N. Arlicot

Stability of antibiotics in portable pumps used for bronchial superinfection: guidelines for prescribers.

OBJECTIVES. The aims of this study were (1) to collect data on the stability of antibiotics in portable pumps for the treatment of bronchial superinfection in patients with cystic fibrosis and (2) to provide guidelines for prescribers. METHODS. The stability over 72 hours, in portable pumps stored at 35°C, of piperacillin plus tazobactam, ticarcillin plus clavulanic acid, cefsulodin, cefepime, and aztreonam was checked at 3 different concentrations. Stability was assessed through visual examination, pH measurements, and direct measurements of drug concentrations by using high-performance liquid chromatography. All parameters were measured at time 0, time 0 plus 24 hours, and time 0 plus 72 hours. RESULTS. Degradation rates for penicillin plus β-lactamase inhibitor combinations remained <10% at time 0 plus 24 hours for all drugs, but the rate for piperacillin reached 12% for the highest concentration tested. The cephalosporins cefepime and cefsulodin had significant respective degradation rates of 18% and 28% at time 0 plus 24 hours and 60% and 68.5% at time 0 plus 72 hours, which were linked to the storage temperature. Aztreonam seemed to be stable over 72 hours. CONCLUSIONS. This work provides data on drug stability that were lacking, allowing recommendations for physicians to optimize the safety and efficacy of antibiotic treatment of patients with cystic fibrosis. Piperacillin plus tazobactam and ticarcillin plus clavulanic acid infusions must be limited to 24 hours, and patients receiving cefepime or cefsulodin must wear a cold pack close to the ambulatory drug-delivery device during the infusion.

Could 18 F-DPA-714 PET imaging be interesting to use in the early post-stroke period?

BackgroundCerebral stroke is a severe and frequent condition that requires rapid and reliable diagnosis. If administered shortly after the first symptoms manifest themselves, IV thrombolysis has been shown to increase the functional prognosis by restoring brain reperfusion. However, a better understanding of the pathophysiology of stroke should help to identify potential new therapeutic targets. Stroke is known to induce an inflammatory brain reaction that involves overexpression of the 18-kDa translocator protein (TSPO) in glial cells and infiltrated leukocytes, which can be visualised by positron emission tomography (PET). We aimed to evaluate post-stroke neuroinflammation using the PET TSPO radioligand 18u2009F-DPA-714.MethodsNine patients underwent 18u2009F-DPA-714 PET and magnetic resonance imaging (MRI) between 8 and 18xa0days after the ictus. Co-registration of MRI and PET images was used to define three volumes of interest (VOIs): core infarction, contralateral region, and cerebellum ipsilateral to the stroke lesion. Time activity curves were obtained from each VOI, and ratios of mean and maximum activities between the VOIs were calculated.ResultsWe observed an increased uptake of 18u2009F-DPA-714 co-localised with the infarct tissue and extension beyond the region corresponding to the damage in the blood brain barrier. No correlation was identified between 18u2009F-DPA-714 uptake and infarct volume. 18u2009F-DPA-714 uptake in ischemic lesion (mainly associated with TSPO expression in the infarct area and in the surrounding neighbourhood) slowly decreased from 10xa0min pi to the end of the PET acquisition, remaining higher than that in both contralateral region and ipsilateral cerebellum.ConclusionOur results show that 18u2009F-DPA-714 uptake after acute ischemia is mainly associated with TSPO expression in the infarct area and in the surrounding neighbourhood. We also demonstrated that the kinetics of 18u2009F-DPA-714 differs in injured tissue compared to normal tissue. Therefore, 18u2009F-DPA-714 may be useful in assessing the extent of neuroinflammation associated with acute stroke and could also help to predict clinical outcomes and functional recovery, as well as to assess therapeutic strategies, such as the use of neuroprotective/anti-inflammatory drugs.

