[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.

[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.

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.

[Emerging Acinetobacter baumannii infections and factors favouring their occurrence]. / Infections émergentes à Acinetobacter baumannii et circonstances favorisant leur survenue.

During the last decade, Acinetobacter baumannii (AB) has been increasingly responsible for infections occurring in three particular contexts (in terms of patients and environment). Community AB pneumonia is severe infections, mainly described around the Indian Ocean, and which mainly concern patients with major co-morbidities. AB is also responsible for infections occurring among soldiers wounded in action during operations conducted in Iraq or Afghanistan. Lastly, this bacterium is responsible for infections occurring among casualties from natural disasters like earthquakes and tsunamis. Those infections are often due to multidrug-resistant strains, which can be implicated in nosocomial outbreaks when patients are hospitalized in a local casualty department or during their repatriation thereafter. The source of the contaminations which lead to AB infections following injuries (warfare or natural disasters) is still poorly known. Three hypotheses are usually considered: a contamination of wounds with environmental bacteria, a wound contamination from a previous cutaneous or oropharyngeal endogenous reservoir, or hospital acquisition. The implication of telluric or agricultural primary reservoirs in human AB infections is a common hypothesis which remains to be demonstrated by further specifically designed studies.

[In vitro activity of tigecycline on 760 bacterial strains isolated in the hospital university of Angers--2006-2009 TEST study]. / Activité in vitro de la tigécycline vis-à-vis de 760 souches bactériennes isolées au CHU d'Angers--le programme TEST 2006-2009.

Tigecycline (TGC), an antibiotic belonging to glycylcyclines, is active against Gram-positive bacteria, including multi-resistant bacteria, and most of the Gram-negative bacteria, including extended spectrum ß-lactamase-producers (ESBL) and Acinetobacter sp. TGC is not active on Pseudomonas aeruginosa. The microbiological laboratory from the university hospital of Angers participates in the Tigecycline Evaluation and Surveillance Trial (TEST) since 2006. The objective of this study is to evaluate the effectiveness of TGC and of various comparators against nosocomial and community-acquired pathogens. We also evaluated the effectiveness of TGC on a panel of strains isolated between 2006 and 2009 in the university hospital of Angers. Minimum inhibitory concentrations (MIC) were determined using the microdilution method. A total of 760 clinical strains were tested. TGC had a very good activity against Gram-positive bacteria, with 100 % of susceptibility for all the strains tested, irrespective of their resistance profile. Concerning Gram-negative bacteria, TGC was active against 93 % of Enterobacteriaceae, with a MIC 90 not exceeding 2mg/L. Whole of the 20 strains ESBL-producers tested were susceptible to TGC. Acinetobacter sp. were also inhibited at low concentrations of TGC, with a MIC 90 of 1mg/L. These results suggest that TGC can be a useful therapeutic alternative, especially for infections involving multiresistant bacteria.

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.

[Surgical-site infections following varicose vein surgery according to a continuous series of 408 interventions in a teaching hospital]. / Infections du site opératoire sur ablation de varices d'après une série continue de 408 interventions réalisées dans un centre hospitalier universitaire.

OBJECTIVE: To determine the incidence of surgical-site infections (SSI) following varicose vein surgery in the vascular surgery ward of a French teaching hospital. PATIENTS AND METHODS: A prospective surveillance of SSI was conducted during one year, with a 30-day postoperative follow-up. SSI cases were identified by using the definitions of the Centers for Disease Control (CDC, USA). Data acquisition and analysis were performed with the Epi-Info 6.04 software (CDC). RESULTS: Three quarters of the 408 included interventions were characterized by a NNIS score equal to 0. All patients underwent a hair removing practice before intervention. Hair removing methods were very heterogeneous and often not in accordance with national recommendations (e.g. mechanic shaving for 44.6% of patients). The incidence of SSI was 1.2% (95% confidence interval=[0.2-2.2]). All infections were identified after hospital discharge. Four infected patients out of five presented obesity or excess weight, and two patients had diabetes mellitus. The mean age of infected patients was significantly higher than non-infected ones (70.4 years versus 52.0; p<0.01). All SSI had consequences like rehospitalization, reintervention, or antimicrobial therapy. CONCLUSION: According to our results, SSI following varicose vein surgery are scarce and mainly concerned high-risk patients. However, in an aim of prevention, it seems necessary to homogenize hair removing methods in this ward.

[Antibacterial activity against 224 clinical bacterial strains of JCA 250 and JCA 251 compounds containing essential oils provided from Aroma Technologies research]. / Étude de la sensibilité de 224 bactéries isolées d'infections hospitalières vis-à-vis des composés JCA 250 et JCA 251 à base d'huiles essentielles issus de la recherche Aroma Technologies.

OBJECTIVE: It was to determine the antibacterial spectrum of JCA 250 and JCA 251, two naturally occurring compounds from Aroma Technologies research, on a bacterial population isolated from clinical infections. METHOD: Two hundred and twenty-four bacterial strains were tested. The minimum inhibitory concentrations (MIC) of JCA 250 and JCA 251 were determined by agar dilution method. Tests were performed in triplicate. RESULTS: The mean MIC was 0.20% for JCA 250 and 0.15% for JCA 251. JCA 251 regularly exhibited greater activity. All Enterobacteriaceae were inhibited at concentrations less or equal to 0.15% for JCA 250 or JCA 251. For strict aerobes, the MIC values were more spread out. Two Pseudomonas aeruginosa strains differed from the population with JCA 251 MIC of 0.25 and 0.40%. Concerning Gram-positive cocci, all the strains were inhibited with less or equal to 0.25% of compound. The most resistant population were the Enterococci and the Lactobacilli, with MIC more or equal to 0.2% for JCA 250 or JCA 251. Anaerobes showed MIC closely grouped for a heterogeneous bacterial group. One Propionibacterium sp. strain came apart from the group and was inhibited with a MIC of 0.5%. CONCLUSION: The overall results showed an interesting antibacterial activity on bacteria isolated from clinical samples. Most of the bacterial strains were inhibited at a concentration of 0.2%. The highest mean values were obtained for commensal bacteria from the flora, which is of particular interest in this study.

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.

[Evaluation of the impact of different lengths of pre-enrichment in a nutritive broth and prolonged incubation of MRSA-ID, a chromogenic agar medium, on its performances for identifying methicillin-resistant Staphylococcus aureus in screening samples]. / Evaluation de l'influence des conditions de culture sur les performances du milieu gélosé sélectif MRSA-ID pour l'identification de Staphylococcus aureus résistant à la méticilline dans les prélèvements de dépistage.

MRSA-carrier screening is recommended to prevent MRSA dissemination in hospitals. Rapid and specific detection of MRSA in the laboratory is a key element in enabling control measures. Our objective was to evaluate the impact of different lengths of pre-incubation in a nutritive broth and prolonged incubation of MRSA-ID, a chromogenic agar medium, on its performances for identifying MRSA in screening samples. According to our results, short-length pre-enrichments only provided a weak increase of sensitivity as compared to the absence of pre-enrichment. On the contrary, the sensitivity increase provided by an overnight pre-enrichment was significant. The prolongation of incubation in the chromogenic agar medium (48 hours instead of 24 hours) did not provide any significant increase of sensitivity but was associated with a strong and significant loss of specificity. Therefore, it seems relevant to reject prolonged incubation of selective agar media and to make a choice between the absence of pre-enrichment (faster results) and an overnight pre-enrichment (higher sensitivity), according to local epidemiology and local practices implemented for prevention.

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.

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.

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.