Contribution of a clinical pharmacist with infectious diseases training in an antimicrobial stewardship program

La littérature scientifique suggère que différentes approches sont nécessaires pour lutter contre les phénomènes de résistance aux agents antimicrobiens et qu’une seule stratégie n’existe pas (« One Health »). Dans les hôpitaux, les programmes de gestion des anti-infectieux (« antimicrobial stewardship ») sont recommandés internationalement. Ce projet doctoral a pour objectif principal de démontrer l’intérêt et le rôle du pharmacien clinicien spécialisé en maladies infectieuses dans un de ces programmes. Il est le reflet d’une partie des actions menées par le Groupe de Gestion de l’Antibiothérapie (GGA) du CHU de Liège depuis qu’un pharmacien clinicien a renforcé le groupe en 2010. Ce travail doctoral est composé de quatre études qui sont regroupées en deux thématiques. La première aborde la promotion du bon usage des anti-infectieux (études 1 et 2) et la seconde, le développement et la validation de nouvelles pratiques cliniques (études 3 et 4). La première étude était une étude prospective, non contrôlée, de type « série chronologique interrompue » permettant d’auditer la qualité de documentation sur l’antibiothérapie dans les dossiers médicaux informatisés avant et après la mise en place d’une combinaison d’interventions réalisée par le GGA. L’objectif principal de cette étude était d’améliorer le taux de documentation de 3 indicateurs de qualité dans les dossiers médicaux informatisés: (1) l’indication de traitement par antibiotique(s), (2) l’antibiothérapie et (3) la durée/date de réévaluation de l’antibiothérapie. Cette étude a démontré l’impact positif de l’implémentation d’une série d’interventions menées par le pharmacien clinicien et elle a été associée à des changements significatifs dans les taux de documentation des 3 indicateurs de qualité.La deuxième étude a été de réaliser une étude qualitative sur la nystatine en cas de candidose oropharyngée (COP). Suite au constat d’une utilisation importante et inappropriée de nystatine sous forme de soins de bouche au CHU de Liège, une revue de la littérature a été réalisée par le pharmacien clinicien afin d’évaluer la balance bénéfice/risque de la nystatine en cas de COP et d’élaborer des recommandations pratiques institutionnelles. Cette revue de la littérature a souligné que la nystatine en soin de bouche n’a qu’une indication, la COP bénigne, et que les données évaluant son efficacité et sa sécurité en cas de COP sont limitées. Après analyse de la situation au CHU de Liège, le bain de bouche contenant de la nystatine, de la lidocaïne et de l’hydrocortisone et, préparé par la pharmacie du CHU de Liège sur base du Formulaire Thérapeutique Magistral (FTM), a été retiré du formulaire thérapeutique de l’hôpital pour les raisons suivantes : dosage inadéquat de nystatine, association inappropriée de trois molécules en cas de COP, et utilisation inappropriée de la nystatine dans l’institution. La troisième étude a consisté à démontrer la stabilité d’une perfusion de céfuroxime à une concentration de 90 mg/mL. La céfuroxime est une céphalosporine de deuxième génération appartenant à la classe des beta;-lactamines. L’administration en perfusion continue ou prolongée des beta;-lactamines permet l’amélioration du profil pharmacocinétique/pharmacodynamique des beta;-lactamines et donc leur efficacité. Cependant, ce mode d’administration soulève des problèmes pratiques tels que la stabilité des solutions perfusées sur une période de 24 heures. Cette étude a démontré la stabilité d'une solution à 90 mg/mL de céfuroxime sodique reconstituée avec du NaCl 0.9% et conservée dans des seringues en polypropylène pendant 2 jours à 25°C et pendant au moins 14 jours à 4°C. Par conséquent, cette solution peut être utilisée en perfusion continue sur 24 heures dans les unités de soin. La quatrième étude se concentrait sur la neurotoxicité associée aux perfusions continues de céfépime à 4 g/jour dans une étude de cohorte rétrospective monocentrique. L’objectif principal était d’évaluer l’incidence de la neurotoxicité ainsi que les facteurs de risque associés à ce type de perfusion. Les objectifs secondaires étaient d’analyser les concentrations plasmatiques de céfépime et de définir un seuil de toxicité. Nos résultats suggèrent qu’une perfusion continue de céfépime à 4 g/jour, adaptée à la fonction rénale, est un bon compromis pour la balance bénéfice/risque quand le céfépime est prescrit empiriquement. Une attention particulière doit être accordée aux patients présentant un antécédent neurologique. De plus, nous recommandons le