Nosocomial Sepsis in Neonatal Intensive Care: Inevitable or Preventable?

I. Bersani; C. P. Speer

doi:10.1055/s-0032-1321837

Zeitschrift für Geburtshilfe und Neonatologie, Table of Contents

Z Geburtshilfe Neonatol 2012; 216(04): 186-190
DOI: 10.1055/s-0032-1321837

Review

Nosocomial Sepsis in Neonatal Intensive Care: Inevitable or Preventable?

Die nosokomiale Sepsis in der neonatalen Intensivmedizin: Schicksalshaft oder vermeidbar?

I. Bersani

¹University Children’s Hospital, University of Würzburg

²University Hospital “A. Gemelli”, Rome, Italy

,

C. P. Speer

¹University Children’s Hospital, University of Würzburg

› Author Affiliations

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.

Key words

granulocyte colony-stimulating factor - granulocyte-macrophage colony-stimulating factor - intravenous immunoglobulins - hygienic strategies - neonates - nosocomial sepsis

Schlüsselwörter

Frühgeborene - nasokomiale Sepsis - hämatopoetische Wachstumsfaktoren - intravenöse Immunglobulinsubstitution

Full Text

References

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