Late-onset neonatal sepsis: recent developments

Ying Dong, Christian P Speer, Ying Dong, Christian P Speer

Abstract

The incidence of neonatal late-onset sepsis (LOS) is inversely related to the degree of maturity and varies geographically from 0.61% to 14.2% among hospitalised newborns. Epidemiological data on very low birth weight infants shows that the predominant pathogens of neonatal LOS are coagulase-negative staphylococci, followed by Gram-negative bacilli and fungi. Due to the difficulties in a prompt diagnosis of LOS and LOS-associated high risk of mortality and long-term neurodevelopmental sequelae, empirical antibiotic treatment is initiated on suspicion of LOS. However, empirical therapy is often inappropriately used with unnecessary broad-spectrum antibiotics and a prolonged duration of treatment. The increasing number of multidrug-resistant Gram-negative micro-organisms in neonatal intensive care units (NICU) worldwide is a serious concern, which requires thorough and efficient surveillance strategies and appropriate treatment regimens. Immunological strategies for preventing neonatal LOS are not supported by current evidence, and approaches, such as a strict hygiene protocol and the minimisation of invasive procedures in NICUs represent the cornerstone to reduce the burden of neonatal LOS.

Keywords: Infectious Diseases; Microbiology; Neonatology.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Figures

Figure 1
Figure 1
Major causative pathogens of neonatal late-onset sepsis and their incidence by geographical areas.

