Elisavet Diamanti

Use of Tigecycline in Pediatric Patients With Infections Predominantly Due to Extensively Drug-Resistant Gram-Negative Bacteria

Background. Emergence of extensively drug-resistant (XDR) bacteria has forced clinicians to use off-label antimicrobial agents such as tigecycline. We present our experience on salvage use of tigecycline for the treatment of infections caused by XDR Gram-negative bacteria in critically ill children and review published cases. Methods. We conducted a retrospective chart review in pediatric departments of a tertiary level hospital from January 2009 to May 2014. Patients were identified using pharmacy database. For the literature review, relevant articles were identified from PubMed. Results. In our case series, 13 children (7 males) with a median age of 8 years (range, 2.5 months-14 years) received tigecycline for ≥2 days as treatment for healthcare-associated infections including 5 bacteremias, 6 lower respiratory tract infections, and 3 other infections. Isolated pathogens were XDR Gram-negative bacteria except 1. A loading dose (range, 1.8-6.5 mg/kg) was given in all except 2 cases. Maintenance dose was given at 1-3.2 mg/kg q12 h. Other antimicrobials including colistin and aminoglycosides (85% and 62%, respectively) were coadministered to all patients. No serious adverse events were detected in these very ill children. Twenty cases of children treated with tigecycline were previously published, mostly for multidrug-resistant/XDR bacteria. An episode of acute pancreatitis and neutrophil engraftment delay in 2 cases were reported during tigecycline treatment. Analyzing reported and all our cases together, mortality in bloodstream infections was 86%, whereas in nonbacteremic cases it was 24% (P = .009). Conclusions. Tigecycline, given at the range of administered doses as salvage therapy and in combination with other antimicrobial agents, seemed to be well tolerated in a series of mainly critically ill pediatric patients and demonstrated relatively good clinical response in nonbacteremic patients.

Effect of Gestational Diabetes and Intrauterine Growth Restriction on the Offspring's Circulating Galanin at Birth

CONTEXT Experimental studies linked gestational diabetes mellitus (GDM) and intrauterine growth restriction (IUGR) with altered expression of the offsprings hypothalamic galanin mRNA, possibly contributing to the development of obesity and metabolic syndrome in later life. We hypothesized that plasma galanin levels at birth would reflect presumably altered hypothalamic galanin expression and production that cannot be assessed in the human offspring. OBJECTIVE Our objective was to investigate whether neonates born to GDM mothers or being IUGR differ from healthy ones in circulating galanin at birth. DESIGN, PATIENTS, AND METHODS Twenty-five neonates born to GDM mothers, 25 with IUGR, and 15 healthy neonates (controls) were prospectively studied. Neonatal plasma galanin levels were assayed immediately after birth by using enzyme immunoassay. RESULTS Neonatal plasma galanin showed a high variability within each group and did not differ significantly among the three groups of neonates. No correlation between plasma galanin and anthropometric maternal and neonatal data was found. Multiple linear regression confirmed that the neonatal group (infants of diabetic mothers, IUGR, and controls) was not an independent predictor for galanin levels at birth after controlling for possible confounders, i.e. maternal body mass index and weight gain during pregnancy and neonatal body mass index. CONCLUSIONS Circulating galanin levels at birth are not affected by GDM and IUGR, providing no evidence for alternations in hypothalamic galanin expression and secretion in humans, as they were previously documented in experimental models. This fact precludes the use of plasma galanin as an early indicator for the development of obesity and metabolic syndrome in this high-risk population.

Comparable effect of conventional ventilation versus early high-frequency oscillation on serum CC16 and IL-6 levels in preterm neonates

