An experience of multidisciplinary tutorials sessions about antibiotics in the third year of pharmacy studies in Angers, France: learning assessment and evaluation of students' feelings by a mixed approach.

For undergraduate pharmacy students, the first step of antimicrobial stewardship learning objectives is to integrate antimicrobial knowledge from the foundational sciences. We hypothesised that using a multidisciplinary approach including two sessions of tutorials could be relevant in term of students' interest, satisfaction and learning retention time. The evaluation of students' feelings was based on a questionnaire including different dimensions and three focus groups with four students. Quantitative data were analysed with the EPI-INFO 7.2 software and a thematic analysis was implemented for qualitative data by using NVivo 12 software. The evaluation of students' learning concerned both short-time learning retention (STLR) and medium-time learning retention (MTLR), six months after the last session. Overall, 63 students responded to the questionnaire. Most of them appreciated the tutorials according to the different dimensions envisaged. Focus groups confirmed the interest of students for the multidisciplinary approach, interactions with teachers and opportunities of learning transfers. Concurrently, a lack of self-efficacy, low confidence towards the other students, external regulation of motivation and poor autonomy were recorded for some participants. Finally, there was no significant decrease between the scores of the STLR assessment and those of the MTLR assessment (58.5 ± 12.1/100 and 54.4 ± 8.9/100, respectively).

Emergence and spread of Mycobacterium ulcerans at different geographic scales.

The classical lineage of Mycobacterium ulcerans is the most prevalent clonal group associated with Buruli ulcer in humans. Its reservoir is strongly associated with the environment. We analyzed together 1,045 isolates collected from 13 countries on two continents to define the evolutionary history and population dynamics of this lineage. We confirm that this lineage spread over 7,000 years from Australia to Africa with the emergence of outbreaks in distinct waves in the 18th and 19th centuries. In sharp contrast with its global spread over the last century, transmission chains are now mostly local, with little or no dissemination between endemic areas. This study provides new insights into the phylogeography and population dynamics of M. ulcerans, highlighting the importance of comparative genomic analyses to improve our understanding of pathogen transmission. IMPORTANCE: Mycobacterium ulcerans is an environmental mycobacterial pathogen that can cause Buruli ulcer, a severe cutaneous infection, mostly spread in Africa and Australia. We conducted a large genomic study of M. ulcerans, combining genomic and evolutionary approaches to decipher its evolutionary history and pattern of spread at different geographic scales. At the scale of villages in an endemic area of Benin, the circulating genotypes have been introduced in recent decades and are not randomly distributed along the river. On a global scale, M. ulcerans has been spreading for much longer, resulting in distinct and compartmentalized endemic foci across Africa and Australia.

A clinical decision rule to rule out bloodstream infection in the emergency department: retrospective multicentric observational cohort study.

BACKGROUND: We aimed to identify patients at low risk of bloodstream infection (BSI) in the ED. METHODS: We derived and validated a prediction model to rule out BSI in the ED without the need for laboratory testing by determining variables associated with a positive blood culture (BC) and assigned points according to regression coefficients. This retrospective study included adult patients suspected of having BSI (defined by at least one BC collection) from two European ED between 1 January 2017 and 31 December 2019. The primary end point was the BSI rate in the validation cohort for patients with a negative Bacteremia Rule Out Criteria (BAROC) score. The effect of adding laboratory variables to the model was evaluated as a second step in a two-step diagnostic strategy. RESULTS: We analysed 2580 patients with a mean age of 64 years±21, of whom 46.1% were women. The derived BAROC score comprises 12 categorical clinical variables. In the validation cohort, it safely ruled out BSI without BCs in 9% (58/648) of patients with a sensitivity of 100% (95% CI 95% to 100%), a specificity of 10% (95% CI 8% to 13%) and a negative predictive value of 100% (95% CI 94% to 100%). Adding laboratory variables (creatinine ≥177 µmol/L (2.0 mg/dL), platelet count ≤150 000/mm3 and neutrophil count ≥12 000/mm3) to the model, ruled out BSI in 10.2% (58/570) of remaining patients who had been positive on the BAROC score. The BAROC score with laboratory results had a sensitivity of 100% (95% CI 94% to 100%), specificity of 11% (95% CI 9% to 14%) and negative predictive value of 100% (95% CI 94 to 100%). In the validation cohort, there was no evidence of a difference in discrimination between the area under the receiver operating characteristic for BAROC score with versus without laboratory testing (p=0.6). CONCLUSION: The BAROC score safely identified patients at low risk of BSI and may reduce BC collection in the ED without the need for laboratory testing.

