Z Geburtshilfe Neonatol 2012; 216(04): 186-190
DOI: 10.1055/s-0032-1321837
Review
© Georg Thieme Verlag KG Stuttgart · New York

Nosocomial Sepsis in Neonatal Intensive Care: Inevitable or Preventable?

Die nosokomiale Sepsis in der neonatalen Intensivmedizin: Schicksalshaft oder vermeidbar?
I. Bersani
1   University Children’s Hospital, University of Würzburg
2   University Hospital “A. Gemelli”, Rome, Italy
,
C. P. Speer
1   University Children’s Hospital, University of Würzburg
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 29. Mai 2012

accepted after revision 26. Juni 2012

Publikationsdatum:
27. August 2012 (online)

Abstract

Very low birth weight (VLBW) infants are at high risk to develop a neonatal nosocomial sepsis. The incidence of neonatal nosocomial, late-onset sepsis (LOS) is about 20–30%, but a rate of up to 43% has been reported among neonates with a birth weight of 400–750 g. Preventive and treatment strategies for neonatal sepsis in VLBW infants are aiming to enhance the infant’s host defence mechanisms. Neonatal immunodeficiencies include quantitative and qualitative deficits in phagocytes, complement components, and immunoglobulins. A considerable number of immune strategies has been investigated in carefully designed multicentre trials. These include exchange transfusion, neutrophil transfusion, hematopoietic growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF), intravenous immunoglobulins (IVIG), and others. Since none of these interventions was able to reduce the mortality rate of immature preterm infants, the current evidence does not support the use of any of the immune strategies for prevention or treatment of neonatal sepsis. Decreasing the burden of intensive care and following strict hygiene programs at NICUs may be the most promising current strategies to minimise nosocomial infection.

Zusammenfassung

Sehr unreife Frühgeborene haben ein hohes Risiko an einer nosokomialen Sepsis zu erkran­ken. Bis zu 30% der Frühgeborenen mit einem Geburtsgewicht <1 500 g und mehr als 40% mit einem Geburtsgewicht von 400–750 g entwickeln im Verlauf der intensivmedizinischen Behandlung eine Sepsis, die zu einer erhöhten Letalität und Morbidität dieser Hochrisikopatienten beiträgt. Verschiedene präventive und therapeutische Strategien wurden in überwie­gend kontrollierten, randomisierten Studien mit dem Ziel untersucht, eine Reihe von partiellen Immundefizienzen unreifer Frühgeborener wie die quantitativen und qualitativen Funktionseinschränkungen im Phagozyten- und humoralen Immunsystem zu korrigieren. Zu diesen Strategien gehören die Austauschtransfusion, Granulozy­tentransfusion, die Gabe von hämatopoetischen Wachstumsfaktoren (GM-CSF, G-CSF), die intravenöse Immunglobulinsubstitution u. a. Da keine dieser Interventionen die Sterblichkeit von unreifen Frühgeborenen reduzieren konnte, sollte bei fehlender Evidenz von einem klinischen Einsatz dieser Strategien zur Prävention und Behandlung der nosokomialen Sepsis Frühgeborener abgesehen werden. Eine reduzierte Dauer und Intensität der intensivmedizinischen Maßnahmen sowie strikte Hygienevorschriften sind vermutlich die Strate­gien, die am ehesten zu einer Abnahme der Sepsisinzidenz beitragen können.

