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In general&#44; early neonatal sepsis is considered when the clinical condition appears within the first 72<span class="elsevierStyleHsp" style=""></span>h of life&#46; The exception to this definition is neonatal sepsis caused by <span class="elsevierStyleItalic">Streptococcus agalactiae</span>&#44; which&#44; although having a perinatal etiology&#44; can occur within the first 7 days of life&#46; Late neonatal sepsis is that which starts after 72<span class="elsevierStyleHsp" style=""></span>h of life&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> For the purposes of this article&#44; early neonatal sepsis will be considered as starting within the first 72<span class="elsevierStyleHsp" style=""></span>h of life and late neonatal sepsis after 72<span class="elsevierStyleHsp" style=""></span>h of life&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The etiological agents of early and late neonatal sepsis are quite distinct&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Early neonatal sepsis is acquired in the peripartum period&#44; before or during childbirth&#59; therefore&#44; the microorganisms are usually from the maternal genitourinary tract&#46; According to data from the American Neonatology Network&#44; Gram-positive microorganisms are the etiological agents in 62 &#37; of early neonatal sepsis cases&#44; and in 43 &#37; of the total&#44; the identified microorganism is <span class="elsevierStyleItalic">Streptococcus agalactiae</span>&#46; Gram-negative microorganismscomprise 37 &#37; of the etiological agents of early neonatal sepsis&#44; of which 29 &#37; are <span class="elsevierStyleItalic">Escherichia coli</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Late neonatal sepsis occurs most often in infants who remain hospitalized for long periods&#44; such as preterm or full-term infants who require prolonged hospitalization and invasive procedures&#44; with the most common microorganisms being those acquired in the hospital setting&#46; According to the American Neonatology Network&#44; in 79 &#37; of the situations the identified microorganisms are Gram-positive&#44; with coagulase-negative <span class="elsevierStyleItalic">Staphylococcus</span> occurring in 57 &#37; of the total and <span class="elsevierStyleItalic">Staphylococcus aureus</span> in 12 &#37;&#46; Gram-negative microorganisms constitute 19 &#37; of the total&#44; with <span class="elsevierStyleItalic">Escherichia coli</span> being the most frequently identified among them&#44; accounting for 7 &#37; of the total&#46; Fungi are found in 6 &#37; of cases of late neonatal sepsis&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Data published by the Brazilian Neonatal Research Network show results that are similar to the American findings regarding the etiological agents of late neonatal sepsis&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Eventually&#44; late sepsis can manifest in newborns in the out-of-hospital setting&#59; the most common microorganisms are those of community origin&#44; such as <span class="elsevierStyleItalic">Staphylococcus aureus</span> and <span class="elsevierStyleItalic">Escherichia coli</span>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Neonatal sepsis can also have a viral etiology&#59; however&#44; the present review focuses on discussing bacterial neonatal sepsis&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Early neonatalsepsis</span><p id="par0040" class="elsevierStylePara elsevierViewall">The incidence of early sepsis in the United States is around 0&#46;77 cases per 1000 live births&#44; and when considering only newborns above 34 weeks of gestational age&#44; it is around 0&#46;5 cases per 1000 live births&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> Since intrapartum antibiotic therapy was implemented for pregnant women colonized with <span class="elsevierStyleItalic">Streptococcus agalactiae</span>&#44; the incidence of early neonatal sepsis has fallen sharply in the United States&#44; and in services that screen and prevent perinatal streptococci infection&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The risk factors for early sepsis that have been pointed out are&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1</span><p id="par0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Streptococcus agalactiae</span> colonization&#58; A pregnant woman colonized with <span class="elsevierStyleItalic">Streptococcus agalactiae</span> who has not undergone intrapartum prophylaxis has a 25-foldhigher probability of having a newbornwith early neonatal sepsis than a non-colonized mother&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2</span><p id="par0055" class="elsevierStylePara elsevierViewall">Amniotic membrane rupture for more than 18<span class="elsevierStyleHsp" style=""></span>h&#58; newborns from mothers with amniotic membrane rupture for more than 18<span class="elsevierStyleHsp" style=""></span>h are four times more likely to have an infection than those born to mothers without rupture&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3</span><p id="par0060" class="elsevierStylePara elsevierViewall">Chorioamnionitis&#58; the presence of chorioamnionitis increases the possibility of early neonatal infection&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p></li></ul></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Diagnosis</span><p id="par0065" class="elsevierStylePara elsevierViewall">The clinical manifestations vary considerably and are nonspecific&#44; which makes the diagnosis of early neonatal sepsis difficult and predisposes to excessive antibiotic use&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The clinical signs are from different systems and can be grouped as follows&#58; a&#41; apnea&#44; difficulty breathing&#44; cyanosis&#59; b&#41; tachycardia or bradycardia&#44; poor perfusion or shock&#59; c&#41; irritability&#44; lethargy&#44; hypotonia&#44; seizures&#59; d&#41; abdominal distension&#44; vomiting&#44; food intolerance&#44; gastric residue&#44; hepatomegaly&#59; e&#41; unexplained jaundice&#59; f&#41; body temperature instability&#59; g&#41; petechiae or purpura&#46; To take into account the clinical signs&#44; ideally the newborn should show manifestations in three distinct systems&#44; or two clinical signs in distinct systems associated with a maternal risk factor&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The Kaiser Permanente Northern California group&#44; which encompasses 14 hospitals with obstetric and neonatal care&#44; was concerned about the over-requesting of tests to rule out neonatal sepsis and the overuse of antibiotics for suspected early neonatal sepsis&#44; and thus created a calculator for newborns with a gestational age of 34 weeks or over&#44; which takes into account gestational age&#44; time of ruptured amniotic membrane&#44; maternal body temperature&#44; presence or absence of <span class="elsevierStyleItalic">Streptococcus agalactiae</span> colonization&#44; and use or non-use of antibiotics in the period immediately prior to delivery to determine the likelihood of a newborn having early neonatal sepsis&#46; Considering the importance of some clinical signs&#44; especially those of respiratory origin&#44; the calculator has been improved by including the newborn&#8217;s clinical signs in the first 24<span class="elsevierStyleHsp" style=""></span>h of life&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a> This calculator is available free of charge Early-Onset Sepsis &#40;EOS calculator for both iPhone and Android&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Studies using retrospective or prospective data were carried out to assess the usefulness and accuracy of the calculator&#46; Applying the calculator has been shown to decrease antibiotic use in late preterm or full-term preterm infants by approximately 40 &#37;&#44; without increasing the risk of false negative results&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;15&#8211;17</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Another strategy that has been used in an attempt to reduce the use of antibiotics and over-requesting of laboratory tests is to take into account the careful and frequent observation of clinical signs in newborns at risk of early neonatal sepsis&#46; A European study that closely observed clinical signs showed a decrease in antibiotic use and decreased hospital length of stay&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> In a recent publication&#44; the American Academy of Pediatrics suggests that close clinical observation within the first 48<span class="elsevierStyleHsp" style=""></span>h may be more effective than the EOS