Epidemiology of candidemia in neonatal intensive care units: a persistent public health problem.

BACKGROUND: Candidemia has become an increasingly important problem in infants hospitalized in the Neonatal Intensive Care Units (NICUs). Candida species are the third most common agents of late-onset infections in critically ill neonates and they are associated with high morbidity and mortality rates. In this study we evaluated the epidemiology of Candida bloodstream infections in the NICU of an Italian university hospital during a 15-year period. Our specific aims were to analyze the change in species distribution and the vitro susceptibility of these yeasts to fluconazole (FCZ) and amphotericin B (AmB). METHODS: A retrospective study of candidemia in the NICU of a university hospital in southern Italy, covering the years 2000-2014 was carried out. The isolates were identified using the VITEK2 yeast identification system and antifungal susceptibility was determined using the E-test method. RESULTS: Among the 57 patients with confirmed candidemia, 60% were males (n = 34 cases) and 82% (n = 47) had a gestational age of 24-32 weeks. Twenty-seven neonates (47%) had a very low birth weight (<1500 g), 20 (35%) an extremely low birth weight (<1000 g), and 10 (18%) a low birth weight (<2500 g). The most important potential risk factors were the placement of a central venous catheter, total parenteral nutrition, and endotracheal intubation (100%, each). Candida albicans was the most frequent yeast (47%), followed by Candida parapsilosis (44%). The proportion of Candida non-albicans increased slightly, from 46% in 2000-2004 to 71% in 2010-2014 (χ2 test for trend, p = 0.030). All isolates were susceptible to FCZ and AmB. CONCLUSIONS: The detection in this epidemiologic study of an increase in Candida non-albicans highlights the importance of correct species-level identification in the rapid diagnosis for an efficient treatment of candidemia. Knowledge of the local epidemiological trends in Candida species isolated in blood cultures will facilitate therapeutic decision-making.

Invasive fungal infections in neonatal intensive care units of Southern Italy: a multicentre regional active surveillance (AURORA project).

INTRODUCTION: During the past years invasive fungal infections (IFIs) have become an increasingly important problem in infants hospitalized in the Neonatal Intensive Care Unit (NICU). Candida species is the third most-common agent of late-onset infections in critically ill neonates, with an estimated incidence of 2.6-10% in very low birth weight and 5.5-20% in extremely low birth weight infants. The aim of this observational study is to evaluate the epidemiology of IFIs among infants admitted to NICUs of one Italian region by a multicenter surveillance (Aurora Project). METHODS: The IFIs surveillance was carried out prospectively in Apulia (Southern Italy) between February 2007 and August 2008. This report focuses on the results from 6 enrolled NICUs. RESULTS: Twenty-one neonates developed IFIs: the overall incidence was 1.3% and crude mortality was 23.8%. Infants weighing < or = 1500 g (4.3%) showed a significantly higher incidence than those > or = 2500 g (0.2%). C. parapsilosis (61.9%) was the most frequent isolated species. The main potential risk factors were having a central venous catheter placed, length of stay in NICU > 7 days and total parenteral nutrition for > 5 days. The (1,3)-beta-D glucan (BDG), mannan antigens and anti-Candida antibodies' evaluation was performed in 7 neonates. All neonates were positive to the BDG; the mannan antigen result was positive in 5 newborns, the anti-mannan antibodies were always negative. All isolates were amphotericin B and fluconazole-susceptible. DISCUSSION: This first prospective study on neonatal fungal infection in one Italian region gives evidence of a preponderance of non-albicans Candida spp and indicates potential utility of BDG as an adjunct diagnostic test.

Gastric electrical activity and gastric emptying in preterm newborns fed standard and hydrolysate formulas.