Next generation antibacterial strategies for regenerative endodontic procedures: A scoping review.

BACKGROUND: The clinical results following regenerative endodontic procedures (REPs) vary according to numerous parameters, including the presence of bacteria. This limitation reduces the indications for REPs and calls for the development of next generation antibacterial strategies (NGAS) providing alternatives to current antibacterial strategies (CAS) such as double or triple antibiotic paste (DAP/TAP) and (Ca(OH)2). OBJECTIVES: The present scoping review aims to describe the current trends regarding the use of such strategies and highlight future perspectives. METHODS: Four databases (PUBMed, Cochrane, ClinicalTrials and Science Direct) were searched until 1st May 2023. RESULTS: A total of 918 records were identified, 133 were screened and assessed for eligibility, and 87 articles were included. The findings show that (1) clinical studies are only available for CAS, (2) although next generation strategies are the most studied approach since 2017, they are all at the pre-clinical stage, (3) most of the next generation strategies use galenic forms which offer cell support and colonization and which simultaneously contain antibacterial molecules as alternatives to CAS and to antibiotics in general, (4) standardization is required for future research, specifically regarding the bacterial strains studied, the use of biofilm studies and the cellular behaviour assessments. CONCLUSION: Although NGAS are promising strategies to improve REPs in the context of infection, the current evidence is mostly limited to pre-clinical studies. Further methodological improvement is required to allow relevant comparisons between studies and to reduce the time from bench to bedside.

Impact of a strategy based on unique blood culture sampling on contamination rate and detection of bloodstream infections in critically ill patients.

BACKGROUND: Unique blood culture (UBC) has been proposed to limit the number of venipuncture and to decrease the risk of BC contaminations (BCC) without affecting their yield. We hypothesized that a multi-faceted program based on UBC in the ICU may reduce the rate of contaminants with a similar performance for bloodstream infections (BSI) identification. METHODS: In a before and after design, we compared the proportion of BSI and BCC. A first 3-year period with multi-sampling (MS) strategy followed by a 4-month washout period, where staff received education and training for using UBC, and a 32-month period, where UBC was routinely used, while education and feedback were maintained. During the UBC period, a large volume of blood (40 mL) was sampled through a unique venipuncture with additional BC collections discouraged for 48 h. RESULTS: Of the 4,491 patients included (35% female patients, mean age 62 years) 17,466 BC were collected. The mean volume of blood per bottle collected increased from 2.8 ± 1.8 mL to 8.2 ± 3.9 mL between the MS and UBC periods, P < 0.01. A 59.6% reduction (95% CI 56.7-62.3; P < 0.001) of BC bottles collected per week was observed between the MS and UBC periods. The rate of BCC per patient decreased between the two periods from 11.2% to 3.8% (73.4% reduction; P < 0.001) for the MS and UBC periods, P < 0.001. Meanwhile, the rate of BSI per patient remained stable at 13.2% and 13.2% for the MS and UBC periods, P = 0.98. CONCLUSIONS: In ICU patients, a strategy based on UBC reduces the contamination rate of cultures without affecting their yield.

BIOFIRE® Blood Culture IDentification 2 (BCID2) panel for early adaptation of antimicrobial therapy in adult patients with bloodstream infections: a real-life experience.

Our objective was to assess the effectiveness of a multiplex PCR panel for blood culture identification (BCID2) on the implementation of appropriate antimicrobial therapy. We conducted a monocentric pre/post study comparing the time to result from direct microscopic examination (DE) to bacterial identification (BI) in positive blood cultures between 2 different periods: P1 without BCID2 and P2 with BCID2. Appropriate treatments prescribed before DE and after DE / BCID2 and after BI / BCID2 were compared using direct proportion comparison and survival analysis. For mono-microbial bloodstream infections, the proportion of appropriate antimicrobial treatment after DE was 50% in P1 vs. 87.5% after BCID2 in P2 (P < 0.001) for Gram-negative bacteria and 33.0% in P1 vs. 64.4% in P2 (P < 0.01) for Gram-positive bacteria. A significant difference (P = 0.04) was recorded with survival curves for Gram positive bacteria. BCID2 seems effective in reducing the time for prescribing appropriate antimicrobials.

Machine-learning approaches prevent post-treatment resistance-gaining bacterial recurrences.