calculator in determining late preterm and full-term newborns with early neonatal sepsis&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">For newborns with a gestational age of 34 weeks or less&#44; the most important risk factor is the presence of chorioamnionitis&#44; defined by maternal hyperthermia equal to or greater than 39<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; or between 38<span class="elsevierStyleHsp" style=""></span>&#176;C and 39<span class="elsevierStyleHsp" style=""></span>&#176;C accompanied by at least one of the following clinical signs&#58; maternal leukocytosis&#44; purulent vaginal discharge&#44; or fetal tachycardia&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The risk of early sepsis is high when preterm birth occurs after spontaneous labor&#44; when there is prolonged rupture of the amniotic membrane&#44; or in the presence of chorioamnionitis&#46; The most adequate approach in these situations is to collect blood culture&#44; cerebrospinal fluid&#44; and complementary exams&#44; and to start empirical antibiotic therapy&#46; The risk of early sepsis is low when the delivery is by caesarean section&#44; without ruptured amniotic membrane and without labor&#59; for instance&#44; in patients with pre-eclampsia who need to have their pregnancy interrupted for obstetric reasons&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Laboratory tests</span><p id="par0100" class="elsevierStylePara elsevierViewall">If early neonatal sepsis is suspected&#44; blood culture and CSF samples should be collected&#46; Urinalysis is not indicated&#44; since urinary infection in early neonatal sepsis is unusual&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Complete blood count &#40;CBC&#41; and serum C-reactive protein have a better negative predictive value than a positive predictive value&#46; The most common CBC findings are immature to total neutrophil ratio &#40;I&#47;T ratio&#41; &#62;0&#46;2&#44; leukopenia &#40;below 5000&#41;&#44; or leukocytosis &#40;&#62;25&#44;000&#41;&#46; Serial low C-reactive protein levels &#40;serum levels below 10<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41; help to rule out the diagnosis of neonatal sepsis in a newborn with negative blood culture&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Antibiotic therapy</span><p id="par0110" class="elsevierStylePara elsevierViewall">The empirical antibiotic treatment protocol in our Unit is ampicillin and gentamicin&#46; This antibiotic regimen covers the microorganisms that most commonly cause early neonatal sepsis&#46; The ampicillin spectrum is adequate for <span class="elsevierStyleItalic">Streptococcus agalactiae</span> and for <span class="elsevierStyleItalic">Listeria</span>&#44; which occurs very rarely in Brazil&#46; Gentamicin has an adequate spectrum for Gram-negative microorganisms and especially for <span class="elsevierStyleItalic">Escherichia coli</span>&#46; After obtaining blood culture results with the antibiogram test&#44; the antibiotic regimen should be established with the specific drug indicated by the results&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">In case of meningitis&#44; with <span class="elsevierStyleItalic">Streptococcus agalactiae</span> being the etiological agent&#44; it is recommended to adjust ampicillin to the appropriate dose indicated for the treatment of meningitis&#46; If the microorganism is unknown or in the case of a Gram-negative microorganism&#44; changing the antibiotic to cefepime is indicated&#46;</p><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Prevention of early neonatal sepsis caused by <span class="elsevierStyleItalic">Streptococcus agalactiae</span></span><p id="par0120" class="elsevierStylePara elsevierViewall">Briefly&#44; the CDC recommends the following for the prevention of sepsis caused by <span class="elsevierStyleItalic">Streptococcus agalactiae</span><a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0125" class="elsevierStylePara elsevierViewall">Universal screening &#40;for all pregnant women&#41; of streptococcal colonization between 35 and 37 weeks of gestation&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0130" class="elsevierStylePara elsevierViewall">During labor or at the time of membrane rupture&#44; chemoprophylaxis should be administered to all pregnant women colonized by streptococcus&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0135" class="elsevierStylePara elsevierViewall">Women with identified streptococcus in urine cultures &#40;at any concentration&#41; during pregnancy should receive intrapartum chemoprophylaxis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8226;</span><p id="par0140" class="elsevierStylePara elsevierViewall">Women who had a previous child with streptococcal infection should receive chemoprophylaxis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8226;</span><p id="par0145" class="elsevierStylePara elsevierViewall">If the screening result is not known&#44; the patient should receive chemoprophylaxis in the following cases&#58; &#40;1&#41; labor at gestational age less than 37 weeks&#59; &#40;2&#41; time of membrane rupture &#62; 18<span class="elsevierStyleHsp" style=""></span>h&#59; &#40;3&#41; presence of fever during labor &#40;&#8805; 38<span class="elsevierStyleHsp" style=""></span>&#176;C&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0150" class="elsevierStylePara elsevierViewall">For intrapartum prophylaxis&#44; the following antimicrobial regimen is recommended&#58; crystalline penicillin&#58; 5000&#44;000 intravenous units as a loading dose and 2&#44;500&#44;000 intravenous units every four hours until delivery&#46; As a second-line therapy&#44; intravenous ampicillin with a loading dose of 2<span class="elsevierStyleHsp" style=""></span>g can be used&#44; and 1<span class="elsevierStyleHsp" style=""></span>g intravenous every four hours until delivery&#46;</p></li></ul></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Late neonatal sepsis</span><p id="par0155" class="elsevierStylePara elsevierViewall">Late neonatal sepsis is that which occurs after 72<span class="elsevierStyleHsp" style=""></span>h of life&#59; it is more frequent in very low birth weight infants with long-term hospitalization in a neonatal intensive care unit &#40;ICU&#41; or in late preterm or full-term infants requiring prolonged hospitalization&#46; The incidence of at least one first positive blood culture after 72<span class="elsevierStyleHsp" style=""></span>h of life in very low birth weight preterm infants &#40;birth weight &#8804;1500<span class="elsevierStyleHsp" style=""></span>g&#41; varies from 20 &#37; to 35 &#37;&#44; depending on the assessed service&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6&#44;22</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">The microorganisms most often associated with late neonatal sepsis are Gram-positive &#40;79 &#37;&#41;&#44; especially coagulase-negative <span class="elsevierStyleItalic">Staphylococcus</span>&#46; Infections caused by Gram-negative microorganisms also occur&#44; and the incidence of fungal sepsis has become important in numerous centers&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">The occurrence of viral infections&#44; especially respiratory syncytial virus and rhinovirus&#44; has been frequently reported in newborns with a clinical picture similar to that of bacterial neonatal sepsis admitted to neonatal ICUs&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">The most important risk factors for late neonatal sepsis are&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">1</span><p id="par0175" class="elsevierStylePara elsevierViewall">Prematurity&#58; compared to full-term infants&#44; preterm infants have lower pro-inflammatory cytokine production&#44; lower natural killer &#40;NK&#41; cell activation&#44; decreased cell-mediated immunity&#44; decreased placental transfer of immunoglobulins&#44; and lower levels of serum complement&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">2</span><p id="par0180" class="elsevierStylePara elsevierViewall">Breach of natural barriers&#58; lesions and lacerations of skin and mucosa can be a portal of entry for bacterial invasion&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">3</span><p id="par0185" class="elsevierStylePara elsevierViewall">Long term indwelling central catheters are portals of entry for bacteria&#46;</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">4</span><p id="par0190" class="elsevierStylePara elsevierViewall">Invasive procedures&#44; <span class="elsevierStyleItalic">e&#46;g&#46;</span>&#44; tracheal intubation&#58; the risk of sepsis increases with the number of times the newborn has been