Ezio Maria Padovani

Pharmacokinetics of amikacin in neonates.

Only a few data have thus far been published on the pharmacokinetics of amikacin in neonates. To gain further information on this issue, we studied a series of 32 neonates who were treated with amikacin for suspected or documented bacterial infection. Nineteen neonates were preterm (mean gestational age = 32.0 +/- 3.6 weeks, mean body weight = 1.74 +/- 0.81 kg) while the remaining 13 were full-term (mean body weight = 3.19 +/- 0.82 kg). The 32 neonates were given amikacin by intramuscular route. A total of 121 concentrations were measured (average number of concentrations per patient = 3.8; range 3-6). To estimate amikacin pharmacokinetic parameters, the serum concentration values of the drug were fitted to the one-compartment pharmacokinetic model. The calculated pharmacokinetic parameters were the following (mean +/- SD): clearance = 64.6 +/- 30.8 ml/h/kg; volume of distribution = 0.655 +/- 0.414 liters/kg; half-life = 7.6 +/- 4.4 h. These results are similar to the values reported previously, with the important exception of the volume of distribution, which was considerably higher in our study. The intraindividual variability of amikacin pharmacokinetics was evaluated by the standard two-stage method yielding an intraindividual variability coefficient of 28.9%. No previous estimate of this parameter has as yet been published. The population parameters of amikacin in neonates, derived from the present study (i.e. coefficient for intraindividual variability and means +/- SD for clearance and volume of distribution), can be applied to a further series of neonates to facilitate the prospective use of the bayesian method for individualizing amikacin dosage.

Evaluation of antibiotic-induced nephrotoxicity in preterm neonates by determining urinary α1-microglobulin

Abstractα1-Microglobulin (α1-m, protein HC), a relatively low molecular weight protein of about 31,000 daltons, was measured in urine of three groups of 34 preterm neonates: group A consisted of 9 healthy preterm neonates; groups B (n=13) and C (n=12) consisted of preterm neonates with suspected or confirmed bacterial infections. Immediately after birth, all group B neonates were treated with ampicillin and aztreonam in combination, and all group C neonates were treated with oxacillin and amikacin in combination. To optimize amikacin administration, computerized individually tailored doses were administered. Urine samples were obtained from a short collection in sterile bags on the 1 st, 4th, and 7th day after delivery in all infants. Urinary α1-m concentrations were measured by a turbidimetric method (latex agglutination photometric immunoassay) and results were expressed as a ratio to urinary creatinine. In group A, urinary α1-m concentrations were stable after birth. In group C, α1-m excretion increased immediately within the 1 st day of treatment, and over the 1st week of life urinary α1-m levels were significantly higher than in group A (P=0.033). These data support the conclusion that amikacin administration was the most important factor inducing renal tubular dysfunction in the neonates of group C.

Low molecular mass proteins and urinary enzymes in amniotic fluid of healthy pregnant women at progressive stages of gestation.

OBJECTIVES Amniotic fluid alpha1-microglobulin (alpha1-m) and beta2-microglobulin (beta2-m) levels, as well as N-acetyl-beta-D-glucosaminidase (NAG) and alanine aminopeptidase (AAP) activities, were measured in the course of uncomplicated pregnancies to assess their variations as gestation progresses. DESIGN AND METHODS Samples were obtained from 141 healthy pregnant women divided into three groups on the basis of gestational stage. Quantitative estimation of proteins was performed immunometrically and enzyme activities were determined spectrophotometrically. RESULTS It was found that, during pregnancy, alpha1-m and beta2-m concentrations as well as AAP activity significantly decrease, although their reduction patterns vary. Controversial results were found for NAG activity: the normalization of values for amniotic fluid creatinine significantly changed the reduction pattern of this enzyme. No statistically significant differences were found between male and female fetuses for amniotic fluid values of the biochemical substances studied. CONCLUSIONS The behavior observed for alpha1-m, beta2-m, and AAP might be linked to the progressive development and maturation of fetal renal tubular function. Amniotic fluid total NAG activity seems not to depend only on fetal urinary excretion.

Routine coagulation tests in newborn and young infants

BackgroundThe diagnostic approach to haemostatic defects in the newborn is challenging and requires appropriate interpretation of coagulation tests according to reference values dependent on the postnatal age.MethodsThis investigation was designed to study the postnatal development of the human coagulation system in newborn infants and to develop appropriate reference ranges for prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FBG) according at the day of birth and for the following postnatal period (days 1, 2, 3, 4, 5, 6, from 7 to 10 and from 11 to 44).ResultsThe mean FBG value was already within the adult reference range in newborns at birth, the mean PT value fell within the adult reference range in infants aged 4 days or more, whereas the mean APTT value was still higher than the upper limit of the adult reference range in infants aged between 11 and 20 days. The prevalence of infants with pathological values according to the actual adult reference ranges was limited for FBG (from 24 to 7%), decreased from 92 to 8% in infants aged 0 and 11–20 days for PT, but remained elevated throughout the observational period for APTT (from 94 to 71%).ConclusionsThe results of the present investigation demonstrate that the actual adult reference ranges for coagulation screening tests, especially PT and APTT, cannot be applied to newborns and young infants.

Tubular proteins and enzyme content in the amniotic fluid

Amniotic fluid is the product of many substances and fetal urine is considered to be one of the principal components. Only a few reports have been published describing the concentration of microglobulins and urinary enzymes in the amniotic fluid. We determined the levels of alpha 1-m, beta 2-m, AAP and NAG, in 154 samples of amniotic fluid (103 early determinations and 51 late determinations) as a function of gestational age. We observed a statistically significant decrease in concentration of alpha 1-m (P < 0.001), beta 2-m (P < 0.01) and AAP (P < 0.001) when early and late amniotic fluid samples were compared. A statistically significant increase of NAG (P < 0.01) and creatinine (P < 0.01) was also found. A significant correlation was observed between alpha 1-m and beta 2-m, and between AAP and NAG, respectively. The potential role of urinary enzyme and microglobulin determination in amniotic fluid as an index of fetal kidney development, is discussed.

