Development of an international survey tool to measure confidence and current antimicrobial stewardship practices of hospital pharmacists.

BACKGROUND: Pharmacists are identified as key members of hospital antimicrobial stewardship (AMS) teams in international guidelines. Developing an international standardized tool to measure hospital pharmacists' confidence and practices of AMS will encourage knowledge sharing and better networking between hospital pharmacists internationally. OBJECTIVES: To develop a survey tool that can be used internationally to assess pharmacists' knowledge, confidence, perceived barriers and current AMS practices. METHODS: A project team was formed to refine the survey tool that was initially used in a previous survey study. Following revision by the project team, a revised survey tool was sent to the ESCMID Study Group for Antimicrobial Stewardship (ESGAP). Feedback from the ESGAP members was considered by the project team to finalize the survey tool. RESULTS: A total of 88 changes were made to the survey tool after revision by the project team. A total of 43/216 (19.9%) of ESGAP members provided feedback on the survey tool, which led to a further 19 revisions. ESGAP members were agreeable to the questions in the survey tool, with >50% agreeing that each question was suitable. The final survey tool consisted of 42 questions, reduced from 72 questions in the original survey. CONCLUSIONS: An international survey tool to measure hospital pharmacists' confidence and practices of AMS was developed. This tool will help the wider hospital pharmacy community in conducting local studies on current AMS practices and to identify areas where further support is needed. Use of a standardized survey tool will also allow individual regions/countries to compare their data with other countries to identify potential quality improvement programmes.

Ifosfamide-induced encephalopathy: Brand-name (HOLOXAN®) vs generic formulation (IFOSFAMIDE EG®).

WHAT IS KNOWN AND OBJECTIVE: Two forms of ifosfamide are commercially available in France: HOLOXAN® (brand-name drug) and IFOSFAMIDE EG® (generic drug). Following the marketing launch of the generic drug, there has been a significant increase in cases of ifosfamide-induced encephalopathy reported in France. Our objective is to compare the incidence of ifosfamide-induced encephalopathy in adult patients treated with HOLOXAN® or IFOSFAMIDE EG®. METHODS: This is a retrospective study of adult patients treated with ifosfamide in two medical centers from 2013 to 2017, with data analysed from medical records. Comparisons of patients were made, according to the formulation used and according to the occurrence of ifosfamide-induced encephalopathy. The groups of patients were compared using a chi-square or Fisher's exact test for qualitative parameters and a Wilcoxon test for quantitative parameters. To include confounding factors in the analysis of the impact of drug formulation on the occurrence of ifosfamide-induced encephalopathy, a generalized linear model was performed with the occurrence of ifosfamide-induced encephalopathy as the dependent parameter, and the formulation and the confounding factors as explanatory parameters. RESULTS AND DISCUSSION: A total of 191 patients were included: 103 patients received HOLOXAN® (53.9%) and 88 patients received IFOSFAMIDE EG® (46.1%). In the HOLOXAN® group, the median infusion time was higher (12 hours vs 3h, P < 0.001) and aprepitant was administered more frequently (78.6% vs 69.7%, P < 0.001) than for the IFOSFAMIDE EG® group. Ifosfamide-induced encephalopathy occurred in 11 patients (5.8%, CI 95% [2.9%, 10.0%]). In the ifosfamide-induced encephalopathy group, median infusion time was higher (12 hours [12; 24] vs 3 hours [2; 12] P < 0.001) and a poor performance status was more frequent (54.5% vs 13.9%, P = 0.002) than in the group without ifosfamide-induced encephalopathy. The frequency of ifosfamide-induced encephalopathy in the HOLOXAN® group was 1.9% (2/103) against 10.2% (9/88) in the IFOSFAMIDE EG® group (P = 0.014). Multivariate analysis revealed that treatment with IFOSFAMIDE EG® resulted in significantly more ifosfamide-induced encephalopathies compared to HOLOXAN® (OR and CI 95%:7.4 [1.4; 39.5], P = 0.018). We identified two other risk factors for ifosfamide-induced encephalopathy: long-term infusion and a performance status of two or higher. WHAT IS NEW AND CONCLUSION: The formation of chloroethylamine in solution could be the cause of more frequent ifosfamide-induced encephalopathies with IFOSFAMIDE EG® compared to HOLOXAN®. Application of these data could help in the choice of ifosfamide formulation in adult patients to decrease the risk of ifosfamide-induced encephalopathy, and more specifically for patients with risk factors.

