Early-onset Bacterial Infection Research Articles

Lipopolysaccharide-binding protein in noninfected neonates and those with suspected early-onset bacterial infection

To investigate postnatal lipopolysaccharide-binding protein (LBP) kinetics in term neonates and to test its diagnostic accuracy for early-onset bacterial infection (EOBI). A total of 99 neonates with clinical and serological signs of EOBI comprised the study group; 198 neonates with risk factors, but without EOBI, served as controls. LBP, C-reactive protein (CRP) and interleukin-8 (IL-8) were determined. LBP in the noninfected group increased until 24 h after birth (P < 0.05 vs 6 h). LBP and CRP correlated strongly in neonates with suspected EOBI (r = 0.63). Although LBP reached a higher sensitivity than CRP 6 and 12 h after clinical suspicion (45 (24-68) and 79% (54-94) vs 9 (0-24) and 39% (17-64); P < 0.05)), EOBI was most reliably detected by IL-8. LBP kinetics were age-dependent. LBP was not sufficiently sensitive in the prediction of EOBI.

Urgences infectieuses néonatales

Early-onset neonatal infections, particularly bacterial and viral (herpes) infections, are a major concern considering the urgent need of the appropriate antiinfective therapy. The two principal etiologic agents of bacterial neonatal infections are group B Streptococcus and Escherichia coli. The diagnosis should rely on obstetrical criteria, clinical signs, microbial exams and inflammatory laboratory studies. It is only with these four data that algorithms can be elaborated. ANAES published in September 2002 new recommendations for the diagnosis and treatment of early-onset bacterial neonatal infections. Indications for antimicrobial therapy depend on whether the newborn is symptomatic or not. The recent ANAES publication gives answers to some clinical situations but some interrogations are remaining. The second emergency is the neonatal herpes simplex virus (HSV) infection. Its incidence in France is low. The most common cause of infection is intrapartum transmission. Clinical manifestations are various, HSV-2 infections are more severe than HSV-1 which is responsible for severe neurological sequellae. Diagnosis is based on specific PCR in blood and CSF. Immediate mucocutaneous protection, antiseptic soaping and intravenous acyclovir in some situations are part of the treatment. Prognosis, ameliorated with acyclovir, is conditioned by an early diagnosis.

Prophylactic versus selective antibiotics for term newborn infants of mothers with risk factors for neonatal infection

Early onset bacterial infection is an important cause of morbidity and mortality in newborn infants. Various factors that increase the risk of neonatal infection have been identified. It is unclear whether asymptomatic newborn infants born to mothers with one or more of these risk factors should receive antibiotics prophylactically rather than selectively if only clinical or microbiological evidence of sepsis emerges. To assess the effect of prophylactic versus selective antibiotic treatment for asymptomatic term neonates born to mothers with risk factors for neonatal infection. We used the standard methods of the Cochrane Neonatal Review Group. We searched MEDLINE (1966 - May 2004), EMBASE (1980 - May 2004), LILACS (1982 - 2003), SciELO (1997 - 2003), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2004), and Centers for Disease Control and Prevention protocols and guidelines on the subject. Randomized controlled trials, or trials using quasi-random methods of allocation, comparing the use of prophylactic versus selective antibiotics in asymptomatic neonates born to mothers with one or more risk factors for infection. We extracted the data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by three reviewers and synthesis of data using relative risk and risk difference. The pre-specified primary outcomes were neonatal mortality, systemic neonatal infection, and need for admission to a neonatal intensive care unit. We identified two small trials undertaken in the 1970s. Both trials had methodological weaknesses. There was no evidence of an effect on any of the primary outcomes, but because the trials were underpowered, clinically important effect sizes may have been missed. There are insufficient data from randomized controlled trials to guide clinical practice. A large randomized controlled trial is needed in asymptomatic term infants born to mothers with risk factors for infection in their babies, which compares the effect of prophylactic versus selective antibiotics on morbidity, mortality and costs.

Evaluation of IL-8-concentrations in plasma and lysed EDTA-blood in healthy neonates and those with suspected early onset bacterial infection.

Plasma IL-8 is a diagnostic parameter of early-onset bacterial infection (EOBI) in neonates but has a short half-life. The detergent-lysed whole-blood (DLWB) IL-8 consists of both extracellular and cell-bound IL-8. The objective of this study was to investigate kinetics of plasma and DLWB IL-8 in healthy newborns and those with suspected EOBI and to test the hypothesis that determination of DLWB IL-8 results in higher sensitivity for EOBI detection. Sixty-one neonates with clinical and serologic signs of EOBI composed the study group; 188 neonates with risk factors but without EOBI served as control subjects. IL-8 concentrations were determined in plasma and DLWB. In the control group, DLWB IL-8 concentrations were 280-fold higher (9599 pg/mL; SD 4433) up to 24 h post partum than corresponding plasma levels (34.2 pg/mL; SD 18.1). The sensitivity of DLWB versus plasma IL-8 for EOBI was 0.97 versus 0.71 after 6 h and 0.70 versus 0.32 after 24 h. Corresponding values for specificity were 0.95 versus 0.90 after 6 h and 0.92 versus 0.99 after 24 h. After 24 h, the negative predictive value for DLWB versus plasma IL-8 was 0.80 versus 0.66. DLWB IL-8 showed a higher sensitivity for EOBI within 6 h after first clinical suspicion than plasma IL-8. It also remained elevated longer. Our results suggest that DLWB IL-8 results in a higher sensitivity for EOBI.