Objective:Clara cell 16 kD protein (CC16) and interleukin (IL)-6 have been used as peripheral blood biomarkers of alveolar leakage and inflammation, respectively. Thus, their measurement in the bloodstream could be used to assess ventilator-induced lung injury. The objective of this study was to evaluate the effect of optimized synchronized intermittent mandatory ventilation (SIMV) and high-frequency oscillatory ventilation (HFOV) on circulating CC16 and IL-6 levels when used as the initial ventilation modes in preterm neonates.Study Design:Single center, prospective, randomized clinical study in preterm neonates (gestational age ⩽30 weeks) requiring mechanical ventilation within the first 2 h of life. Serum CC16 and IL-6 were measured on establishment of the assigned ventilation mode after admission, at days 3 and 14 of life as well as at 36 weeks postmenstrual age. Demographic-perinatal data and clinical parameters were also recorded.Result:Of the 30 neonates studied, 24 (gestational age 27.1±1.7 weeks, birth weight 942±214 g) were finally analyzed, equally assigned into the SIMV and HFOV groups. Both groups had comparable demographic-perinatal characteristics and clinical parameters. Serum CC16 and IL-6 altered significantly over time (repeated-measures analysis of variance, both P<0.001). However, changes were not affected by the ventilation mode. Post hoc analysis showed a significant decrease in CC16 and IL-6 from birth up to 36 weeks postmenstrual age in both groups.Conclusion:In preterm neonates, SIMV and HFOV are associated with comparable circulating CC16 and IL-6 levels. These findings suggest a similar alveolar leakage and systemic inflammation with any of the ventilation modes evaluated when their usage is optimized.

Urine metabolomics in neonates with late-onset sepsis in a case-control study

Although late-onset sepsis (LOS) is a major cause of neonatal morbidity and mortality, biomarkers evaluated in LOS lack high diagnostic accuracy. In this prospective, case-control, pilot study, we aimed to determine the metabolic profile of neonates with LOS. Urine samples were collected at the day of initial LOS evaluation, the 3rd and 10th day, thereafter, from 16 septic neonates (9 confirmed and 7 possible LOS cases) and 16 non-septic ones (controls) at respective time points. Urine metabolic profiles were assessed using non-targeted nuclear magnetic resonance spectroscopy and targeted liquid chromatography-tandem mass spectrometry analysis. Multivariate statistical models with data from either analytical approach showed clear separation between the metabolic profiles of septic neonates (both possible and confirmed) and the controls. Metabolic changes appeared to be related to disease progression. Overall, neonates with confirmed or possible LOS exhibited comparable metabolic profiles indicating similar metabolic alternations upon the onset of clinical manifestations. This methodology therefore enabled the discrimination of neonates with LOS from non-septic individuals, providing potential for further research toward the discovery of LOS-related biomarkers.

AGE-RELATED SERIAL PLASMA CITRULLINE LEVELS IN PRETERM NEONATES

INTRODUCTION: Citrulline is a nonessential amino acid that is synthesized almost exclusively in the small intestine. In adults and children with short-bowel syndrome, citrulline has served as a reliable index of the remaining small intestine length. Citrulline is also a precursor of arginine, the role of which is crucial for neonatal metabolism and growth. OBJECTIVE: We sought to determine serial plasma citrulline levels of preterm neonates to assess levels in accordance with age and intestinal maturation, which may serve as a baseline in the event of intestinal abnormalities such as necrotizing enterocolitis (a devastating complication in this age group). METHODS: We measured serial plasma citrulline levels in 18 clinically stable neonates (gestational age: ≤32 weeks; birth weight: 1000–1750 g) on days 2, 7, 14, 21, and 28. Quantitative analysis of plasma citrulline levels was performed by ion-exchange chromatography with postcolumn derivatization. RESULTS: In the study population, mean plasma citrulline levels showed a statistically significant increase from 19 ± 4 μmol/L on day 2 and 20 ± 4 μmol/L on day 7 to 23 ± 4 μmol/L on day 14, 29 ± 5 μmol/L on day 21, and 31 ± 5 μmol/L on day 28 (P < .01). The route of feeding did not seem to have an affect on plasma levels of citrulline (similar values were obtained from neonates who were fed enterally and parenterally on day 7). CONCLUSIONS: Citrulline levels in normal preterm neonates seem to be age-related and may serve as reference values, which facilitates the evaluation of compromised intestinal function in preterm neonates with severe gastrointestinal problems.