intubated&#59; accidental extubations requiring frequent reintubation are important causes of infection&#46;</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">5</span><p id="par0195" class="elsevierStylePara elsevierViewall">Use of H2 blockers&#58; gastric acidity acts as a barrier to bacterial proliferation and invasion&#59; the use of H2 blockers decreases the defense mechanism and increases the risk of bacterial invasion&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">6</span><p id="par0200" class="elsevierStylePara elsevierViewall">Prolonged use of empirical antibiotic therapy&#58; the use of empirical antibiotic therapy for early neonatal sepsis for more than five days increases the incidence of late neonatal sepsis&#44; especially in units with scarce use of breast milk and over-prescription of third-generation cephalosporins&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a></p></li></ul></p><p id="par0205" class="elsevierStylePara elsevierViewall">It is important to note that late sepsis also occurs in full-term newborns&#44; post-discharge&#46; A study carried out in the United States&#44; analyzing 4255 blood cultures collected from 160&#44;818 full-term newborns who returned to the emergency department&#44; aged between 1 week and 3 months&#44; showed a positivity of 0&#46;57 per 1000 newborns&#44; and the most commonly found microorganism was <span class="elsevierStyleItalic">Escherichia coli</span>&#46; The initial source of infection in these patients was a urinary tract infection&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Screening for urinary tract infection in late neonatal sepsis should always be performed&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Diagnosis</span><p id="par0210" class="elsevierStylePara elsevierViewall">Clinical manifestations&#44; as well as early neonatal sepsis&#44; vary considerably and are nonspecific&#46; The clinical signs originate from different systems and can be grouped as follows&#58; a&#41; apnea&#44; difficulty breathing&#44; cyanosis&#59; b&#41; tachycardia or bradycardia&#44; poor perfusion or shock&#59; c&#41; irritability&#44; lethargy&#44; hypotonia&#44; seizures&#59; d&#41; abdominal distension&#44; vomiting&#44; food intolerance&#44; gastric residue&#44; hepatomegaly&#59; e&#41; unexplained jaundice&#59; f&#41; body temperature instability&#59; g&#41; petechiae or purpura&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">In the case of a preterm newborn hospitalized for a long period in the neonatal ICU with suspected clinical signs of sepsis&#44; the collection of blood culture&#44; CSF&#44; and sterile urine &#40;suprapubic puncture or catheter sample&#41; is recommended for cultures&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">Blood samples containing 1<span class="elsevierStyleHsp" style=""></span>mL of blood should be collected from two separate sites&#46; The most frequently identified microorganism in late neonatal sepsis is coagulase-negative <span class="elsevierStyleItalic">Staphylococcus</span>&#44; and the distinction between finding a contaminating agent or not is attained through the positivity of blood cultures collected at two different sites&#46; The positivity of both blood cultures is indicative that coagulase-negative <span class="elsevierStyleItalic">Staphylococcus</span> is the etiological agent of sepsis&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Complementary laboratory tests&#44; such as complete blood count and C-reactive protein&#44; have a better negative predictive value than a positive predictive value&#44; similarly as in early neonatal sepsis&#46; However&#44; on certain occasions&#44; the result of the serum C-reactive protein level in combination with the clinical picture helps to direct treatment decision-making&#46; The cutoff point for C-reactive protein is 10<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">The clinical picture of the newborn is crucial for the suspicion of neonatal sepsis and&#44; after the result of blood culture&#44; it is the main information to guide the need for treatment&#46; A newborn in good general condition will only be indicated for antibiotic therapy if the blood culture is positive&#44; regardless of the CBC or C-reactive protein results&#46; On the other hand&#44; a newborn with clinical signs showing disease will not have indication for antibiotic therapy only if the blood culture is negative and if they have at least two sequential low C-reactive protein levels 24<span class="elsevierStyleHsp" style=""></span>h apart&#46; In this situation&#44; the clinician should consider that the signs of the disease are of a non-infectious bacterial etiology&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Antibiotic therapy</span><p id="par0235" class="elsevierStylePara elsevierViewall">Empirical antibiotic therapy should take into account the most likely etiological agents and their responses to antibiotic therapy&#46; Although the most common microorganism in late neonatal sepsis is methicillin-resistant coagulase-negative <span class="elsevierStyleItalic">Staphylococcus</span>&#44; this does not mean that the initial empirical regimen should include vancomycin&#46; Several studies have shown that not using vancomycin in the initial empirical antibiotic regimen does not increase mortality&#44; duration of bacteremia&#44; and complications attributed to late neonatal sepsis&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#8211;32</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">The indiscriminate and excessive use of vancomycin is an important factor in the emergence of multiresistant flora and the increased occurrence of invasive fungal infection&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">Krediet et al&#46; studied 66 newborns with sepsis caused by coagulase-negative <span class="elsevierStyleItalic">Staphylococcus</span> who received three distinct treatment regimens&#58; 25 received cephalothin&#44; 15 received vancomycin&#44; and 26 started the treatment with cephalothin and then switched to vancomycin&#46; Although 22 of the 25 cephalothin-treated patients had methicillin-resistant coagulase-negative <span class="elsevierStyleItalic">Staphylococcus</span>&#44; the cephalothin treatment was maintained and the patients recovered without any complications or recurrence&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">Currently&#44; there are antibiotic use management regimens for neonatal ICUs that predict the initial use of oxacillin in the initial empirical regimen for late neonatal sepsis and eventual change to vancomycin&#44; only when there is no improvement in the patient&#39;s clinical condition after 48<span class="elsevierStyleHsp" style=""></span>h of oxacillin use&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#44;32</span></a> Sepsis caused by coagulase-negative <span class="elsevierStyleItalic">Staphylococcus</span> usually has a milder course and a subacute evolution&#44; which allows patients to be observed for 48<span class="elsevierStyleHsp" style=""></span>h on oxacillin use and the eventual change only if there is no adequate response to oxacillin use&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">The empirical antibiotic therapy protocol for late neonatal sepsis in our Unit includes oxacillin and amikacin&#46; Amikacin is used to cover Gram-negative microorganisms that can occur in hospital-acquired sepsis&#46; After microorganism identification&#44; the antibiotic therapy should be directed by the antibiogram test&#44; except in cases of oxacillin-resistant coagulase-negative <span class="elsevierStyleItalic">Staphylococcus</span>&#44; in which it is maintained depending on the <span class="elsevierStyleItalic">in vivo</span> response to oxacillin&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">In case of meningitis&#44; adjustment of antibiotic therapy according to the identified microorganism and antibiogram test are recommended&#46; If the etiological agent is unknown&#44; change of the antibiotic regimen to cefepime is indicated&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Prevention of late neonatal sepsis</span><p id="par0265" class="elsevierStylePara elsevierViewall">Some measures are indicated in the prevention of late neonatal sepsis&#58;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">1</span><p id="par0270" class="elsevierStylePara elsevierViewall">Handwashing or use of alcohol gel&#58; Handwashing and&#47;or use of alcohol gel is the most effective measure to prevent infections&#46; Microorganisms are carried by the hands when handling a patient&#46; The five moments of hand hygiene recommended by the World Health Organization should be emphasized&#58; 1&#46; before contact