Detection and quantification of remote microglial activation in rodent models of focal ischaemia using the TSPO radioligand CLINDE

PurposeNeuroinflammation is involved in stroke pathophysiology and might be imaged using radioligands targeting the 18xa0kDa translocator protein (TSPO).MethodsWe studied microglial reaction in brain areas remote from the primary lesion site in two rodent models of focal cerebral ischaemia (permanent or transient) using [125I]-CLINDE, a promising TSPO single photon emission computed tomography radioligand.ResultsIn a mouse model of permanent middle cerebral artery occlusion (MCAO), ex vivo autoradiographic studies demonstrated, besides in the ischaemic territory, accumulation of [125I]-CLINDE in the ipsilateral thalamus with a binding that progressed up to 3xa0weeks after MCAO. [125I]-CLINDE binding markedly decreased in animals pre-injected with either unlabelled CLINDE or PK11195, while no change was observed with flumazenil pre-treatment, demonstrating TSPO specificity. In rats subjected to transient MCAO, [125I]-CLINDE binding in the ipsilateral thalamus and substantia nigra pars reticulata (SNr) was significantly higher than that in contralateral tissue. Moreover, [125I]-CLINDE binding in the thalamus and SNr was quantitatively correlated to the ischaemic volume assessed by MRI in the cortex and striatum, respectively.ConclusionClinical consequences of secondary neuronal degeneration in stroke might be better treated thanks to the discrimination of neuronal processes using in vivo molecular imaging and potent TSPO radioligands like CLINDE to guide therapeutic interventions.

Are Antibiotic Drugs Well Prescribed in Case of Renal Insufficiency? A Retrospective Study

Renal insufficiency (RI) is a major complication in hospitalized patients. We aim to determinate if the severity of RI is considered for antibiotic prescriptions. A 10-month retrospective study including all in-patients of an orthopedic surgery department, based on the analysis of antibiotic prescriptions of patients with RI, was set up as follows: identification of patients with RI estimated with Cockcroft formula, classification by severity stage, and analysis of antibiotic prescriptions to be adapted to RI. About 10% of patients had RI. Among them, 54 (32%) received antibiotics (on average, 1.75 drugs per patient). Sixteen (17%) of antibiotic prescriptions required either dose adaptation or therapeutic drug monitoring. In all, only four prescriptions were adapted to renal function. In other cases, antibiotics were prescribed according to protocols for patients with normal renal function. Moreover, therapeutic drug monitoring was only performed for half of required cases and then showed values > ULN three times out of four. Creatinine clearance (CrCl) has been calculated for half of patients with RI. In practice, dosage adjustment of antibiotics is done only for patients with severe RI. Within the framework of the introduction of an electronic prescribing technology and medication order pharmaceutical review procedures, CrCl is now systematically calculated and then taken into account by both prescribers and clinical pharmacists.

Impact médico-économique de la surveillance des prescriptions de TEP-18F-FDG

Introduction La tomographie par emission de positons (TEP) au 18F-fluorodesoxyglucose, 18F-FDG, est une modalite d’imagerie indiquee au sein de la strategie diagnostique et therapeutique en cancerologie. Le respect d’un delai entre chimiotherapie (CHT) et examen au 18F-FDG permet de prevenir le risque potentiel de faux negatif lie au phenomene de sideration cellulaire post-CHTxa0; ceci afin d’eviter de surestimer l’efficacite therapeutique sur les lesions tumorales. Une analyse pharmaceutique des prescriptions de TEP au 18F-FDG nous a donc semble pertinente. Au cours de cette analyse, le respect du delai minimal entre CHT et TEP est verifie avec pour objectif d’optimiser le potentiel diagnostique de l’examen. Materiel et methodes Etude prospective sur 24xa0mois. Les dossiers patients (DP) ont ete consultes la veille de l’examen TEP par la radiopharmacie, afin de rechercher l’administration d’une CHT dans les 10xa0jours (CHTxa0 Resultats Au total, 6096xa0examens ont ete realises au cours de l’etude et 5063xa0DP tenus a jour ont pu etre consultes (83xa0% des examens). Cent trente-six patients avec une CHTxa0≤xa010xa0j ont ete declares parmi lesquels 24xa0ont vu leur examen reporte ou annule sans subir de perte de dose, dont 20xa0suite a une CHT et 4xa0a un deces. Les 20xa0doses non injectees equivalent a une economie de 4900xa0euros sur la duree de l’etude. Discussion Cette etude a permis de resensibiliser les demandeurs (oncologues) et prescripteurs (medecins nucleaires) a la criticite du delai entre examen 18F-FDG et CHT afin d’optimiserxa0: –xa0le potentiel diagnostique du patientxa0; –xa0le fonctionnement du service de medecine nucleaire en optimisant les creneaux d’occupation de la camera. Malgre un interet relatif vis-a-vis du cout epargne en regard du cout global de l’ensemble des examens 18F-FDG, cette surveillance presente des avantages importants pour le patient (chance diagnostique, radioprotection, confort), neanmoins la surveillance des patients externes sans DP disponible reste un point a ameliorer.