BACKGROUND: Because infant formulas containing hydrolyzed cow milk protein are used to reduce feeding intolerance and to improve gastric emptying, the effect on gastrointestinal motility of a hydrolysate formula was compared with that of a standard preterm formula. METHODS: Thirty-six preterm newborns with a gestational age of 32.2 +/- 2.3 weeks were assigned randomly to standard formula or hydrolyzed formula. Cutaneous electrogastrography and ultrasound examination of gastric emptying were performed simultaneously to evaluate gastrointestinal motility before and after the test meal. All recording sessions were performed 1 week after infants had reached full enteral feeding. RESULTS: No significant difference in gastrointestinal symptoms was noted in the newborns fed the different formulas. In particular, regurgitation and vomiting were observed in 78% versus 64% of preterm newborns after standard and hydrolyzed formula, respectively (Fisher exact test, not significant). No differences were found in terms of gastric electrical activity and gastric emptying time between the two groups. CONCLUSIONS: It seems unnecessary to use hydrolysate formulas to improve motility in preterm infants.

Gastric electrical activity and gastric emptying in term and preterm newborns.

The aims of this study were to evaluate the gastric electrical activity and gastric emptying in preterm and term newborns and to assess the development of gastric motility by comparing newborns of different gestational ages. The cutaneous electrogastrography and the ultrasonographic study of the gastric emptying were performed before and after milk formula in three groups of infants: 12 preterm newborns with a gestational age of 28-32 weeks, 11 preterm newborns with a gestational age of 32-36 weeks, and 10 full-term newborns with a gestational age of 36-40 weeks. All recording sessions were performed 1 week after infants had reached full enteral feeding. The percentage of normal slow waves was similar in the three groups but it was not predominant compared to tachygastria in the earliest premature infants (59.3% (12.7-92.3) vs. 29.6% (3.7-78.8); P < 0.05). In addition, a progressive increase in the normal slow wave percentage (59.3% (17.4-87.4), 60.9% (38.1-89.7), 77.8% (66.4-84.8); P < 0.05) was observed as gestation advanced. As regards gastric emptying parameters, the antral area was greater and T(1/2) was longer in the preterm newborns of 28-32 weeks than preterm newborns of 32-36 weeks and full-term newborns (fasting antral area: 0.96 cm2 (0.6-1.5), 0.63 cm2 (0.4-1.2), 0.55 cm2 (0.1-0.9) respectively, P < 0.05; T(1/2): 83.4 min (76.0-108.5), 70 min (57.5-89.5) and 71.8 min (54.9-81.2), respectively P < 0.05). The comparisons of gastric emptying curves made among the three groups showed a reduced antral dilatation in preterm newborns of 28-32 weeks compared to full-term newborns at 30 and 60 min after a meal. In conclusion, although enteral feeding is important for the development process of gastrointestinal motility, gastric electrical activity and gastric emptying show an intrinsic maturation depending on the gestational age.

Coagulation and fibrinolytic systems in the ill preterm newborn.

AIM: The activation pattern of the clotting and fibrinolytic systems in 63 preterm infants (GA 31, 6 +/- 2.3 weeks) was studied. METHODS: The infants were divided into four groups: (i) IRDS, (ii) asphyxia at birth, (iii) sepsis, and (iv) mild infection. A control group was composed of preterm infants without any apparent disease (GA 32 +/- 1.8 weeks). RESULTS: During IRDS we found a systemic activation of both coagulation and fibrinolysis at birth which was represented by lower levels of ATIII (27.7 +/- 8.8%) and significantly greater levels of TAT (37.9 +/- 31.9 ng/ml), D-dimers (1242.7 +/- 206.9 ng/ml), tPA Ag (10.9 +/- 5.3 ng/ml) and PAI Ag (59.9 +/- 16.7 ng/ml) than in the control group. In the asphyxiated newborns there were no significant differences from the controls. During their seventh day of life, a significant reduction of all the analysed parameters (TAT, D-dimers, tPA, PAI) and a significant increase in ATIII were seen in the newborns with IRDS, while no significant modification was observed in the newborns with asphyxia at birth. When the newborns with sepsis were compared with those with mild infection, their TAT and PAI values proved to be significantly higher for the first tests (21.7 +/- 18.8 vs 9.2 +/- 6.9 microg/l and 53.6 +/- 14.4 vs 37.7 +/- 10.2 ng/ml respectively). During the second tests, 7 days later, only TAT (16.7 +/- 14.7 vs 6.3 +/- 4 microg/l) levels remained high while D-dimers (1094.2 +/- 400.6 vs 646 +/- 200ng/ml) and tPA (11.3 +/- 8 vs 4.9 +/- 2 ng/ml) were significantly higher in the septic group of newborns than those with mild infection. CONCLUSIONS: These data indicate that there is an activation of the clotting and fibrinolytic systems both in the initial phase of IRDS as well as during sepsis.

[Prognostic value of neonatal pyelectasia diagnosed in utero]. / Valutazione prognostica delle pielectasie neonatali diagnosticate in utero.

Sixty-six children (48 male-18 female) with prenatal diagnosis of pyelectasia that was conformed at birth were examined between 1986-1994. All newborns carried out urinalysis and urine culture and performed a renal sonogram to reconfirm the diagnosis at 1 month of age. After 3 month of life the pelvic dilatation was confirmed in 61 patients while 5 showed a complete disappearance, 61 patients underwent micturitional cystography that evidenced 30 renal units (RU) with moderate to severe vesicoureteral reflux. In the patients without reflux, a scintigraphy was carried out with DTPA or MAG 3 and/or IVP and evidenced a functional junctional pathology in 32 RU and an organic junctional pathology in 24 RU, a primary megaureter with pre-vesical stenosis in 6 RU and a pyelo-ureteral complete double system in 4 RU. The patients with organic stenosis or those patients with parenchymal damage due to the vesicoureteral reflux underwent surgical intervention during the 1st year of life while all the remaining patients are continuously monitored to date with biohumoral exams and echography. With these results we can safely confirm the important role of the sonogram in the initial diagnosis of pyelectasia and to its eventual modifications in order to benefit the patients with a nephro-urological pathology and direct them toward a correct follow up.

[Monitoring and prevention of hospital infections in neonatal intensive care]. / Monitoraggio e profilassi delle infezioni ospedaliere nella terapia intensiva neonatale.

The authors monitored newborns in the Intensive Care Unit and the equipment with culture exams for a period of 6 months in order to evaluate the incidence of microbic infections and eventual clinical manifestations in relation to risk factors and to test the efficacy of the prophylactic and therapeutic measurements adopted. The results evidenced a positivity in the culture exams of 24.4% at the 1st control, 14.3% at the 2nd and no positive results at the 3rd. Only two newborns presented sepsis that was resolved without any consequences. Aimed antimicrobic therapy was begun at the 1st clinical and/or haematochemical sign that could suspect the onset of infection. A careful control of the microbic flora, the use of aimed antibiotic therapy and respect of the hygienic conditions permitted us to obtain an excellent control of the infections the morbidity, mortality, the days of hospitalization and the onset of bacterial resistance.

[Plasma levels of the serum antioxidants (uric acid, ceruloplasmin, transferrin) in term and preterm neonates in the first week of life]. / Livelli plasmatici degli antiossidanti sierici (acido urico, ceruloplasmina, transferrina) in neonati a termine e pretermine nella prima settimana di vita.

Development of serum antioxidants (ceruloplasmin, transferrin, uric acid and bilirubin) an the 1st, 4th, 7th days of life has been evaluated in 50 healthy NGA newborns (25 preterm with 35 +/- 0.6 week of gestational age and 2270 +/- 150 g of weight, 25 a term with 39 +/- 0.8 week of gestational age and 3480 +/- 220 g of weight) and in apparent absence of oxidant stress. The ceruloplasmin values increase from the 1st to 7th days of life and change significantly at the 4th day between a term and preterm newborns (p < 0.01); the transferrin values reduce significantly an the 1st (p < 0.01) and 7th days of life (p < 0.05); the uric acid values reduce in the two groups an the 1st day (p < 0.01). Our results show in the newborn a prevalent antioxidant activity of the studied substances. The plasma levels of uric acid may be compared, in the first week of life, to the hypoxanthine levels as acute ipoxia gauges.