with the patient&#59; 2&#46; before the procedure is performed&#59; 3&#46; after risk of exposure to biological fluids&#59; 4&#46; after contact with the patient&#59; 5&#46; after contact with areas near the patient&#46;</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">2</span><p id="par0275" class="elsevierStylePara elsevierViewall">Appropriate and well-defined care bundles&#44; with central intravascular catheters and endotracheal tubes that are closely followed to reduce contamination&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a></p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">3</span><p id="par0280" class="elsevierStylePara elsevierViewall">Trophic enteral feeding&#58; early onset of trophic feeding stimulates the gastrointestinal tract&#44; stimulating intestinal maturity&#44; preventing villous atrophy&#44; and also decreasing bacterial translocation and invasion through the intestinal mucosa&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a></p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">4</span><p id="par0285" class="elsevierStylePara elsevierViewall">Use of breast milk&#58; breast milk contains significant concentrations of IgA and oligosaccharides that give it anti-infectious properties&#46; The exclusive use of breast milk results in more diverse intestinal microbiota&#44; which leads to a lower probability of infections&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">36&#44;37</span></a></p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">5</span><p id="par0290" class="elsevierStylePara elsevierViewall">Probiotics&#58; although there are meta-analyses showing that probiotics may be useful in preventing late neonatal sepsis&#44; there are still many questions regarding their routine use&#46; The studies were performed with different types of probiotics&#44; different dosages&#44; and highly variable treatment times&#44; which makes the generalization of results very difficult&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">38&#44;39</span></a></p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">6</span><p id="par0295" class="elsevierStylePara elsevierViewall">Lactoferrin&#58; there are conflicting studies regarding the role of lactoferrin as a protective factor against late neonatal sepsis&#46; An Italian collaborative randomized trial included 472 very low birth weight infants&#58; the lactoferrin group with 153 patients&#44; the lactoferrin and probiotic group with 151 patients&#44; and the placebo group &#40;glucose 5 &#37;&#41; with 168 patients&#44; treated from birth to 30 days of life&#46;Late sepsis was significantly lower in the groups that received lactoferrin&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> However&#44; a recently published collaborative randomized clinical trial was carried out in the United Kingdom with 2203 newborns&#44; of gestational age &#60;32 weeks&#58; 1099 in the lactoferrin group up to 34 weeks of corrected gestational age and 1104 in the control group receiving sucrose up to 34 weeks of corrected age&#46; There was no significant difference in the incidence of late sepsis&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> At this time&#44; the indication of lactoferrin as a preventive measure for late neonatal sepsis is still under evaluation&#46;</p></li></ul></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclusions</span><p id="par0300" class="elsevierStylePara elsevierViewall">Management of neonatal sepsis is always a challenge&#46; Neonatal sepsis is a frequent cause of neonatal morbidity and mortality&#44; especially in developing countries&#46; Its diagnosis is difficult&#44; since clinical signs are nonspecific and complementary exams have low accuracy&#46; Continuous observation of the patient&#44; knowing how to take into account clinical signs&#44; and observing risk factors are essential for diagnostic suspicion&#46; When neonatal sepsis is suspected&#44; always collect samples for bacteriological analysis before starting the empirical treatment&#46; The decision to start empirical antibiotic therapy and the choice of the most appropriate treatment regimen are crucial&#46; Avoiding routine vancomycin use in the empirical antibiotic regimen in late neonatal sepsis is important to prevent bacterial resistance and invasive fungal infections&#46; The main protective mechanisms against neonatal sepsis are handwashing and the use of breast milk&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflicts of interest</span><p id="par0305" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest&#46;</p></span></span>"
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            3 => "Estafilococo coagulase negativo"
            4 => "Estreptococo grupo B"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To present current evidence on the etiology&#44; risk factors&#44; diagnosis&#44; and management of early and late neonatal sepsis&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Source of data</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Non-systematic review of the Medline &#40;PubMed&#41;&#44; Scopus&#44; Web of Science&#44; Cochrane&#44; and Google Scholar databases regarding the following terms&#58; neonatal sepsis&#44; early neonatal sepsis&#44; late neonatal sepsis&#44; empirical antibiotic therapy&#44; sepsis calculator&#44; vancomycin&#44; newborn&#44; preterm newborn&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Data synthesis</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Neonatal sepsis is a frequent cause of neonatal morbidity and mortality&#46; Its diagnosis is difficult&#46; Continuous observation of the patient is critical to diagnostic suspicion&#46; When neonatal sepsis is suspected&#44; bacteriological tests should be collected&#46; Vancomycin should not be routinely using in the empirical antibiotic regimen in late neonatal sepsis&#44; and the main protective mechanisms against neonatal sepsis are handwashing and the use of breast milk&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Newborns constitute a group that is more vulnerable to sepsis&#46; Knowledge of risk factors and etiological agents allows a better approach to the newborn with sepsis&#46;</p></span>"
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            "titulo" => "Source of data"
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            "titulo" => "Data synthesis"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Apresentar evid&#234;ncias atuais na etiologia&#44; fatores de risco&#44; diagn&#243;stico e manejo da sepse neonatal precoce e tardia&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Fontes de dados</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Revis&#227;o n&#227;o sistem&#225;tica feita nas bases de dados Medline &#40;PubMed&#41;&#44; Scopus&#44; Web of Science&#44; Cochrane&#44; Google Scholar sobre os temas sepse neonatal&#44; sepse neonatal precoce&#44; sepse neonatal tardia&#44; antibioticoterapia emp&#237;rica&#44; sepsis calculator&#44; vancomicina&#44; rec&#233;m-nascido&#44; rec&#233;m-nascido pr&#233;-termo&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">S&#237;ntese de dados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A sepse neonatal &#233; uma causa frequente de morbimortalidade neonatal&#46; O seu diagn&#243;stico &#233; dif&#237;cil&#46; A observa&#231;&#227;o cont&#237;nua do paciente &#233; fundamental para uma suspei&#231;&#227;o diagn&#243;stica&#46; Ao se suspeitar de sepse neonatal devem-se coletar exames bacteriol&#243;gicos&#46; N&#227;o usar&#44; rotineiramente&#44; vancomicina no esquema emp&#237;rico de antibi&#243;tico na sepse neonatal tardia&#46; Os principais mecanismos protetores da sepse neonatal s&#227;o a lavagem de m&#227;os e o uso do leite materno&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#245;es</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Os rec&#233;m-nascidos constituem um grupo mais vulner&#225;vel &#224; sepse&#46; O conhecimento dos fatores de risco e dos agentes etiol&#243;gicos permite uma melhor abordagem do rec&#233;m-nascido s&#233;ptico&#46;</p></span>"
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            "titulo" => "S&#237;ntese de dados"
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      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Procianoy RS&#44; Silveira RC&#46; The challenges of neonatal sepsis management&#46; J Pediatr &#40;Rio J&#41;&#46; 2020&#59;96&#40;S1&#41;&#58;80&#8211;6&#46;</p>"
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Review article
The challenges of neonatal sepsis management
Os desafios no manejo da sepse neonatal
Renato Soibelmann Procianoy
Corresponding author
rprocianoy@gmail.com

Corresponding author.
