Is Tocilizumab Plus Dexamethasone Associated with Superinfection in Critically Ill COVID-19 Patients?

BACKGROUND: Dexamethasone and tocilizumab are used to treat severely ill COVID-19 patients admitted to intensive care units (ICUs). We explored whether combination therapy increased the risk of superinfection compared to dexamethasone alone. METHODS: This observational, retrospective study included critically ill COVID-19 adult patients admitted to our ICU because of respiratory failure. Patients received dexamethasone with (Group 1) or without (Group 2) tocilizumab. Data were collected from electronic medical files. RESULTS: A total of 246 patients were included, of whom 150 received dexamethasone and tocilizumab, while 96 received dexamethasone alone. Acute respiratory distress syndrome was evident on admission in 226 patients, 56 of whom required mechanical ventilation (MV). Superinfections, mainly respiratory, were diagnosed in 59 patients, including 34/150 (23%) in Group 1 and 25/96 (26%) in Group 2 (p = 0.32). After multivariate analysis, the factors associated with a higher risk of superinfection included hematological malignancy (hazard ratio (HR): 2.47 (1.11-5.47), p = 0.03), MV (HR: 3.74 (1.92-7.26), p = 0.0001), and a higher SAPS-II score on admission (HR: 1.03 (1.01-1.06), p = 0.006). CONCLUSION: In critically ill COVID-19 patients, the addition of tocilizumab to dexamethasone was not associated with an increased risk of superinfection

Sécurisation de la dispensation des chimiothérapies anticancéreuses per os en retrocession hospitalière

Au cours de notre expérience de dispensation de médicaments de chimiothérapie anticancéreuse, en rétrocession, nous nous sommes rendus compte de la difficulté de compréhension du traitement pour ces patients. L'évolution des traitements de chimiothérapie anticancéreuse va vers la voie orale, voie moins agressive et facilitant l'hospitalisation à domicile. Pour autant la voie orale ne diminue pas la toxicité de ces médicaments. L'administration n'étant alors plus encadrée par des professionnels de santé, notre rôle de pharmacien nous pousse à tout mettre en oeuvre pour faciliter et sécuriser la prise. Après une présentation de la capécitabine, de l'étoposide, du tégafur, du témozolomide et de la vinorelbine, nous nous pencherons sur l'analyse des prescriptions qui présentent quelques particularités. Puis nous détaillerons l'aspect légal des rétrocessions hospitalières, activité de rétrocession au sein du service pharmacie de l'hôpital Saint André du Centre Hospitalier Universitaire de Bordeaux. Enfin nous présenterons les outils que nous avons mis en place afin de sécuriser la dispensation de tels médicaments à des patients externes.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Contribution à la réalisation d'un cederom pédagogique en hématologie (cas cliniques illustrés)

LIMOGES-BU Médecine pharmacie (870852108) / SudocLYON1-BU Santé (693882101) / SudocSudocFranceF

Etude in vitro des effets cytotoxiques et apoptotiques induits par divers agents anticancéreux sur cultures cellulaires de glioblastomes humains

Le glioblastome est la tumeur maligne la plus agressive du SNC, avec une médiane de survie d'environ 1 an. Malgré les progrès des techniques chirurgicales et le développement de nouveaux protocoles de radio- et chimiothérapie, le pronostic reste très sombre : de nouvelles stratégies thérapeutiques sont donc nécessaires. En conséquence, nous avons développé un modèle in vitro capable d'évaluer l'effet d'agents anticancéreux sur des primocultures de cellules obtenues à partir de patients atteints de glioblastome. Les anticancéreux restés proviennent de différentes classes pharmacologiques : alkylants (témozolomide, carboplatine, BCNU), anti-EGFR (geftinib) et inhibiteur du protéasome (bortezomib). L'effet cytotoxique des anticancéreux a été évalué par un test de viabilité cellulaire au MTT. L'induction d'apoptose a été mesurée par cytométrie de flux à l'aide de la sonde fluorescente TMRM. L'expression de EGFR et bcl-2 a été déterminée par western blot. Sur la lignée DBTRG05-MG surexprimant ZGFR, les résultats montrent une augmentation de la cytotoxicité du ténozolomide et du carboplatine par l'addition de geftinib. Ceci n'est pas observé sur la lignée U87-MG, n'exprimant pas RGFR. Le bortezomib montre une importante toxicité à très faible concentration sur les 2 lignées. Le modèle de culture primaire a permis de montrer les différences interindividuelles vis à vis des anticancéreux testés, et d'évaluer l'effet de nouvelles molécules. Des corrélations ont été établies entre résultats in vitro et efficacité clinique. Enfin, la détermination d'EGFR et bcl-2 sur chaque primoculture a permis de déterminer un profil de bon ou mauvais répondeur.Glioblastoma multiforme is a malignant astrocytic tumor with median survival of about 12 months. Despite advances in surgical techniques and in the development of new protocols in radio- and chemotherapy, the prognosis remains poor and new therapeutic strategies are required. Therefore, we developed an in vitro model able to evaluate anticancer drug toxicity on cells obtained from individual glioblastoma patients. Anticancer agents tested were from different pharmacological classes alkylating agents (temozolomide, carboplatin and BCNU), tyrosine kinase inhibitor of EGFR (geftinib) and proteasome inhibitor (bortezomib). A cytotoxicity test using MTT was used to evaluate in vitro drug efficacy. Apoptosis was measured by flow cytometry using a fluorescent probe TMRM. EGFR and bcl-2 expressions were determined by a western blotting technique. On glioblastoma DBTRG05-MG cell line expressing high levels of EGFR, our results show a potentiation of temozolomide and carboplatin cytotoxity by the anti-EGFR grftinib. This is not observed on U87-MG cell line which do not express EGFR. Bortezomib shows a great toxicity on the two cell lines, at very low concentrations. The primary culture model permits to determine individual response for each patient, shows interindividual differences between patients and allow us to evaluate the in vitro efficacy of new molecules. Then, we could establish a correlation between the in vitro data determined with our study model and the clinical efficacy evaluated in the patient file. EGFR and bcl-2 status were assessed on each primoculture leading us to determinz a good and bad responder profile.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