The Mediterranean diet adherence by pregnant women delivering prematurely: association with size at birth and complications of prematurity

Abstract Background: The Mediterranean diet (MD) is associated with decreased risk of metabolic syndrome and gestational diabetes due to the anti-inflammatory and antioxidative properties of its components. The aim was to investigate the potential association of MD adherence (MDA) during pregnancy by mothers delivering prematurely, with intrauterine growth as expressed by neonates’ anthropometry at birth and complications of prematurity. Participants and methods: This is a single-center, prospective, observational cohort study of 82 women who delivered preterm singletons at post conceptional age (PCA) ≤ 34 weeks and their live-born neonates. Maternal and neonatal demographic and clinical data were recorded. All mothers filled in a food frequency questionnaire, and the MDA score was calculated. Based on 50th centile of MD score, participants were classified into high-MDA and low-MDA groups. Results: The low-MDA mothers had significantly higher pregestational BMI and rates of overweight/obesity (odd ratios (OR) 3.5) and gestational hypertension/preeclampsia (OR 3.8). Neonates in the low-MDA group had significantly higher incidence of intrauterine growth restriction (IUGR) (OR 3.3) and lower z-scores of birth weight and BMI. Regarding prematurity-related complications, the low MDA-group was more likely to develop necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity (OR 3.2, 1.3, and 1.6, respectively), while they were less likely to develop respiratory distress syndrome (OR 0.49), although the differences were not statistically significant. However, adjustment for confounders revealed MDA as a significant independent predictor of hypertension/preeclampsia, IUGR, birth weight z-score, necrotizing enterocolitis, and bronchopulmonary dysplasia. Conclusions: High MDA during pregnancy may favorably affect intrauterine growth and certain acute and chronic complications of prematurity as well as maternal hypertension/preeclampsia.

Effect of Gestational Diabetes on Circulating Levels of Maternal and Neonatal Carnitine

Objectives: Free carnitine is reported to decrease in normal pregnancies whereas data on the effect of gestational diabetes mellitus (GDM) on maternal and offspring carnitine status are lacking. This study aimed to assess changes in carnitine status in mothers with GDM and the offspring. Subjects/methods: Prospective case-control study of 54 pairs of mothers - neonates (27 with GDM and 27 with normal pregnancies) and 26 non-pregnant controls. Serum glucose, lipids, and total fatty acids, blood β-hydroxybutyric acid, and whole blood carnitine were assessed in mothers before labor and neonates at birth. Carnitine was assessed in dried blood-spots on Guthrie paper using Tandem Mass Spectrometry. Results: Compared to the controls, both groups of mothers had lower free carnitine and acylcarnitine and higher triglyceride and fatty acid levels. Compared to their respective maternal group, both groups of neonates had significantly higher free carnitine and acylcarnitine and lower triglyceride and fatty acid levels. Free carnitine and acylcarnitine, were comparable between the two maternal groups, whereas they were significantly higher in neonates of GDM mothers versus healthy neonates. Conclusions: Well controlled GDM does not exacerbate changes in free carnitine, acylcarnitine, and fatty acid levels in pregnant women, albeit it is associated with increased carnitine in the newborn indicating enhanced fatty acid oxidation. The potential association of carnitine changes with macrosomia and long-term consequences in the offspring of GDM needs further investigation.

Early Abnormal Aeeg Activity is Associated with Adverse Short-Term Outcome in Premature Infants

Aim: To identify specific early aEEG features that could be used as prognostic markers for severe brain injury in premature infants.Methods: In 115 preterm infants, 25-32 wks‘ GA at birth, the aEEG recordings during the first 72 hours of life were correlated with head ultrasonographic(HUS) findings. Continuity(Co), sleep-wake cycling(Cy) and lower border(LB) of the aEEG were evaluated by semiquantitative analysis, applying pre-established criteria. The brain ultrasound was classified as seriously abnormal [intraventricular hemorrhage(IVH) 3-4, periventricular leucomalacia(PVL)], mildly abnormal (IVH 1-2, mild/moderate echodensities) or normal.Results: The infants were divided in four groups based on brain injury severity. Group A (n=72, normal HUS), group B (n=16, IVH 1-2 or mild/ moderate echodensities), group C (n=21, IVH 3-4) and group D (n=6, PVL). 18 infants (16 of group C and 2 of group D) died during hospitalisation. Significantly lower values of all aEEG features were found in group C infants [Co(p:0.003), Cy(p:0.003), LB(p:0.046)]. The presence of pathological tracings (burst-suppression, continuous low voltage, isoelectric activity) or discontinuous low-voltage, the absence of Cy and LB < 3µV in the initial aEEG displayed a sensitivity of 88.9%, 63% and 51.9% respectively, for severe brain injury or death. Logistic regression analysis of aEEG features after controlling for any potential confounding influence of GA, revealed significant relationship between Co and the presence of severe injury(83.19% of cases with early adverse outcome could correctly classified using Co).Conclusion: Pathological tracings or discontinuous low-voltage in the initial aEEG are predictive for poor short-term outcome in VLBW neonates.

