Importance:Progressive multifocal leukoencephalopathy (PML) is a life-threatening demyelinating disease caused by reactivation of the JC virus (JCV) in immunocompromised patients. While immune checkpoint inhibitors (ICIs) show therapeutic potential, responses vary and predictive biomarkers are lacking. Objective:To determine whether pretreatment JCV- and/or BK virus-specific T cells in the blood are associated with treatment efficacy. Design, Setting, and Participants:This retrospective cohort study included 111 patients with PML who were treated with ICIs stratified by peripheral virus-specific T cell presence (ELISpot/flow cytometry) between August 2021 and May 2024, with a median (IQR) follow-up of 7 (1-13) months. Of 112 patients with definite PML across 39 centers, 1 patient refused participation; 111 patients were included. Exposure:Patients received pembrolizumab (n = 81), nivolumab (n = 28), or atezolizumab (n = 2) per availability and prescribing practices at participating centers. Main Outcome and Measures:Clinical outcomes, diagnostic parameters, and immune-related adverse events were compared; association of virus-specific T-cell responses with survival was analyzed using the Kaplan-Meier method. Results:The study cohort consisted of 111 patients (median [IQR] age, 61 [50-70] years; 74 male [66.6%]). Twenty-one patients had detectable virus-specific T cells prior to therapy, 22 were T cell-negative and 68 had an unknown T-cell status. T cell-positive patients showed significantly higher response rates and improved survival compared to both T cell-negative patients (18/21 [86%] vs 5/22 [23%]; P < .001; median survival time, none [95% CI, undefined] vs 136.5 days [95% CI, 19 to ∞]; P = .002) and those with unknown T-cell status (18/21 [86%] vs 29/68 [43%]; P = .001; median survival time, none vs 162 days [95% CI, 66 to ∞]; P = .004). They achieved better functional outcomes (median [IQR] modified Rankin Scale score, 3 [2-4] vs 4 [3-6]; P = .009) and lower JC viral load in cerebrospinal fluid (median [IQR], 0 copies/mL [0-502.5] vs 2500 copies/mL [0-6900]; P = .01) during follow-up compared to T cell-negative patients. Immune-related adverse events were most frequent in T cell-negative patients (10/20 [50%]), including the most severe events, and least frequent in T cell-positive patients (2/20 [10%]) (P = .02). Conclusions and Relevance:Preexisting functional virus-specific T cells were associated with better clinical response, longer survival, and lower toxicity in PML. These findings suggest the likely importance of preexisting antiviral immunity for successful ICI therapy.

La phagothérapie, qui utilise des bactériophages pour traiter les infections bactériennes, connaît un regain d’intérêt face à l’antibiorésistance et aux infections liées au biofilm. Nous avons réalisé une revue des publications (2019–2025) concernant l’utilisation clinique de phages de qualité pharmaceutique produits selon les bonnes pratiques de fabrication. Près de 500 patients ont été rapportés, principalement dans des infections sévères à bactéries multirésistantes. Huit essais cliniques publiés totalisent 135 patients, majoritairement en phase précoce, tandis que de nombreux essais restent en cours ou non publiés. En France, le programme « PHAGEinLYON Clinic » a centralisé 786 avis et permis le traitement compassionnel de 135 patients, surtout pour des infections ostéoarticulaires, pulmonaires et des bactériémies/endocardites. Les données disponibles indiquent une bonne tolérance et des signaux d’efficacité encourageants, mais le niveau de preuve demeure limité. Le développement d’essais cliniques adaptés à cette approche personnalisée est indispensable pour définir la place de la phagothérapie dans l’arsenal thérapeutique moderne.

Mycoplasma pneumoniae (MP), primarily a respiratory pathogen, can cause extra-pulmonary manifestations including cold agglutinin syndrome (CAS). We conducted a national, multicenter, observational, ambispective study to describe the characteristics, risk factors, and outcomes of MP-associated CAS. Adult patients hospitalized for a MP-infection with CAS (hemolytic anemia with hemoglobin < 10 g/dL and C3 positive direct anti-globulin test) were included. Recovery was defined as hemoglobin > 10 g/dL off therapy. We also compared MP-infected patients with or without CAS. Sixty patients (51.7% of females; median age of 48.5 years) were included. CAS was diagnosed a median of 10 days after MP-infection symptoms onset. At diagnosis, the median hemoglobin level was 6.9 g/dL, and 71.7% of patients received red blood cell transfusions. Intensive care unit (ICU) admission was required in 45% of patients, and 16.7% experienced a venous thromboembolic event (VTE). Seventeen patients (28.3%) received glucocorticoids alone, while 40 (66.7%) did not receive any specific treatment for CAS. After a median follow-up of 56 (30-83) days, 90% of patients achieved recovery, while 2 patients (3.3%) died from sepsis and pulmonary embolism. Glucocorticoid use did not significantly impact the rate or timing of recovery. Compared with MP-infected patients from the MYCADO cohort study (n = 1267), CAS patients had significantly more VTE (p < 0.0001) and ICU admissions (p = 0.03). MP-associated CAS typically occurs 10 days after the first symptoms of MP infection and is associated with ICU admissions and VTE. Overall, the prognosis of CAS is good, and glucocorticoids do not appear to influence outcomes.