Fight Against Antimicrobial Resistance: We Always Need New Antibacterials but for Right Bacteria.

Antimicrobial resistance in bacteria is frightening, especially resistance in Gram-negative Bacteria (GNB). In 2017, the World Health Organization (WHO) published a list of 12 bacteria that represent a threat to human health, and among these, a majority of GNB. Antibiotic resistance is a complex and relatively old phenomenon that is the consequence of several factors. The first factor is the vertiginous drop in research and development of new antibacterials. In fact, many companies simply stop this R&D activity. The finding is simple: there are enough antibiotics to treat the different types of infection that clinicians face. The second factor is the appearance and spread of resistant or even multidrug-resistant bacteria. For a long time, this situation remained rather confidential, almost anecdotal. It was not until the end of the 1980s that awareness emerged. It was the time of Vancomycin-Resistance Enterococci (VRE), and the threat of Vancomycin-Resistant MRSA (Methicillin-Resistant Staphylococcus aureus). After this, there has been renewed interest but only in anti-Gram positive antibacterials. Today, the threat is GNB, and we have no new molecules with innovative mechanism of action to fight effectively against these bugs. However, the war against antimicrobial resistance is not lost. We must continue the fight, which requires a better knowledge of the mechanisms of action of anti-infectious agents and concomitantly the mechanisms of resistance of infectious agents.

Pharmacist participation in antimicrobial stewardship in Australian and French hospitals: a cross-sectional nationwide survey.

Background: Hospital pharmacists are an integral part of antimicrobial stewardship (AMS) programmes globally. Currently, little is known as to how hospital pharmacists see their role and involvement within the AMS framework. Objectives: To assess the current level of involvement of Australian and French hospital pharmacists in AMS programmes and identify barriers limiting their involvement in AMS. Methods: Hospital pharmacists throughout Australia and France were invited to participate in a nationwide online survey throughout March-May 2016. The survey was promoted through the national hospital pharmacists' association in Australia, while a stratified sampling method was used in France to invite pharmacists working in a variety of hospital settings. Results: Invitations to participate in this survey were sent to 334 Australian pharmacists and 482 French pharmacists. Responses from 133 Australian and 126 French pharmacists were included for analysis. A total of 78.4% (203/259) of pharmacists reported the presence of an AMS programme. Pharmacists were most likely to be involved in AMS through assessing total antibiotic consumption and participating in AMS committee meetings. Barriers to participating in AMS included a lack of time and substantial non-clinical activities limiting involvement in AMS. Differences in responses were found between the two countries. Conclusions: While the majority of pharmacists reported the presence of an AMS programme, multiple barriers to participation were identified by pharmacists in both countries. Further research should consider how to overcome the identified barriers to optimize the involvement of pharmacists in AMS.

Rapid antigen test use for the management of group A streptococcal pharyngitis in community pharmacies.

Despite group A streptococci being an infrequent cause of pharyngitis in adult outpatients, sore throat remains a common indication for antibiotic prescription. This prospective multicentre non-randomised study describes a community pharmacy-based antimicrobial stewardship intervention consisting in the implementation of rapid antigen testing (RAT) for the management of adults with sore throat. Trained pharmacists triaged patients presenting with symptoms of pharyngitis using the modified Centor score. Those at risk for streptococcal infection were tested with RAT. Patients with a positive RAT were invited to consult a physician, whereas others were offered a symptomatic treatment. All patients received educational leaflets and were asked to fill in a follow-up form 7 days later. Ninety-eight pharmacies in one French region participated, and 559 patients were included over 6 months. RAT was proposed in 367 (65.7%) cases, and it was positive in 28 (8.3%). The follow-up form was returned by 140 (38.5%) participants. Of these, 10/10 patients with positive RAT further consulted a physician and were prescribed an antibiotic treatment, whereas 96.5% (110/114) of patients with negative results and not having any other reason to seek for doctor's advice did not consult. All participants found the intervention useful. Pharmacists spent 6-15 min to perform the intervention, and 98.6% (73/74) of pharmacists giving a feedback declared to be ready to implement this intervention in daily practice, if endorsed and reimbursed. Our results suggest that a pharmacy-based programme for the management of sore throat is feasible and could increase adherence to guidelines.

