Aminoglycoside use in a pediatric hospital: there is room for improvement-a before/after study.

UNLABELLED: Aminoglycoside prescriptions were rarely evaluated in children care facilities. Because of risk of toxicity, these narrow spectrum antibiotics are commonly misused. In this study, we evaluate aminoglycoside prescription and assess the impact of an information campaign on modalities of prescription and monitoring practices in a pediatric hospital. This prospective study, before/after diffusion of local recommendations, has been conducted over 6 months. All computerized prescriptions were analyzed. A semi-passive diffusion of local recommendations to prescribers allowed researchers to differentiate between a pre-intervention (P1) and post-intervention period (P2). Endpoints were the improvement of administered doses (mg/kg), modalities of administration, treatment duration, indications, and the presence of pharmacological monitoring. Three hundred and ten prescriptions were analyzed (P1 = 163, P2 = 147). Most common sites of infection treated were as follows: joint-bone (33 %), urinary tract (17 %) and intra-abdominal (15 %). Among all prescriptions, respectively, 12 and 13 % were avoidable. Short-duration treatment and single daily dosing seem to be widely achieved, but despite an improvement between the two periods, 45 % of prescribed doses in P2 were still below our recommendations (77 % in P1). CONCLUSION: The semi-passive diffusion of recommendations has not improved significantly medical practices. Active diffusion with a regular monitoring could be useful to improve the use of aminoglycosides. WHAT IS KNOWN: • Misuse of aminoglycosides has been frequently described and evaluated in adult hospitals. • This misuse could be explained by their nephrotoxicity and their low therapeutic index. What is New: • Through this study, conducted in a pediatric hospital, we highlighted that practitioners misunderstand the aminoglycoside pharmacokinetic and pharmacodynamic targets and 12.3 % of aminoglycoside prescriptions could be avoided. • Finally, we showed that a semi-passive diffusion of local recommendations is not enough to improve aminoglycoside prescriptions.

Physico-chemical stability of busulfan in injectable solutions in various administration packages.

BACKGROUND AND OBJECTIVES: Busulfan is used as part of a conditioning regimen prior to hematopoietic stem cell transplantation for the treatment of certain cancers and immune deficiency syndromes. Due to its instability in aqueous preparations, busulfan for infusion is prepared from a concentrate and has a relatively short shelf life once prepared. The purpose of this study was to identify the most suitable storage container and temperature to maximize the shelf life of busulfan therapeutic infusions prepared from Busilvex(®). METHODS: Busilvex(®) 6 mg/mL was diluted to 0.55 mg/mL with 0.9 % NaCl and aliquots dispensed into polypropylene syringes, polyvinyl chloride bags, and glass bottles. Three storage temperatures were evaluated: 2-8 °C, 13-15 °C (thermostatically controlled chamber), and room temperature (20 ± 5 °C). At set time points, samples were analysed for busulfan content, using a high-performance liquid chromatography (HPLC) system with ultraviolet detection. The change in pH and osmolarity on storage was also determined, and solutions were inspected visually for formation of a precipitate or colour change. To determine the contribution of precipitation to loss of busulfan content on storage, samples from one time series were treated with the solvent dimethylacetamide prior to HPLC separation and quantitation of busulfan. RESULTS: The results of the active substance content monitoring study over a 48-h period demonstrate that busulfan solution is stable at a 5 % threshold, at 2-8 °C for 16 h in syringes, 14 h in glass bottles, and 6 h in bags. In addition, the period of stability decreases as the temperature increases (4 h at 20 ± 5 °C). The solution is considered to be stable, subject to precipitation liable to be observed regardless of the temperature. CONCLUSION: The best stability was observed for busulfan solutions placed at 2-8 °C in syringes. This study demonstrated that precipitation, in addition to hydrolysis, has a significant influence on the busulfan content.