Active clinical trials for "Neonatal Sepsis"

Background: Neonatal sepsis is the leading cause of mortality in preterm newborns. The autonomic nervous system modulates the response to sepsis through the cholinergic anti-inflammatory reflex. However, premature neonates exhibit immaturity of the autonomic nervous system, which could increase the risk of sepsis. Kangaroo Care (skin-to-skin contact) may promote autonomic nervous system modulation and maturation in preterm newborns with sepsis. The objective of this study is to determine the effect of Kangaroo Care on heart rate variability in preterm newborns with late-onset clinical sepsis. Methods: A cross-over randomized clinical trial will be conducted, including 20 preterm infants with late-onset sepsis. The autonomic nervous system will be assessed using heart rate variability analysis. The study interventions consist of routine care in an incubator and Kangaroo Care. Randomization will be performed using a four-block permuted design for the two intervention sequences AB: Kangaroo Care - incubator care, or BA: incubator care - Kangaroo Care. Heart rate variability will be recorded using a Polar Rs800 monitor and analyzed with Kubios software. Discussion: This study will provide information on the relationship between Kangaroo Care and autonomic nervous system activity in preterm neonates with late-onset sepsis. These data will contribute to the understanding of the cholinergic anti-inflammatory reflex in neonates and the capacity of skin-to-skin contact to modulate autonomic activity in neonatal infection. Thus, the study seeks to provide initial evidence for the use of skin-to-skin contact as a non-pharmacological therapeutic intervention in neonatal sepsis.

A multicentre, international case-control study to develop a biobank of sera from 150 cases of serotype III GBS disease and associated clinical information from seven countries (Malawi, Uganda, UK, the Netherlands, Italy and France), with 3:1 (450) serotype matched healthy controls.

Diagnosis of neonatal sepsis remains a challenge due to non-specific signs and diagnostic inaccuracies. Studies have shown that this could lead to overdiagnosis and overuse of antibiotic treatment, with potential long-term adverse effects. A systems approach towards diagnosing neonatal sepsis has been shown to have high accuracy in initial studies. This study aims to recruit a large validation cohort to confirm findings.

The PARENT study will examine platelet and endothelial associated proteins in preterm infants being investigated for late onset sepsis (LOS) to see if infants with fulminant sepsis can be prospectively identified using these markers

The purpose of this study is to describe the population pharmacokinetic characteristics of piperacillin/tazobactam after intravenous administration in pregnant women during pregnancy and delivery, and to evaluate pharmacodynamic effectiveness and safety of piperacillin/tazobactam in pregnant women whose baby are at high risk of developing early-onset sepsis after birth.

Breast milk contains many microorganisms including bacteria that are beneficial to health (probiotics), but also bacteria that are generally considered pathogenic. Several studies have described an increased risk of infections due to pathogenic germs in breast milk in premature newborns whose digestive system is immature and whose digestive flora is modified by repeated antibiotic treatments. However, a breastfed baby is better protected against infectious diseases than a bottle-fed baby. The objective of this study is to define the breast milk microbiota of infants with confirmed early or late neonatal bacterial infection compared to the breast milk microbiota of infants with no evidence of bacterial infection. For that purpose, an exploration will be performed using the principle of "Microbial Culturomics" and targeted metagenomics (16S ribosomal RNA gene sequencing).

Rationale: Early diagnosis of sepsis in neonates is complicated as the signs and symptoms are nonspecific. Although blood culture is the gold standard for the diagnosis, false-negative results and long incubation period of 36-72 hours limits the use of blood culture to rule out sepsis at initial suspicion. Since delay in diagnosis may lead to progressive deterioration, antibiotics are often started empirically at initial sepsis suspicion, awaiting results of the blood culture. Consequently, uninfected infants are often unnecessarily exposed to empirical antibiotics. To reduce unnecessary treatment of non-infected infants, an early, sensitive and specific diagnostic tool would be helpful to guide clinicians faster when to discontinue antibiotics. Molecular Culture (MC) via IS-pro is a novel, advanced, molecular culture technique which is able to culture bacteria within 4 hours after blood sampling. MC might thus be a potential diagnostic tool to detect or rule out sepsis in infants quickly, however data on MC for diagnosis of sepsis in this population is limited. Objective: The aim of this study is to evaluate whether MC is of additive predictive value for the diagnosis sepsis in this vulnerable group. Study design: Prospective observational cohort study. Study population: All infants suspected for neonatal sepsis of both early and late onset will be eligible for study participation. They will be treated according to the standard local guidelines. Intervention (if applicable): In case of a suspicion of sepsis at birth, blood will be collected for a conventional blood culture as part of standard care. Additionally, a blood sample will be collected from the umbilical cord for MC. In case of a suspicion of sepsis not directly postpartum, an additional blood sample will be taken for MC analysis, directly following sampling for conventional culture, implying no extra phlebotomy. Main study parameters/endpoints: The main study parameter is the discordance in positive and negative outcomes of MC compared to outcomes of conventional blood culture. As the diagnostic accuracy of the conventional blood culture (the current gold standard) is being questioned, the predictive value of MC versus conventional blood culture towards clinical sepsis will also be tested.