Despite susceptibility testing, recurrent infections are common and are associated with resistance. Using whole-genome sequencing, Stracy et al. demonstrated that recurrence is often driven by a different strain than the original infection. By machine-learning analysis, they developed an algorithm for patient-specific recommendations to minimize antimicrobial resistance (AMR) at the individual-patient level.

A combined field study of Buruli ulcer disease in southeast Benin proposing preventive strategies based on epidemiological, geographic, behavioural and environmental analyses.

Buruli ulcer is a neglected tropical disease caused by M. ulcerans, an environmental mycobacterium. This cutaneous infectious disease affects populations with poor access to sanitation, safe water and healthcare living in rural areas of West and Central Africa. Stagnant open bodies of surface water and slow-running streams are the only risk factor identified in Africa, and there is no human-to-human transmission. Appropriate and effective prevention strategies are required for populations living in endemic areas. Based on a multidisciplinary approach in an area in which Buruli ulcer is endemic in South Benin, we investigated the link between all human-environment interactions relating to unprotected water and behaviors associated with Buruli ulcer risk likely to affect incidence rates. We characterised the sources of water as well as water bodies and streams used by communities, by conducting a prospective case-control study directly coupled with geographic field observations, spatial analysis, and the detection of M. ulcerans in the environment. A full list of the free surface waters used for domestic activities was generated for a set of 34 villages, and several types of human behaviour associated with a higher risk of transmission were identified: (i) prolonged walking in water to reach cultivated fields, (ii) collecting water, (iii) and swimming. Combining the results of the different analyses identified the risk factor most strongly associated with Buruli ulcer was the frequency of contact with unprotected and natural water, particularly in regularly flooded or irrigated lowlands. We confirm that the use of clean water from drilled wells confers protection against Buruli ulcer. These specific and refined results provide a broader scope for the design of an appropriate preventive strategy including certain practices or infrastructures observed during our field investigations. This strategy could be improved by the addition of knowledge about irrigation practices and agricultural work in low-lying areas.

Confocal spectral microscopy, a non-destructive approach to follow contamination and biofilm formation of mCherry Staphylococcus aureus on solid surfaces.

Methods to test the safety of wood material for hygienically sensitive places are indirect, destructive and limited to incomplete microbial recovery via swabbing, brushing and elution-based techniques. Therefore, we chose mCherry Staphylococcus aureus as a model bacterium for solid and porous surface contamination. Confocal spectral laser microscope (CSLM) was employed to characterize and use the autofluorescence of Sessile oak (Quercus petraea), Douglas fir (Pseudotsuga menziesii) and poplar (Populus euramericana alba L.) wood discs cut into transversal (RT) and tangential (LT) planes. The red fluorescent area occupied by bacteria was differentiated from that of wood, which represented the bacterial quantification, survival and bio-distribution on surfaces from one hour to one week after inoculation. More bacteria were present near the surface on LT face wood as compared to RT and they persisted throughout the study period. Furthermore, this innovative methodology identified that S. aureus formed a dense biofilm on melamine but not on oak wood in similar inoculation and growth conditions. Conclusively, the endogenous fluorescence of materials and the model bacterium permitted direct quantification of surface contamination by using CSLM and it is a promising tool for hygienic safety evaluation.

Cerebral epidural empyema due to Bartonella henselae: a case report.

BACKGROUND: Cat scratch disease frequently involves a benign, self-limited disease. Neurological forms associated with Bartonella henselae are uncommon, consisting mostly in neuroretinitis, encephalitis and meningitis. Cerebral epidural empyema has never described. CASE PRESENTATION: An adult patient was hospitalized for isolated headaches. Magnetic Resonance Imaging (MRI) identified typical features of cerebral epidural empyema. The diagnosis of B. henselae was performed incidentally by 16S rDNA gene sequencing on the abscess fluid, and confirmed by specific qPCR. We report here the first case, to our knowledge, of cerebral epidural empyema associated with B. henselae. Further follow-up visits allowed identifying frequent cat scratches on the scalp as the presumptive source of infection. CONCLUSIONS: This case report alerts about such atypical clinical presentation, which requires an extensive clinical investigation. It also emphasizes on the usefulness of additional molecular diagnosis techniques in such CNS infection cases.

Teaching bacterial infections in pharmaceutical studies: why not 'with students' instead of 'to students'?