, Rita C. Silveira
Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Departamento de Pediatria, Serviço de Neonatologia, Porto Alegre, RS, Brazil
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Neonatal sepsis is a clinical syndrome with hemodynamic changes and other systemic clinical manifestations resulting from the presence of pathogenic microorganisms &#40;bacteria&#44; viruses&#44; or fungi&#41; in normally sterile fluid&#44; such as blood or cerebrospinal fluid &#40;CSF&#41; in the first month of life&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Neonatal sepsis is an important cause of neurocognitive sequelae and neonatal mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Neonatal sepsis is classified according to the time of onset as early or late&#46; In general&#44; early neonatal sepsis is considered when the clinical condition appears within the first 72<span class="elsevierStyleHsp" style=""></span>h of life&#46; The exception to this definition is neonatal sepsis caused by <span class="elsevierStyleItalic">Streptococcus agalactiae</span>&#44; which&#44; although having a perinatal etiology&#44; can occur within the first 7 days of life&#46; Late neonatal sepsis is that which starts after 72<span class="elsevierStyleHsp" style=""></span>h of life&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> For the purposes of this article&#44; early neonatal sepsis will be considered as starting within the first 72<span class="elsevierStyleHsp" style=""></span>h of life and late neonatal sepsis after 72<span class="elsevierStyleHsp" style=""></span>h of life&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The etiological agents of early and late neonatal sepsis are quite distinct&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Early neonatal sepsis is acquired in the peripartum period&#44; before or during childbirth&#59; therefore&#44; the microorganisms are usually from the maternal genitourinary tract&#46; According to data from the American Neonatology Network&#44; Gram-positive microorganisms are the etiological agents in 62 &#37; of early neonatal sepsis cases&#44; and in 43 &#37; of the total&#44; the identified microorganism is <span class="elsevierStyleItalic">Streptococcus agalactiae</span>&#46; Gram-negative microorganismscomprise 37 &#37; of the etiological agents of early neonatal sepsis&#44; of which 29 &#37; are <span class="elsevierStyleItalic">Escherichia coli</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Late neonatal sepsis occurs most often in infants who remain hospitalized for long periods&#44; such as preterm or full-term infants who require prolonged hospitalization and invasive procedures&#44; with the most common microorganisms being those acquired in the hospital setting&#46; According to the American Neonatology Network&#44; in 79 &#37; of the situations the identified microorganisms are Gram-positive&#44; with coagulase-negative <span class="elsevierStyleItalic">Staphylococcus</span> occurring in 57 &#37; of the total and <span class="elsevierStyleItalic">Staphylococcus aureus</span> in 12 &#37;&#46; Gram-negative microorganisms constitute 19 &#37; of the total&#44; with <span class="elsevierStyleItalic">Escherichia coli</span> being the most frequently identified among them&#44; accounting for 7 &#37; of the total&#46; Fungi are found in 6 &#37; of cases of late neonatal sepsis&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Data published by the Brazilian Neonatal Research Network show results that are similar to the American findings regarding the etiological agents of late neonatal sepsis&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Eventually&#44; late sepsis can manifest in newborns in the out-of-hospital setting&#59; the most common microorganisms are those of community origin&#44; such as <span class="elsevierStyleItalic">Staphylococcus aureus</span> and <span class="elsevierStyleItalic">Escherichia coli</span>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Neonatal sepsis can also have a viral etiology&#59; however&#44; the present review focuses on discussing bacterial neonatal sepsis&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Early neonatalsepsis</span><p id="par0040" class="elsevierStylePara elsevierViewall">The incidence of early sepsis in the United States is around 0&#46;77 cases per 1000 live births&#44; and when considering only newborns above 34 weeks of gestational age&#44; it is around 0&#46;5 cases per 1000 live births&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> Since intrapartum antibiotic therapy was implemented for pregnant women colonized with <span class="elsevierStyleItalic">Streptococcus agalactiae</span>&#44; the incidence of early neonatal sepsis has fallen sharply in the United States&#44; and in services that screen and prevent perinatal streptococci infection&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The risk factors for early sepsis that have been pointed out are&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1</span><p id="par0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Streptococcus agalactiae</span> colonization&#58; A pregnant woman colonized with <span class="elsevierStyleItalic">Streptococcus agalactiae</span> who has not undergone intrapartum prophylaxis has a 25-foldhigher probability of having a newbornwith early neonatal sepsis than a non-colonized mother&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2</span><p id="par0055" class="elsevierStylePara elsevierViewall">Amniotic membrane rupture for more than 18<span class="elsevierStyleHsp" style=""></span>h&#58; newborns from mothers with amniotic membrane rupture for more than 18<span class="elsevierStyleHsp" style=""></span>h are four times more likely to have an infection than those born to mothers without rupture&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3</span><p id="par0060" class="elsevierStylePara elsevierViewall">Chorioamnionitis&#58; the presence of chorioamnionitis increases the possibility of early neonatal infection&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p></li></ul></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Diagnosis</span><p id="par0065" class="elsevierStylePara elsevierViewall">The clinical manifestations vary considerably and are nonspecific&#44; which makes the diagnosis of early neonatal sepsis difficult and predisposes to excessive antibiotic use&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The clinical signs are from different systems and can be grouped as follows&#58; a&#41; apnea&#44; difficulty breathing&#44; cyanosis&#59; b&#41; tachycardia or bradycardia&#44; poor perfusion or shock&#59; c&#41; irritability&#44; lethargy&#44; hypotonia&#44; seizures&#59; d&#41; abdominal distension&#44; vomiting&#44; food intolerance&#44; gastric residue&#44; hepatomegaly&#59; e&#41; unexplained jaundice&#59; f&#41; body temperature instability&#59; g&#41; petechiae or purpura&#46; To take into account the clinical signs&#44; ideally the newborn should show manifestations in three distinct systems&#44; or two clinical signs in distinct systems associated with a maternal risk factor&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The Kaiser Permanente Northern California group&#44; which encompasses 14 hospitals with obstetric and neonatal care&#44; was concerned about the over-requesting of tests to rule out neonatal sepsis and the overuse of antibiotics for suspected early neonatal sepsis&#44; and thus created a calculator for newborns with a gestational age of 34 weeks or over&#44; which takes into account gestational age&#44; time of ruptured amniotic membrane&#44; maternal body temperature&#44; presence or absence of <span class="elsevierStyleItalic">Streptococcus agalactiae</span> colonization&#44; and use or non-use of antibiotics in the period immediately prior to delivery to determine the likelihood of a newborn having early neonatal sepsis&#46; Considering the importance of some clinical signs&#44; especially those of respiratory origin&#44; the calculator has been improved by including the newborn&#8217;s clinical signs in the first 24<span class="elsevierStyleHsp" style=""></span>h of life&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a> This calculator is available free of charge Early-Onset Sepsis &#40;EOS calculator for both iPhone and Android&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Studies using retrospective or prospective data were carried out to assess the usefulness and accuracy of the calculator&#46; Applying the calculator has been shown to decrease antibiotic use in late preterm or full-term preterm infants by approximately 40 &#37;&#44; without increasing the risk of false negative results&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;15&#8211;17</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Another strategy that has been used in an attempt to reduce the use of antibiotics and over-requesting of laboratory tests is to take into account the careful and frequent observation of clinical signs in newborns at risk of early neonatal sepsis&#46; A European study that closely observed clinical signs showed a decrease in antibiotic use and decreased hospital length of