[Rapid diagnosis of bacteremia by genomic identification]. / Diagnostic rapide des bactériémies par identification génomique.

Our objective was to make a focus on the methods for rapid diagnosis of bacteremia by genomic identification. We also aimed to evaluate the interest of using them in the laboratory practice. The different methods currently available have been presented according to their technologic approach. It is also possible to classify these methods according to the data provided, only bacterial and/or resistance gene identification or also bacterial susceptibility to antibiotics. In case of mono-microbial blood cultures, the performances recorded with these methods are very good as compared to the subcultures on agar media. Nevertheless, they are better for identifications (>90%) than for susceptibility to antibiotics (>80%). Numerous studies demonstrated the positive impact of these methods for decreasing the time necessary to the prescription of an appropriate antimicrobial treatment. However, it is noteworthy that an appropriate organization of the laboratory and a strategy of antimicrobial stewardship in the hospital are necessary. Concurrently, the impact on the patient outcome has not been clearly demonstrated. Lastly, few medico-economic studies have been reported. However, as these methods have a substantial cost, their utilization strategy must be economically viable.

Effects of students' peer teaching in a new pharmacokinetics teaching format.

INTRODUCTION: The aim of this work was to evaluate the impact of a teaching method in pharmacokinetics (PK) in terms of satisfaction and performance in the final test of students. MATERIAL AND METHODS: This method consisted of the development of a practical problem and a peer-tutored solution by small groups of three or four students. Students enrolled in the second year of pharmaceutical studies had to generate a PK practical problem, to propose a solution and to conduct a peer-tutored solution of the practical problem completed by another student group in a learning-connected classroom. Student's performance was assessed by individual semi-structured interviews and by comparing the scores obtained in the final test with those obtained in previous years. RESULTS: More than 70% of the students were highly satisfied with the new format of the PK course, especially concerning the development and the design of a practical problem. More than 94% of the students considered that the content of the lecture-based teaching was at least adapted and in accordance with the objectives of the PK course. Students reported very constructive discussions and interactions with peers and the teacher. In addition, students significantly increased their score at the final PK test compared to previous years (53.27±19.10% in 2015-2017 vs. 71.30±13.47% in 2018-2019, P<.0001). CONCLUSION: This new method including peer teaching was applied in PK and allowed to significantly increase the performance and the satisfaction of the students in PK.

Cefoxitin-based combination for ESBL-producing Enterobacteriaceae endocarditis.

BACKGROUND: Endocarditis due to extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae is a rare but challenging condition. Its treatment relies on carbapenems alone or in combination, and no alternative has been described to date. The cephamycin cefoxitin has been used for treatment of mild ESBL-producing Enterobacteriaceae infections. CASE PRESENTATION: We report two patients with nosocomial endocarditis due to ESBL-producing Escherichia coli and Klebsiella pneumoniae who underwent clinical failure or adverse event, respectively, during treatment with imipenem-cilastatin. The first patient was subsequently treated with cefoxitin combined with ciprofloxacin with a favorable outcome. In the second patient, the endocarditis relapsed following a 6-week treatment with cefoxitin and fosfomycin. In time-kill assays, the cefoxitin/ciprofloxacin and cefoxitin/fosfomycin combinations showed synergistic effect. CONCLUSION: These cases illustrate that cefoxitin is an interesting alternative to carbapenems, even in severe infections such as endocarditis. Pharmacokinetic optimization and combination with another synergistic antibiotic should be considered whenever possible.

[Smoking, vaping among hospital staff during the Covid-19 pandemic: Appraisal of the "tobacco-free hospital, campus" campaign in Brest]. / Tabagisme et vapotage dans un CHRU en période de pandémie de covid-19 : Point de la campagne Hôpital et Campus Sans Tabac à Brest.

