Cloxacillin versus vancomycin for presumed late-onset sepsis in the Neonatal Intensive Care Unit and the impact upon outcome of coagulase negative staphylococcal bacteremia: a retrospective cohort study

BACKGROUND: Coagulase negative staphylococcus (CONS) is the main cause of late-onset sepsis in Neonatal Intensive Care Units (NICU). Although CONS rarely causes fulminant sepsis, vancomycin is frequently used as empiric therapy. Indiscriminate use of vancomycin has been linked to the emergence of vancomycin resistant organisms. The objective of this study was to compare duration of CONS sepsis and mortality before and after implementation of a policy of selective vancomycin use and compare use of vancomycin between the 2 time periods. METHODS: A retrospective study was conducted of infants ≥4 days old, experiencing signs of sepsis with a first positive blood culture for CONS, during two 12-month periods. Late-onset sepsis was treated empirically with vancomycin and gentamicin during period 1, and cloxacillin and gentamicin during period 2. The confidence interval method was used to assess non-inferiority of the outcomes between the two study groups. RESULTS: There were 45 episodes of CONS sepsis during period 1 and 37 during period 2. Duration of sepsis was similar between periods (hazard ratio of 1.00, 95%CI: 0.64, 1.57). One death during period 2 was possibly related to CONS sepsis versus none in period 1. Vancomycin was used in 97.8% of episodes in period 1 versus 81.1% of episodes in period 2. CONCLUSION: Although we failed to show non-inferiority of duration of sepsis in the cloxacillin and gentamicin group compared to the vancomycin and gentamicin group, duration of sepsis was clinically similar. Restricting vancomycin for confirmed cases of CONS sepsis resistant to oxacillin appears effective and safe, and significantly reduces vancomycin use in the NICU

Inflammatory Gene Regulatory Networks in Amnion Cells Following Cytokine Stimulation: Translational Systems Approach to Modeling Human Parturition

A majority of the studies examining the molecular regulation of human labor have been conducted using single gene approaches. While the technology to produce multi-dimensional datasets is readily available, the means for facile analysis of such data are limited. The objective of this study was to develop a systems approach to infer regulatory mechanisms governing global gene expression in cytokine-challenged cells in vitro, and to apply these methods to predict gene regulatory networks (GRNs) in intrauterine tissues during term parturition. To this end, microarray analysis was applied to human amnion mesenchymal cells (AMCs) stimulated with interleukin-1β, and differentially expressed transcripts were subjected to hierarchical clustering, temporal expression profiling, and motif enrichment analysis, from which a GRN was constructed. These methods were then applied to fetal membrane specimens collected in the absence or presence of spontaneous term labor. Analysis of cytokine-responsive genes in AMCs revealed a sterile immune response signature, with promoters enriched in response elements for several inflammation-associated transcription factors. In comparison to the fetal membrane dataset, there were 34 genes commonly upregulated, many of which were part of an acute inflammation gene expression signature. Binding motifs for nuclear factor-κB were prominent in the gene interaction and regulatory networks for both datasets; however, we found little evidence to support the utilization of pathogen-associated molecular pattern (PAMP) signaling. The tissue specimens were also enriched for transcripts governed by hypoxia-inducible factor. The approach presented here provides an uncomplicated means to infer global relationships among gene clusters involved in cellular responses to labor-associated signals

Plasma guanosine 3 ',5 '-cyclic monophosphate and severity of peri/intraventricular haemorrhage in the preterm newborn