Early-onset bacterial infection in Brazilian neonates with respiratory distress: a hospital-based study.

We investigated infants with respiratory distress within 4 days of birth whose mothers had not received antibiotic prophylaxis to evaluate the frequency and etiology of bacterial infection and associated risk factors. The study was conducted on 261 infants suffering respiratory distress admitted to a Brazilian neonatal intensive care unit, 94 per cent of whom were born prematurely. Gestational and delivery history; bacteriological cultures of blood, cerebrospinal fluid, tracheal aspirates and urine; complete and differential blood counts; a urinary group B streptococcal latex antigen test; and a chest radiograph were analysed. Indications of infection were found in 38.7 per cent and confirmed in 11.9 per cent of the neonates. Gram-positive (70.9 per cent) and gram-negative bacteria (29.1 per cent) were found in 31 cases of confirmed early bacteremia. Group B Streptococcus was the predominant causative agent (19.4 per cent) in infants exhibiting confirmed infection. Culture-proven infection was more frequent among infants delivered vaginally (adjusted OR = 2.53, p = 0.05) or born to mothers with signs of intra-amniotic infection (adjusted OR = 2.83, p = 0.04). Preventive measures against early bacterial infection in preterm infants from this population are strongly warranted.

Nosocomial Infections in the Neonatal Intensive Care Unit

After completing this article, readers should be able to: 1. List the primary pathogens involved in late-onset infections. 2. List the major risk factors for nosocomial sepsis. 3. Describe practices that can reduce the risk of nosocomial infections. Improvements in antenatal management and neonatal intensive care over the past 10 to 15 years have changed the prognosis for preterm infants. More than 85% of infants born at 25 weeks’ gestation now survive their preterm birth. This has resulted in a dramatic change in the populations of infants occupying neonatal intensive care beds. The average length of stay for a term or near-term infant who has surgical or respiratory problems is about 15 days; the length of stay for preterm infants born at 26 weeks’ gestation is more than 2 months. The duration of hospitalization is inversely related to gestational age. The population of extremely low-birthweight (ELBW) infants who remain hospitalized for extended periods of time (and who undergo numerous invasive procedures) is most susceptible to nosocomial infections. Nosocomial infections are defined as those that occur beyond 48 hours after birth and are caused by pathogens that are not maternally derived. Such infections are 100 times more common than early-onset bacterial infections, which are caused by pathogens acquired in utero or perinatally. Recent data from the National Institute of Child Health and Human Development-sponsored “Neonatal Network” indicated that 29% of infants born at 25 to 28 weeks’ gestation and 46% of infants born at less than 25 weeks’ gestation experience a serious nosocomial infection during hospitalization in the NICU. The morbidity and mortality from nosocomial infections is enormous. In the United States, more than 2,000,000 nosocomial infections (in infants and adults) occur each year, and 50% to 60% are caused by resistant organisms. It has been estimated that 9,600 to 20,000 patients die each …

Interleukin‐8 in neonatal sepsis

This study was conducted to evaluate the accuracy and kinetics of interleukin 8 (IL-8) as a test for early-onset bacterial infections (EOBI) in neonates and to examine whether IL-8 would allow unnecessary antibiotic therapy to be reduced. First, IL-8 was measured 378 times on admission, along with C-reactive protein (CRP), immature to total neutrophil ratio (IT ratio) and blood cultures, in full-term and preterm neonates with suspected EOBI. Combined culture-proven and clinical EOBI were detected on admission by the combination of IL-8 > 70 pg ml -1 and/or CRP > 10 mg l -1 with 92% sensitivity and 74% specificity. An increased IL-8 was found in 62% of the infected infants, while CRP was still normal. In a second study period, IL-8 was determined prospectively in 331 infants who presented clinical signs of EOBI or had a birth history of amniotic infection. Antibiotic therapy was restricted to those infants with suspected infection who also had an increased IL-8 and/or CRP (n = 158). Another 39 infants received antibiotics on the basis of clinical signs despite negative IL-8 and CRP. Of 150 non-infected infants in whom IT ratio, IL-8 and CRP were available, treatment would have been indicated for 93 infants based on IT ratio and/or CRP (n = 77) or clinical signs (n = 16), hut was only initiated in 55 infants based on IL-8 and/or CRP (n = 28) or clinical signs (n = 27), an apparent reduction in unnecessary antibiotic therapy of 40%. Conclusion: The combination of IL-8 and CRP is a reliable test for the diagnosis of EOBI and may be helpful in enabling antibiotic therapy to be reduced in newborn infants.