Public knowledge and behaviours concerning antibiotic use and resistance in France: a cross-sectional survey.

PURPOSE: To evaluate knowledge and behaviours concerning antibiotics and bacterial resistance in the French population, and to identify the socio-demographic factors associated with a high level of such knowledge and appropriate behaviours. METHODS: A survey of the general population was conducted in 2015 in northeast France. The 44-item standardized questionnaire used comprised three parts, focusing on the assessment of knowledge, behaviours, and the collection of main socio-demographic characteristics of respondents (gender, age, having children, education level, and profession). The association of these characteristics with the level of knowledge about antibiotics, and with related behaviours, as well as the association between knowledge and behaviours was identified in a bivariate analysis (Chi-2 tests) and a multivariate analysis when necessary (logistic regression). RESULTS: The 200 respondents had quite a good level of knowledge about antibiotics for several points: the lack of effectiveness of antibiotics for colds (75.5%), the risk of inefficacy of antibiotics when misused (93%), and the effects of overconsumption on bacterial resistance (92%). Conversely, the effects of different doses and treatment durations on resistance were less well known. Inappropriate behaviours were frequent, especially non-adherence to dosing schedules and to treatment duration (35.5%), and self-medication practices (18%). Female gender, older age, and having children were independently associated with a good level of knowledge. A low level of education and older age were associated with appropriate behaviours. CONCLUSIONS: No association was found between knowledge and behaviours, highlighting the relevance of national public information campaigns to limit the misuse of antibiotics.

Physicochemical stability of pevonedistat at 50, 100 and 200 µg/mL diluted in 0.9% sodium chloride and at 10 mg/mL in partially used vials.

OBJECTIVES: Pevonedistat is a new cytotoxic used in association with azacitidine for the treatment of acute myeloid leukaemia and high-risk myelodysplastic syndromes. The manufacturer indicates an 18-hour stability after dilution in dextrose 5% or 0.9% sodium chloride (0.9% NaCl) at 2-8°C. No information is given for re-using vials of pevonedistat.Our objectives were to study the physico-chemical stability of 50 and 200 µg/mL pevonedistat diluted in 0.9% NaCl, in glass tubes, 100 µg/mL in 0.9% NaCl in polyolefin infusion bags, and 10 mg/mL partially used vials with a Spike. All preparations were stored at 2-8°C, protected from light. MATERIALS AND METHODS: Due to the limited quantity of pevonedistat available for this study, we prepared test solutions at 50 and 200 µg/mL in glass tubes in a small volume of 20 mL. Inorder to verify the absence of a sorption phenomenon of the molecule onto polyolefin, we prepared two infusion bags at 100 µg/mL. We tested concentrated solution at 10 mg/mL. At each analysis time, we tested three samples of each condition by high performance liquid chromatography (HPLC) coupled with a photodiode array detector. Physical stability was evaluated by a visual and sub-visual inspection. We measured pH at each analysis time. RESULTS: Diluted solutions at 50 and 200 µg/mL in tubes and at 100 mg/mL in infusion bags retained more than 95% of the initial concentration for 14 days, the concentrated solution at 10 mg/mL did so for 7 days. No physical changes were detected visually or sub-visually. We found that pH values remained stable. CONCLUSION: All diluted solutions remained physically and chemically stable for 14 days, the concentrated solution did so for 7 days. No interactions between the polyolefin bag and pevonedistat were demonstrated. This new data allows re-using the concentrated solution of pevonedistat in a commercial glass vial with a Spike, and storing a preparation in case of non-administration.

Enhancing pharmaceutical decision support system: evaluating antithrombotic-focused algorithms for addressing drug-related problems.