A poorly controlled cerebral circulation. caused by excessive production of nitric oxide. has been suggested as predisposing to peri/intraventricular haemorrhage (PIVH) in the immature neonate. It is hypothesized that a relation exists between plasma cyclic GMP (cGMP) as an effector of endogenous vasodilatory nitric oxide production and severity of PIVH. In 83 consecutively admitted preterm neonates, nitric oxide production was assessed by measuring plasma cGMP at 0. 24, 48, 72 and 168 h of age. Simultaneously. cranial ultrasound investigations were performed and haemodynamic parameters registered. The investigations showed that 60 neonates (72%) had no PIVH: 18 neonates (22%) had mild to moderate PIVH: and 5 neonates (6%) had severe PIVH. At 48 and 72 h of age, CGMP levels of infants with severe PIVH were significantly higher than those of infants with no or only, mild PIVH. whereas at 72 and at 168 h, infants with moderate PIVHs had significantly higher cyclic cGMP levels than infants without PIVH. Finally. at 168 h of age infants with mild PIVH also had higher cyclic cGMP values than those of infants without PIVH. Maximal cGMP values preceded the final extension of PIVH in moderate and severe PIVHs. Blood pressure Support was necessary significantly more often in infants with moderate and severe PIVH. A logistic regression model revealed that cGMP was significantly associated with PIVH, irrespective of gestational age, mean arterial pressure or severity of infant respiratory distress syndrome. Conclusion: Increased cGMP levels are associated with the development of PIVH. It is suggested that vasodilatory nitric oxide-induced impairment of cerebral autoregulation plays a role here

Microbiological factors associated with neonatal necrotizing enterocolitis:protective effect of early antibiotic treatment

Aim: The incidence of necrotizing enterocolitis (NEC) strongly increased in an neonatal intensive care unit (NICU) in 1997 and 1998 compared with previous years, which coincided with increased incidence of nosocomial sepsis. Specific risk factors related to this NICU and a possible relationship between NEC and nosocomial sepsis were studied retrospectively, including all patients with NEC since 1990 and matched controls. Methods: Clinical and bacteriological data from the period before the development of NEC and a similar period for the controls were collected retrospectively and corrected for birthweight and gestational age. Statistical analysis was performed by a stepwise regression model. Results: Data of 104 neonates with NEC and matched controls were analysed. The median day of onset of NEC was 12 d (range 1-63 d). Significant risk factors for NEC were: insertion of a peripheral artery catheter [odds ratio (OR) 2.3, 95% confidence interval (95% CI) 1.3-3.9] and a central venous catheter (OR 5.6, 95% CI 3.1-10.1), colonization with Klebsiella sp. (OR 3.4, 95% CI 1.5-7.5) and Escherichia coli (OR 2.1, 95% CI 1.0-4.5), and the occurrence of sepsis, in particular due to coagulase-negative staphylococci (OR 2.6, 95% CI 1.4-5.1). The risk for NEC was decreased after the early use ( Conclusion: Insertion of central venous and peripheral arterial catheters is positively associated with NEC, as is colonization with the Gram-negative bacilli Klebsiella and E. coli and the occurrence of sepsis, particularly due to coagulase-negative staphylococci. Early treatment with amoxicillin-clavulanate and gentamicin is negatively associated with NEC and may be protective against NEC

In-line filters in central venous catheters in a neonatal intensive care unit

Nosocomial sepsis remains an important cause of morbidity in neonatal intensive care units. Central venous catheters (CVCs) and parenteral nutrition (TPN) are major risk factors. In-line filters in the intravenous (IV) administration sets prevent the infusion of particles, which may reduce infectious complications. We randomized infants to in-line filter ( for clear fluids and lipid emulsions) or no filter placement. Sepsis, nursing time and costs were assessed. IV sets without filters were changed every 24 h, IV-sets with filters every 96 h. Of 442 infants with a CVC, 228 were randomized to filter placement, 214 to no filter. No differences were found in clinical characteristics, CVC-use, and catheter days. Nosocomial sepsis occurred in 37 (16.2%) infants with filters, in 35 ( 16.3%) in the group without filter ( NS). Nursing time to change the IV-administration sets was 4 min shorter in the filter-group (P <0.05). Costs of materials used were comparable. In conclusion, the incidence of sepsis when using filters was not reduced but the nursing time for changing the intravenous sets was reduced without a difference in costs