Vancomycin cerebrospinal fluid concentrations after intravenous administration in premature infants

OBJECTIVE: Staphylococcal species are the most common cause of nosocomial infections in the neonate. Because of staphylococcal resistance patterns, vancomycin has become the drug of choice for treatment. Although the blood stream is the usual site of infection, premature infants are at increased risk for the development of meningitis. The aim of this study was to determine vancomycin cerebrospinal fluid (CSF) concentration and penetration following intravenous (IV) administration in critically ill premature infants. STUDY DESIGN: A multiple-dose, open-label, case series was performed at a level III neonatal intensive care unit in a university teaching hospital. Three critically ill premature infants, 26 to 31 weeks of gestation requiring a course of IV vancomycin for suspected or proved sepsis were studied. Vancomycin was administered intravenously at 20 mg/kg, every 18 to 24 hours over 60 minutes. Serum and CSF vancomycin concentrations were obtained and pharmacokinetic analysis and CSF penetration was calculated. RESULTS: Serum vancomycin pharmacokinetics were consistent with those previously reported. CSF vancomycin concentrations ranged from 2.2 to 5.6 micrograms/ml and the calculated vancomycin CSF penetration ranged from 26% to 68%. CONCLUSIONS: CSF penetration of vancomycin after IV administration was much higher than that reported in older infants and children. This higher penetration may improve clinical outcomes in neonates with central nervous system infections. These data should be encouraging to clinicians who choose to use IV vancomycin for neonatal meningitis.     

Pulmonary function tests as a predictor of chronic lung disease in ventilated preterm infants

BACKGROUND: The objective of this study was to determine if the value of respiratory system compliance and lung resistance could be a good predictor of chronic lung disease (CLD) in an early stage of this disease. METHODS: The study was carried out on 48 preterms infant (BW < 1500 g) who were ventilated for respiratory distress, calculating pulmonary mechanics at 3, 5, 7 and 10 days of life with a standardized protocol of measurements. RESULTS: Infants who did not develop CLD showed higher values of respiratory system dynamic compliance (Crsdyn) than the CLD group since the 5th day of life (p < 0.001). The values of lung resistance show a statistical significant difference between groups since the 7th day of life. CONCLUSIONS: These findings indicate that, with a well standardized method of measurements, the value of Crsdyn can well be a good predictor and a sensible prognostic factors for CLD.     

Pulmonary complications and respiratory function changes after bone marrow transplantation in children

We prospectively assessed the frequency of pulmonary complications and the natural course of lung function after bone marrow transplantation (BMT), as well as the effect of several risk factors in a homogeneous group of 39 children who underwent allogeneic or autologous BMT for haematological malignancies between 1992 and 1995. Four patients developed pneumonia within the first 3 months and three 3-6 months after BMT. A considerable percentage of acute bronchitis was recorded throughout the follow-up. Three patients died after the 6 month visit because of pneumonia (two patients) and pulmonary aspergillosis (one patient). No patients had obstructive lung disease syndrome. At 3 months after BMT, forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and transfer factor of the lung for carbon monoxide (TL,CO) significantly decreased, but FEV1/FVC ratio and maximal expiratory flow at 25% of FVC remained unchanged, suggesting a restrictive defect with diffusion impairment. At 18 months, there was a progressive recovery in lung function, although only 11 patients had normalized. Seropositivity for cytomegalovirus had a significant effect on lung function whereas graft-versus-host disease also had an effect, although it was not statistically significant. Baseline respiratory function, type of transplant, type of conditioning regimen and respiratory infections did not significantly affect the outcome of BMT. The high frequency of severe lung function abnormalities found in this study, suggests a careful functional monitoring in all subjects undergoing bone marrow transplantation, even in the absence of respiratory symptoms.     

Development of skin barrier function in premature infants

ANCA directed against PR3 are highly specific for Wegener's granulomatosis and microscopic polyangiitis, and have been implicated in the pathogenesis of small vessel vasculitis. Most PR3-ANCA are directed against conformational epitopes on PR3. This study was designed to determine whether the cleavage of the N-terminal activation dipeptide of PR3 is required for the binding of PR3-ANCA. Recombinant PR3 (rPR3) variants were expressed in the epithelial cell line, 293. As confirmed by radiosequencing, the rPR3 secreted into the 293 cell culture supernatant is N-terminally unprocessed. Two enzymatically inactive rPR3 mutants were expressed in 293 cells: rPR3-S176A and delta-rPR3-S176A. rPR3-S176A contains the N-propetide Ala-2-Glu-1, delta-rPR3-S176A does not. Culture supernatants of rPR3-S176A and delta-rPR3-S176A expressing 293 cells were used as sources of target antigen for PR3-ANCA testing by capture ELISA. Forty unselected consecutive PR3-ANCA+ sera were tested. With delta-rPR3-S176A as antigen all 40 were recognized, compared with only 34 of 40 when rPR3-S176A served as target antigen. The majority of the serum samples contained a mixture of antibodies reacting with epitopes accessible on the mature and on the proform of PR3. In conclusion, the cleavage of the N-terminal activation dipeptide of PR3 is not an absolute requirement for recognition by all PR3-ANCA. However, a substantial proportion of PR3-ANCA recognize (a) target antigen(s) exposed only after the conformational change of PR3 associated with the N-terminal processing. In 15% of sera this PR3-ANCA subset occurred exclusively. PR3-ANCA subtypes can be differentiated using specifically designed rPR3 variants as target antigens, and non-haematopoietic mammalian cells without regulated secretory pathway can be used for their expression.     