stay&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> In a recent publication&#44; the American Academy of Pediatrics suggests that close clinical observation within the first 48<span class="elsevierStyleHsp" style=""></span>h may be more effective than the EOS calculator in determining late preterm and full-term newborns with early neonatal sepsis&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">For newborns with a gestational age of 34 weeks or less&#44; the most important risk factor is the presence of chorioamnionitis&#44; defined by maternal hyperthermia equal to or greater than 39<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; or between 38<span class="elsevierStyleHsp" style=""></span>&#176;C and 39<span class="elsevierStyleHsp" style=""></span>&#176;C accompanied by at least one of the following clinical signs&#58; maternal leukocytosis&#44; purulent vaginal discharge&#44; or fetal tachycardia&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The risk of early sepsis is high when preterm birth occurs after spontaneous labor&#44; when there is prolonged rupture of the amniotic membrane&#44; or in the presence of chorioamnionitis&#46; The most adequate approach in these situations is to collect blood culture&#44; cerebrospinal fluid&#44; and complementary exams&#44; and to start empirical antibiotic therapy&#46; The risk of early sepsis is low when the delivery is by caesarean section&#44; without ruptured amniotic membrane and without labor&#59; for instance&#44; in patients with pre-eclampsia who need to have their pregnancy interrupted for obstetric reasons&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Laboratory tests</span><p id="par0100" class="elsevierStylePara elsevierViewall">If early neonatal sepsis is suspected&#44; blood culture and CSF samples should be collected&#46; Urinalysis is not indicated&#44; since urinary infection in early neonatal sepsis is unusual&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Complete blood count &#40;CBC&#41; and serum C-reactive protein have a better negative predictive value than a positive predictive value&#46; The most common CBC findings are immature to total neutrophil ratio &#40;I&#47;T ratio&#41; &#62;0&#46;2&#44; leukopenia &#40;below 5000&#41;&#44; or leukocytosis &#40;&#62;25&#44;000&#41;&#46; Serial low C-reactive protein levels &#40;serum levels below 10<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41; help to rule out the diagnosis of neonatal sepsis in a newborn with negative blood culture&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Antibiotic therapy</span><p id="par0110" class="elsevierStylePara elsevierViewall">The empirical antibiotic treatment protocol in our Unit is ampicillin and gentamicin&#46; This antibiotic regimen covers the microorganisms that most commonly cause early neonatal sepsis&#46; The ampicillin spectrum is adequate for <span class="elsevierStyleItalic">Streptococcus agalactiae</span> and for <span class="elsevierStyleItalic">Listeria</span>&#44; which occurs very rarely in Brazil&#46; Gentamicin has an adequate spectrum for Gram-negative microorganisms and especially for <span class="elsevierStyleItalic">Escherichia coli</span>&#46; After obtaining blood culture results with the antibiogram test&#44; the antibiotic regimen should be established with the specific drug indicated by the results&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">In case of meningitis&#44; with <span class="elsevierStyleItalic">Streptococcus agalactiae</span> being the etiological agent&#44; it is recommended to adjust ampicillin to the appropriate dose indicated for the treatment of meningitis&#46; If the microorganism is unknown or in the case of a Gram-negative microorganism&#44; changing the antibiotic to cefepime is indicated&#46;</p><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Prevention of early neonatal sepsis caused by <span class="elsevierStyleItalic">Streptococcus agalactiae</span></span><p id="par0120" class="elsevierStylePara elsevierViewall">Briefly&#44; the CDC recommends the following for the prevention of sepsis caused by <span class="elsevierStyleItalic">Streptococcus agalactiae</span><a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0125" class="elsevierStylePara elsevierViewall">Universal screening &#40;for all pregnant women&#41; of streptococcal colonization between 35 and 37 weeks of gestation&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0130" class="elsevierStylePara elsevierViewall">During labor or at the time of membrane rupture&#44; chemoprophylaxis should be administered to all pregnant women colonized by streptococcus&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0135" class="elsevierStylePara elsevierViewall">Women with identified streptococcus in urine cultures &#40;at any concentration&#41; during pregnancy should receive intrapartum chemoprophylaxis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8226;</span><p id="par0140" class="elsevierStylePara elsevierViewall">Women who had a previous child with streptococcal infection should receive chemoprophylaxis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8226;</span><p id="par0145" class="elsevierStylePara elsevierViewall">If the screening result is not known&#44; the patient should receive chemoprophylaxis in the following cases&#58; &#40;1&#41; labor at gestational age less than 37 weeks&#59; &#40;2&#41; time of membrane rupture &#62; 18<span class="elsevierStyleHsp" style=""></span>h&#59; &#40;3&#41; presence of fever during labor &#40;&#8805; 38<span class="elsevierStyleHsp" style=""></span>&#176;C&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0150" class="elsevierStylePara elsevierViewall">For intrapartum prophylaxis&#44; the following antimicrobial regimen is recommended&#58; crystalline penicillin&#58; 5000&#44;000 intravenous units as a loading dose and 2&#44;500&#44;000 intravenous units every four hours until delivery&#46; As a second-line therapy&#44; intravenous ampicillin with a loading dose of 2<span class="elsevierStyleHsp" style=""></span>g can be used&#44; and 1<span class="elsevierStyleHsp" style=""></span>g intravenous every four hours until delivery&#46;</p></li></ul></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Late neonatal sepsis</span><p id="par0155" class="elsevierStylePara elsevierViewall">Late neonatal sepsis is that which occurs after 72<span class="elsevierStyleHsp" style=""></span>h of life&#59; it is more frequent in very low birth weight infants with long-term hospitalization in a neonatal intensive care unit &#40;ICU&#41; or in late preterm or full-term infants requiring prolonged hospitalization&#46; The incidence of at least one first positive blood culture after 72<span class="elsevierStyleHsp" style=""></span>h of life in very low birth weight preterm infants &#40;birth weight &#8804;1500<span class="elsevierStyleHsp" style=""></span>g&#41; varies from 20 &#37; to 35 &#37;&#44; depending on the assessed service&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6&#44;22</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">The microorganisms most often associated with late neonatal sepsis are Gram-positive &#40;79 &#37;&#41;&#44; especially coagulase-negative <span class="elsevierStyleItalic">Staphylococcus</span>&#46; Infections caused by Gram-negative microorganisms also occur&#44; and the incidence of fungal sepsis has become important in numerous centers&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">The occurrence of viral infections&#44; especially respiratory syncytial virus and rhinovirus&#44; has been frequently reported in newborns with a clinical picture similar to that of bacterial neonatal sepsis admitted to neonatal ICUs&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">The most important risk factors for late neonatal sepsis are&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">1</span><p id="par0175" class="elsevierStylePara elsevierViewall">Prematurity&#58; compared to full-term infants&#44; preterm infants have lower pro-inflammatory cytokine production&#44; lower natural killer &#40;NK&#41; cell activation&#44; decreased cell-mediated immunity&#44; decreased placental transfer of immunoglobulins&#44; and lower levels of serum complement&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">2</span><p id="par0180" class="elsevierStylePara elsevierViewall">Breach of natural barriers&#58; lesions and lacerations of skin and mucosa can be a portal of entry for bacterial invasion&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">3</span><p id="par0185" class="elsevierStylePara elsevierViewall">Long term indwelling central catheters are portals of entry for bacteria&#46;</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">4</span><p id="par0190" class="elsevierStylePara elsevierViewall">Invasive procedures&#44; <span class="elsevierStyleItalic">e&#46;g&#46;</span>&#44; tracheal intubation&#58; the risk of sepsis increases with the number of times the newborn has been intubated&#59; accidental extubations requiring frequent reintubation are important causes of infection&#46;</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">5</span><p id="par0195" class="elsevierStylePara elsevierViewall">Use of H2 blockers&#58; gastric acidity