J Antimicrob Chemother

BACKGROUND: Combination therapy with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir has been suggested as an approach to improve the outcome of patients with moderate/severe COVID-19 infection. OBJECTIVES: To examine the safety of combination therapy with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir. METHODS: This was an observational cohort study of patients hospitalized for COVID-19 pneumonia treated with hydroxychloroquine and darunavir/ritonavir or lopinavir/ritonavir. Clinical evaluations, electrocardiograms and the pharmacokinetics of hydroxychloroquine, darunavir and lopinavir were examined according to clinical practice and guidelines. RESULTS: Twenty-one patients received hydroxychloroquine with lopinavir/ritonavir (median age 68 years; 10 males) and 25 received hydroxychloroquine with darunavir/ritonavir (median age 71 years; 15 males). During treatment, eight patients (17.4%) developed ECG abnormalities. Ten patients discontinued treatment, including seven for ECG abnormalities a median of 5 (range 2-6) days after starting treatment. All ECG abnormalities reversed 1-2 days after interrupting treatment. Four patients died within 14 days. ECG abnormalities were significantly associated with age over 70 years, coexisting conditions (such as hypertension, chronic cardiovascular disease and kidney failure) and initial potential drug interactions, but not with the hydroxychloroquine concentration. CONCLUSIONS: Of the patients with COVID-19 who received hydroxychloroquine with lopinavir or darunavir, 17% had ECG abnormalities, mainly related to age or in those with a history of cardiovascular disease

Outcomes of targeted treatment in immunocompromised patients with asymptomatic or mild COVID-19: a retrospective study

Abstract The aim of this study was to describe the outcomes of targeted COVID-19 treatments in immunocompromised patients with asymptomatic or mild COVID-19 during the period of expansion of the different Omicron subvariants in France. A retrospective monocentric observational study was performed. All immunocompromised patients aged 18 or more, with asymptomatic SARS-CoV-2 infection or mild COVID-19, and who had received a targeted treatment with sotrovimab, tixagevimab/cilgavimab, nirmatrelvir/ritonavir or remdesivir at the Bordeaux University Hospital from 1st January 2022 to 31st December 2022 were eligible. The primary outcomes of interest was defined as a composite of either (i) progression to moderate (WHO-Clinical Progression Scale at 4 or 5) or severe COVID-19 (WHO-CPS ≥ 6), or (ii) the occurrence of COVID-19-related death. The secondary outcomes of interest were the components of the primary outcome. Outcomes were collected until day 30 after targeted treatment administration or at discharge for patients still hospitalised in relation with COVID-19 at day 30. 223 immunocompromised patients received targeted treatment for asymptomatic SARS-CoV-2 infection or mild COVID-19: 114 received sotrovimab, 50 tixagevimab/cilgavimab, 49 nirmatrelvir/ritonavir, and 10 remdesivir. Among 223 treated patients, 10 (4.5%) progressed to moderate or severe disease: three patients (1.3%) progressed to moderate COVID-19 and 7 (3.1%) patients progressed to severe disease. Among them, 4 (1.8%) died of COVID-19. More than 95% of immunocompromised patients with asymptomatic SARS-CoV-2 infection or mild COVID-19 treated by targeted therapies during the Omicron subvariants era did not progress to moderate or severe disease