OBJECTIVES: To evaluate the efficacy of integrating antithrombotic-focused pharmaceutical algorithms (PAs) into a pharmaceutical decision support system (PDSS) for detecting drug-related problems (DRPs) and facilitating pharmaceutical interventions. METHODS: A set of 26 PAs (12.4%) out of a total of 210 were created to model patient situations involving antithrombotics, and their contributions were compared with the entire PDSS system.The observational prospective study was conducted between November 2019 and June 2023 in two health facilities with 1700 beds. Pharmacists, who followed a DRP resolution strategy to support human supervision, analysed alerts generated by these encoded PAs. They registered their interventions and the acceptance by physicians. RESULTS: From 3290 alerts analysed targeting antithrombotics, the pharmacists issued 1170 interventions of which 676 (57.8%) were accepted by physicians. With the 184 other PAs, from 9484 alerts the pharmacists issued 3341 interventions of which 1785 were accepted (53.4%).Results indicate that the detection of DRPs related to antithrombotics usage represents a high proportion of those detected by the PDSS, highlighting the importance of incorporating tailored PA elements at the modelling stage. CONCLUSIONS: The system evolves alongside the physiological changes associated to the patient situations, adapts the alerts and complements the current care. Therefore, we recommend that all PDSS should integrate specific algorithms targeting DRPs associated with antithrombotics to enhance pharmaceutical interventions and improve patient safety.

Pseudomonas aeruginosa Infections in Patients with Severe COVID-19 in Intensive Care Units: A Retrospective Study.

Patients hospitalized in ICUs with severe COVID-19 are at risk for developing hospital-acquired infections, especially infections caused by Pseudomonas aeruginosa. We aimed to describe the evolution of P. aeruginosa infections in ICUs at CHRU-Nancy (France) in patients with severe COVID-19 during the three initial waves of COVID-19. The second aims were to analyze P. aeruginosa resistance and to describe the antibiotic treatments. We conducted a retrospective cohort study among adult patients who were hospitalized for acute respiratory distress syndrome due to COVID-19 and who developed a hospital-acquired infection caused by P. aeruginosa during their ICU stay. Among the 51 patients included, most were male (90%) with comorbidities (77%), and the first identification of P. aeruginosa infection occurred after a median ICU stay of 11 days. Several patients acquired infections with MDR (27%) and XDR (8%) P. aeruginosa strains. The agents that strains most commonly exhibited resistance to were penicillin + ß-lactamase inhibitors (59%), cephalosporins (42%), monobactams (32%), and carbapenems (27%). Probabilistic antibiotic treatment was prescribed for 49 patients (96%) and was subsequently adapted for 51% of patients after antibiogram and for 33% of patients after noncompliant antibiotic plasma concentration. Hospital-acquired infection is a common and life-threatening complication in critically ill patients. Efforts to minimize the occurrence and improve the treatment of such infections, including infections caused by resistant strains, must be pursued.

Hospital antimicrobial stewardship team perceptions and usability of a computerized clinical decision support system.

BACKGROUND: Antimicrobial stewardship (AMS) programs aim to optimize antibiotic use through a panel of interventions. The implementation of computerized clinical decision support systems (CDSSs) offers new opportunities for semiautomated antimicrobial review by AMS teams. This study aimed to evaluate the perceived facilitators, barriers and benefits of end-users related to a commercial CDSS recently implemented in a hospital and to assess its usability. METHODS: A mixed-method approach was used among AMS team members nine months after the implementation of the CDSS in a university hospital in northeastern France. A qualitative analysis based on individual semistructured interviews was conducted to collect end-users' perceptions. A quantitative analysis was performed using the System Usability Scale (SUS). RESULTS: Eleven AMS team members agreed to participate. The qualitative analysis revealed technical, organizational and human barriers and facilitators of CDSS implementation. Effective collaboration with information technology teams was crucial for ensuring the installation and configuration of the software. CDSS adoption by the AMS team required time, human resources, training, adaptation and a clinical leader. Moreover, the CDSS had to be well designed, user-friendly and provide benefits to AMS activities. The quantitative analysis indicated that the CDSS was a "good" system in terms of perceived ease of use (median SUS score: 77.5/100). CONCLUSIONS: This study shows the value of the studied CDSS to support AMS activities. It reveals barriers, facilitators and benefits to the implementation and adoption of the CDSS. These barriers and facilitators could be considered to facilitate the implementation of the software in other hospitals.

