Treatment Of Early-onset Neonatal Sepsis Research Articles

Syndecan-1 Level, a Marker of Endothelial Glycocalyx Degradation, Is Associated With Fetal Exposure to Chorioamnionitis and Is a Potential Biomarker for Early-Onset Neonatal Sepsis.

The goal of this investigation was to identify the association between Syndecan-1 (S1) serum levels in preterm newborns exposed to chorioamnionitis (CA) in utero and the potential of S1 as a biomarker of early-onset neonatal sepsis. A cohort of preterm newborns born <33 weeks gestational age was recruited. Within 48 hours of birth, 0.5 mL of blood was drawn to obtain S1 levels, measured via ELISA. Placentas were examined and classified as having (1) no CA, (2) CA without umbilical cord involvement, or (3) CA with inflammation of the umbilical cord (funisitis). S1 levels were compared between preterm newborns without exposure to CA verus newborns with exposure to CA (including with and without funisitis). Preterm newborns exposed to CA were found to have significantly elevated S1 levels compared to those unexposed. Although S1 levels could not differentiate fetal exposure to CA from exposure to CA with funisitis, the combined CA groups had significantly higher S1 levels compared to those not exposed to CA. S1 level has the potential to become a clinically useful biomarker that could assist in the management of mothers and preterm newborns with CA and funisitis. Furthermore, S1 level could aid in the diagnosis and treatment of early-onset neonatal sepsis.

Modern approaches to diagnosis and treatment of early-onset neonatal sepsis

Early-onset neonatal sepsis (EOS) remains the leading cause of morbidity and mortality, especially among premature babies. Therefore, accurate diagnosis, prompt monitoring of the course of the disease and an effective therapeutic strategy are a guarantee of improving the quality of medical care for newborns, as well as an important reserve for reducing perinatal losses. The aim of the work to summarize modern views on the diagnosis and treatment of early-onset neonatal sepsis in newborns with perinatal pathology. Results and their discussion. An analytical review of modern literature data on problematic issues of EOS diagnostics is carried out. The approaches are stated and the main directions of EOS management at the present stage are formulated. It was revealed that the lack of a consensus definition of neonatal sepsis, the nonspecificity of clinical data is a limiting factor in the timely accurate identification of the septic process. Insufficient diagnostic value of existing laboratory tests leads to defects in the registry and monitoring of this disease, the inability to conduct an objective assessment of the existing epidemiological and microbiological situation in the health care system and the subsequent effective implementation of preventive measures. Conclusions. In the conditions of modern scientific realities, none of the existing laboratory tests can sufficiently reliably confirm or deny the presence of EOS in a newborn child, which determines the search for new promising laboratory tests with high diagnostic and prognostic potential. The optimal treatment strategy for newborns with EOS is broad-spectrum antibiotics. However, today the global problem of excessive irrational prescribing of antibacterial drugs is associated with the formation of multidrug-resistant strains of bacteria, as well as the development of long-term adverse effects, which requires improved diagnostic and treatment algorithms for children who are in the risk group of the development of neonatal sepsis by implementing a comprehensive approach using modern accurate tests in the dynamics of the disease

Assessing the impact of introducing a satellite blood culture incubator within a tertiary neonatal unit on length of hospital stay

Timely recognition and treatment of early-onset neonatal sepsis (EONS) reduces mortality and morbidity. The National Institute for Health and Care Excellence (NICE) recommends early initiation of antibiotics in babies with...

Effect of hypothermia treatment on gentamicin pharmacokinetics in neonates with hypoxic-ischaemic encephalopathy: A systematic review and meta-analysis.

Hypothermia is the current standard therapy for asphyxiated neonates with hypoxic-ischaemic encephalopathy (HIE). Gentamicin is used for the empirical treatment of early-onset neonatal sepsis. We investigated the influence of hypothermia treatment on gentamicin pharmacokinetics and suggested the appropriate dosing recommendations for gentamicin in neonates with HIE receiving hypothermia treatment. We searched studies published until February 2017 in MEDLINE using PubMed, EMBASE and the Cochrane Library. Three independent reviewers screened the literature and extracted data from each study. All of the studies that reported the blood concentrations or pharmacokinetic parameters of gentamicin in hypothermic neonates with HIE were included in this review. Articles were excluded if they were not original research. A total of 8 observational studies met the inclusion criteria. Meta-analyses were performed in which the mean difference of gentamicin for the trough concentration and clearance between hypothermic and normothermic neonates were 0.81mg/L (95% confidence interval [-0.07, 1.69]) and -0.21 mL/kg/min (95% confidence interval [-0.31, -0.12]), respectively. The factors affecting gentamicin clearance in hypothermic neonates with HIE were gestational age, birthweight and serum creatinine. Gentamicin clearance is decreased in neonates with HIE receiving hypothermia treatment compared to those not receiving hypothermia treatment. Modified gentamicin dosing regimens are required to avoid potential toxicity related to higher concentrations during hypothermia treatment.