 
  • References

  • 1 Makhoul IR, Sujov P, Smolkin T et al. Epidemiological, clinical, and microbiological characteristics of late-onset sepsis among very low birth weight infants in Israel: a national survey. Pediatrics 2002; 109: 34-39
  • 2 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: 285-291
  • 3 Stoll BJ, Gordon T, Korones SB et al. Late-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network. J Pediatr 1996; 129: 63-71
  • 4 Karlowicz MG, Buescher ES, Surka AE. Fulminant late-onset sepsis in a neonatal intensive care unit, 1988–1997, and the impact of avoiding empiric vancomycin therapy. Pediatrics 2000; 106: 1387-1390
  • 5 Zafar N, Wallace CM, Kieffer P et al. Improving survival of vulnerable infants increases neonatal intensive care unit nosocomial infection rate. Arch Pediatr Adolesc Med 2001; 155: 1098-1104
  • 6 Gill AW. Analysis of neonatal nosocomial infection rates across the Australian and New Zealand Neonatal Network. J Hosp Infect 2009; 72: 155-162
  • 7 Vergnano S, Menson E, Kennea N et al. Neonatal infections in England: the NeonIN surveillance network. Arch Dis Child Fetal Neonatal Ed 2011; 96: F9-F14
  • 8 Isaacs D, Barfield C, Clothier T et al. Late-onset infections of infants in neonatal units. J Paediatr Child Health 1996; 32: 158-161
  • 9 Isaacs D. A ten year, multicentre study of coagulase negative staphylococcal infections in Australasian neonatal units. Arch Dis Child Fetal Neonatal Ed 2003; 88: F89-93
  • 10 Ballow M, Cates KL, Rowe JC et al. Development of the immune system in very low birth weight (less than 1 500 g) premature infants: concentrations of plasma immunoglobulins and patterns of infections. Pediatr Res 1986; 20: 899-904
  • 11 Brodie SB, Sands KE, Gray JE et al. Occurrence of nosocomial bloodstream infections in six neonatal intensive care units. Pediatr Infect Dis J 2000; 19: 56-65
  • 12 Glasgow TS, Young PC, Wallin J et al. Association of intrapartum antibiotic exposure and late-onset serious bacterial infections in infants. Pediatrics 2005; 116: 696-702
  • 13 Bizzarro MJ, Dembry LM, Baltimore RS et al. Case-control analysis of endemic Serratia marcescens bacteremia in a neonatal intensive care unit. Arch Dis Child Fetal Neonatal Ed 2007; 92: F120-F126
  • 14 Samanta S, Farrer K, Breathnach A et al. Risk factors for late onset Gram-negative infections: a case-control study. Arch Dis Child Fetal Neonatal Ed 2011; 96: F15-F18
  • 15 Freeman J, Platt R, Epstein MF et al. Birth weight and length of stay as determinants of nosocomial coagulase-negative staphylococcal bacteremia in neonatal intensive care unit populations: potential for confounding. Am J Epidemiol 1990; 132: 1130-1140
  • 16 Graham 3rd PL, Begg MD, Larson E et al. Risk factors for late onset Gram-negative sepsis in low birth weight infants hospitalized in the neonatal intensive care unit. Pediatr Infect Dis J 2006; 25: 113-117
  • 17 Birch P, Ogden S, Hewson M. A randomised, controlled trial of heparin in total parenteral nutrition to prevent sepsis associated with neonatal long lines: the Heparin in Long Line Total Parenteral Nutrition (HILLTOP) trial. Arch Dis Child Fetal Neonatal Ed 2010; 95: F252-F257
  • 18 Anderson-Berry A, Brinton B, Lyden E et al. Risk factors associated with development of persistent coagulase-negative staphylococci bacteremia in the neonate and associated short-term and discharge morbidities. Neonatology 2011; 99: 23-31
  • 19 Centers for Disease Control and Prevention CDC . Early-onset and late-onset neonatal group B streptococcal disease – United States, 1996–2004. MMWR Morb Mortal Wkly Rep 2005; 54: 1205-1208
  • 20 Stoll BJ, Hansen NI, Sanchez PJ et al. Early onset neonatal sepsis: the burden of group B streptococcal and E. coli disease continues. Pediatrics 2011; 127: 817-826
  • 21 Tosson AM, Speer CP. Microbial pathogens causative of neonatal sepsis in Arabic countries. J Matern Fetal Neonatal Med 2011; 24: 990-994
  • 22 Macharashvili N, Kourbatova E, Butsashvili M et al. Etiology of neonatal blood stream infections in Tbilisi, Republic of Georgia. Int J Infect Dis 2009; 13: 499-505
  • 23 Daley AJ, Isaacs D. Ten-year study on the effect of intrapartum anti­biotic prophylaxis on early onset group B streptococcal and ­Escherichia coli neonatal sepsis in Australasia. Pediatr Infect Dis J 2004; 23: 630-634
  • 24 Manzoni P, Rizzollo S, Decembrino L et al. Recent advances in prevention of sepsis in the premature neonates in NICU. Early Hum Dev 2011; 87 (Suppl. 01) S31-S33
  • 25 Aiello AE, Larson EL. What is the evidence for a causal link between hygiene and infections?. Lancet Infect Dis 2002; 2: 103-110
  • 26 Boyce JM, Pittet D. Guideline for Hand Hygiene in Health-Care Settings. Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. Society for Healthcare Epidemiology of America/Association for Professionals in Infection Control/Infectious Diseases Society of America. MMWR Recomm Rep. 2002. 51. 1-45 quiz CE41–CE44
  • 27 Centers for Disease Control and Prevention . New CDC. hand hygiene guidelines. Home Healthc Nurse 2003; 21: 367-369
  • 28 Ng PC, Wong HL, Lyon DJ et al. 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 2004; 89: F336-F340
  • 29 McLaughlin AC, Walsh F. Individual differences in judgments of hand hygiene risk by health care workers. Am J Infect Control 2011; 39: 456-463
  • 30 Tibballs J. Teaching hospital medical staff to handwash. Med J Aust 1006 164Ö: 395-398
  • 31 Lam BC, Lee J, Lau YL. Hand hygiene practices in a neonatal intensive care unit: a multimodal intervention and impact on nosocomial infection. Pediatrics 2004; 114: e565-e571
  • 32 Rubin LG, Sanchez PJ, Siegel J et al. Evaluation and treatment of neonates with suspected late-onset sepsis: a survey of neonatologists’ practices. Pediatrics 2002; 110: e42
  • 33 Schwab F, Geffers C, Barwolff S et al. Reducing neonatal nosocomial bloodstream infections through participation in a national surveillance system. J Hosp Infect 2007; 65: 319-325
  • 34 Urlichs F, Speer CP. Neutrophil function in preterm and term infants. NeoReviews 2004; 5: e417-e429
  • 35 Suri M, Harrison L, Van de Ven C et al. Immunotherapy in the prophylaxis and treatment of neonatal sepsis. Curr Opin Pediatr 2003; 15: 155-160
  • 36 Cohen-Wolkowiez M, Benjamin Jr DK, Capparelli E. Immunotherapy in neonatal sepsis: advances in treatment and prophylaxis. Curr Opin Pediatr 2009; 21: 177-181
  • 37 Tarnow-Mordi W, Isaacs D, Dutta S. Adjunctive immunologic interventions in neonatal sepsis. Clin Perinatol 2010; 37: 481-499
  • 38 Bossi E, Meister B, Pfenninger J. Exchange transfusion for severe neonatal septicemia. Pediatrics 1981; 67: 941
  • 39 Pammi M, Brocklehurst P. Granulocyte transfusions for neonates with confirmed or suspected sepsis and neutropenia. Cochrane Database Syst Rev 2011; CD003956
  • 40 Mohan P, Brocklehurst P. Granulocyte transfusions for neonates with confirmed or suspected sepsis and neutropaenia. Cochrane Database Syst Rev 2003; CD003956
  • 41 Banerjea MC, Speer CP. The current role of colony-stimulating factors in prevention and treatment of neonatal sepsis. Semin Neonatol 2002; 7: 335-349
  • 42 Carr R, Modi N, Dore C. G-CSF and GM-CSF for treating or preventing neonatal infections. Cochrane Database Syst Rev 2003; CD003066
  • 43 Carr R, Brocklehurst P, Dore CJ et al. Granulocyte-macrophage colony stimulating factor administered as prophylaxis for reduction of sepsis in extremely preterm, small for gestational age neonates (the PROGRAMS trial): a single-blind, multicentre, randomised controlled trial. Lancet 2009; 373: 226-233
  • 44 Kuhn P, Messer J, Paupe A et al. A multicenter, randomized, placebo-controlled trial of prophylactic recombinant granulocyte-colony stimulating factor in preterm neonates with neutropenia. J Pediatr 2009; 155: 324-330 e321