In pharmaceutical studies, a course of bacteriology based on case studies provided by the teacher was transformed in a course based on a combination of student/teacher co-creation of cases and peer reviewing. Our objectives were to describe the perception of students about the new format and to assess the impact of changing on the learning outcomes. For teaching evaluation, we used a questionnaire and focus groups. The assessment of learning outcome was performed by comparing the students' scores in final tests with the previous and the revised course formats. The students embraced the creation of cases in small groups with the teacher. In addition, they reported a perception of weakened hierarchy between the teacher and themselves, an increase of their self-confidence and a better ability to transfer their learning to their professional activities in community pharmacies. Lastly, their opinion about the transferability of this format in other disciplines were divided.

Impact of ceftriaxone and temocillin on fecal abundance of extended-spectrum ß-lactamase producing Escherichia coli in a mouse model.

BACKGROUND: Gut colonization by ESBL-producing Enterobacteriaceae (ESBL-PE) is widespread and is promoted by antibiotic exposure. Higher fecal abundance of ESBL-PE promotes the dissemination of the bacteria in the environment and is associated with increased risk of infection. Ceftriaxone and temocillin are commonly used antibiotics with a different activity on gut flora. Their impact on fecal abundance of ESBL-producing Enterobacteriaceae has not been studied. The objective of this study was to compare the propensity of ceftriaxone and temocillin to modify the abundance of ESBL-producing Escherichia coli in feces of colonized mice. METHODS: Mice received broad-spectrum antibiotics in order to disrupt their normal gut flora. A CTX-M-type ESBL-producing E. coli clinical isolate was then administered orally, leading to durable colonization. Thirty days later, mice received either temocillin or ceftriaxone with drinking water at a concentration simulating human intestinal exposure. Third-generation-cephalosporin resistant (3GCR) E. coli were enumerated in feces on selective medium before, 2 days and 10 days after the end of antibiotic exposure. The experiment was performed with two E. coli isolates with different temocillin minimum inhibitory concentrations. RESULTS: Exposure to ceftriaxone induced an increase in the fecal abundance of 3GCR E. coli. In contrast, temocillin had no effect or transiently decreased the number of 3GCR E. coli. Results obtained with the two strains were similar. CONCLUSION: Contrary to ceftriaxone, temocillin does not promote expansion of ESBL-producing E. coli in feces of colonized mice. Thus temocillin may be a therapeutic of choice when a temocillin-susceptible strain infection is suspected or proven to prevent the expansion of ESBL-PE in a previously colonized patient.

[Applying active learning in pharmaceutical studies by the way of team-based learning]. / Mobilisation des pédagogies actives dans les études pharmaceutiques à travers les travaux de groupes.

Currently, the most used pedagogical approach in pharmaceutical studies is transmissive teaching, in which students usually adopt a passive attitude. The aim of this article is to present the main characteristics of active learning, and to point how it can be integrated in pharmaceutical studies by the way of team-based learning. According to its different characteristics, team-based learning is an authentic method of active learning. This pedagogical method includes a preparation time, usually individually performed, and followed by the group work itself, in which the case method is the most frequently used. Team-based learning also allows students to work in interdisciplinarity and facilitates interactions between peers. The wide majority of the studies demonstrate that students acclaim this pedagogical approach as compared to more conventional teaching methods, and that their satisfaction increases their commitment in the tasks proposed in the course. Even though the results of studies concerning the impact of team-based learning on student retention and scores in tests are somewhat discordant, this pedagogical approach allows the acquisition or the reinforcement of skills that will be useful to students in their future professional life, like collaborative work and confidence in their ability to complete a task.

Survival of Bacterial Strains on Wood (Quercus petraea) Compared to Polycarbonate, Aluminum and Stainless Steel.

Healthcare-associated infections (HAI) remain a burden in healthcare facilities, environmental surfaces being a potential reservoir for healthcare-associated pathogens. In this context, exploration of materials with potential antimicrobial activities represents a way forward for the future. Here, we explored the survival of four bacterial species commonly involved in HAI (Acinetobacter baumannii, Enterococcus faecalis, Klebsiella pneumoniae, Staphylococcus aureus), on oak versus three other materials (aluminum, polycarbonate, stainless steel). Twenty microliters of each bacterial suspension (approximatively 107 bacteria) were deposited on each material. Bacterial counts were measured by grinding and culturing on day 0, 1, 2, 6, 7 and 15. Analyses were performed in triplicate for each material and each time evaluated. It appeared that the bacteria viable count decreased rapidly on transversal and tangential oak compared with the other materials for all bacterial species. Furthermore, no difference was noticed between transversal and tangential oak. These results underline the potential for use of oak materials in healthcare facilities, a consideration that should be supported by further investigations.