The Determination of Procalcitonin Concentration in Early-Onset Neonatal Infection.

The aim of this study was to assess the clinical usefulness of blood procalcitonin (PCT) levels for the diagnosis and therapeutic monitoring of early-onset neonatal sepsis (EONS). PCT as well as C-reactive protein (CRP) levels and white blood cell (WBC) count were measured in venous blood from 57 infected and 72 uninfected neonates. Differences between groups for PCT, CRP, and WBC levels were significant. The threshold value on the receiver operating characteristic curve in the prediction of EONS was 5.33 ng/mL for PCT, 9.3 mg/L for CRP, and 14.9 × 109/L for WBC. There was no effect of antibiotic administered to the mother on PCT, CRP, and WBC levels in neonatal blood sampled before treatment of EONS. Evidently reduced PCT levels are observed after 2 days of treatment. The authors conclude that prenatal antibiotic therapy does not reduce the value of PCT levels in blood for the diagnosis of EONS.

Early Onset Neonatal Sepsis in Canada: 2011-2012

Abstract BACKGROUND: Canadian and US studies suggest that the organisms responsible for early-onset neonatal sepsis (EONS) are changing, with an increase in Escherichia coli (EC) as well as antibiotic-resistant organisms. Current Canadian guidelines for prevention and treatment of EONS are based on Group B streptococcus (GBS) as the likely organism. Population-level data may inform updates to these national strategies. OBJECTIVES: To determine the incidence, types of organisms and corresponding resistance patterns involved in EONS in Canada. To identify how the organisms are affected by maternal antibiotic prophylaxis and other factors. DESIGN/METHODS: Cases of EONS (defined as positive blood and/or cerebrospinal fluid (CSF) culture at &amp;lt;7 days of age) between January 2011 and December 2012 were identified through the Canadian Paediatric Surveillance Program (CPSP). Neonates were excluded if they were asymptomatic with a positive culture likely to be a contaminant, or if the CSF culture was positive as a result of an intracranial procedure. RESULTS: Over the 2-year period, 127 cases meeting our criteria were identified, and there were 754,849 total Canadian live births. The incidence for EONS was 0.17/1000 live births. 79.5% of cases presented within the first 24 hours of life, while 15% presented between 72 h-7 days. GBS accounted for 41.7% of cases, while EC accounted for 35.4%. Resistance was noted in 33.9% of cases overall. 55.6% of EC were resistant, with ampicillin resistance being the most common. The species of infecting organism was significantly associated with gestational age, very low birth weight, age at presentation, the mother having received GBS prophylaxis, and rupture of membranes lasting more than 18 h. GBS was most common in term and EC in preterm neonates. The overall EONS case fatality rate was 11%, with most of these being deaths from EC. CONCLUSION: Our study suggests a lower rate of EONS than historically suggested, with differing dominant organisms based on gestational ages of the neonates. Later ages at presentation and high rates of resistance especially among EC cases further complicate the picture. We recommend a review of the Canadian prevention and treatment guidelines based on our findings.

Extended-Interval Dosing of Aminoglycosides in Pediatrics: A Narrative Review

Aminoglycosides (AGs) are frequently used in pediatric settings, especially for empiric treatment of early-onset neonatal sepsis. Although AGs are used for several decades, the optimum method of administration and their dosing schemes needs more clarification. The risks of ototoxicity and nephrotoxicity, two main toxicities associated with AGs, have been contributed to the peak and trough plasma levels, respectively. One approach to decrease these potential toxicities of AGs is to administer higher doses with a prolonged interval, named extended-interval dosing (EID). Post-antibiotic effect (PAE) and concentration-dependent killing of AGs provide rational basis for the efficacy of EID. PAE refers to the extended bactericidal activity of AGs against many Gram-negative organisms after the drug was removed by metabolism. One concern is that the higher initial peak concentration with EID may be accompanied with more toxicities, especially ototoxicity. It was demonstrated that due to saturation of binding site of AGs in renal and cochlear tissues, transiently higher concentration of AGs does not cause additional nephrotoxicity or ototoxicity. Experience and clinical evidence regarding EID in pediatrics is suboptimal. In this review, we presented the rational and studies focusing on EID in pediatric setting. The overall finding of trials is that in pediatric setting, EID is a safe and effective dosing method. The risk of serum drug concentration outside the therapeutic range is lower in neonates treated with EID, leading to less need of therapeutic drug monitoring (TDM) with EID. Moreover, there are evidences supporting lower chance of bacterial resistance with EID compared with traditional dosing approach.