dosage plasmatique du céfépime en routine afin d’individualiser les posologies et d’éviter le risque de neurotoxicité lié à son utilisation. Notre seuil de toxicité de 63.2 mg/mL est une donnée concrète pour une adaptation posologique optimale du céfépime. Ce travail a permis de souligner la contribution d’un pharmacien clinicien aux actions menées par le GGA, en proche collaboration avec de nombreux secteurs. Il a confirmé que le pharmacien clinicien est une ressource essentielle au succès du programme de gestion des anti-infectieux.Scientific literature suggests that different approaches are necessary to tackle antimicrobial resistance (AMR) (« One Health »). Introduction of antimicrobial stewardship (AMS) programs in hospitals is recommended internationally. The main objective of this thesis is to demonstrate the interest and the role of a clinical pharmacist with infectious diseases training in one of these programs. This work reflects the actions driven by the antimicrobial stewardship team (AST) of the University Hospital of Liège since a clinical pharmacist strengthened the group in 2010. Four studies are presented in this thesis which is divided in two parts. The first one is the promotion of the appropriate use of antimicrobials (studies 1 and 2) and, the second part, the development and validation of new clinical practices (studies 3 and 4).The first study was a prospective, uncontrolled, interrupted time series (ITS) to audit the quality of documentation on antibiotic therapy in the medical records before and after a combined intervention strategy from the AST. The primary outcome measure was the documentation rate on three quality indicators in the computerized medical records: (1) indication for treatment, (2) antibiotics prescribed, and (3) duration or review date. The study demonstrated the successful implementation of a combined intervention strategy from the AST and the potential intervention of the clinical pharmacist. This strategy was associated with significant changes in the documentation rate in the computerized medical records for the three quality indicators.The second study was a qualitative study on nystatin for oropharyngeal candidiasis (OPC). The AST emphasized an important and inappropriate use of mouthwash containing nystatin. We reviewed the scientific literature on the efficacy and safety of nystatin for OPC and we shared some practical institutional recommendations. This review highlighted that nystatin mouthwash is only indicated for mild OPC and the evidence on the efficacy and safety of nystatin for OPC is sparse. In our hospital, we decided to stop the production of mouthwash containing nystatin, lidocaine and hydrocortisone for these reasons: inappropriate dose of nystatin, inappropriate association of three active substances in case of OPC and inappropriate use of nystatin in our institution. The third study aimed to determine the stability of a 90 mg/mL cefuroxime sodium solution. Cefuroxime is a second generation cephalosporin belonging to beta;-lactams antibiotics. Continuous infusions (CI) of beta;-lactams antibiotics increase pharmacokinetic/pharmacodynamic target attainment. However, this way of administration brings about some practical issues such as stability. This study showed that a 90 mg/mL cefuroxime sodium infusion syringe was stable for 48 h when stored at 25 °C and for at least 14 days when stored at 4 °C. Therefore, this solution may be used as a CI and also may be prepared safely in advance.The fourth study was a single-centre retrospective cohort study to investigate neurotoxicity related to CI of 4 g/day cefepime. The primary objective was to evaluate the incidence of neurotoxicity related to CI of cefepime and the associated risk factors. The secondary objectives were to analyze the plasma cefepime concentrations and to define the threshold above which neurotoxicity occurs. Our results suggest that 4 g/day of cefepime adapted to RF and infused over 24 hours is a trade-off for the risk/benefit ratio, when used empirically. Special attention should be paid for patients with an underlying brain disease. We recommend routine cefepime TDM to individualize its dosing and also to avoid the risk of neurotoxicity related to its use. Our threshold concentration of 63.2 mg/L is a concrete data for an optimal dose adjustment strategy.This thesis highlighted the contribution of a clinical pharmacist to the actions driven by the antimicrobial stewardship team, in close collaboration with many sectors. It confirmed that the clinical pharmacist is an essential resource for the success of the antimicrobial stewardship program

