Early and Late Infections in Newborns: Where Do We Stand? A Review

Cortese, Francesca; Scicchitano, Pietro; Gesualdo, Michele; Filaninno, Antonella; Giorgi, Elsa De; Schettini, F; Laforgia, Nicola; Ciccone, Marco Matteo

doi:10.1016/j.pedneo.2015.09.007

Cited by 236 publications

(200 citation statements)

References 57 publications

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“…7 In the remaining seven LOS cases, Staphylococcus aureus, E. coli or Enterobacter spp. were detected, and these microbes are frequently found in the stool.…”

Section: Discussionmentioning

confidence: 99%

Elevated levels of circulating cell-free DNA and neutrophil proteins are associated with neonatal sepsis and necrotizing enterocolitis in immature mice, pigs and infants

et al. 2017

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Preterm infants are highly susceptible to late-onset sepsis (LOS) and necrotizing enterocolitis (NEC), but disease pathogenesis and specific diagnostic markers are lacking. Circulating cell-free DNA (cfDNA) and immune cell-derived proteins are involved in multiple immune diseases in adults but have not been investigated in preterm neonates. We explored the relation of circulating neutrophil-associated proteins and cfDNA to LOS and/or NEC. Using a clinically relevant preterm pig model of spontaneous LOS and NEC development, we investigated neutrophil-associated proteins and cfDNA in plasma, together with cytokines in gut tissues. The changes in cfDNA levels were further studied in preterm pigs and neonatal mice with induced sepsis, and in preterm infants with or without LOS and/or NEC. Fifteen of 114 preterm pigs spontaneously developed both LOS and NEC, and they showed increased intestinal levels of IL-6 and IL-1b and plasma levels of cfDNA, neutrophil-associated proteins, and proteins involved in platelet-neutrophil interaction during systemic inflammation. The abundance of neutrophil-associated proteins highly correlated with cfDNA levels. Further, Staphylococcus epidermidis challenge of neonatal mice and preterm pigs increased plasma cfDNA levels and bacterial accumulation in the spleen. In infants, plasma cfDNA levels were elevated at LOS diagnosis and 1-6 d before NEC. In conclusion, elevated levels of plasma cfDNA and neutrophil proteins are associated with LOS and NEC diagnosis.

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“…7 In the remaining seven LOS cases, Staphylococcus aureus, E. coli or Enterobacter spp. were detected, and these microbes are frequently found in the stool.…”

Section: Discussionmentioning

confidence: 99%

Elevated levels of circulating cell-free DNA and neutrophil proteins are associated with neonatal sepsis and necrotizing enterocolitis in immature mice, pigs and infants

et al. 2017

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“…However, we must also consider congenital syphilis as a risk factor for the concomitant occurrence of infections with distinct etiology in these newborns. Recently, Cortese et al published a review on early and late infections in newborns, which continue to lead to high morbidity and mortality in this age group [20].…”

Section: Discussionmentioning

confidence: 99%

Syphilis during Pregnancy: A Study of 879,831 Pregnant Women in Brazil

Oliveiraa¹,

Moraes²,

Álvaro³

et al. 2016

Epidemiology (Sunnyvale)

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Background: The World Health Organization (WHO) estimates that approximately 350 million new cases of curable sexually transmitted disease (STD) are reported annually in individuals aged 15 to 49 years. Furthermore, the WHO estimates that syphilis during pregnancy causes more than 300,000 fetal and newborn deaths annually and increases the risk of premature death for approximately 215,000 children. In Brazil, more than 100,000 cases were reported during pregnancy between 2005 and 2014. In 2013 alone, approximately 14,000 cases of syphilis in children younger than one year were reported. The present study evaluated the prevalence of syphilis in pregnant women and identified factors involved in the dynamics of disease maintenance.