Thyroid function in premature infants. The hypothyroxinemia of prematurity

Advances of perinatal and neonatal medicine have been associated with a progressive reduction in mortality of premature infants and a progressive increase in number of the surviving very low birth weight (VLBW) cohort less than 28 to 32 weeks gestation age. Hypothalamic-pituitary-thyroid (HPT) function is immature in most premature infants, and this is particularly true of the VLBW group. Accumulated information has allowed development of a unique nosology of HPT system disorders in these infants to facilitate thyroid function testing, test interpretation, and patient management.     

Reference ranges for newer thyroid function tests in premature infants

OBJECTIVE: To establish reference ranges for recently developed assays of thyroid function in premature infants. METHODS: We measured serum free thyroxine (T4) by direct equilibrium dialysis and serum thyrotropin by a sensitive immunometric method in 104 preterm infants (25 to 36 weeks of gestational age) during the first week of life. RESULTS: The free T4 level correlated positively with gestational age (p < 0.0001; r2 = 0.09) and differed significantly between adjacent gestational age groups (p < 0.05). Free T4 concentrations (mean +/- SD) for the 25- to 27-, 28-to 30-, 31- to 33-, and 34- to 36-week groups were 18.0 +/- 5.2, 25.7 +/- 9.0, 30.9 +/- 9.0, 36.0 +/- 10.3 pmol/L (1.4 +/- 0.4, 2.0 +/- 0.7, 2.8 +/- 0.8 ng/dl), respectively. Two reference ranges for free T4 were determined, one for 25 to 30 weeks (6.4 to 42.5 pmol/L (0.5 to 3.3 ng/dl) and one for 31 to 36 weeks (16.7 to 60.5 pmol/L (1.3 to 4.7 ng/dl)). The logarithm of the value for thyrotropin correlated positively with gestational age (p < 0.001; r2 = 0.08); one reference range of 0.5 to 29 mU/L was determined for thyrotropin. CONCLUSION: This study extends information on thyroid function of preterm infants and establishes reference ranges for this population.     

Hydrocephalus in premature infants

In the light of personal observations from the years 1948-1974 the author discusses the incidence of hydrocephalus in premature babies. The material observed confirms the generally accepted view that the incidence of hydrocephalus is higher in premature babies than in full-term babies. The author analyzes the causes which may be responsible for this finding and concludes that noxious factors during early or late pregnancy are the main cause although perinatal injuries play also a significant role.     

Pulmonary yellow hyaline membrane disease. New variant in premature infants with intrahepatic cholestasis

Two premature female infants with a new variant of pulmonary hyaline membrane disease had both received assisted ventilation with high oxygen concentrations. Postmortem examination showed straw-yellow hyaline membranes lining the terminal bronchioles and alveoli. Pneumonocytes and macrophages also contained straw-yellow pigments in the cytoplasm. These yellow membranes and pigments in pneumonocytes and in macrophages stained positively for bile and negatively for iron. Both infants had severe intrahepatic cholestasis. Cholestasis and pulmonary changes due to oxygen toxicity are believed to be the main features leading to this curious entity.     