acts as a barrier to bacterial proliferation and invasion&#59; the use of H2 blockers decreases the defense mechanism and increases the risk of bacterial invasion&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">6</span><p id="par0200" class="elsevierStylePara elsevierViewall">Prolonged use of empirical antibiotic therapy&#58; the use of empirical antibiotic therapy for early neonatal sepsis for more than five days increases the incidence of late neonatal sepsis&#44; especially in units with scarce use of breast milk and over-prescription of third-generation cephalosporins&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a></p></li></ul></p><p id="par0205" class="elsevierStylePara elsevierViewall">It is important to note that late sepsis also occurs in full-term newborns&#44; post-discharge&#46; A study carried out in the United States&#44; analyzing 4255 blood cultures collected from 160&#44;818 full-term newborns who returned to the emergency department&#44; aged between 1 week and 3 months&#44; showed a positivity of 0&#46;57 per 1000 newborns&#44; and the most commonly found microorganism was <span class="elsevierStyleItalic">Escherichia coli</span>&#46; The initial source of infection in these patients was a urinary tract infection&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Screening for urinary tract infection in late neonatal sepsis should always be performed&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Diagnosis</span><p id="par0210" class="elsevierStylePara elsevierViewall">Clinical manifestations&#44; as well as early neonatal sepsis&#44; vary considerably and are nonspecific&#46; The clinical signs originate from different systems and can be grouped as follows&#58; a&#41; apnea&#44; difficulty breathing&#44; cyanosis&#59; b&#41; tachycardia or bradycardia&#44; poor perfusion or shock&#59; c&#41; irritability&#44; lethargy&#44; hypotonia&#44; seizures&#59; d&#41; abdominal distension&#44; vomiting&#44; food intolerance&#44; gastric residue&#44; hepatomegaly&#59; e&#41; unexplained jaundice&#59; f&#41; body temperature instability&#59; g&#41; petechiae or purpura&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">In the case of a preterm newborn hospitalized for a long period in the neonatal ICU with suspected clinical signs of sepsis&#44; the collection of blood culture&#44; CSF&#44; and sterile urine &#40;suprapubic puncture or catheter sample&#41; is recommended for cultures&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">Blood samples containing 1<span class="elsevierStyleHsp" style=""></span>mL of blood should be collected from two separate sites&#46; The most frequently identified microorganism in late neonatal sepsis is coagulase-negative <span class="elsevierStyleItalic">Staphylococcus</span>&#44; and the distinction between finding a contaminating agent or not is attained through the positivity of blood cultures collected at two different sites&#46; The positivity of both blood cultures is indicative that coagulase-negative <span class="elsevierStyleItalic">Staphylococcus</span> is the etiological agent of sepsis&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Complementary laboratory tests&#44; such as complete blood count and C-reactive protein&#44; have a better negative predictive value than a positive predictive value&#44; similarly as in early neonatal sepsis&#46; However&#44; on certain occasions&#44; the result of the serum C-reactive protein level in combination with the clinical picture helps to direct treatment decision-making&#46; The cutoff point for C-reactive protein is 10<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">The clinical picture of the newborn is crucial for the suspicion of neonatal sepsis and&#44; after the result of blood culture&#44; it is the main information to guide the need for treatment&#46; A newborn in good general condition will only be indicated for antibiotic therapy if the blood culture is positive&#44; regardless of the CBC or C-reactive protein results&#46; On the other hand&#44; a newborn with clinical signs showing disease will not have indication for antibiotic therapy only if the blood culture is negative and if they have at least two sequential low C-reactive protein levels 24<span class="elsevierStyleHsp" style=""></span>h apart&#46; In this situation&#44; the clinician should consider that the signs of the disease are of a non-infectious bacterial etiology&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Antibiotic therapy</span><p id="par0235" class="elsevierStylePara elsevierViewall">Empirical antibiotic therapy should take into account the most likely etiological agents and their responses to antibiotic therapy&#46; Although the most common microorganism in late neonatal sepsis is methicillin-resistant coagulase-negative <span class="elsevierStyleItalic">Staphylococcus</span>&#44; this does not mean that the initial empirical regimen should include vancomycin&#46; Several studies have shown that not using vancomycin in the initial empirical antibiotic regimen does not increase mortality&#44; duration of bacteremia&#44; and complications attributed to late neonatal sepsis&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#8211;32</span></a></p><p id="par0240" class="elsevierStylePara elsevierViewall">The indiscriminate and excessive use of vancomycin is an important factor in the emergence of multiresistant flora and the increased occurrence of invasive fungal infection&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">Krediet et al&#46; studied 66 newborns with sepsis caused by coagulase-negative <span class="elsevierStyleItalic">Staphylococcus</span> who received three distinct treatment regimens&#58; 25 received cephalothin&#44; 15 received vancomycin&#44; and 26 started the treatment with cephalothin and then switched to vancomycin&#46; Although 22 of the 25 cephalothin-treated patients had methicillin-resistant coagulase-negative <span class="elsevierStyleItalic">Staphylococcus</span>&#44; the cephalothin treatment was maintained and the patients recovered without any complications or recurrence&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">Currently&#44; there are antibiotic use management regimens for neonatal ICUs that predict the initial use of oxacillin in the initial empirical regimen for late neonatal sepsis and eventual change to vancomycin&#44; only when there is no improvement in the patient&#39;s clinical condition after 48<span class="elsevierStyleHsp" style=""></span>h of oxacillin use&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#44;32</span></a> Sepsis caused by coagulase-negative <span class="elsevierStyleItalic">Staphylococcus</span> usually has a milder course and a subacute evolution&#44; which allows patients to be observed for 48<span class="elsevierStyleHsp" style=""></span>h on oxacillin use and the eventual change only if there is no adequate response to oxacillin use&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">The empirical antibiotic therapy protocol for late neonatal sepsis in our Unit includes oxacillin and amikacin&#46; Amikacin is used to cover Gram-negative microorganisms that can occur in hospital-acquired sepsis&#46; After microorganism identification&#44; the antibiotic therapy should be directed by the antibiogram test&#44; except in cases of oxacillin-resistant coagulase-negative <span class="elsevierStyleItalic">Staphylococcus</span>&#44; in which it is maintained depending on the <span class="elsevierStyleItalic">in vivo</span> response to oxacillin&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">In case of meningitis&#44; adjustment of antibiotic therapy according to the identified microorganism and antibiogram test are recommended&#46; If the etiological agent is unknown&#44; change of the antibiotic regimen to cefepime is indicated&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Prevention of late neonatal sepsis</span><p id="par0265" class="elsevierStylePara elsevierViewall">Some measures are indicated in the prevention of late neonatal sepsis&#58;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">1</span><p id="par0270" class="elsevierStylePara elsevierViewall">Handwashing or use of alcohol gel&#58; Handwashing and&#47;or use of alcohol gel is the most effective measure to prevent infections&#46; Microorganisms are carried by the hands when handling a patient&#46; The five moments of hand hygiene recommended by the World Health Organization should be emphasized&#58; 1&#46; before contact with the patient&#59; 2&#46; before the procedure is performed&#59; 3&#46; after risk of exposure to biological fluids&#59; 4&#46; after contact with the patient&#59; 5&#46; after contact with areas near the patient&#46;</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">2</span><p id="par0275" class="elsevierStylePara elsevierViewall">Appropriate and well-defined care bundles&#44; with central intravascular catheters and endotracheal tubes that are closely followed to reduce contamination&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a></p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">3</span><p id="par0280" class="elsevierStylePara elsevierViewall">Trophic enteral feeding&#58; early onset of trophic feeding stimulates