Fluid-unresponsive hypotension needing cardiotropic drug treatment is a serious complication in very preterm neonates with suspected late-onset sepsis (LOS; defined as culture positive or negative bloodstream infection or necrotizing enterocolitis occurring >48 hours of age). In Canada, ~250 very preterm neonates receive cardiotropic drugs for LOS related fluid-unresponsive hypotension every year; of these ~35-40% die. Unlike for adult patients, there is little evidence to inform practice. While several medications are used by clinicians, the most frequently used medications are Dopamine (DA) and Norepinephrine (NE). However, their relative impact on patient outcomes and safety is not known resulting in significant uncertainty and inter- and intra-unit variability in practice. Conducting large randomized trials in this subpopulation can be operationally challenging and expensive. Comparative effectiveness research (CER), is a feasible alternative which can generate high-quality real-world evidence using real-world data, by comparing the impact of different clinical practices. Aim: To conduct a national CER study, using a pragmatic clinical trial design, in conjunction with the existing infrastructure of the Canadian Neonatal Network to identify the optimal management of hypotension in very preterm neonates with suspected LOS. Objective: To compare the relative effectiveness and safety of pharmacologically equivalent dosages of DA versus NE for primary pharmacotherapy for fluid-unresponsive hypotension in preterm infants born ≤ 32 weeks gestational age with suspected LOS. Hypothesis: Primary treatment with NE will be associated with a lower mortality Methods: This CER project will compare management approach at the unit-level allowing inclusion of all eligible patients admitted during the study period. 15 centers in Canada have agreed to standardize their practice. All eligible patients deemed circulatory insufficient will receive fluid therapy (minimum 10-20 cc/kg). If hypotension remains unresolved: Dopamine Units: start at 5mics/kg/min, increase every 16-30 minutes by 5 mics/kg/min to a maximum dose of 15 mics/kg/min or adequate response Norepinephrine Units: start at 0.05 mics/kg/min, increase every 16-30 minutes by 0.05 mics/kg/min to maximum dose of 0.15/mics/kg/min or adequate response

Maternal and neonatal infections are among the most frequent causes of maternal and neonatal deaths, and current antibiotic strategies have not been effective in preventing many of these deaths. Recently, a randomized clinical trial conducted in a single site in The Gambia showed that treatment with oral dose of 2 g azithromycin vs. placebo for all women in labor reduced selected maternal and neonatal infections. However, it is unknown if this therapy reduces maternal and neonatal sepsis and mortality. The A-PLUS trial includes two primary hypotheses, a maternal hypothesis and a neonatal hypothesis. First, a single, prophylactic intrapartum oral dose of 2 g azithromycin given to women in labor will reduce maternal death or sepsis. Second, a single, prophylactic intrapartum oral dose of 2 g azithromycin given to women in labor will reduce intrapartum/neonatal death or sepsis.

There are significant variations in antimicrobial consumption across Canadian Neonatal Intensive Care Units (NICUs). Inappropriate and overuse of antibiotics can result in antimicrobial resistance and adverse outcomes among vulnerable neonatal populations. There are limited data on broad-spectrum antimicrobial use, multi-drug resistant organisms (MDRO) prevalence, and effective NICU-specific antimicrobial stewardship strategies. The aim of this study is to develop and implement NICU-specific antimicrobial stewardship strategies at both national and individual unit levels to promote optimal antimicrobial use and decrease the incidence of MDROs.