References

    1. Qazi SA, Stoll BJ. Neonatal sepsis: a major global public health challenge. Pediatr Infect Dis J 2009;28:S1–2.
    1. Boghossian NS, Page GP, Bell EF, et al. . Late-onset sepsis in very low birth weight infants from singleton and multiple-gestation births. J Pediatr 2013;162:1120–4.
    1. Vergnano S, Menson E, Kennea N, et al. . Neonatal infections in England: the NeonIN surveillance network. Arch Dis Child Fetal Neonatal Ed 2011;96:F9–14.
    1. 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:e7–13.
    1. Hammoud MS, Al-Taiar A, Thalib L, et al. . Incidence, aetiology and resistance of late-onset neonatal sepsis: a five-year prospective study. J Paediatr Child Health 2012;48:604–9.
    1. Bizzarro MJ, Raskind C, Baltimore RS, et al. . Seventy-five years of neonatal sepsis at Yale: 1928–2003. Pediatrics 2005;116:595–602.
    1. Shim GH, Kim SD, Kim HS, et al. . Trends in epidemiology of neonatal sepsis in a tertiary center in Korea: a 26-year longitudinal analysis, 1980–2005. J Korean Med Sci 2011;26:284–9.
    1. van den Hoogen A, Gerards LJ, Verboon-Maciolek MA, et al. . Long-term trends in the epidemiology of neonatal sepsis and antibiotic susceptibility of causative agents. Neonatology 2010;97:22–8.
    1. Lahra MM, Beeby PJ, Jeffery HE. Intrauterine inflammation, neonatal sepsis, and chronic lung disease: a 13-year hospital cohort study. Pediatrics 2009;123:1314–19.
    1. Al-Taiar A, Hammoud MS, Cuiqing L, et al. . Neonatal infections in China, Malaysia, Hong Kong and Thailand. Arch Dis Child Fetal Neonatal Ed 2013;98:F249–55.
    1. Tröger B, Göpel W, Faust K, et al. . Risk for late-onset blood-culture proven sepsis in very-low-birth weight infants born small for gestational age: a large multicenter study from the German Neonatal Network. Pediatr Infect Dis J 2014;33:238–43.
    1. Morioka I, Morikawa S, Miwa A, et al. . Culture-proven neonatal sepsis in Japanese neonatal care units in 2006–2008. Neonatology 2012;102:75–80.
    1. Leal YA, Álvarez-Nemegyei J, Velázquez JR, et al. . Risk factors and prognosis for neonatal sepsis in southeastern Mexico: analysis of a four-year historic cohort follow-up. BMC Pregnancy Childbirth 2012;12:48.
    1. 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;110:285–91.
    1. Stoll BJ, Hansen NI, Adams-Chapman I, et al. . Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA 2004;292:2357–65.
    1. Dong Y, Speer CP. The role of Staphylococcus epidermidis in neonatal sepsis: guarding angel or pathogenic devil? Int J Med Microbiol 2014;304:513–20.
    1. Rasigade JP, Raulin O, Picaud JC, et al. . Methicillin-resistant Staphylococcus capitis with reduced vancomycin susceptibility causes late-onset sepsis in intensive care neonates. PLoS ONE 2012;7:e31548.
    1. Lepainteur M, Royer G, Bourrel AS, et al. . Prevalence of resistance to antiseptics and mupirocin among invasive coagulase-negative staphylococci from very preterm neonates in NICU: the creeping threat? J Hosp Infect 2013;83:333–6.
    1. Tsai MH, Chu SM, Hsu JF, et al. . Risk factors and outcomes for multidrug- resistant Gram-negative bacteremia in the NICU. Pediatrics 2014;133:e322–9.
    1. Meem M, Modak JK, Mortuza R, et al. . Biomarkers for diagnosis of neonatal infections: A systematic analysis of their potential as a point-of-care diagnostics. J Glob Health 2011;1:201–9.
    1. Ng PC, Lam HS. Biomarkers in neonatology: the next generation of tests. Neonatology 2012;102:145–51.
    1. Kasper DC, Altiok I, Mechtler TP, et al. . Molecular detection of late-onset neonatal sepsis in premature infants using small blood volumes: proof-of-concept. Neonatology 2013;103:268–73.
    1. Edmond K, Zaidi A. New approaches to preventing, diagnosing, and treating neonatal sepsis. PLoS Med 2010;7:e1000213.
    1. Altun O, Almuhayawi M, Ullberg M, et al. . Clinical evaluation of the FilmArray blood culture identification panel in identification of bacteria and yeasts from positive blood culture bottles. J Clin Microbiol 2013;51:4130–6.
    1. Cernada M, Serna E, Bauerl C, et al. . Genome-wide expression in profiles in very low birth weight infants with neonatal sepsis. Pediatrics 2014;133:e1203–11.
    1. Fairchild KD. Predictive monitoring for early detection of sepsis in neonatal ICU patients. Curr Opin Pediatr 2013;25:172–9.
    1. Moorman JR, Carlo WA, Kattwinkel J, et al. . Mortality reduction by heart rate characteristic monitoring in very low birth weight neonates: a randomized trial. J Pediatr 2011;159:900–6.
    1. Manzoni P, Mostert M, Stronati M. Lactoferrin for prevention of neonatal infections. Curr Opin Infect Dis 2011;24:177–82.
    1. Bion J, Richardson A, Hibbert P, et al. . ‘Matching Michigan’: a 2-year stepped interventional programme to minimise central venous catheter-blood stream infections in intensive care units in England. BMJ Qual Saf 2013;22:110–23.
    1. Kaplan HC, Lannon C, Walsh MC, et al. . Ohio statewide quality-improvement collaborative to reduce late-onset sepsis in preterm infants. Pediatrics 2011;127:427–35.
    1. Bersani I, Speer CP. Nosocomial sepsis in neonatal intensive care: inevitable or preventable? Z Geburtshilfe Neonatol 2012;216:186–90.
    1. Gastmeier P, Sohr D, Schwab F, et al. . Ten years of KISS: the most important requirements for success. J Hosp Infect 2008;70(Suppl 1):11–16.