Meropenem: continuous or extended infusion?

peer reviewe

Quality of documentation on antibiotic treatment in medical records: evaluation of the long-term impact of an antimicrobial stewardship intervention

Background: In 2016, the antimicrobial stewardship team (AST) of the University Hospital of Liège, Belgium published a prospective, uncontrolled, interrupted time series study demonstrating the successful implementation of a combined intervention strategy from the AST to improve the quality of documentation on antibiotic therapy in the computerized medical records between 2012 and 2014. Since 2016, the AST repeated a point prevalence surveys (PPS) twice a year about that topic. Materials/methods: We aimed to evaluate if the impact of the interventions remained stable over time on the documentation rate of 3 quality indicators: (1) the indication (2) the antibiotics prescribed and (3) the expected duration or review date, with a goal of achieving 90 % compliance on each indicator. Using the PPS approach, a clinical pharmacist and physician, both from the AST, identified patients receiving one or more antibacterial agents from the Medication Administration Record (MAR). Patients seen in the outpatients or dialysis department or the emergency room, and those who underwent a specific medical intervention or surgery the same day were excluded. Results: From 2016-2019, six PPS were performed. Overall 4691 patient MARs were reviewed from a total of 34 wards: 1118 (23.8 %) took one or more antibiotics, 84.9 % for the treatment of an infection, which was slightly lower than previous results (26-28 % and 82-83 %, respectively). The medical records of 949 patients receiving antibiotics for infection were carefully reviewed and analyzed. On average, 90.4 % (vs 90.3 % in comparison with our previous results) had an indication documented; 95.1 % (vs 95.6 %) had documentation of the antibiotics prescribed; and 65.2 % (vs 67.7 %) had a duration or review date documented. Conclusions: In our institution, the quality of documentation on antibiotic therapy remained stable over a 5 years period of time, with 90 % or more compliance on average for two quality indicators: the indication and the antibiotics prescribed, but less than 70 % for duration or review date. This last point should be analyzed and new interventions should be considered to reach 90 % compliance for this quality indicator

Antimicrobial Stewardship Programs in 13 Belgian hospitals: a survey from the french association of belgian hospital pharmacists

Background: Since 2002, the Belgian Antibiotic Policy Coordibnation Committee (BAPCOC) has supported the development of antimicrobial stewardship (AMS) teams in Belgian hospitals with policy guidance and federal funding. A Royal Decree of 12 February 2008 has consolidated the minimum composition, mandate and tasks of AMS teams. However, between 2017 and 2019, the European Centre for Disease Prevention and Control (ECDC) and the Belgian Health Care Knowledge Centre (KCE) emphasized flaws in our national strategies and policies on antimicrobial resistance. This survey evaluated if the essential and the minimum standards for AMS programs in Belgian hospitals were fulfilled after more than 10 years of activities. Materials/methods: A questionnaire survey was performed based on the international consensus approach developed by Pulcini et al. in 2019. Seven core elements and their related 29 checklist items for global hospital AMS programs were assessed. All the items are weighted identically: 1 point per hospital regardless of the type of hospital or the number of beds. The results are expressed in percentages. Results: Completed questionnaires were provided by 13 hospitals (8 primary, 3 secondary and 2 tertiary hospitals). Figure 1 showed the results of the seven core elements. The core elements number 3 (Available expertise on infection management) and 6 (Monitoring and surveillance) gained good scores. The core elements number 1 (Senior hospital management leadership towards antimicrobial stewardship) and number 7 (Reporting and feedback) have to be improved in the future. The sub-analysis of the 29 items emphasized within the core elements which questions can still be improved. Conclusions: This survey confirmed on the ground what is reflected in the ECDC and KCE reports: the effectiveness of the belgian AMS teams could be improved. This survey could help BAPCOC to easily underline which core elements need improvement

Stability of 90 mg/ml cefuroxime sodium solution for administration by continuous infusion

peer reviewedContinuous infusions of beta-lactam antibiotics increase pharmacokinetic/pharmacodynamic target attainment. However, this way of administration brings about some practical issues such as stability. This study aims to determine the stability of a 90 mg/mL cefuroxime sodium solution. Cefuroxime sodium was reconstituted and mixed with 50-mL 0.9% saline to produce 90 mg/mL solution in polypropylene syringes which were stored at 4 degrees C, 25 degrees C and 40 degrees C. Cefuroxime sodium concentration was determined periodically over 14 days using a stability-indicating high-performance liquid chromatographic method with ultra-violet detection. The loss in concentration was less than 10% after 2 days of storage at 25 degrees C and less than 5% after 14 days of storage at 4 degrees C. The concentration fell below 60% after 1 day at 40 degrees C. Solutions darken in appearance with time and heat. A 90 mg/mL cefuroxime sodium solution stored in polypropylene syringes is stable for 2 days at 25 degrees C and for at least 14 days at 4 degrees C

Decreased antibiotic consumption in the Belgian community: Is it credible?

peer reviewe

Decreased Antibiotic Consumption in the Belgian Community: Is It Credible?

peer reviewe