Costo económico marginal del fracaso terapéutico con ampicilina más amikacina en el tratamiento de la sepsis neonatal temprana

Objective To evaluate the marginal cost of therapeutic failure with Ampicillin/amikacin as the first-line antibiotic treatment of early-onset neonatal sepsis (ENS). Methods Out of a total of 121 newborns, 86 failed to respond to Ampicillin/amikacin when it was used as first-line treatment within their first 72 h of life. All of them were admitted to the NICU between 2001 and 2005 with suspicion of sepsis. After this failure to respond, vancomycin and/or cefotaxime were used as the second treatment option for these newborns. Using a full cost method we performed a cost analysis with an activity-based-costing (ABC) perspective, identifying the costs generated by these 86 patients. Results The costs comprising medication, hospitalization, supplies and clinical staff salaries were higher when vancomycin and/or cefotaxime were used (350,924 dollars or 275,116 euros) compared to those generated with an Ampicillin/amikacin regimen (159,251 dollars or 124,878 euros). When compared as protective factors, the relative risk was 1.09 (95% CI; 0.39–2.1 P=0.8) for Ampicillin/amikacin vs. 0.02 (95% CI; 0.04–0.32 P<0.05) for vancomycin and/or cefotaxime. Conclusions Even though vancomycin and/or cefotaxime are initially more costly, there is a cost saving derived from the use of this antibiotic treatment as the first-line therapeutic option instead of as a rescue therapy when a lower-efficacy regimen (Ampicillin/amikacin) has failed.

Assessing the efficacy of the recombinant human granulocyte colony-stimulating factor "rhG-CSF" in the treatment of early neonatal sepsis in premature neonates

OBJECTIVE: To evaluate the efficacy of the recombinant human granulocyte colony-stimulating factor (rhG-CSF) in the treatment of early-onset neonatal sepsis among premature infants.MATERIALS AND METHODS: A double-blind, randomized, placebo-controlled trial was performed among forty-four preterm neonates who had "clinical diagnosis" of early-onset sepsis. The treatment group (n=22) received 10 micro g/kg/d of rhG-CSF, IV once daily for three consecutive days, and the placebo group (n=22) received the same volume of a visually-indistinguishable vehicle. Prior to the first dose, and prior to the second and third doses, and again 10 days after the first dose, we measured tumor necrosis factor-a, interleukin-6, granulocyte-macrophagocyte colony-stimulating factor, G-CSF, leukocyte count, absolute neutrophil count, immature/total neutrophil ratio, platelet count, and hemoglobin concentration. A bone marrow aspiration was performed seven days after the first dose, and both the neutrophil storage pool (NSP) percent and the NSP/NPP (neutrophil proliferative pool) ratios were tabulated.RESULTS: The treatment and placebo groups were of similar gestational age (29-/+ 3 vs 31-/+ 3 weeks) and birth weight (1376 -/+ 491 vs 1404 -/+ 508 grams). They had similar Apgar scores and 24 hour SNAP scores. No deaths occurred during the first week of life among the treatment group while three deaths occurred in the placebo group. RhG-CSF treatment did not alter the serum concentrations of the cytokines measured (except for G-CSF). Serum G-CSF levels, blood leukocyte counts, absolute neutrophil counts, NSP percentages, and NSP/NPP ratios were higher in the treatment group 24 hours and 72 hours after dosing. The occurrence of a subsequent infection over the two week period following dosing was significantly lower in the treatment group (n=2) than in the placebo group (n=9; p<0.02, RR 0.19 [0.05-0.78]). The overall mortality rate during the entire hospitalization was not different between treatment and placebo groups.CONCLUSIONS: Administration of rhG-CSF to premature neonates with the clinical diagnosis of early-onset sepsis was associated with lower incidence of nosocomial infection over the ensuing three weeks period, but it did not change the overall mortality rate.