Microbiota network and mathematic microbe mutualism in colostrum and mature milk collected in two different geographic areas: Italy versus Burundi

Human milk is essential for the initial development of newborns, as it provides all nutrients and vitamins, such as vitamin D, and represents a great source of commensal bacteria. Here we explore the microbiota network of colostrum and mature milk of Italian and Burundian mothers using the auto contractive map (AutoCM), a new methodology based on artificial neural network (ANN) architecture. We were able to demonstrate the microbiota of human milk to be a dynamic, and complex, ecosystem with different bacterial networks among different populations containing diverse microbial hubs and central nodes, which change during the transition from colostrum to mature milk. Furthermore, a greater abundance of anaerobic intestinal bacteria in mature milk compared with colostrum samples has been observed. The association of complex mathematic systems such as ANN and AutoCM adopted to metagenomics analysis represents an innovative approach to investigate in detail specific bacterial interactions in biological samples.

Familial haemophagocytic lymphohistiocytosis: Survival of a premature twin with immuno-chemotherapy and bone marrow transplantation from an HLA-identical unrelated donor

UNLABELLED We describe a premature twin born at 30 wk of gestational age, affected with familial haemophagocytic lymphohistiocytosis. Two different mutations were identified in his DNA: one inherited from the mother and one from the father. Haemophagocytosis had been confirmed in his twin brother, who died soon after birth, as well as in the re-evaluation of the autopsy of his older sister, who died 1 y earlier. At 26 d of age, chemotherapy and immune-suppressive treatment were started according to the HLH-94 protocol. At 6 mo of age, a bone marrow transplant from an HLA-identical, unrelated volunteer was performed. Now at 32 mo of age, the infant is healthy and without signs of graft-versus-host disease. CONCLUSION This case report shows that immuno-chemotherapy and allogenic bone marrow transplant are feasible even in premature infants affected with familial haemophagocytic lymphohistiocytosis, which should be ruled out in unknown bleeding disorders of neonates.

Serendipitous Diagnosis of Infracardiac Total Anomalous Pulmonary Venous Return by Umbilical Venous Catheter Blood Gas Samples

Total anomalous pulmonary venous return (TAPVR) is a rare congenital heart defect that occurs when all four pulmonary veins connect to the systemic venous circulation. We describe a full-term male neonate who presented with cyanosis and mild tachypnea shortly after birth. One umbilical artery and the umbilical vein were catheterized, and oxygen treatment was provided. Four echocardiograms indicated severe pulmonary hypertension and were negative for any congenital heart defects. After the umbilical artery catheter was removed, high partial pressure of oxygen was detected in blood samples drawn from the umbilical venous catheter that was positioned below the diaphragm. Based on this finding, TAPVR was suspected and confirmed with angiography through a central venous catheter. The neonate underwent a successful surgical repair to correct the cardiac defect.

Levels of Growth Factors and IgA in the Colostrum of Women from Burundi and Italy

Colostrum is produced in the first days postpartum. It is a known source of immune mediators for a newborn within the first week of life. Although it is still unclear if colostrum composition varies between populations, recent data suggest differences. Hepatocyte growth factor (HGF); transforming growth factor-β (TGF-β) 1, 2, and 3; and immunoglobulin A (IgA) are key immunological components of colostrum that stimulate neonatal gastrointestinal and immune system development. We aimed to investigate the differences in the concentration between immune markers in the colostrum of mothers living in Burundi and Italy, and to identify the factors associated with differences. In this cross-sectional birth cohort study, a total of 99 colostrum samples from Burundian (n = 23) and Italian (n = 76) women were collected at 0 to 6 days postpartum. A clinical chemistry analyser was used for IgA quantification and electro-chemiluminescence, for HGF and TGFβ1-3 assessment. A univariate analysis and multivariate linear regression model were used for statistical testing. The concentrations of TGF-β2 (p = 0.01) and IgA (p < 0.01) were significantly higher in the colostrum from the women residing in Burundi than in Italy, both in a univariate analysis and upon the adjustment for confounding factors. A similar trend is seen for HGF, reaching statistical significance upon a multivariate analysis. We found a moderate to strong positive correlation between the TGF-β isoforms and IgA concentration in both countries (p < 0.01), with stronger concentration in the colostrum from Burundi. The results of this study are in support of previous data, suggesting that concentration of the immune active molecules is higher in the human milk of women residing in developing countries. However, with a small sample size, caution must be applied, as the findings require further confirmation. Future work should also be focused on other factors (e.g., lipid and microbial composition), as well as the investigation into colostrum and between populations comparison, adjusting for potential confounders.

Familial haemophagocytic lymphohistiocytosis: Survival of a premature twin with immuno-chemotherapy and bone marrow transplantation from an HLA-identical unrelated donor: Clinical observations

We describe a premature twin born at 30 wk of gestational age, affected with familial haemophagocytic lymphohistiocytosis. Two different mutations were identified in his DNA: one inherited from the mother and one from the father. Haemophagocytosis had been confirmed in his twin brother, who died soon after birth, as well as in the re‐evaluation of the autopsy of his older sister, who died 1 y earlier. At 26 d of age, chemotherapy and immune‐suppressive treatment were started according to the HLH‐94 protocol. At 6 mo of age, a bone marrow transplant from an HLA‐identical, unrelated volunteer was performed. Now at 32 mo of age, the infant is healthy and without signs of graft‐versus‐host disease.