    1. Tourneur E, Chassin C. Neonatal immune adaptation of the gut and its role during infections. Clin Dev Immunol 2013;2013:270301.
    1. Eckburg PB, Bik EM, Bernstein CN, et al. . Diversity of the human intestinal microbial flora. Science 2005;308:1635–8.
    1. Fanaro S, Chierici R, Guerrini P, et al. . Intestinal microflora in early infancy: composition and development. Acta Paediatr 2003;91:48–55.
    1. Madan JC, Salari RC, Saxena D, et al. . Gut microbial colonisation in premature neonates predicts neonatal sepsis. Arch Dis Child Fetal Neonatal Ed 2012;97:F456–62.
    1. 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.
    1. Sherman MP. New concepts of microbial translocation in the neonatal intestine: mechanisms and prevention. Clin Perinatol 2010;37:565–79.
    1. Gewolb IH, Schwalbe RS, Taciak VL, et al. . Stool microflora in extremely low birth weight infants. Arch Dis Child 1999;80:F167–73.
    1. Stewart CJ, Marrs EC, Magorrian S, et al. . The preterm gut microbiota: changes associated with necrotizing enterocolitis and infection. Acta Paediatr 2012;101:1121–7.
    1. Nair V, Soraisham AS. Probiotics and prebiotics: role in prevention of nosocomial sepsis in preterm infants. Int J Pediatr 2013;2013:874726.
    1. Jacobs SE, Tobin JM, Opie GF, et al. . Probiotic effects on late-onset sepsis in very preterm infants: a randomized controlled trial. Pediatrics 2013;132:1055–62.
    1. Hay WW., Jr Strategies for feeding the preterm infant. Neonatology 2008;94:245–54.
    1. Morgan J, Bombell S, McGuire W. Early trophic feeding versus enteral fasting for very preterm or very low birth weight infants. Cochrane Database Syst Rev 2013;3:CD000504.
    1. Sweeney B, Puri P, Reen DJ. Induction and modulation of apoptosis in neonatal monocytes by polyunsaturated fatty acids. J Pediatr Surg 2007;42:620–8.
    1. Flidel-Rimon O, Friedman S, Lev E, et al. . Early enteral feeding and nosocomial sepsis in very low birthweight infants. Arch Dis Child Fetal Neonatal Ed 2004;89:F289–92.
    1. Rønnestad A, Abrahamsen TG, Medbø S, et al. . Late-onset septicemia in a Norwegian national cohort of extremely premature infants receiving very early full human milk feeding. Pediatrics 2005;115:e269–76.
    1. Newburg DS, Walker WA. Protection of the neonate by the innate immune system of developing gut and of human milk. Pediatr Res 2007;61:2–8.
    1. 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;302:1421–8.
    1. Pammi M, Abrams SA. Oral lactoferrin for the prevention of sepsis and necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev 2011;(10):CD007137.
    1. 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;155:324–30.
    1. Carr R, Brocklehurst P, Doré 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): single-blind, multicentre randomized controlled trial. Lancet 2009;373:226–33.
    1. 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;330:1107–13.
    1. Brocklehurst P, Farrell B, King A, et al. ; INIS Collaborative Group. Treatment of neonatal sepsis with intravenous immune globulin. N Engl J Med 2011;365:1201–11.
    1. DeJonge M, Burchfield D, Bloom B, et al. . Clinical trial of safety and efficacy of INH-A21 for the prevention of nosocomial staphylococcal bloodstream infection in premature infants. J Pediatr 2007;151:260–5.
    1. Levy O, Wynn JL. A prime time for trained immunity: innate immune memory in newborns and infants. Neonatology 2014;105:136–41.
    1. Quach C, Milstone AM, Perpête C, et al. . Chlorhexidine Bathing in a Tertiary Care Neonatal Intensive Care Unit: Impact on Central Line–Associated Bloodstream Infections. Infect Control Hosp Epidemiol 2014;35:158–63.
    1. Sankar MJ, Paul VK. Efficacy and safety of whole body skin cleansing with chlorhexidine in neonates—a systemic review. Pediatr Infect Dis J 2013;32:e227–34.
    1. Ponnusamy V, Venkatesh V, Clarke P. Skin antisepsis in the neonate: what should we use? Curr Opin Infect Dis 2014;27:244–50.
    1. Ness MJ, Davis DM, Carey WA. Neonatal skin care: a concise review. Int J Dermatol 2013;52:14–22.
    1. Tollin M, Jagerbrink T, Haraldsson A, et al. . Proteome analysis of vernix caseosa. Pediatr Res 2006;20:430–4.
    1. Cogen AL, Nizet V, Gallo RL. Skin microbiota: a source of disease or defence? Br J Dermatol 2008;158:442–55.
    1. Russell AB, Sharland M, Heath PT. Improving antibiotic prescribing in neonatal units: time to act. Arch Dis Child Fetal Neonatal Ed 2012;97:F141–6.
    1. Muller-Pebody B, Johnson AP, Heath PT, et al. . Empirical treatment of neonatal sepsis: are the current guidelines adequate? Arch Dis Child Fetal Neonatal Ed 2011;96:F4–8.
    1. Fernando AM, Heath PT, Menson EN. Antimicrobial policies in the neonatal units of the United Kingdom and Republic of Ireland. J Antimicrob Chemother 2008;61:743–5.
    1. Anthony M, Bedford-Russell A, Cooper T, et al. . Managing and preventing outbreaks of Gram-negative infections in UK neonatal units. Arch Dis Child Fetal Neonatal Ed 2013;98:F549–53.
    1. Kuppala VS, Meinzen-Derr J, Morrow AL, et al. . Prolonged initial empirical antibiotic treatment is associated with adverse outcomes in premature infants. J Pediatr 2011;159:720–5.
    1. Lesprit P, Brun-Buisson C. Hospital antibiotic stewardship. Curr Opin Infect Dis 2008;21:344–9.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi