BedBiopsy: Diagnostic performance of bedside ultrasound-guided bone biopsies for the management of diabetic foot infection.

OBJECTIVE: We aimed to assess the feasibility and diagnostic performance of ultrasound-guided bone biopsies at the bedside of diabetic patients admitted for suspected foot osteitis not requiring surgery. RESEARCH DESIGN AND METHODS: In this retrospective monocentric study, we compared the performance of ultrasound-guided (n = 29 consecutive patients, Dec.2020-Oct.2022) versus surgical (n = 24 consecutive patients, Jan.2018-Nov.2020) bone biopsies at confirming or ruling out diabetic foot osteitis (primary outcome). RESULTS: Patient characteristics were similar in the two intervention groups, including arteritis prevalence (62.3 %), SINBAD score, and wound location (phalanges 36 %, metatarsus 43 %, and calcaneus 21 %). However, the ultrasound-guided group was older (67 ± 11 versus 60 ± 13 years respectively, P = 0.047) and had more type 2 diabetes (97 % versus 75 %, P = 0.038). Diagnostic performance (i.e., capacity to confirm or rule out suspected osteitis) was similar for ultrasound-guided (28/29 cases: 25 confirmations, 3 invalidations) and surgical (24 confirmations/24) biopsies, P = 0.358. No biopsy-related side effect or complication was observed for either intervention, even for patients on antiaggregation and/or anticoagulation therapy. The mean (± standard deviation) time necessary to perform the biopsy was shorter in the ultrasound-guided group (2.6 ± 3.0 versus 7.2 ± 5.8 days, respectively, P < 0.001) and wound evolution at three months was more favorable (83.3 versus 41.2 %, P = 0.005) (94.4 % versus 66.7 %, respectively, patients with new surgical procedure within six months excluded; P = 0.055). Even though not statistically significant, healing rates in terms of wound and osteitis at six months were also better in the ultrasound-guided group (wound: 40.9 % versus 36.8 %; P = 0.790, and osteitis: 81.8 vs 55.6 % P = 0.071). CONCLUSION: In diabetic patients with suspected foot osteitis not requiring surgery, bedside ultrasound-guided bone biopsies may constitute a promising alternative to surgical biopsies. This intervention provided excellent tolerance and microbiological documentation, short lead-times, and more favorable wound prognosis.

HIV-1 infection in South Kivu (Democratic Republic of Congo): high genotypic resistance to antiretrovirals.

BACKGROUND: Panzi General Reference Hospital (HGR Panzi) in the Democratic Republic of Congo follows a large number of patients living with HIV-1 (PLWHIV). Although antiretrovirals (ARVs) are available, HIV-1 viral load (HIV-VL) measurement has only been implemented in the hospital since 2018. No data on ARV resistance levels and ARV dosage in plasma have yet been published for this region. We determined the prevalence of virological failure due to ARV resistance amongst patients and assessed the degree of genotypic resistance of the viral strains. METHODS: We performed an HIV-VL test and determined dosage of ARVs on samples collected from 205 PLWHIV at HGR Panzi between 2017 and 2018, including 13 ARV-naive patients. Genotypic resistance testing was performed on all samples with detectable HIV-VLs, and interpreted with the Agence Nationale de Recherches sur le Sida (ANRS) 2018 algorithm. RESULTS: Baseline resistance to NNRTIs was found in 2 of the 13 treatment-naive individuals (15%). ARV dosage was non-optimal for 44/192 of treated patients (22.9%), with an HIV-VL ≥1000 IU/mL for 40/192 (20.8%) of them. In particular, treatment-experienced viruses presented resistance to at least one NRTI (52.5%), to at least one NNRTIs (70%) or to at least one PIs (15%). Finally, two samples contained viruses with resistance polymorphism in the integrase gene. CONCLUSIONS: The high level of resistance to ARVs observed during this study, mainly due to treatment compliance default, fully justifies the implementation of means for closer patient monitoring. The provision of VL tests and therapeutic education management tools in a PLWHIV follow-up remains an absolute necessity to best adapt the current treatment lines in this region.

Safety and efficacy of switching to elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate in treatment-experienced people with HIV: a multicenter cohort study.

OBJECTIVES: We assessed the virologic efficacy of switching to co-formulated elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate (E/C/F/TDF) in patients with controlled HIV infection. METHODS: We conducted a retrospective multicenter observational cohort study including adult patients with controlled HIV-1 infection on any stable antiretroviral (ART) regimen, who switched to E/C/F/TDF. Success was measured by the proportion of patients with plasma viral load < 50 copies/ml at W48 using the FDA snapshot algorithm. We also assessed risk factors associated with virological failure (VF). RESULTS: 382 patients with HIV RNA < 50 copies/mL who switched to E/C/F/TDF were included in the study. Most patients (69.9%) were male, with median age 44 years (IQR 38-51), who had been on ART for a median of 7 years (IQR 4-13). Median CD4 count was 614/mm3 and 24.6% of the patients had a history of previous virological failure. The reasons for switching were simplification (67.0%) and tolerance issues (22.0%). At week 48, 314 (82.0% [95% CI 78.4-86.0]) patients had HIV RNA < 50 copies/mL, 13 (3.5% [95% CI 3.64-8.41]) experienced virological failure. Genotype at failure was available in 6/13 patients with detection of resistance-associated mutations to integrase inhibitors and NRTIs in 5/6 (83.3%) patients. We found no predictive factor associated with virological failure except for a borderline significance with the duration of viral suppression before the switch. Tolerability of E/C/F/TDF was good with 23/382 (6.0%) patients experiencing mild adverse reactions. CONCLUSION: In our cohort, switching well-suppressed patients to E/C/F/TDF resulted in few virologic failures and was well tolerated. However, resistance to integrase inhibitors emerged in patients with virological failure.

Association Between Increased Linezolid Plasma Concentrations and the Development of Severe Toxicity in Multidrug-Resistant Tuberculosis Treatment.

BACKGROUND: Treatment of multidrug-resistant (MDR) tuberculosis with linezolid is characterized by high rates of adverse events. Evidence on therapeutic drug monitoring to predict drug toxicity is scarce. This study aimed to evaluate the association of linezolid trough concentrations with severe toxicity. METHODS: We retrospectively assessed consecutive patients started on linezolid for MDR tuberculosis between 2011 and 2017. The primary outcome was severe mitochondrial toxicity (SMT) due to linezolid, defined as neurotoxicity or myelotoxicity leading to drug discontinuation. The impact of plasma linezolid trough concentrations >2 mg/L was assessed in multivariate Cox proportional hazards models including time-varying covariates. RESULTS: SMT occurred in 57 of 146 included patients (39%) at an incidence rate of 0.38 per person-year (95% confidence interval, .30-.49). A maximum linezolid trough concentration >2 mg/L was detected in 52 patients (35.6%), while the mean trough concentration was >2 mg/L in 22 (15%). The adjusted hazard ratio for SMT was 2.35 (95% confidence interval, 1.26-4.38; P = .01) in patients with a mean trough concentration >2 mg/L and 2.63 (1.55-4.47; P < .01) for SMT after the first detection of a trough concentration >2 mg/L. In an exploratory analysis, higher maximum trough concentrations were dose-dependently associated with toxicity, while lowering elevated trough concentrations did not restore baseline risk. CONCLUSIONS: Linezolid trough concentrations >2 mg/L are strongly associated with the development of severe treatment-emergent toxicity in patients treated for MDR tuberculosis. Pending further prospective evidence, an individual risk-benefit assessment on the continuation of linezolid treatment is warranted in any patient with trough concentrations >2 mg/L.

Automated HPLC-MS/MS assay for the simultaneous determination of ten plasma antibiotic concentrations.

Therapeutic drug monitoring (TDM) of antibiotics (ATB) in patients with serious bacterial infections allows optimization of the efficacy of the treatment while reducing the risk of toxicity. Notably, early measurement of plasma beta-lactam concentration has been shown to be associated with reduced mortality in intensive care patients. In this context, a rapid, robust, and accurate assay method is essential for daily TDM. A fully automated procedure for quantification of the plasma concentrations of ten ATB was developed. The ATB were divided into two calibration pools, with Pool 1: aztreonam, ceftobiprole, cefoxitin, avibactam, tazobactam and Pool 2: metronidazole, ceftriaxone, daptomycin, ceftolozane, moxifloxacin. Sample preparation consisting of acetonitrile plasma protein precipitation and H20 dilution was applied to all analytes. This procedure was carried out by an automated sample preparation system directly coupled to a liquid chromatography-tandem mass spectrometry (LC-MS/MS) system. Since the instrument extracts sample n while sample n-1 is in the LC-MS/MS system, the delay between obtaining the results for two samples corresponds to the analytical run time, which is less than 7 min. The method was validated according to the Food and Drug Administration guidelines. The method was sensitive (lower limit of quantification 0.1-1 mg/L, depending on the ATB), accurate (intra/inter-assay bias -14.8 to 14.2 %) and precise (intra/inter-assay CVs 1.27 to 16.3 %). Application of the TDM assay was illustrated by the report of an intensive care patient treated with the ceftazidime/aztreonam/avibactam combination. Four assays were performed in 8 days with results returned within 24 h to quickly manage the dose regimen in this patient. An automated, simple, rapid, robust LC-MS/MS analysis was developed and validated for the simultaneous quantification of plasma concentrations of 10 ATB and was applied with success to perform TDM. This method provides a shorter turnaround time than classic sample batch-based analytical methods.

Revised Definitions of Tuberculosis Resistance and Treatment Outcomes, France, 2006-2019.

Definitions of resistance in multidrug-resistant tuberculosis (MDR TB) and extensively drug-resistant tuberculosis (XDR TB) have been updated. Pre-XDR TB, defined as MDR TB with additional resistance to fluoroquinolones, and XDR TB, with additional resistance to bedaquiline or linezolid, are frequently associated with treatment failure and toxicity. We retrospectively determined the effects of pre-XDR/XDR TB resistance on outcomes and safety of MDR TB treatment in France. The study included 298 patients treated for MDR TB at 3 reference centers during 2006-2019. Of those, 205 (68.8%) cases were fluoroquinolone-susceptible MDR TB and 93 (31.2%) were pre-XDR/XDR TB. Compared with fluoroquinolone-susceptible MDR TB, pre-XDR/XDR TB was associated with more cavitary lung lesions and bilateral disease and required longer treatment. Overall, 202 patients (67.8%) had favorable treatment outcomes, with no significant difference between pre-XDR/XDR TB (67.7%) and fluoroquinolone-susceptible MDR TB (67.8%; p = 0.99). Pre-XDR/XDR TB was not associated with higher risk for serious adverse events.

Use of Whole-Genome Sequencing to Explore Mycobacterium tuberculosis Complex Circulating in a Hotspot Department in France.

The Seine-Saint-Denis is the French metropolitan department with the highest incidence of tuberculosis (TB). Our aim was to explore epidemiological and phylogenetic characteristics of TB strains in this hotspot department. We performed WGS on 227 strains of Mycobacterium tuberculosis complex isolated from patients at the Avicenne Hospital from 2016 to 2021 and randomly selected to represent the clinical diversity of French TB localization. Clinical and demographic data were recorded for each TB patient. The mean age of patients was 36 years old. They came from Africa (44%), Asia (27%), Europe (26%) and America (3%). Strains isolated from extrapulmonary samples were associated with Asian patients, whereas strains isolated from pulmonary samples were associated with European patients. We observed a high level of lineage diversity in line with the known worldwide diversity. Interestingly, lineage 3 was associated with lymph node TB. Additionally, the sensitivity of WGS for predicting resistance was 100% for rifampicin, isoniazid and ethambutol and 66.7% for pyrazinamide. The global concordance with drug-susceptibility testing using the phenotypic approach was 97%. In microbiology laboratories, WGS turns out to be an essential tool for better understanding local TB epidemiology, with direct access to circulating lineage identification and to drug susceptibilities to first- and second-line anti-TB drugs.

Invasive Rhinosinusitis Caused by Alternaria infectoria in a Patient with Autosomal Recessive CARD9 Deficiency and a Review of the Literature.

Phaeohyphomycoses comprise a heterogeneous group of fungal infections caused by dematiaceous fungi and have primarily been reported in patients with underlying acquired immunodeficiencies, such as hematological malignancies or solid-organ transplants. Over the past decade, a growing number of patients with phaeohyphomycosis but otherwise healthy were reported with autosomal recessive (AR) CARD9 deficiency. We report a 28-year-old woman who presented with invasive rhinosinusitis caused by Alternaria infectoria. Following a candidate gene sequencing approach, we identified a biallelic loss-of-function mutation of CARD9, thereby further broadening the spectrum of invasive fungal diseases found in patients with inherited CARD9 deficiency. In addition, we reviewed 17 other cases of phaeohyphomycosis associated with AR CARD9 deficiency. Physicians should maintain a high degree of suspicion for inborn errors of immunity, namely CARD9 deficiency, when caring for previously healthy patients with phaeohyphomycosis, regardless of age at first presentation.

Brief Report: Efficacy and Safety of Efavirenz, Raltegravir, and Dolutegravir in HIV-1/TB Coinfection. A Multicenter Retrospective Cohort Study in France.

BACKGROUND: There are limited data comparing the efficacy and safety of raltegravir and dolutegravir to that of efavirenz in HIV-1/tuberculosis (TB) coinfected patients. METHODS: We conducted a 10-year retrospective study in 4 centers in France. We included all HIV-1/tuberculosis coinfected patients starting antiretroviral therapy with a rifampicin-based regimen, with a plasma HIV RNA level (VL) > 1000 copies/mL. The primary endpoint was the proportion of patients with virological success that is, with VL <50 copies/mL at W48 using an Intention-To-Treat analysis, using last-observation-carried-forward to impute missing data. We also assessed antiretroviral therapy safety, analyzing treatment discontinuation for adverse events. RESULTS: Between 2010 and 2020, 117 patients were included. Thirty-nine (33.3%) were treated with raltegravir and 2 nucleoside reverse transcriptase inhibitors (NRTIs), 19 (16.2%) with dolutegravir (and 2 NRTIs) and 59 (50.4%) with efavirenz (and 2 NRTIs). At W48, the primary endpoint was achieved in 24 patients (61.5%) in the raltegravir group, in 12 (63.2%) in the dolutegravir group, and in 41 (69.5%) in the efavirenz group using an Intention-To-Treat analysis ( P = 0.68). Emergence of drug resistance in patients with virological failure, defined as a VL >50 copies/mL, was observed in 3 patients with efavirenz and one patient with raltegravir. Rate of treatment discontinuation for drug-related adverse events was 10.3%, 10.6%, 16.9% for raltegravir, dolutegravir and efavirenz respectively ( P = 0.67). CONCLUSIONS: In this retrospective cohort study, raltegravir and dolutegravir yielded similar efficacy and safety results to efavirenz for the treatment of HIV-1/TB coinfected patients.

Impaired antibody response to COVID-19 vaccination in advanced HIV infection.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) vaccination is reportedly efficient in people with HIV (PWH) but vaccine trials included participants with normal CD4+ T-cell counts. We analyzed seroconversion rates and antibody titers following two-dose vaccination in PWH with impaired CD4+ T-cell counts. METHODS: We collected retrospective postvaccination SARS-COV-2 serology results available in a university hospital for PWH vaccinated between March and September, 2021 who were tested for antispike antibodies from 8 to 150 days following dose 2. Antibody titers were compared in PWH with CD4+ T-cell count less than 200 cells/µl, 200 < CD4+ T-cell counts < 500 cells/µl and CD4+ T-cell count greater than 500 cells/µl at vaccination. RESULTS: One hundred and five PWH were included: n = 54 in the CD4+ T-cell count less than 500 cells/µl group (n = 18 with CD4+ <200 cells/µl, n = 36 with 200 < CD4+ < 500 cells/µl) and 51 in the CD4+ T-cell count greater than 500 cells/µl group. They received two doses of BNT162b2 (75%), mRNA-1273 (8.5%), or ChAdOx1 nCoV-19 (16.5%). The median time from vaccine dose 2 to serology was consistent across all groups (73 days, interquartile range [29-97], P = 0.14). Seroconversion rates were 100% in the CD4+ T-cell count greater than 500 cells/µl group but 89% in participants with CD4+ T-cell counts less than 500 cells/µl (22 and 5.5% seronegative in the CD4+ T-cell counts <200 cells/µl and 200 < CD4+ < 500 cells/µl groups, respectively). Median antibody titers were 623.8 BAU/ml [262.2-2288] in the CD4+ greater than 500 cells/µl group versus 334.3 BAU/ml [69.9-933.9] in the CD4+ less than 500 cells/µl group (P = 0.003). They were lowest in the CD4+ less than 200 cells/µl group: 247.9 BAU/ml [5.88-434.9] (P = 0.0017) with only 44% achieving antibody titers above the putative protection threshold of 260 BAU/ml. CONCLUSION: PWH with CD4+ T-cell counts less than 500 cells/µl and notably less than 200 cells/µl had significantly lower seroconversion rates and antispike antibody titers compared with PWH with CD4+ T-cell counts greater than 500 cells/µl, warranting the consideration of targeted vaccine strategies in this fragile population.

[ 18 F]FDG Positron Emission Tomography for Initial Staging and Healing Assessment at the End of Therapy in Lymph Nodes and Bone Tuberculosis.

Objective: In extra-pulmonary tuberculosis, therapeutic management is difficult in the absence of reliable tool to affirm healing at the end of treatment. In this prospective multicenter study, we evaluated [18F]FDG-PET for this purpose. Methods: Forty-two patients out of 55 included patients could be analyzed. Additionally to usual biological, histological and morphological explorations, [18F]FDG-PET was performed at diagnosis (PET1), at the end of treatment (PET2), indeed 6 months later. Then patients were followed until 12 months after end of prescribed treatment. Results: PET1 was positive in 97.6% of patients and discovered unknown injured sites in 52.7% of cases. PET2 was positive in 83.3% of uncured patients, and in 82.3% of cured patients. The sum and mean value of SUVmax measured in PET/CT lesions decreased between PET1 and PET2 in all patients. Mean value of SUVmax (MSUV) and sum value of SUVmax on PET2 showed the highest AUC on ROC curves for the diagnosis of healing at the end of prescribed treatment; MSUV 3.5 on PET2 had a sensitivity of 76.5% and a specificity of 80.0% to affirm healing at the end of prescribed treatment. Conclusions: [18F]FDG-PET/CT was useful at diagnosis, discovering unknown lesions in 52.7% of cases. MSUV on PET2 was the best criteria to affirm healing at the end of prescribed treatment.

Lymphoma in HIV-2-infected patients in combination antiretroviral therapy era.

OBJECTIVE: To describe lymphoma in HIV-2-infected patients and compare their characteristics with lymphoma in HIV-1-infected patients. DESIGN: Ancillary analysis from a single center prospective cohort of HIV-lymphoma. METHODS: We report on 16 patients with HIV-2-lymphoma diagnosed after 1996 and included in a prospective cohort of HIV lymphoma. Five additional HIV-2-infected patients coinfected with HIV-1 or/and HTLV-I (6 lymphomas) are separately reported. The incidence of lymphoma in HIV-2-infected patients was evaluated in the French multicentric HIV-2 cohort. RESULTS: Incidence of lymphoma in the French HIV-2 cohort was estimated as 0.6/1000 patient-years. In our series, the median CD4+ cell count was 166 × 106/l at the time of lymphoma diagnosis and 50% of patients had undetectable plasma HIV-2-RNA. Lymphomas were non-Hodgkin lymphoma (n = 12) and classical Hodgkin lymphoma (n = 4). Similarly to HIV-1-lymphoma, clinical presentation was aggressive in most cases. All but one patient received intensive chemotherapy. Complete remission was achieved in 13 cases and 1 patient relapsed. The overall survival was not statistically different from that observed in patients with HIV-1 lymphoma. The six additional lymphomas observed in five HIV-2-infected patients coinfected with HIV-1 or/and HTLV-I presented with similar clinical presentation but worse prognosis. CONCLUSION: Despite the lower pathogenicity of HIV-2, the risk of developing lymphoma seems to be close to that observed in HIV-1 population with similar lymphoma characteristics. Compared with HIV-1, HIV-2-infected patients developed lymphoma later in their life but at a similar CD4+ cell count level.

Molecular characterization and genetic diversity of Loa loa parasites responsible of a long-delayed filarial infection in an immigrant patient inhabited in Paris.

A 21-year-old young boy who lived alone since one year and a half ago in Paris was referred due to severe vertigo. He is originally from Ivory Coast but lived from 2011 to 2017 in Douala city in west of Cameroon. Beside vertigo, he complained from headache, sudden abdominal pain and edema in both left and right forearms for about two years. General examination demonstrated a healthy condition with no subcutaneous nodules and swelling on any other part of the body, not splenomegaly or lymphadenopathy. Moreover, the eyes were normal with clear lens. Blood count analysis revealed a hypereosinophilia (2670*106/L, N: <500*106/L). A couple of direct and May-Grunwald-Giemsa stained smears, analyzed by microscopy revealed the semitransparent cylindrical worms with almost 300 µm length and 45 µm width identified as Loa loa. The identity of the worm was then confirmed by bidirectional sequencing of 450 bp fragment of internal transcribed spacer 1 (ITS1-rDNA). Based on Neighbor-Joining phylogenetic tree, our isolate was clustered tightly with other few Loa species from Gabon in the same clade. No hybrid was observed among processed sequences since all species groups were discriminated separately. In the current case, he was originally from Ivory Coast but absence of medical and epidemiological evidences as well as the residency of our patient for 6 years in Cameroon made us suspicious that the patient has been most likely infected by L. loa worms in this country. The patient was treated by a couple of ivermectin (200 µg/kg for 3 days) and diethylcarbamazine (3 mg/kg, 2 times per day for 4 weeks) and a favorable evolution was observed within few weeks. Regarding at least one year and a half interval between the probable Loa loa infection in Cameroon and diagnosis, Loa loa worms are competent to persist in the human host for several years. Consequently, the clinicians should be aware of this parasitosis among the travelers or immigrants coming from endemic regions in Africa.

Management of Tuberculosis: Are the Practices Homogeneous in High-Income Countries?

Objectives: To evaluate and compare practices regarding the diagnosis, isolation measures, and treatment of tuberculosis (TB) in high-income countries and mainly in Europe. Materials and Methods: A survey was conducted from November 2018 to April 2019 within the European Society of Clinical Microbiology and Infectious Diseases Study Group for Mycobacterial Infections (ESGMYC). The practices observed were compared to the main international guidelines. Results: Among 136 ESGMYC members, 64 (17 countries) responded to the questionnaire. In their practice, two (20.7%) or three sputum samples (79.3%) were collected for the diagnosis of pulmonary TB, alternatively induced sputum (n = 37, 67.2%), bronchoscopy (34, 58.6%), and gastric aspirates (15, 25.9%). Nucleic acid amplification tests (NAATs) were performed by 41 (64%) respondents whatever the smear result and by 47 (73%) in case of smear-positive specimens. NAAT and adenosine deaminase measurement were used for extrapulmonary TB diagnosis in 83.6 and 40.4% of cases, respectively. For isolation duration, 21 respondents (42.9%) were keeping isolation until smear negativity. An initial treatment without ethambutol was offered by 14% (n = 9) of respondents. Corticosteroid therapy, cerebrospinal fluid opening pressure testing, and repeated lumbar puncture were carried out for central nervous system TB by 79.6, 51.9, and 46.3% of the respondents, respectively. For patients with human immunodeficiency virus-TB coinfection, the preferred antiretroviral therapy included dolutegravir 50 mg twice a day (56.8%). Comparing with the recommendations of the main guidelines, the practices are not totally consistent. Conclusion: This study shows heterogeneous practices, particularly for diagnosis, and isolation, although rapid molecular testing is implemented in most centers. More standardization might be needed.

AntibioGame®: A serious game for teaching medical students about antibiotic use.

INTRODUCTION: Measures for controlling antimicrobial resistance are urgently required. We describe here AntibioGame®, a serious game for improving the training of medical students in antibiotic use in primary care. OBJECTIVE: We aimed to design a serious game for antibiotics teaching and to evaluate its usability and playability by medical students. METHODS: We used various gamification techniques (e.g. use of mascots, avatars, rewards, leader board) and cartoon graphics in the design of AntibioGame®. This game implements clinical case templates built from a list of learning goals defined by a medical team through an analysis of clinical practice guidelines. The game was evaluated by asking medical students to rate their satisfaction and the usability and playability of the game on an electronic form and through group discussions. The electronic form was derived from the MEEGA + scale, a five-point Likert scale including 32 items for assessing both usability and playability. RESULTS: AntibioGame® is a case-based game in which students play the role of a doctor meeting patients in consultation and helping other health professionals to solve their problems, as in real life. The scenarios are realistic and cover situations frequently encountered in primary care. The 57 medical students enrolled found the game attractive, usable, fun, and appropriate for learning. Game quality was considered "good" (score = 60 on the MEEGA + scale). All the students said they would recommend the game, 96 % liked it and 81 % would use it for revision. CONCLUSION: AntibioGame® is a promising tool for improving knowledge in antibiotic prescription that could easily be included in multifaceted programs for training medical students.

Helping GPs to extrapolate guideline recommendations to patients for whom there are no explicit recommendations, through the visualization of drug properties. The example of AntibioHelp® in bacterial diseases.

INTRODUCTION: Clinical decision support systems (CDSS) implementing clinical practice guidelines (CPGs) have 2 main limitations: they target only patients for whom CPGs provide explicit recommendations, and their rationale may be difficult to understand. These 2 limitations result in poor CDSS adoption. We designed AntibioHelp® as a CDSS for antibiotic treatment. It displays the recommended and nonrecommended antibiotics, together with their properties, weighted by degree of importance as outlined in the CPGs. The aim of this study was to determine whether AntibioHelp® could increase the confidence of general practitioners (GPs) in CPG recommendations and help them to extrapolate guidelines to patients for whom CPGs provide no explicit recommendations. MATERIALS AND METHODS: We carried out a 2-stage crossover study in which GPs responded to clinical cases using CPG recommendations either alone or with explanations displayed through AntibioHelp®. We compared error rates, confidence levels, and response times. RESULTS: We included 64 GPs. When no explicit recommendation existed for a particular situation, AntibioHelp® significantly decreased the error rate (-41%, P value = 6x10-13), and significantly increased GP confidence (+8%, P value = .02). This CDSS was considered to be usable by GPs (SUS score = 64), despite a longer interaction time (+9-22 seconds). By contrast, AntibioHelp® had no significant effect if there was an explicit recommendation. DISCUSSION/CONCLUSION: The visualization of weighted antibiotic properties helps GPs to extrapolate recommendations to patients for whom CPGs provide no explicit recommendations. It also increases GP confidence in their prescriptions for these patients. Further evaluations are required to determine the impact of AntibioHelp® on antibiotic prescriptions in real clinical practice.