Larger Dose Reductions of Vancomycin Required in Neonates with Patent Ductus Arteriosus Receiving Indomethacin versus Ibuprofen.

Ibuprofen and indomethacin are commonly used to induce ductus arteriosus closure in preterm neonates. Our group previously reported that ibuprofen decreased vancomycin clearance by 16%. In this study, we quantified the impact of indomethacin coadministration on vancomycin clearance by extending our vancomycin population pharmacokinetic model with a data set containing vancomycin concentrations measured in preterm neonates comedicated with indomethacin. The modeling data set includes concentration-time data of vancomycin administered alone or in combination with either ibuprofen or indomethacin collected in the neonatal intensive care units of UZ Leuven (Leuven, Belgium) and São Francisco Xavier Hospital (Lisbon, Portugal). The derived vancomycin pharmacokinetic model was subsequently used to propose dose adjustments that yield effective vancomycin exposure (i.e., area under the concentration-time curve from 0 to 24 h [AUC0-24] between 300 to 550 mg·h/liter, with a probability of <0.1 of subtherapeutic exposure) in preterm neonates with patent ductus arteriosus. We found that indomethacin coadministration reduced vancomycin clearance by 55%. Model simulations showed that the most recent vancomycin dosing regimen, which was based on an externally validated model, requires 20% and 60% decreases of the loading and maintenance doses of vancomycin, respectively, when aiming for optimized exposure in the neonatal population. By analyzing vancomycin data from preterm neonates comedicated with indomethacin, we found a substantial decrease in vancomycin clearance of 55% versus a previously reported 16% for ibuprofen. This decrease in clearance impacts vancomycin dosing, and we anticipate that other drugs eliminated by glomerular filtration are likely to be affected to a similar extent as vancomycin.

[Epidemiological study of salmonelloses in the Moldavia area]. / Contributii la studiul epidemiologic al salmonelozelor pe teritoriul Moldovei.

A study was carried out on the epizooto-epidemiologic potential of certain domestic and wild animal species (cold-blooded), of the environment (residual waters) and food products, and their role in maintaining Salmonella endemics (others than the typhoid-parathyphoid group). Account was kept of the incidence of Salmonella and its circulation in subjects exposed to occupational risks and in the mass of the population, including those with clinically manifest salmonellosis and the clinically healthy carriers. The results showed the importance of domestic animals in maintaining the endemic (fowl 15%, swine 10%, bovine 5%). The isolated serotypes were identical to those found in residual eaters, in patients and in carriers. The sensitivity test to antibiotics revealed resistance to more than two antibiotics in 65%, except for the strains isolated from reptiles. Reorganization measures appear necessary in order to restrict the circulation of Salmonella in farm animals and to reduce the risks of infection in humans.