991 Serum and Urine Cystatin C and Neutrophil Gelatinase-Associated Lipocalin |[lpar]|NGAL|[rpar]| in Asphyxiated Term Neonates: Preliminary Results

Background: Cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) are novel biomarkers of acute kidney injury (AKI). Objective: To evaluate CysC and NGAL in the serum and urine of term neonates with AKI secondary to acute asphyxia. Patients-methods: Prospective study in term neonates with severe acute asphyxia and AKI (n=8, serum creatinine ≥1.5 mg/dL or rising values >0.3 mg/dL from baseline) and healthy term ones (n=10). Blood and urine samples were obtained on day 1 and 3 of life (DOL) for CysC and NGAL measurement (ELISA). Results: Serum CysC was increased in neonates with asphyxia-AKI vs. healthy ones without the differences being significant (DOL 1; 2.04±1.02 mg/L vs. 1.85±0.35 mg/L, p=0.609, DOL 3; 2.04±1.13 vs.1.65±0.35 mg/L, p=0.435). Similarly, serum NGAL was higher -although not significantlyon DOL 1 (155.3±140 ng/mL vs. 55.2±33 ng/mL, p=0.087) and DOL 3 (144.2±151 ng/mL vs. 23.9±9.6 ng/mL, p=0.109) in neonates with AKI. In the latter group, however, significantly increased urine values of CysC (DOL 1; 275±0.127 ng/mL vs. 42±127 ng. L, p=0.003, DOL 3; 279±102 vs. 51.6±38 ng/ mL, p=0.001) and NGAL (DOL 1; 16.8±4.1 ng/ mL vs. 10.8±5.3 ng/mL, p=0.03, DOL 3; 16.6±6.2 vs.12.3±6.7 ng/mL, p=0.226) were observed. Serum creatinine was significantly positively correlated with serum and urine CysC and NGAL. Unlike NGAL, a significant positive correlation was found between serum and urine CysC. Conclusions: In asphyxiated term neonates with AKI, CysC and NGAL significantly increase only in urine. Thus, their measurement in urine may be better than in serum for AKI evaluation in term neonates.

594 Early Prediction of Long Term Outcome of Low Risk Premature Neonates with the Aeeg

Background and aims: Preterm infants of lower gestational age(GA) display advanced maturation of aEEG in comparison to others of higher GA at the same post conceptional age(PCA). Brain ontogeny follows specific developmental stages and any deviations from this process may influence later cognitive function. To investigate the association between aEEG evolution during the neonatal period and outcome of premature infants with different GA. Methods: 84 clinically stable preterm infants(GA 26-32 wks) without ultrasonographic evidence of neurological abnormalities at birth were assessed at the age of 3 years (Bayleys screening test, III edition) aEEG traces of all neonates were recorded within the first 72 h of life and then weekly until discharge. Four aspects of each tracing (continuity, sleep-wake cycling, bandwidth, and amplitude of the lower border)were evaluated applying pre-established criteria. Results: None of the children had gross motor disturbances, but one, and severe developmental delays. The children were divided into group A (n=23, mild developmental problems) and group B(n=61 normal for the age). Both groups had comparable initial neonatal characteristics. Group A showed higher scores in all 4 components of the aEEG as compared to group B, with significant differences around 31-32 wks PCA. Total score(T) of the 4 aspects of aEEG was significantly higher between 28-32wks (figure). Conclusions: Accelerated maturation of cerebral function seems to be associated with long-term cognitive and behavioral deficits without overt effects on motor development in preterm infants who were neurologically normal in the neonatal period.