the gastrointestinal tract&#44; stimulating intestinal maturity&#44; preventing villous atrophy&#44; and also decreasing bacterial translocation and invasion through the intestinal mucosa&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a></p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">4</span><p id="par0285" class="elsevierStylePara elsevierViewall">Use of breast milk&#58; breast milk contains significant concentrations of IgA and oligosaccharides that give it anti-infectious properties&#46; The exclusive use of breast milk results in more diverse intestinal microbiota&#44; which leads to a lower probability of infections&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">36&#44;37</span></a></p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">5</span><p id="par0290" class="elsevierStylePara elsevierViewall">Probiotics&#58; although there are meta-analyses showing that probiotics may be useful in preventing late neonatal sepsis&#44; there are still many questions regarding their routine use&#46; The studies were performed with different types of probiotics&#44; different dosages&#44; and highly variable treatment times&#44; which makes the generalization of results very difficult&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">38&#44;39</span></a></p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">6</span><p id="par0295" class="elsevierStylePara elsevierViewall">Lactoferrin&#58; there are conflicting studies regarding the role of lactoferrin as a protective factor against late neonatal sepsis&#46; An Italian collaborative randomized trial included 472 very low birth weight infants&#58; the lactoferrin group with 153 patients&#44; the lactoferrin and probiotic group with 151 patients&#44; and the placebo group &#40;glucose 5 &#37;&#41; with 168 patients&#44; treated from birth to 30 days of life&#46;Late sepsis was significantly lower in the groups that received lactoferrin&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> However&#44; a recently published collaborative randomized clinical trial was carried out in the United Kingdom with 2203 newborns&#44; of gestational age &#60;32 weeks&#58; 1099 in the lactoferrin group up to 34 weeks of corrected gestational age and 1104 in the control group receiving sucrose up to 34 weeks of corrected age&#46; There was no significant difference in the incidence of late sepsis&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> At this time&#44; the indication of lactoferrin as a preventive measure for late neonatal sepsis is still under evaluation&#46;</p></li></ul></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclusions</span><p id="par0300" class="elsevierStylePara elsevierViewall">Management of neonatal sepsis is always a challenge&#46; Neonatal sepsis is a frequent cause of neonatal morbidity and mortality&#44; especially in developing countries&#46; Its diagnosis is difficult&#44; since clinical signs are nonspecific and complementary exams have low accuracy&#46; Continuous observation of the patient&#44; knowing how to take into account clinical signs&#44; and observing risk factors are essential for diagnostic suspicion&#46; When neonatal sepsis is suspected&#44; always collect samples for bacteriological analysis before starting the empirical treatment&#46; The decision to start empirical antibiotic therapy and the choice of the most appropriate treatment regimen are crucial&#46; Avoiding routine vancomycin use in the empirical antibiotic regimen in late neonatal sepsis is important to prevent bacterial resistance and invasive fungal infections&#46; The main protective mechanisms against neonatal sepsis are handwashing and the use of breast milk&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflicts of interest</span><p id="par0305" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest&#46;</p></span></span>"
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            3 => "Coagulase-negative <span class="elsevierStyleItalic">Staphylococcus</span>"
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            0 => "Sepse neonatal"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To present current evidence on the etiology&#44; risk factors&#44; diagnosis&#44; and management of early and late neonatal sepsis&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Source of data</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Non-systematic review of the Medline &#40;PubMed&#41;&#44; Scopus&#44; Web of Science&#44; Cochrane&#44; and Google Scholar databases regarding the following terms&#58; neonatal sepsis&#44; early neonatal sepsis&#44; late neonatal sepsis&#44; empirical antibiotic therapy&#44; sepsis calculator&#44; vancomycin&#44; newborn&#44; preterm newborn&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Data synthesis</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Neonatal sepsis is a frequent cause of neonatal morbidity and mortality&#46; Its diagnosis is difficult&#46; Continuous observation of the patient is critical to diagnostic suspicion&#46; When neonatal sepsis is suspected&#44; bacteriological tests should be collected&#46; Vancomycin should not be routinely using in the empirical antibiotic regimen in late neonatal sepsis&#44; and the main protective mechanisms against neonatal sepsis are handwashing and the use of breast milk&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Newborns constitute a group that is more vulnerable to sepsis&#46; Knowledge of risk factors and etiological agents allows a better approach to the newborn with sepsis&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Apresentar evid&#234;ncias atuais na etiologia&#44; fatores de risco&#44; diagn&#243;stico e manejo da sepse neonatal precoce e tardia&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Fontes de dados</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Revis&#227;o n&#227;o sistem&#225;tica feita nas bases de dados Medline &#40;PubMed&#41;&#44; Scopus&#44; Web of Science&#44; Cochrane&#44; Google Scholar sobre os temas sepse neonatal&#44; sepse neonatal precoce&#44; sepse neonatal tardia&#44; antibioticoterapia emp&#237;rica&#44; sepsis calculator&#44; vancomicina&#44; rec&#233;m-nascido&#44; rec&#233;m-nascido pr&#233;-termo&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">S&#237;ntese de dados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A sepse neonatal &#233; uma causa frequente de morbimortalidade neonatal&#46; O seu diagn&#243;stico &#233; dif&#237;cil&#46; A observa&#231;&#227;o cont&#237;nua do paciente &#233; fundamental para uma suspei&#231;&#227;o diagn&#243;stica&#46; Ao se suspeitar de sepse neonatal devem-se coletar exames bacteriol&#243;gicos&#46; N&#227;o usar&#44; rotineiramente&#44; vancomicina no esquema emp&#237;rico de antibi&#243;tico na sepse neonatal tardia&#46; Os principais mecanismos protetores da sepse neonatal s&#227;o a lavagem de m&#227;os e o uso do leite materno&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#245;es</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Os rec&#233;m-nascidos constituem um grupo mais vulner&#225;vel &#224; sepse&#46; O conhecimento dos fatores de risco e dos agentes etiol&#243;gicos permite uma melhor abordagem do rec&#233;m-nascido s&#233;ptico&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Procianoy RS&#44; Silveira RC&#46; The challenges of neonatal sepsis management&#46; J Pediatr &#40;Rio J&#41;&#46; 2020&#59;96&#40;S1&#41;&#58;80&#8211;6&#46;</p>"
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                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46;I&#46; Shane"
                            1 => "P&#46;J&#46; Sanchez"
                            2 => "B&#46;J&#46; Stoll"
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                      ]
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                  ]
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                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(17)31002-4"
                      "Revista" => array:7 [
                        "tituloSerie" => "Lancet&#46;"
                        "fecha" => "2017"
                        "volumen" => "390"
                        "paginaInicial" => "1770"
                        "paginaFinal" => "1780"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28434651"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Predictors of mortality in neonates and infants hospitalized with sepsis or serious infections in developing countries&#58; a systematic review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46;D&#46; Liang"
                            1 => "N&#46; Kotadia"
                            2 => "L&#46; English"
                            3 => "N&#46; Kissoon"
                            4 => "J&#46;M&#46; Ansermino"
                            5 => "J&#46; Kabakyenga"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3389/fped.2018.00277"
                      "Revista" => array:5 [
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Article information
ISSN: 00217557
Original language: English
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Jornal de Pediatria (English Edition)
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