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“…[2][3][4][5][6][7][8][9] These patients may suffer from early-onset sepsis with Streptococcus agalactiae (incidence rate 0.43% (95% confidence interval (CI) 0.37-0.49)), while Listeria monocytogenes should also be considered. 10 Because asphyxia due to infection is difficult to distinguish from asphyxia without infection, antibiotics, such as amoxicillin, are frequently used. 11 For efficacy, as a surrogate marker, the time that the nonprotein-bound concentration in blood exceeds the minimum inhibitory concentration (T>MIC) should be at least 40-50% in these patients.…”

Section: What This Study Adds To Our Knowledgementioning

confidence: 99%

Population Pharmacokinetics of Amoxicillin in Term Neonates Undergoing Moderate Hypothermia

Bijleveld

Mathôt

Lee

et al. 2017

Clin Pharma and Therapeutics

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The pharmacokinetics (PK) of amoxicillin in asphyxiated newborns undergoing moderate hypothermia were quantified using prospective data (N 5 125). The population PK was described by a 2-compartment model with a priori birthweight (BW) based allometric scaling. Significant correlations were observed between clearance (Cl) and postnatal age (PNA), gestational age (GA), body temperature (TEMP), and urine output (UO). For a typical patient with GA 40 weeks, BW 3,000 g, 2 days PNA (i.e., TEMP 33.58C), and normal UO, Cl was 0.26 L/h (interindividual variability (IIV) 41.9%) and volume of distribution of the central compartment was 0.34 L/kg (IIV of 114.6%). For this patient, Cl increased to 0.41 L/h at PNA 5 days and TEMP 37.08C. The respective contributions of both covariates were 23% and 27%. Based on Monte Carlo simulations we recommend 50 and 75 mg/kg/24h amoxicillin in three doses for patients with GA 36-37 and 38-42 weeks, respectively. Study HighlightsWHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? þ To date, there are no data on the effect of moderate hypothermia on the pharmacokinetics (PK) of amoxicillin in term neonates. Only few studies have been performed to evaluate the PK of this antibiotic in noncooled (pre)term neonates. WHAT QUESTION DID THIS STUDY ADDRESS? þ To our knowledge, this is the first prospective study evaluating and describing the PK of amoxicillin during all phases of controlled hypothermia in newborns, e.g., the hypothermic, rewarming, and normothermic phases.WHAT THIS STUDY ADDS TO OUR KNOWLEDGE þ A description of the PK properties of amoxicillin in term newborns with hypoxic-ischemic encephalopathy (HIE) due to perinatal asphyxia receiving hypothermia treatment. Gestational age (GA), postnatal age (PNA), urine output, and body temperature were significant covariates on amoxicillin clearance (Cl). HOW THIS MIGHT CHANGE CLINICAL PHARMA-COLOGY OR TRANSLATIONAL SCIENCE þ Based on the newly developed PK-model, we advise an amoxicillin dosing regimen of 50 or 75 mg/kg/24h in three doses for patients with GA 36 or GA 38-42 weeks, respectively.Term neonates who experience a severe hypoxic-ischemic insult during birth and develop encephalopathy are treated with hypothermia.1,2 This improves long-term outcomes and reduces mortality rates.2-9 These patients may suffer from early-onset sepsis with Streptococcus agalactiae (incidence rate 0.43% (95% confidence interval (CI) 0.37-0.49)), while Listeria monocytogenes should also be considered.10 Because asphyxia due to infection is difficult to distinguish from asphyxia without infection, antibiotics, such as amoxicillin, are frequently used.11 For efficacy, as a surrogate marker, the time that the nonprotein-bound concentration in blood exceeds the minimum inhibitory concentration (T>MIC) should be at least 40-50% in these patients.12 Although b-lactam antibiotics such as amoxicillin are considered safe due to the wide therapeutic range, excessive accumulation can lead to the development of adverse drug events, such as seizures and crystalluria. 13Despi...

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Early and Late Infections in Newborns: Where Do We Stand? A Review

Cited by 236 publications

References 57 publications

Elevated levels of circulating cell-free DNA and neutrophil proteins are associated with neonatal sepsis and necrotizing enterocolitis in immature mice, pigs and infants

Elevated levels of circulating cell-free DNA and neutrophil proteins are associated with neonatal sepsis and necrotizing enterocolitis in immature mice, pigs and infants

Syphilis during Pregnancy: A Study of 879,831 Pregnant Women in Brazil

Population Pharmacokinetics of Amoxicillin in Term Neonates Undergoing Moderate Hypothermia

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