Wood materials for limiting the bacterial reservoir on surfaces in hospitals: would it be worthwhile to go further?

Aim: To assess the activity of Quercus petraea (oak) on five bacterial species/genus frequently involved in hospital-acquired infections for evaluating the interest of going further in exploring the possibilities of using untreated wood as a material in the hospital setting. Materials & methods: We studied the activity of Q. petraea by the disk diffusion method. Results:Q. petraea was active on Staphylococcus aureus and Acinetobacter coalcoaceticus-baumannii complex, two bacterial species particularly resistant in the hospital environment, independently from their resistance to antibiotics, and was slightly active on Pseudomonas aeruginosa. Concurrently, Q. petraea was not active on Enterococci and Escherichia coli. Conclusion: Overall, untreated wood material presented antimicrobial properties that could have an impact on the cross-transmission of certain bacterial species in healthcare settings.

Experimental Parameters Influence the Observed Antimicrobial Response of Oak Wood (Quercus petraea).

The present investigation aimed to utilize a direct wood disc diffusion method to study the influence of plane of cutting, cutting method, sterilization method, and origin of tree on the antimicrobial activity of wood material. Six oak wood trees (Quercus petraea) were collected from 3 different locations in France. They were cut into 4 mm thick slices with either transverse (RT), tangential (LT) or radial (LR) faces. Round discs (diameter 9.95 ± 0.1 mm) were cut from the slices via a laser machine or a manual punch machine, and were sterilized with gamma irradiation (25 kGy) or autoclaving (121 °C). The antimicrobial activity of wood was tested using a direct diffusion method against Staphylococcus aureus and Acinetobacter baumannii isolates. The zone of inhibition around the wooden disc was recorded following the recommendations used for antibiotics tests. The results showed that S. aureus was more susceptible than A. baumannii, to the chemicals that diffused from the wood. The transverse face discs exhibited higher antimicrobial activity. Samples that had been sterilized by autoclaving showed significantly (p < 0.05) lower antimicrobial activity, whereas the cutting method and origin of tree did not influence the antimicrobial activity of wood material. Therefore, the choice of sterilization method and cutting planes must be taken into account while studying and interpreting the antibacterial properties of wood material.

Performance of penicillinase detection tests in Staphylococcus epidermidis: comparison of different phenotypic methods.

BACKGROUND: Staphylococcus epidermidis is the leading coagulase negative staphylococci (CoNS) species associated with healthcare associated infections. In order to de-escalate antimicrobial therapy, isolates of S. epidermidis lacking the blaZ gene should be eligible for targeted antimicrobial therapy. However, testing the susceptibility of coagulase negative staphylococci (CoNS) to penicillin G is no longer recommended by EUCAST, given the low performances for penicillinase detection in CoNS. The objective of this work was to determine a phenotypic method with high performance for detecting penicillinase production in S. epidermidis. RESULTS: Four techniques for the detection of penicillinase production (disk diffusion, zone edge test, nitrocefin test, Minimal Inhibitory Concentration (MIC) by automated system Vitek2®) were evaluated on 182 S. epidermidis isolates, using identification of blaZ gene by PCR as the reference method. The performance of the methods for penicillinase detection was compared by the sensitivity, the specificity, the negative predictive value and the positive predictive value, and with Cohen's kappa statistical test. Among the 182 S. epidermidis included in this study, 55 carried the blaZ gene. The nitrocefin test, characterized by a poor sensitivity (91%), was therefore excluded from S. epidermidis penicillinase detection. The algorithm proposed here for the penicillinase detection in S. epidermidis involved two common antimicrobial susceptibility techniques: disk diffusion method and MIC by Vitek2® system. Disk diffusion method, interpreted with a 26 mm breakpoint for penicillin G, was associated with a high sensitivity (98%) and specificity (100%). This method was completed with zone edge test for S. epidermidis with penicillin G diameter from 26 to 35 mm (sensitivity of 98%). The Vitek2® system is associated with a low sensitivity (93%) and a high specificity (99%) This low sensitivity is associated with false negative results, in isolates with 0.12 mg/L Penicillin G MIC values and blaZ positive. Thus for penicillin G MIC of 0.06 mg/L or 0.12 mg/L, a second step with disc diffusion method is suggested. CONCLUSIONS: According to our results, the strategy proposed here allows the interpretation of penicillin G susceptibility in S. epidermidis isolates, with an efficient detection of penicillin G resistance.