  • 45 Ohlsson A, Lacy JB. Intravenous immunoglobulin for preventing infection in preterm and/or low-birth-weight infants. Cochrane Database Syst Rev 2004; CD000361
  • 46 Ohlsson A, Lacy J. Intravenous immunoglobulin for suspected or subsequently proven infection in neonates. Cochrane Database Syst Rev 2010; CD001239
  • 47 Fanaroff AA, Korones SB, Wright LL et al. A controlled trial of intravenous immune globulin to reduce nosocomial infections in very-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med 1994; 330: 1107-1113
  • 48 Brocklehurst P, Farrell B, King A et al. Treatment of neonatal sepsis with intravenous immune globulin. N Engl J Med 2011; 365: 1201-1211
  • 49 Shah PS, Kaufman DA. Antistaphylococcal immunoglobulins to prevent staphylococcal infection in very low birth weight infants. Cochrane Database Syst Rev 2009; CD006449
  • 50 Alfaleh K, Bassler D. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev 2008; CD005496
  • 51 Alfaleh K, Anabrees J, Bassler D. Probiotics reduce the risk of necrotizing enterocolitis in preterm infants: a meta-analysis. Neonatology 2010; 97: 93-99
  • 52 Alfaleh K, Anabrees J, Bassler D et al. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev 2011; CD005496
  • 53 Romeo MG, Romeo DM, Trovato L et al. Role of probiotics in the prevention of the enteric colonization by Candida in preterm newborns: incidence of late-onset sepsis and neurological outcome. J Perinatol 2011; 31: 63-69
  • 54 Manzoni P, Mostert M, Leonessa ML et al. Oral supplementation with Lactobacillus casei subspecies rhamnosus prevents enteric colonization by Candida species in preterm neonates: a randomized study. Clin Infect Dis 2006; 42: 1735-1742
  • 55 Mihatsch WA, Braegger CP, Decsi T et al. Critical systematic review of the level of evidence for routine use of probiotics for reduction of mortality and prevention of necrotizing enterocolitis and sepsis in preterm infants. Clin Nutr 2012; 31: 6-15
  • 56 Garland SM, Tobin JM, Pirotta M et al. The ProPrems trial: investigating the effects of probiotics on late onset sepsis in very preterm infants. BMC Infect Dis 2011; 11: 210
  • 57 Venkatesh MP, Abrams SA. Oral lactoferrin for the prevention of sepsis and necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev 2010; CD007137
  • 58 Pammi M, Abrams SA. Oral lactoferrin for the prevention of sepsis and necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev 2011; CD007137
  • 59 Pammi M, Abrams SA. Oral lactoferrin for the treatment of sepsis and necrotizing enterocolitis in neonates. Cochrane Database Syst Rev 2011; CD007138
  • 60 Manzoni P, Rinaldi M, Cattani S et al. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial. JAMA 2009; 302: 1421-1428
  • 61 Manzoni P, Stolfi I, Messner H et al. Bovine lactoferrin prevents invasive fungal infections in very low birth weight infants: a randomized controlled trial. Pediatrics 2012; 129: 116-123
  • 62 Tubman TR, Thompson SW, McGuire W. Glutamine supplementation to prevent morbidity and mortality in preterm infants. Cochrane Database Syst Rev 2005; CD001457
  • 63 Tubman TR, Thompson SW, McGuire W. Glutamine supplementation to prevent morbidity and mortality in preterm infants. Cochrane Database Syst Rev 2008; CD001457
  • 64 Moe-Byrne T, Wagner JV, McGuire W. Glutamine supplementation to prevent morbidity and mortality in preterm infants. Cochrane Database Syst Rev 2012; 3 CD001457
  • 65 Darlow BA, Austin NC. Selenium supplementation to prevent short-term morbidity in preterm neonates. Cochrane Database Syst Rev 2003; CD003312
  • 66 Marti-Carvajal AJ, Sola I, Lathyris D et al. Human recombinant activated protein C for severe sepsis. Cochrane Database Syst Rev 2012; 3 CD004388
  • 67 Haque KN, Pammi M. Pentoxifylline for treatment of sepsis and necrotizing enterocolitis in neonates. Cochrane Database Syst Rev 2011; CD004205