Interleukin‐8: a valuable tool to restrict antibiotic therapy in newborn infants

This study was conducted to evaluate the accuracy and kinetics of interleukin 8 (IL‐8) as a test for early‐onset bacterial infections (EOBI) in neonates and to examine whether IL‐8 would allow “unnecessary” antibiotic therapy to be reduced. First, IL‐8 was measured 378 times on admission, along with C‐reactive protein (CRP), immature to total neutrophil ratio (IT ratio) and blood cultures, in full‐term and preterm neonates with suspected EOBI. Combined culture‐proven and clinical EOBI were detected on admission by the combination of IL‐8 ≥ 70 pg ml−1 and/or CRP &gt; 10 mg 1−1 with 92% sensitivity and 74% specificity. An increased IL‐8 was found in 62% of the infected infants, while CRP was still normal. In a second study period, IL‐8 was determined prospectively in 331 infants who presented clinical signs of EOBI or had a birth history of amniotic infection. Antibiotic therapy was restricted to those infants with suspected infection who also had an increased IL‐8 and/or CRP (n= 158). Another 39 infants received antibiotics on the basis of clinical signs despite negative IL‐8 and CRP. Of 150 non‐infected infants in whom IT ratio, IL‐8 and CRP were available, treatment would have been indicated for 93 infants based on IT ratio and/or CRP (n= 77) or clinical signs (n= 16), but was only initiated in 55 infants based on IL‐8 and/or CRP (n= 28) or clinical signs (n= 27), an apparent reduction in “unnecessary” antibiotic therapy of 40%. Conclusion: The combination of IL‐8 and CRP is a reliable test for the diagnosis of EOBI and may be helpful in enabling antibiotic therapy to be reduced in newborn infants.

Il-1 beta, Il-6, Il-8 and G-CSF in the diagnosis of early-onset neonatal infections.

To determine whether inflammatory cytokine concentrations (Il-1 beta, Il-6, Il-8 and G-CSF) in umbilical cord blood are useful predictors of an early-onset neonatal infection. 240 women and their newborns were enrolled in our study and umbilical cord blood samples collected from neonates (n = 240) were subjected to ELISA for Il-1 beta, Il-6, Il-8 and G-CSF. Clinical outcome of the neonates was followed and documented. Placenta histology was also available in majority of the cases (n = 195). Early-onset neonatal infection was diagnosed in 5.4% of neonates (13/240) and placental examination showed histologic chorioamnionitis in 17.9% (35/195). Both Il-1 beta and Il-6 cord blood concentrations were elevated in association with histologic chorioamnionitis (Il-1 beta-2.7 vs. 2.1 pg/ml, p < 0.05 and Il-6 15.6 vs. 12.8 pg/ml, p < 0.005). Only Il-6 was elevated (16.0 vs. 13.2 pg/ml, p < 0.05) in neonates with early-onset bacterial infections. ROC analysis showed acceptable diagnostic performance of Il-6 in the identification of acute histologic chorioamnionitis and clinical neonatal infection. Il-6 in umbilical cord blood seems to be a promising predictor for early-onset neonatal infections.

Bacterial Infection in Newborns with Respiratory Distress: The Role of Group B β-Hemolytic Streptococcus (GBS) in Brazilian Newborns. 1333

Respiratory distress (RD) within the first days of life is a common sign of early-onset bacterial infection. The bacterial etiology of early-onset neonatal infection varies from one population to another. Gram-positive organisms such as GBS are an infrequent cause of neonatal infection in some tropical countries. In Brazil, there role of GBS in neonatal infection is unknown. The aim of this study was to determine the frequency of bacterial infection in Brazilian newborns with RD considering the relative distribution of each pathogen. All of 261 consecutively admitted newborns who had RD within 96 hours of life (excluding aspiration syndromes, transient tachypnea, cardiac disease or congenital anomalies) were evaluated. Before the use of antibiotics, a blood culture, a urine culture, a latex test to detect GBS antigen in concentrated urine samples and leukocyte counts were done. Infants with positive blood cultures for pathogenic non-contaminant organisms were considered to have a confirmed infection. A true infection with S. epidermidis was considered in the presence of suggestive clinical and laboratory evidence. Infants with negative blood culture and positive GBS antigen urine tests with negative urine culture were considered to have presumed infection by GBS if clinical and laboratory signs were present. The newborns studied had a median gestational age of 32 weeks and a median birth weight of 1400 g. Screening of pregnant women for GBS colonization was not done. Only 3 of the 37 (8.1%) mothers of these newborns received antibiotics prior to delivery. Overall, there were 37/261 (14.2%) newborns with bacterial infection. The majority (78.4%) of neonatal infections were caused by Gram-positive organisms (29/37). The remaining 8 (21.6%) newborns were infected by Gram-negative organisms. GBS was the single most frequently detected pathogen among infected infants (35%) followed by S.epidermidis (13.5%), E. coli (10.8%), S. viridans (10.8%), other streptococci (10.8%), S. aureus (8.1%),H. influenzae (5.4%) and P. mirabilis (5.4%). Taking into account that GBS was detected in 5% (13/261) of all newborns with RD and that this organism has emerged as the major pathogen detected in this population, the implementation of regimens for prevention of GBS disease is strongly warranted.