Endothelium derived substances may play a role in the physiological adaptation processes at the time of birth. The aim of this study was to investigate plasma concentrations of activation markers of the endothelium (endothelin-1, thrombomodulin, von Willebrand factor), of the coagulation and the fibrinolytic systems (thrombin-antithrombin III complex, D-dimer, plasmin-alpha2-antiplasmin complex) during the first days of life. Venous blood from peripheral veins was collected from 79 healthy newborns and for comparison from 38 healthy infants and schoolchildren, as well as from 17 healthy adults. Except for endothelin and von Willebrand factor, the concentrations of activation markers were significantly higher in the newborn group. During the first 12 days of life thrombomodulin, thrombin-antithrombin III complex, and plasmin-alpha2-antiplasmin complexes showed a continuous decline whereas the concentrations of endothelin, von Willebrand factor and D-dimer did not change. The highest D-dimer concentrations were found at low umbilical arterial pH and after birth by vaginal operation suggesting an influence of birth stress. Thrombomodulin was correlated with endothelin (r=+0.471) and with von Willebrand factor (r=-0.415). In conclusion, endothelial, coagulation, and fibrinolytic systems are activated in newborns which might occur during birth by the mechanical stress, the adaptation of circulation, and the short-term hypoxic state. An additional intrauterine activation should also be considered.

For the prophylaxis of septicemia with coagulase-negative staphylococci in a high-risk very-low-birth-weight population, we administered 5 mg/kg of vancomycin every 12 h. Distribution volume and half-life of vancomycin were determined. Serum peak and trough levels were obtained on day 3 of treatment. With this low-dose regimen, serum concentrations in the therapeutic range were achieved in 35 of the 45 patients. Distribution volume and half-life were 0.692 liters/kg and 7.4 h, respectively. The distribution volume was not related to the gestational age; the half-life in the group of patients with a gestational age <30 weeks was considerably higher. The 10 small-for-gestational-age children had a significantly smaller distribution volume. The vancomycin trough levels correlated with the serum creatinine concentrations and, therefore, with the gestational age. Our study indicates that this low vancomycin dose is sufficient in very-low-birth-weight infants to achieve therapeutic serum levels, being suitable for both prophylaxis and sepsis therapy.

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VLBW-infants below 1500 g of birth weight have a quite high risk to acquire a nosocomial sepsis. 20-40% of all infants exhibit signs of nosocomial infection once during neonatal intensive care. The rate of infection is related to technique and amount of used invasive devices as to gestational age. Coagulase-negative staphylococci (CONS) and gram-negative organisms contribute most to these cases of sepsis. In a three phase study we tried to demonstrate the efficacy of different mechanisms to change the rate of nosocomial sepsis. During the first phase a strict hygienical protocol was enforced as isolation, care with sterile gloves and aseptic techniques in introducing and maintaining i.v. lines. In a second phase we started a randomized controlled study of prophylactic vancomycin (10 mg/kg/day in two doses). In a third phase we added an oral antibiotic regime with cefixime for all patients with positive cultures for gramnegative organisms under the hypothesis of translocation from the gut as the way of infection. During the first phase 23.7% of 76 patients enrolled acquired CONS-sepsis, 0.52% gramnegative sepsis. During the second phase (41 patients) 6 patients in the control group acquired CONS-sepsis, none in the vancomycin-group. The rate of gramnegative infections was not different (4 and 3 cases). During the third phase (vancomycin plus cefixime eventually in cases of positive stool cultures) no case of nosocomial sepsis occurred (35 patients, 11 positive cultures). The management used in phase 3 reduced the rate of nosocomial infections in VLBW-infants drastically.