Intravenous Hydroxypropyl ß-Cyclodextrin Formulation of Letermovir: A Phase I, Randomized, Single-Ascending, and Multiple-Dose Trial.

Letermovir is a novel antiviral in clinical development for prophylaxis against human cytomegalovirus in immunocompromised transplant recipients. This two-part, single-center, randomized, double-blind, placebo-controlled trial evaluated the safety and pharmacokinetics of a hydroxypropyl ß-cyclodextrin (HPßCD)-based intravenous formulation of letermovir in healthy women. Subjects received single, escalating doses (120, 240, 480, 720, and 960 mg; 6 letermovir, 2 placebo per cohort) or multiple, once-daily doses (240 mg; 8 letermovir, 4 placebo) of HPßCD-formulated letermovir and the associated pharmacokinetic profiles and adverse events were investigated. Single-dose and multiple-dose regimens were generally well tolerated. Single-dose escalation resulted in a slightly more-than-dose-proportional increase in the area under the letermovir plasma concentration-time curve (AUC), whereas increase in the maximal observed letermovir plasma concentration (Cmax ) was dose proportional. After once-daily dosing, accumulation ratios in AUC and Cmax were 1.22 and 1.03, respectively. The terminal half-life was 28.3 h, supporting once-daily dosing (EudraCT Number: 2012-001603-20).

[The development of an aerobic intestinal microflora in newborn infants]. / Die Entwicklung der aeroben Darmflora bei Neugeborenen.

The microbial colonization of the intestinal tract was studied in 60 newborn babies from three hospitals, with special regard to the typical hospital "problem" strains. Escherichia coli was the predominant initial colonizing species. Opportunistic pathogens were repeatedly detected. Some 30% of E. coli strains showed beta-hemolysis. Distinct differences between the three clinics were noted with respect to the detection frequency of the species isolated, hemolytic bacteria, the predominating E. coli strains, the occurrence of Candida albicans, and the time course of colonization of the gut by E coli. The microbial environment of the respective neonatal unit has a great influence on the initial intestinal colonization by aerobic microorganisms.