INTRODUCTION: In the framework of a "tobacco-free hospital and campus" campaign, we conducted a study on the prevalence of smoking and vaping among a university hospital (CHRU) staff. The study took place in late 2020 (from 1 September to 15 December), and involved self-assessment of the impact of the covid-19 pandemic on smoking. MATERIAL AND METHOD: A cross-sectional study was carried out using an online questionnaire, which was distributed by email and QR code posting and included socio-professional details as well as data on participants' smoking and vaping. RESULTS: There were 782 responses, representing a participation rate of 13.5%. The sample included 73.3% women and 22.7% men; 28.9% nurses, 24.9% medical staff, 3.6% nursing assistants and 42.6% other professional categories. The overall smoking rate was 13%. Sixty-two (7.9%) participants vaped; 37 (5%) vaped exclusively, 25 (3.2%) combined smoking and vaping. Men smoked more than women: 23.7% vs. 9.4% (P < 0.01). Medical staff smoked and vaped less than other categories; 6.2% vs 14.8% (P < 0.01) and 4.1% vs 9.1% respectively (P=0.02). Doctors were more often non-smokers: OR=2.71 (95% CI: 1.14-6.46). Among smokers, 25% said they had increased their cigarette consumption during the covid-19 pandemic, frequently as a means of combating stress or fatigue. CONCLUSION: This study showed a lower smoking rate than in the literature, possibly due to the high participation of physicians. Ours were the initial estimates of vaping among hospital staff.

[Engagement of students enrolled in fifth year of pharmacy studies in their academic or salaried pharmaceutical activities during the first period of lockout due to the COVID-19 pandemic (16th March-11th May 2020)]. / Engagement d'étudiants de cinquième année de pharmacie dans leurs activités pharmaceutiques, académiques et salariées, au cours de la première période de confinement liée à la pandémie de COVID-19 (16 mars­11 mai 2020).

OBJECTIVES: To characterize the engagement of students enrolled in the fifth year of pharmaceutical studies in the management of the health crisis due to the COVID-19 pandemic, and to identify some determinants of this engagement during this period. METHODS: With the health crisis, new missions have been entrusted during hospital internships, whereas certain internship sites were removed in hospitals and as part of the health service organization. In addition, some students who were no longer in internship returned to the hospital setting for helping in critical activities. Student engagement was studied with a questionnaire and focus groups including six or seven students in each group. RESULTS: Forty-three students participated to the study. The answers to the questionnaire highlighted that they were engaged, that they usually did not wait for compensation, and that most of them were satisfied by their activity during the crisis. The thematic analysis demonstrated that despite a feeling of frustration, which was often associated with the interruption of rewarded activities, and despite a stress due to the particular context, student engagement was supported by a better consideration of the pharmacist's role as a professional in public health and by a better acknowledgement of this role by other health professionals. CONCLUSION: This level of engagement is particularly encouraging because it is the witness of the ability of pharmacists to mobilize for general interest, even in adverse context.

Long-term contamination of sink drains by carbapenemase-producing Enterobacterales in three intensive care units: characteristics and transmission to patients.

This study aimed to describe the contamination of sink drains (SDs) with carbapenemase-producing Enterobacterales (CPE) in three intensive care units (ICUs), and to assess the risk of transmission to hospitalized patients. All SDs were sampled monthly for CPE screening by culture. Rectal screening for CPE carriage was conducted weekly for hospitalized patients. CPE were isolated from 22% of SD samples. Some SDs remained colonized with the same strain for several months. No CPE acquisition occurred among hospitalized patients during the study. Certain strategies, such as systematic sampling of SDs in ICUs for screening for contamination by CPE, should be discouraged apart from during outbreaks.

Stenotrophomonas maltophilia susceptibility to ceftazidime-avibactam combination versus ceftazidime alone.

OBJECTIVE: To compare the minimum inhibitory concentrations (MIC) of the ceftazidime-avibactam (CZA) combination versus ceftazidime alone (TZ) for Stenotrophomonas maltophilia. PATIENTS AND METHODS: MIC comparison was performed by E-tests. We assumed that CZA was more effective in vitro than TZ alone when CZA led to a category change from "Resistant" with TZ alone to "Susceptible" or "Intermediate" with CZA, or if the MIC of CZA was at least 4-fold lower than the MIC of TZ for TZ-susceptible isolates. RESULTS: For the 54 clinical isolates included in the study, CZA showed better results in terms of the proportion of susceptible isolates (66.7% vs. 38.9%, P<0.01), MIC50 (2µg/mL vs. 12µg/mL, P<0.05), and MIC distribution. According to our definition, CZA was also more effective in vitro than TZ alone for 50% of the isolates. CONCLUSION: Using CZA for empirical treatments in severe or polymicrobial infections with S. maltophilia seems appropriate.