[Neonatal infections and premature rupture of fetal membranes]. / Infezioni neonatali e rottura prematura delle membrane.

The premature rupture of the membranes is still a cause of concern due to the related risk of infection and respiratory disorders. The study included sixty-two neonates whose mothers had ruptured their membranes for at least 48 hours (group A) and 42 neonates with a high risk of infection (low birth weight, prematurity) (group B) in order to assess whether antibiotic prophylaxis used in pregnant women with premature rupture of the membranes is sufficient to reduce the risk of severe neonatal infection. The results obtained show that there is an increased frequency of RDS, jaundice and mortality in group A, whereas in group B there was a greater frequency of sepsis and urinary tract infections. Antibiotic prophylaxis therefore allows the frequency of neonatal infections following the rupture of membranes to be reduced, thus enabling the birth to be delayed in order to induce pulmonary maturity.

[Proposed scoring system for the early diagnosis of infection in neonates]. / Proposta di uno score per la diagnosi precoce di infezione in epoca neonatale.

Infections are currently often responsible for neonatal morbidity and mortality. The present study examines the possibility of reducing this incidence by the early diagnosis of infections. With this in mind the early clinical signs of infection were examined as well as the results of certain quickly and easily performed blood and blood chemical tests which were scored from 0 to 2. The results showed that newborns with scores less than 5 should be considered free of sepsis, those scoring 5-7 should arouse suspicion of sepsis, while sepsis should be considered definitely present in those scoring greater than 7. This scoring system presented 100% sensitivity, 88.2% specificity as well as 100% positive and an 88.2% negative predictive value. The system is therefore considered reliable as well as easy to use.

[Glycerol erythrocyte lysis test in the 1st month of life in neonates at term and premature infants]. / Il test di lisi eritrocitaria al glicerolo nel primo mese di vita in neonati a termine e pretermine.

Foetal erythrocytes have an enhanced resistance to osmotic haemolysis that they retain for the first 5 days after birth, particularly in premature newborns. The erythrocyte fragility test was used to study the increased resistance to osmotic haemolysis in 155 healthy newborns (50 NGA born to term, 55 NGA premature and 50 SGA born to term) as well as 31 newborns (20 born to term and 11 premature) with aspecific hyperbilirubinaemia. The drug used was glycerol which is specific in its reaction to alterations in erythrocyte membrane stability and made it possible to assess changes arising in the first month after birth, both naturally and in response to phototherapy. The results show a much higher resistance in neonatal than adult erythrocytes that gradually decrease during the first month after birth without, however, falling to adult levels. No changes in resistance attributable to the phototherapy adopted in newborns with hyperbilirubinaemia were encountered. The glycerol test proved extremely sensitive in the diagnosis of neonatal haemolytic anaemias easy to use so that congenital spherocytosis can be identified earlier than is otherwise possible.

Postnatal development of prekallikrein (Fletcher factor) in man.

The aim of the present study was to determine the concentration of plasma prekallikrein in healthy infants during the first year of life. Prekallikrein levels evaluated by a chromogenic substrate assay were low in the first 15 days of life and increased progressively from the third week of life, reaching normal adult values after the third month of life. The low levels of prekallikrein during the neonatal age reflect the impaired ability of liver cells to synthesize proteins.

Post-natal development of protein C in full-term newborns.

The purpose of this study was to determine the concentration of Protein C in the blood of full-term healthy newborns. The levels of Protein C, evaluated by electroimmunoassay, were low in the first 5 days of life and lower than the critical adult thrombotic level. The antigenic activity increased progressively from the 2nd week of life and the adult values were reached after the 6th month. The reduction of Protein C levels may impair the ability of the newborn to control consumptive disorders, thus exposing the infants to the risk of thrombotic conditions in neonatal age.