Stability of 10-mg/mL and 50-mg/mL ketamine oral solutions.

PURPOSE: Ketamine is an anesthetic agent commonly used for the induction of anesthesia. Ketamine is also given to control pain, for treatment of posttraumatic stress disorder, and to induce bronchodilation in refractory asthma. Moreover, ketamine therapy is gaining ground as an intervention for patients with treatment-resistant depression and individuals who have depression with serious suicidal ideation. Recently, the drug has been used to disrupt maladaptive reward memories in individuals with harmful alcohol consumption behaviors. The stability of 10-mg/mL and 50-mg/mL ketamine solutions stored at ambient and refrigeration temperatures was assessed over 90 days. METHODS: Three batches of 10-mg/mL and 50-mg/mL ketamine solutions were stored for 90 days under two temperature conditions (2°C-8°C and 22°C-25°C) in amber plastic bottles. Chemical stability was assessed using a stability-indicating high-performance liquid chromatography assay. At each study time, visual inspection and pH assessments of ketamine concentration and pH were conducted. RESULTS: For all solutions tested at each condition, the ketamine concentration remaining was at least 98% of the initial concentration over 90 days of storage. Throughout the study period, solution pH remained stable and the color and odor of the suspensions remained unchanged. CONCLUSION: Extemporaneously compounded 10-mg/mL and 50-mg/mL oral solutions of ketamine prepared in a flavored suspending excipient and stored in amber polypropylene plastic bottles were stable for at least 90 days at both ambient and refrigeration temperatures.

Stewardship program on carbapenem prescriptions in a tertiary hospital for adults and children in France: a cohort study.

Antimicrobial stewardship programs aim at reducing the overuse of broad-spectrum antibiotics such as carbapenems, but their impact remains unclear. We compared the use of carbapenems between paediatric and adult subjects admitted to a French tertiary hospital and described the intervention of an antibiotic stewardship team (AST). As part of AST routine activity, all adult and paediatric patients receiving carbapenems are identified in real time using a computer-generated alert system and reviewed by the AST. Data associated with carbapenem prescriptions were extracted for 2 years (2014-2015) and were compared between paediatric and adult wards. Prescription appropriateness (i.e. no clinically suitable narrower spectrum alternative to carbapenem for de-escalation) and AST intervention were analysed. In total, 775 carbapenem prescriptions for 291 children and 262 adults were included. Most patients (95%) had a comordity and 52% had known recent carriage of extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBLE). Most carbapenem prescriptions came from intensive care units (n = 269, 35%) and were initiated for urinary tract (n = 200, 27%), sepsis (n = 181, 25%), and lung (n = 153, 21%) infections. Carbapenems were initiated empirically in 537 (70%) cases, and an organism was isolated in 523 (67%) cases. Among the isolated organisms, 47% (n = 246) were ESBLE and 90% (n = 468) were susceptible to carbapenems, but an alternative existed in 61% (n = 320) of cases according to antibiotic susceptibility testing. Among prescriptions reviewed by the AST, 39% (n = 255) were considered non-appropriate and led to either antibiotic discontinuation (n = 47, 7%) or de-escalation (n = 208, 32%). Non-appropriate prescriptions were more frequent in paediatric wards (p = 0.01) and in microbiologically documented infections (p = 0.013), and less observed in immunocompromised patients (p = 0.009) or with a known ESBLE carriage (p < 0.001). Tailored stewardship programs are essential to better control carbapenem use and subsequent antimicrobial resistance.

Assessment of practices for suspended oral drugs by tablet crushing in pediatric units.

The aim of this study was to assess the impact of suspended drug by tablet crushing in our pediatric hospital in term of targeted dose and to identify parameters involved in the potential variability. Four usually crushed pediatric drug substances were selected: amiodarone, warfarin, hydrocortisone and captopril. Each tablet was crushed in a bag using a crusher device. Once crushed, a pre-determined volume of water was added using oral syringes before taking the necessary volume to obtain the targeted drug amount. For each drug, operators among pharmacy technicians and nurses investigated 2 targeted doses (high and low). Each suspension was assayed 3 times using the corresponding validated HPLC procedure. Statistical analysis was performed (GraphPad Prism®) to evaluate the impact of operators, the level of suction in bag, and actual drug doses. To investigate the impact of formulation change on syringe drug content, five generic drugs of amiodarone were selected. Syringes contents were compared using one-way ANOVA. Drug loss in syringe ranged from 8.1% to 54.1%. The drug loss represented 18.9% to 30.5% for amiodarone, 0.1% to 5.5% for captopril, 5.6% to 19.7% for warfarin and 5.0% to 30.7% for hydrocortisone. The comparison of level sampling of suspensions presented significant differences for amiodarone, hydrocortisone, and warfarin. Comparison of operators demonstrated significant difference between pharmacy technician and nurse (p = 0.0251). Finally, comparison of 5 generic drugs for amiodarone showed some statistical difference between the syringes content obtained when using the original medicine as compared to the generics. The physicochemical properties of each drug substance and the formulation of the drug product may both factor that should be considered. As a result, crushing tablets in water for oral administration needs a case by case assessment. Although appropriate pediatric formulations are lacking, suspend the crushed material in a given volume of water should be discouraged and not recommended because far from good practice.