Extended-spectrum ß-lactamase Enterobacteriaceae (ESBLE) in intensive care units: strong correlation with the ESBLE colonization pressure in patients but not same species.

Sink drains of six intensive care units (ICUs) were sampled for screening contamination with extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBLE). A high prevalence (59.4%) of sink drain contamination was observed. Analysing the data by ICU, the ratio 'number of ESBLE species isolated in sink drains/total number of sink drains sampled' was highly correlated (Spearman coefficient: 0.87; P = 0.02) with the ratio 'number of hospitalization days for patients with ESBLE carriage identified within the preceding year/total number of hospitalization days within the preceding year'. Concurrently, the distribution of ESBLE species differed significantly between patients and sink drains.

Acinetobacter pittii isolated more frequently than Acinetobacter baumannii in blood cultures: the experience of a French hospital.

This study assessed the characteristics of hospital-acquired Acinetobacter calcoaceticus-Acinetobacter baumannii complex bloodstream infections (BSI). From 2010 to 2017, A. calcoaceticus-A. baumannii complex BSI were investigated. Of 73 cases, 54.8% were associated with Acinetobacter pittii, 39.7% with Acinetobacter baumannii and 5.5% with Acinetobacter nosocomialis. Multi-drug-resistant isolates were significantly higher in A. baumannii BSI. Thirty-day mortality was no different between A. baumannii or non-baumannii A. calcoaceticus-A. baumannii complex BSI. In contrast with other studies, this study found that most hospital-acquired A. calcoaceticus-A. baumannii complex BSI were associated with non-baumannii A. calcoaceticus-A. baumannii complex species. This study found that these species were important hospital-acquired pathogens, and emphasizes the importance of A. calcoaceticus-A. baumannii complex species identification.

Two novel variants of uncertain significance in GP9 associated with Bernard-Soulier syndrome: Are they true mutations?

Bernard-Soulier syndrome (BSS) is an autosomal recessive major thrombocytopathy, the symptoms of which are mainly marked by mucocutaneous bleeding. This rare disease, initially described in the 1970s, is the result of an abnormal formation of the glycoprotein complex Ib-IX-V (GP Ib-IX-V), a platelet receptor of von Willebrand factor. A large number of mutations, sometimes involving the GP9 gene, have been described as possibly responsible for the disease. We report here the case of a BSS patient who presented with persistent thrombocytopenia (31x109/L) and decreased surface expression of GPIb-IX-V on large platelets with anisocytosis. Thorough molecular analyses disclosed two previously unreported GP9 variants, respectively c.230T>A (p.Leu77Gln) and c.255C>A (p.Asn85Lys). Both are likely to modify the conformation of GP-IX interactions with other glycoproteins of the Ib-IX-V complex and thus proper expression of this complex on the membrane of platelets.

p53 dysregulation in B-cell malignancies: More than a single gene in the pathway to hell.

TP53 deletion or mutation is frequent in B-cell malignancies and is associated with a low response rate. We describe here the p53 landscape in B-cell malignancies, from B-Acute Lymphoblastic Leukemia to Plasma Cell Leukemia, by analyzing incidence of gain or loss of function of actors both upstream and within the p53 pathway, namely MYC, RAS, ARF, MDM2, ATM and TP53. Abnormalities are not equally distributed and their incidence is highly variable among malignancies. Deletion and mutation, usually associated, of ATM or TP53 are frequent in Diffuse Large B-Cell Lymphoma and Mantle Cell Lymphoma. MYC gain, absent in post-GC malignancies, is frequent in B-Prolymphocytic-Leukemia, Multiple Myeloma and Plasma Cell Leukemias. RAS mutations are rare except in MM and PCL. Multiple Factorial Analysis notes that MYC deregulation is closely related to TP53 status. Moreover, MYC gain, TP53 deletion and RAS mutations are inversely correlated with survival. Based on this landscape, we further propose targeted therapeutic approaches for the different B-cell malignancies.

Lymphocyte expansion after unrelated cord blood allogeneic stem cell transplantation in adults.

Limited information is available regarding the incidence and features of lymphocyte expansions after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Large granular lymphocytes (LGL) expansions have been reported after bone marrow or peripheral blood, but not after unrelated cord blood (UCB) allo-HSCT, associated with indolent clinical courses and favorable outcomes. Here, we considered 85 recipients of UCB allo-HSCT to more broadly define the impact of lymphocytosis, not limited to LGL. Sustained lymphocytosis was observed in 21 (25%) patients at a median onset of 12.6 months and with a median duration of 12 months. Immunophenotypic analysis showed predominantly CD8+ T and/or polyclonal B-cell expansions. Three patients only had monoclonal T-cell expansion. CMV reactivation was significantly more frequent in the group of patients with lymphocytosis (76% vs 28%, P=0.0001), but was not associated with survival. Conversely, 2-year disease-free survival and overall survival were significantly higher for lymphocytosis patients (85% vs 55%, P=0.01 and 85% vs 63%, P=0.03, respectively). In conclusion, expansion of T or B lymphocytes after UCB allo-HSCT in adults is not a rare event. Although occurring relatively late after transplant, this feature is predictive of a better outcome for the patients.

New parameters on the hematology analyzer XN-10 (SysmexTM) allow to distinguish childhood bacterial and viral infections.

INTRODUCTION: Complete blood counts (CBC) performed for infected children admitted for fever mostly disclose leukocytosis. Yet, the recently developed XN-10® provides novel CBC parameters which could be useful to ascertain infection and discriminate between bacterial and viral etiologies. These were the main objectives of the study presented here. METHODS: Blood samples from 90 children, 1 month to 5 years old, admitted to an emergency unit for fever benefited from a CBC, C-reactive protein, and procalcitonin assays. For 58, a bacterial infection was documented while a viral cause was disclosed for 32. Concomitantly, 30 healthy children of the same age range were selected as a control group. RESULTS: Complete blood counts parameters and leukocyte differentials allowed to statistically significantly disclose infection, compared to reference children, in the age group of 1-5 years old. Among the eight novel discriminant parameters, a particular interest appeared for Neutr-RI and Delta-He. They both were successfully incorporated in a score together with age and immature granulocytes (IG). ROC curves and AUCs were calibrated using a Hosmer-Lemeshow test. Moreover, novel lymphocyte parameters allowed to segregate bacterial and viral infections in the whole group of 90 febrile children. CONCLUSION: Complete blood counts is the most broadly performed rapid laboratory investigation. Here, we show that XN-10® provides complementary information allowing to confirm infection in febrile children, moreover discriminating between bacterial or viral origin.

First report of Oxa-72-producing Acinetobacter calcoaceticus in Lebanon.

Emergence of carbapenem-resistant Acinetobacter spp. has been increasingly reported worldwide. We report here the first detection of an Acinetobacter calcoaceticus isolate from vegetables in Lebanon carrying the bla Oxa-72 gene. These findings show that the Lebanese environment may constitute a potential reservoir for this antibiotic resistance gene.

Flow cytometry in hematological nonmalignant disorders.

Multiparameter flow cytometry (MFC) has become an integral part of the diagnosis and classification of hematological malignancies. However, several nonmalignant or premalignant disorders may benefit from this technology in hematology laboratories. This review provides information on the normal immunophenotypic characteristics of peripheral blood leukocyte subsets and their modifications in several clinical conditions. The usefulness of MFC and the specific markers that can be investigated in hyperlymphocytosis, infection, hypereosinophilia, paroxysmal nocturnal hemoglobinuria, and large granular lymphocyte disorders is described. Mention is also made of the developments of MFC for analyses of red blood cells or platelets.

A case report of Mycoplasma hominis brain abscess identified by MALDI-TOF mass spectrometry.

We report the case of a 43-year-old man with a Mycoplasma hominis brain abscess occurring after a cranial trauma, which was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The presence of colonies on classic blood agar plates and the use of MALDI-TOF MS, a valuable diagnostic tool that identified M. hominis due to its presence in the VITEK MS database, allowed the rapid diagnosis of this infection.