Perceptions of infection control professionals toward electronic surveillance software supporting inpatient infections: A mixed methods study.

BACKGROUND: Electronic surveillance software (ESS) collects multiple patient data from hospital software to assist infection control professionals in the prevention and control of hospital-associated infections. This study aimed to understand the perceptions of end users (i.e., infection control professionals) and the facilitators and barriers related to a commercial ESS named ZINC and to assess its usability. METHODS: A mixed-method research approach was adopted among infection control professionals 10 months after the implementation of commercial ESS in the university hospital of Nancy, France. A qualitative analysis based on individual semistructured interviews was conducted to collect professionals' perceptions of ESS and to understand barriers and facilitators. Qualitative data were systematically coded and thematically analyzed. A quantitative analysis was performed using the System Usability Scale (SUS). RESULTS: Thirteen infection control professionals were included. Qualitative analysis revealed technical, organizational and human barriers to the installation and use stages and five significant facilitators: the relevant design of the ESS, the improvement of infection prevention and control practices, the designation of a champion/superuser among professionals, training, and collaboration with the developer team. Quantitative analysis indicated that the evaluated ESS was a "good" system in terms of perceived ease of use, with an overall median SUS score of 85/100. CONCLUSIONS: This study shows the value of ESS to support inpatient infections as perceived by infection control professionals. It reveals barriers and facilitators to the implementation and adoption of ESS. These barriers and facilitators should be considered to facilitate the installation of the software in other hospitals.

A new function in the Stabilis database: physical compatibility and incompatibility of injectable drugs to secure Y-site administration.

OBJECTIVES: In intensive care units, the mixing of injectable drugs via Y-site administration is often necessary. However, some mixtures can lead to physical incompatibility or chemical instability. To assist healthcare professionals, several databases such as Stabilis compile compatibility and stability data. The objectives of this study were to update the online database Stabilis by adding physical compatibility data to the website and to characterise the incompatibility data already present in the database by specifying the phenomenon at the origin of the incompatibility and its time of occurrence. METHODS: Bibliographic sources referenced in Stabilis were evaluated using several criteria. After the evaluation, studies were rejected or the data they contain were added to the database. Data entries contained the following information: name of the two injectable drugs involved in the mixture and their concentration if available, the dilution solvent and the phenomenon at the origin of the incompatibility and its time of occurrence for incompatibility data. Three functions of the website were modified, including the 'Y-site compatibility table' function, which allows creation of customised compatibility tables. RESULTS: A total of 1184 bibliographic sources were evaluated, 77.3% (n=915) of which were scientific articles, 20.5% (n=243) were Summaries of Product Characteristics and 2.2% (n=26) were communications in a pharmaceutical congress. After evaluation, 28.9% (n=342) of the sources were rejected. From the 71.1% (n=842) sources selected, 8073 (70.2%) compatibility data entries and 3433 incompatibility data entries (29.8%) were made. With the addition of these data, the database contained compatibility and incompatibility data for 431 injectable drugs. CONCLUSIONS: Since the update, the 'Y-site compatibility table' function has seen its traffic increased by about 66% (∼1500 tables per month compared with ∼2500 tables per month). Stabilis is now more complete to offer significant help to healthcare professionals with their problems of drug stability and compatibility.

Physicochemical stability of cefiderocol, a novel siderophore cephalosporin, in syringes at 62.5 mg/mL for continuous administration in intensive care units.

