosocomial Infections in the Neonatal Intensive Care Unit NeoReviews, March 1, 2003; 4(3): e81 - 89. [Full Text] [PDF]
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K. J. Nazemi, E. S. Buescher, R. E. Kelly Jr, and M. G. Karlowicz Central Venous Catheter Removal Versus In Situ Treatment in Neonates With Enterobacteriaceae Bacteremia Pediatrics, March 1, 2003; 111(3): e269 - 274. [Abstract] [Full Text] [PDF]
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 OTHER ARTICLES NOTED (Nov 01 to 18 Oct 02) Evid. Based Nurs., January 1, 2003; 6(1): e1 - 1. [Full Text] [PDF]
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S. D. Kicklighter Antifungal Agents and Fungal Prophylaxis in the Neonate NeoReviews, December 1, 2002; 3(12): e249 - 255. [Full Text] [PDF]
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 A Large, Multicenter Study of Late-Onset Neonatal Sepsis Journal Watch Infectious Diseases, September 20, 2002; 2002(920): 2 - 2. [Full Text]
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