Pseudomonas aeruginosa bloodstream infections in children: a 9-year retrospective study.

P. aeruginosa bloodstream infection (BSI) is associated with high hospital mortality. Empirical combination therapy is commonly used, but its benefit remains debated. The purpose of this study was to describe in a paediatric population, demographical characteristics and outcome of children treated for P. aeruginosa BSI receiving either a combined or single antibacterial therapy. We performed a retrospective, single-centre, cohort study of hospitalized children with P. aeruginosa BSI from 2007 to 2015. A total of 118 bloodstream infections (BSI) were analysed (102 (86.4%) hospital-acquired, including 52 (44.1%) hospitalized in intensive care unit). In immunocompromised children, 52% of BSI episodes were recorded. Recent medical history revealed that 68% were hospitalized, 31% underwent surgery and 67% had a prior antibiotic therapy within the last 3 months. In-hospital mortality was similar for patients receiving single or combined anti-Pseudomonas therapy (p = 0.78). In multivariate analysis, independent risk factors for in-hospital mortality were neutropenia (OR = 6.23 [1.94-20.01], hospitalization in ICU (OR = 5.24 [2.04-13.49]) and urinary tract infection (OR = 4.40 [1.02-19.25]).Conclusion: P. aeruginosa BSI mainly occurred in immunocompromised children. Most infections were hospital-acquired and associated with high mortality. Combination therapy did not improve survival. What is Known: • P. aeruginosa bloodstream infection (BSI) is associated with high hospital mortality. Empirical combination therapy is commonly used but its benefit remains debated. What is New: • This is the largest cohort of Pseudomonas aeruginosa bacteraemia in children ever published. P. aeruginosa Bloodstream mainly occurred in immunocompromised children. Most infections were hospital-acquired and associated with high mortality. Combination therapy did not improve survival.

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.

[Varicella-zoster virus and pregnancy]. / Varicelle, zona et grossesse.

The incidence of varicella is low in pregnant women, and estimated around 1/1000 pregnancies. Vaccination is the cornerstone of prevention, but is contraindicated during pregnancy. Varicella is more severe in pregnant women. The risk of viral pneumonia is not increased, but VZV-associated pneumonia is usually more severe in pregnant women. Infection between 0-20 WG is associated with a 2 % risk of congenital varicella syndrome. Infection between D-5 and D+2 of delivery is associated with high risk of severe neonatal infection. Non-immune pregnant women with significant exposure to VZV require post-exposure prophylaxis with specific anti-VZV immunoglobulins that should be administered ideally within 4 days post-exposure and maximum within 10 days of exposure. Anti-VZV immunoglobulins are available in France in the context of an approved expanded access to an investigational new drug. Pregnant women with varicella should receive within 24 hours antiviral treatment based either on valaciclovir or, in case of severe infection, intravenous aciclovir. Both drugs were shown safe during pregnancy, even during the first trimester. Neonates born from mothers who developed varicella between D-5 and D+2 of delivery should also receive as soon as possible specific anti-VZV immunoglobulins.

Current ciprofloxacin usage in children hospitalized in a referral hospital in Paris.

BACKGROUND: Fluoroquinolones are used with increasing frequency in children with a major risk of increasing the emergence of FQ resistance. FQ use has expanded off-label for primary antibacterial prophylaxis or treatment of infections in immune-compromised children and life-threatening multi-resistant bacteria infections. Here we assessed the prescriptions of ciprofloxacin in a pediatric cohort and their appropriateness. METHODS: A monocenter audit of ciprofloxacin prescription was conducted for six months in a University hospital in Paris. Infected site, bacteriological findings and indication, were evaluated in children receiving ciprofloxacin in hospital independently by 3 infectious diseases consultants and 1 hospital pharmacist. RESULTS: Ninety-eight ciprofloxacin prescriptions in children, among which 52 (53.1%) were oral and 46 (46.9%) parenteral, were collected. 45 children had an underlying condition, cystic fibrosis (CF) (21) or an innate or acquired immune deficiency (24). Among CF patients, the most frequent indication was a broncho-pulmonary Pseudomonas aeruginosa infection (20). In non-CF patient, the major indications were broncho-pulmonary (25), urinary (8), intra-abdominal (7), operative site infection (5) and bloodstream/catheter (2/4) infection. 62.2% were microbiologically documented. Twenty-three (23.4%) were considered "mandatory", 48 (49.0%) "alternative" and 27 (27.6%) "unjustified". CONCLUSION: In our university hospital, only 23.4% of fluoroquinolones prescriptions were mandatory in children, especially in Pseudomonas aeruginosa healthcare associated infection. Looking to the ecological risk of fluoroquinolones and the increase consumption in children population we think that a control program should be developed to control FQ use in children. It could be done with the help of an antimicrobial stewardship team.