INTRODUCTION: Cefiderocol is a new siderophore time-dependent antibiotic of last resort. The manufacturer reports a stability of 6 hours for the infusion solution diluted in normal saline (NS) or dextrose 5% in water (D5W) for a concentration between 7.5 and 20 mg/mL. Optimising its effectiveness by continuous infusion is crucial. The aim of this work was to study the physicochemical stability of cefiderocol diluted in NS or D5W in polypropylene syringes for 48 hours at a concentration of 62.5 mg/mL stored at room temperature, protected or not from light. MATERIALS AND METHODS: Three preparations for each condition were performed. At each time of the analysis, one sample for each preparation was analysed in triplicate by a validated high performance liquid chromatography method coupled to a photodiode array detector at 260 nm. Particle contamination, absorbance measurement, visual inspection and pH measurement were assessed. The limit of stability was set at 90% of the initial concentration, without physical modification. RESULTS: The linearity was validated with an R² of 0.9999. The coefficients of variation for repeatability and intermediate precision were less than 2%. In NS and D5W, cefiderocol retained more than 90% of the initial concentration after 12 hours in syringes, exposed or not to light. Two degradation products (nos 2 and 11, observed during forced degradation) were detected during the stability study. The absorbance at 410 nm increased progressively, regardless of the storage conditions. The particulate contamination test met the specifications of the container. pH values were all between 5.22 and 5.32. No visual changes were detected. CONCLUSION: In polypropylene syringes, cefiderocol 62.5 mg/mL (3 g in 48 mL) diluted in NS or D5W was stable for 12 hours at room temperature. These new data allow the use of cefiderocol in continuous infusion.

[Organizational and budgetary impacts of the implementation of CAR-T cell therapies in a French academic hospital]. / Impacts organisationnels et budgétaires de la mise en place des thérapies CAR-T cells au sein d'un centre hospitalier académique français.

Belonging to the family of advanced therapy medicinal products, CAR-T cells have changed the management of hematological malignancies. These treatments are known to involve many actors in a complex process. The quotation of hospital stays associated with this therapeutic strategy is also unusual since there is currently no specific quotation. From November 2021 to May 2022, a study was conducted at the Nancy University Hospital to evaluate the organizational impact of CAR-T cell therapy on hospital actors and the budgetary impact of stays in care centers. Through this study, we have shown significant and variable organizational impacts: from 3.12% of an additional full-time equivalent for an administrative manager to 41.5% for a clinical research associate. These times, when compared to the hourly rates of the actors, generated high costs: 6582.81 € per patient, i.e. 15.60% of the total cost of hospitalization. Taking into account the current refund of hospital stays and the costs calculated above, the balance of an average hospital stay is a deficit of 674.10 € [±10,224.79] with a median of 1334.97 €. This study highlighted the workload generated by the management of these new therapies, as well as the fragile balance of financing hospital stays. To date, it seems necessary and even essential to adapt the quotations of the acts dedicated to CAR-T cells activity and to provide adequate funding through an adapted pricing system.

Relevance of fluoroquinolone use in hospitals in the Lorraine region of France before and after corrective measures: an investigation by the Antibiolor Network.

OBJECTIVES: This study of fluoroquinolone use was carried out before and after an educational intervention run by Antibiolor, a regional network to all hospitals in the Lorraine region of France. METHODS: The relevance of fluoroquinolone prescription according to regional guidelines was assessed using a standard card filled out by physicians and pharmacists at the voluntarily participating hospitals. A therapeutic index of adequacy was established for each card. The initial survey took place in January 2008, with feedback and proposals for corrective measures in January 2009. The second survey was organized in June 2009. The results of the 2 surveys were compared. RESULTS: Twenty-four hospitals completed a total of 1336 cards in the first survey (S1) and 944 cards in the second (S2). The appropriateness of indications for fluoroquinolone use improved by 57% between the 2 surveys. All the criteria analyzed (choice of drug, dosage, treatment duration) were significantly improved in S2 compared to S1, as was the adequacy index (70% improvement). CONCLUSIONS: In view of the consequences of fluoroquinolone use, many hospitals in Lorraine were keen to participate in this study, confirming its feasibility over a large area. In view of the study results, the book of guidelines was re-examined and republished at the conclusion of S2. Greater adherence to guidelines was noted in S2, demonstrating the benefit of assessing the situation thoroughly before proposing corrective measures and evaluating their impact.

High concentrated etoposide solutions, additional physical stability data in dextrose 5.