Efficacy of dead-space washout in mechanically ventilated premature newborns

The prosthetic dead space makes a significant contribution to the total dead space in low-birth-weight premature newborns receiving artificial ventilation in response to respiratory distress. Use of an endotracheal tube with capillaries molded into the tube wall enables washout of the dead space without insertion of a tracheal catheter. In 10 premature newborns (mean gestational age, 27.5 +/- 2.2 wk; mean weight, 890 +/- 260 g) receiving continuous positive-pressure ventilation (Paw = 12.7 +/- 1.8 cm H2O; FIO2 = 39 +/- 17%), tracheal gas insufflation (TGI) for CO2 washout was conducted using this technique. The flow of tracheal insufflation (0.5 L/min) was derived from the inspiratory line of the ventilator circuit and blown into the trachea. Intratracheal pressures showed little or no TGI-related modification ( < 1 cm H2O). A control system enabled TGI discontinuation in the event of a pressure rise. At constant ventilation pressure, PaCO2 decreased by 12.1 +/- 5.9 mm Hg (delta PaCO2 = -26 +/- 12%) under TGI, whereas PaO2 remained unchanged. While maintaining PaCO2 constant, peak inspiratory pressure (PIP) was decreased by 5.4 +/- 1.7 cm H2O (delta PIP = -22.0 +/- 8.3%). TGI showed immediate efficacy (PCO2 reduction of at least 5 mm Hg) in nine of the 10 newborns who then received chronic TGI (14 to 138 h). TGI appears to be an effective method, suitable for long-term clinical application, enabling a reduction in the aggressive nature of conventional ventilation.     

Pulmonary function studies after smoke inhalation

Pulmonary function studies were performed within 72 hours of injury in seven patients with smoke inhalation injury diagnosed by positive 133Xe scintiphotographs and in eight patients with burns of similar size but with negative 133Xenon scans. The former patients showed decreased peak flow, decreased flow at 25, 50, and 75 per cent of vital capacity, and an elevated pulmonary resistance. In addition, single breath nitrogen tests revealed evidence of maldistribution of ventilation/perfusion abnormalities. Total lung capacity, functional residual capacity, and compliance (both dynamic and static) were similar in the two groups. Pulmonary function studies can be of assistance in evaluating smoke inhalation, estimating the severity, and following the course of patients with this disorder.     

Perinatal intussusception in premature infants

Intussusception is common in infants aged 5 to 18 months, but there have been only 12 reports of its occurrence among premature infants. Nine of these previously reported cases with adequate data and one new case are reviewed. Many of the infants were believed to have necrotizing enterocolitis, leading to an average 12-day interval between the onset of signs and the operation. Bilious emesis or nasogastric contents, bloody stool, and intestinal dilation without pneumatosis intestinalis were common. A contrast enema showed the intussusception in only 1 of 7 cases. Most cases were diagnosed in the operating room and underwent successful primary anastomosis, with no recurrences. A pathological lead point was identified in 2 of the 10 cases. The overall mortality rate was 23%; the one death since 1970 was secondary to attempted hydrostatic reduction. These cases may represent what, in the absence of premature delivery, would have been the intrauterine development of intussusception likely leading to small bowel atresia.     

Learning in premature infants.

Examined instrumental learning in premature infants by using a teddy bear that "breathed" quietly at a rate that reflected the infant's respiration rate. At 33 wks conceptional age (CA), 45 infants were provided with a breathing bear (BRB) or a nonbreathing bear (NBRB). The baby was monitored by time-lapse video for 3-day periods at the beginning and end of a 2-wk intervention period. The BRB babies decreased their latency to contact the bear over time, whereas the NBRB babies showed the opposite pattern. For the BRB babies, decreased contact latencies were correlated with increased total contact and increased contact frequencies. Thus, by 35 wks CA, premature infants learned to find and make contact with a reinforcing source of stimulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Digoxin pharmacokinetics in premature infants

The use of camera renography under experimental conditions is described. The conductivity of the ileo-ureter formed by various surgical techniques in 24 dogs and the function of the operated kidney were studied. The non-invasive examination lasted for 20 minutes and was performed with two different labelled drugs (131I-iodohippurate and 99mTc-DTPA) and a gamma-camera calculator system. The results have shown that the ileo-ureter provided with a direct single layer uretero-ileal anastomosis ensured best the transport of urine and so it seems to be most promising for human application.     

Ultrasonography and neuropathological findings in premature infants

At most maternity units all premature infants are investigated by cranial ultrasonography as a routine. We examined the correlation between autopsy findings and ultrasound examination in 30 premature newborn. The ultrasound examination demonstrated bleeding in 17 (65%) of the 26 cases where autopsy had revealed bleeding. In these 17 patients good correlation was found between the degree of bleeding in the two examinations (ultrasonography and autopsy). In ten patients autopsy showed periventricular leucomalacia, but ultrasonography showed this condition in only two of these. In five cases bleeding made the examination and interpretation of the ultrasound findings difficult. In three patients ultrasonography was thought to be normal, while autopsy demonstrated periventricular leucomalacia.     

Pulmonary disorders in infants

Pulmonary disorders in infants are intimately related to the pulmonary development during the antenatal, neonatal and infantile period. In this review, normal pulmonary development is considered and several pulmonary disorders such as pulmonary hypoplasia, pulmonary sequestration, congenital cystic adenomatoid malformation, hyaline membrane disease, bronchopulmonary dysplasia, Wilson-Mikity syndrome and perinatal pneumonia are presented in light of the current literature.