OBJECTIVES: According to the manufacturers, the concentration of etoposide solutions should not exceed 0.4 mg/mL due to a risk of precipitation. Stability studies at higher concentrations were conducted and notably demonstrated 28 day stability up to 1.75 mg/mL for etoposide solutions in 5% dextrose (D5W). Nevertheless, colleagues report precipitation even at 0.4 mg/mL in their daily practice. The objective of this work was to reassess the physical stability of highly concentrated etoposide solutions in D5W (1.2 mg/mL), over a large number of preparations and under different manufacturing processes. METHODS: To study the impact of manufacturing process, etoposide was taken with a spike or a needle and injected in three types of D5W containers (Easyflex, Viaflo and Ecoflac). Forty preparations were made for each container. For half of the preparations, a homogenisation was performed by a syringe rinse. Physical stability was realised by two examiners, with a visual examination searching for the appearance of a precipitate, daily during the first week, then twice a week until day 56. RESULTS: Hundred and eighteen solutions were clear and colourless. Precipitates were observed for two solutions: one in an Easyflex bag on day 4 and one in an Ecoflac container on day 35. CONCLUSIONS: The physical stability at 1.2 mg/mL in D5W remains validated. Precipitations are rare and concern less than 2% of preparations. The appearance of a precipitate does not seem to be correlated to the kind of container or manufacturing process. A rinse was performed for these two solutions to assess a mechanical pressure effect more important on the solution, which could lead to a higher risk of precipitations. However, this is not observed in our daily practice, especially at lower concentrated solutions. We only recommend using an administration set with an in-line micro-filter as a precaution in case of precipitations.

Stability Studies of 16 Antibiotics for Continuous Infusion in Intensive Care Units and for Performing Outpatient Parenteral Antimicrobial Therapy.

The use of continuous infusion to improve the therapeutic efficacy of time-dependent antibiotics has been demonstrated. There is still a lack of data to safely perform these continuous infusions. The objectives in this study were to evaluate the stability by using stability-indicating methods (High-Performance Liquid Chromatography) of 16 antibiotics in concentrated solutions, especially for administration in intensive care units and solutions in elastomeric diffusers at 37 °C for outpatient parenteral antimicrobial therapy. The solutions were considered stable if the percentage of the drug was ≥90%, and the colour and clearness remained unchanged. In syringes, the stability data vary from 4 to 8 h (h) for meropenem in Dextrose 5% (D5W) and Normal Saline (NS), respectively, 6 h for cefotaxime, 12 h for cefoxitin, and 24 h for aztreonam, cefazolin, cefepime, cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam in NS and D5W, and in water for injection for cloxacillin. A stability period of 48 h has been validated for vancomycin (D5W), aztreonam, and piperacillin/tazobactam. Cefoxitin, cefazolin, cefepime, cefotaxime, cloxacillin, and piperacillin are unstable for diffuser administration. In diffusers, stability times vary from 6 h for cefiderocol, 8 h for ceftazidime, 12 h for ceftazidime/avibactam and ceftolozane/tazobactam (NS), 24 h for temocillin (NS) and piperacillin/tazobactam (D5W), up to 48 h for aztreonam and vancomycin. Solutions stored at 37 °C are less stable and allow the administration of seven antibiotics using diffusers.

Evaluating antibiotic stewardship and healthcare-associated infections surveillance assisted by computer: protocol for an interrupted time series study.

INTRODUCTION: Antibiotic resistance is one of the most pressing health threats that mankind faces now and in the coming decades. Antibiotic resistance leads to longer hospital stays, higher medical costs and increased mortality. In order to tackle antibiotic resistance, we will implement in our tertiary care university hospital a computerised-decision support system (CDSS) facilitating antibiotic stewardship and an electronic surveillance software (ESS) facilitating infection prevention and control activities. We describe the protocol to evaluate the impact of the CDSS/ESS combination in adult inpatients. METHODS AND ANALYSIS: We conduct a pragmatic, prospective, single-centre, before-after uncontrolled study with an interrupted time-series analysis 12 months before and 12 months after the introduction of the CDSS for antibiotic stewardship (APSS) and ESS for infection surveillance (ZINC). APSS and ZINC will assist, respectively, the antibiotic stewardship and the infection prevention and control teams of Nancy University Hospital (France). We will evaluate the impact of the CDSS/ESS on the antibiotic use in adult (≥18 years) inpatients (hospitalised ≥48 hours). The primary outcome is the prescription rate by all healthcare professionals from the hospital of all systemic antibiotics expressed in defined daily doses/1000 patients/month. Concurrently, we will assess the safety of the intervention, its impact on the appropriateness of antibiotic prescriptions and on additional precautions (isolation precautions) as recommended in guidelines, and on bacterial epidemiology (multidrug-resistant bacteria and Clostridioides difficile infections) in the hospital. Finally, we will evaluate the users' satisfaction and the cost of this intervention from the hospital perspective. ETHICS AND DISSEMINATION: The protocol has been approved by the Ethics Committee of Nancy University Hospital and registered on the ClinicalTrials platform. Results will be disseminated through conferences' presentations and publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04976829.

Pharmaceutical algorithms set in a real time clinical decision support targeting high-alert medications applied to pharmaceutical analysis.

BACKGROUND: Pharmaceutical analysis of the prescription has to prop up the quality of patients' medication management in a context of medication's risk acculturation. But this activity remains highly variable. Medication-related clinical decision support may succeed in reducing adverse drug events and healthcare costs. PURPOSE: This study aims to present AVICENNE as a real time medication-related clinical decision support (rt-CDS) applied to pharmaceutical analysis and its ability to detect Drug related problems (DRP) consecutively resolved by pharmacists. Basic procedures A Medication-related rt-CDS is created by integrating the software PharmaClass® (Keenturtle), 5 health data streams on the patient and Pharmaceutical algorithms (PA). PA are created by modeling the pharmaceutical experiment about DRP and the thread of their criticality. They are partially encoded as computerized rules in Pharmaclass® allowing alerts' issue. An observational prospective study is conducted during 9-months among 1000 beds in 2 health facilities. The first step is to identify alerts as DRP; their resolution follows with clear guidelines worked out for the pharmaceutical analysis. A basis on predictive positive values (PPV) of the PA is being built today helping to know the performance of DRP detection and resolution. Main findings 71 PA are encoded as rules into Pharmaclass®: 40 targeted serious adverse drug events. 1508 alerts are analyzed by pharmacists. Among them 921 DRPs were characterized and 540 pharmaceutical interventions transmitted of which 219 were accepted by prescribers. Three PPV are defined depending on software, pharmacist and patient. Principal conclusion Clinical pharmacy societies should host, share and update a national corpus of PA and exploit its educational interest.

Observational study of drug-related problems and clinical pharmacists' interventions in a French paediatric hospital.

OBJECTIVES: Paediatric inpatients are a high-risk population for drug-related problems, yet there is a lack of data concerning drug-related problems and pharmaceutical interventions in paediatric hospitals in France. The objective of this study was to describe drug-related problems, pharmaceutical interventions and the acceptance rate of physicians based on the characteristics of both medication order and pharmaceutical interventions. METHODS: A 12-month, monocentric, observational and prospective study was conducted from 1 June 2016 to 31 May 2017 in a French university paediatric hospital. Prescription analysis was performed at the central pharmacy. The data were collected by querying the drug prescription database of the e-prescription software. Data on drugs, prescribers, drug-related problems and interventions were recorded. The primary outcome was the measurement of the number of drug-related problems in paediatric hospitalised patients (medical and surgical wards). Secondary outcomes were classification of drug-related problems and pharmaceutical interventions. Physician acceptance of pharmaceutical interventions was additionally assessed. RESULTS: The main types of drug-related problems were supratherapeutic dosage (33.8%), improper administration (22.9%) and subtherapeutic dosage (16.8%). A total of 1742 pharmaceutical interventions were recorded. The rate of pharmaceutical interventions was 2.48 per 100 drug prescriptions. Acceptance rate of physicians was 51.7%. Some 530 different drugs were involved. The drugs most frequently involved in pharmaceutical interventions were drugs for the nervous system (31.3%) and anti-infectives (20.2%). Pharmaceutical interventions related to dose adjustment accounted for half of the interventions ahead of drug choice interventions (35.4%). CONCLUSIONS: This study illustrates the frequency of drug-related problems in paediatric inpatients and the ability of pharmacists to identify them in their daily work. However, it also highlights the difficulty in obtaining physician acceptance (or even clear refusal) of pharmaceutical interventions with a review of the prescription at the central pharmacy.