Background An epidemic of Mycoplasma pneumoniae infection has been observed in France since September, 2023. We aimed to describe the characteristics of adults hospitalised for M pneumoniae infection and identify factors associated with severe outcomes of infection. Methods MYCADO is a retrospective observational study including adults hospitalised for 24 h or more in 76 hospitals in France for a M pneumoniae infection between Sept 1, 2023, and Feb 29, 2024. Clinical, laboratory, and imaging data were collected from medical records. We identified factors associated with severe outcomes of infection, defined as a composite of intensive care unit (ICU) admission or in-hospital death, using multivariable logistic regression. Findings 1309 patients with M pneumoniae infection were included: 718 (549%) were men and 591 (451%) were women; median age was 43 years (IQR 31-63); 288 (220%) had chronic respiratory failure; 423 (323%) had cardiovascular comorbidities; and 105 (80%) had immunosuppression. The most common symptoms were cough (1098 [839%]), fever (1023 [782%]), dyspnoea (948 [724%]), fatigue (550 [420%]), expectorations (473 [361%]), headache (211 [161%]), arthromyalgia (253 [193%]), ear, nose, and throat symptoms (202 [154%]), diarrhoea (138 [105%]), and vomiting (132 [101%]). 156 (119%) of 1309 patients had extra-respiratory manifestations, including 36 (28%) with erythema multiforme, 19 (15%) with meningoencephalitis, 44 (34%) with autoimmune haemolytic anaemia, and 17 (13%) with myocarditis. The median hospital stay was 8 days (IQR 6-11). 424 (324%) patients had a severe outcome of infection, including 415 (317%) who were admitted to the ICU and 28 (21%) who died in hospital. Those more likely to present with severe outcomes of infection were patients with hypertension, obesity, chronic liver failure, extra-respiratory manifestations, pulmonary alveolar consolidation or bilateral involvement on CT scan, as well as elevated inflammatory markers, lymphopenia or neutrophilic polynucleosis, and those who did not versus did receive any antibiotic active against M pneumoniae before admission. Interpretation This national, observational study highlighted unexpected, atypical radiological presentations, a high proportion of transfers to the ICU, and an association between severity and delayed administration of effective antibiotics. This should remind clinicians that no radiological presentation can rule out M pneumoniae infection, and encourage them to reassess patients early after prescribing a beta-lactam, or even to discuss prescribing macrolides as first-line treatment in the context of an epidemic. Copyright (c) 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

Introduction Mycoplasma pneumoniae (MP) is mostly responsible for infections of the lower respiratory tract but can also be associated with extrapulmonary manifestations, including cold antibody autoimmune hemolytic anemia (cAIHA). While the detection of cold agglutinins (CA) is relatively common in MP infection, symptomatic and/or severe forms of cAIHA are rare in this context. This association is poorly described in the literature as no large series of patients have been reported so far. The outbreak of MP infections that occurred in Northern Europe and France during last fall and winter gave rise to an unusual number of MP-associated cAIHAs. The aim of this study were to better describe the characteristics, the management and outcome of patients diagnosed with MP-associated cAIHA. and to assess the usefulness of glucocorticoids (GC) in this setting. Patients and Methods We conducted an ambispective (retrospective and prospective), observational, multicenter, national study. Patients were recruited by i) call for observations throughout the network of the French national society of internal medicine (SNFMI) and the French reference center for autoimmune cytopenias (CERECAI) and ii) identification of cases included in the MYCADO study (a large national multicenter observational study of MP infections). To be included, patients had to be 18 years of age or older, have a confirmed MP infection requiring hospitalization associated with cAIHA, with a nadir hemoglobin (Hb) level < 10 g/dL and a positive direct antiglobulin test with a C3d pattern. Results In total, 50 patients (50% of females, with a median age [IQR] of 47 [38.5-63.5] years) at diagnosis were included. Of these, 24 (48%) had risk factors for respiratory infection (active smoking in 16 (32%) patients, asthma in 6 (12%) others), 21 (42%) had cardiovascular risk factors (hypertension, diabetes, dyslipidemia, or obesity), 4 (8%) had a history of malignant hemopathy, and 4 (8%) patients were immunocompromised. Forty-eight (96%) patients had respiratory signs related to MP infection, 20 (40%) had gastrointestinal manifestations (31.3%), 14/40 (35%) had “dark” urine and 1 (2%) had acrocyanosis. Eight (16%) patients had venous thromboembolism (including pulmonary embolism in 7 (14%)) and 22 (44%) had to be admitted in intensive care unit. The median Hb level at cAIHA diagnosis was 7 [5.9-9.8] g/dL, with a median reticulocytes count of 90 [60-144] x 109/L, and median LDH, haptoglobin, and undirect bilirubin levels of respectively 676 [470-1358] IU/L, 0 [0-0.38] g/L and 16 [7.7-51] μmol/L. Thirty-nine (78%) patients required red blood cell (RBC) transfusions, with a mean of 3 packed RBC/patient. Nineteen (38%) patients received one or more treatments “specifically” for AIHA, including GC in 14 (25%) cases and erythropoietin in 4 (8%). All patients received antibiotics, mostly macrolides (92% of the patients) for treating MP infection MP infection resolved completely without sequelae in 43/50 (86%) cases. After a mean follow-up of 54 [27-80] days after cAIHA onset, 39/47 (83%) patients were in complete remission (defined by a stable Hb level beyond 10 g/dL off therapy), 6 (12.7%) in partial remission (defined by an increase of at least 2 g/dL of the Hb level from baseline but below 10 g/dL) and 2 (4%) patients died (one from septic shock secondary and one from pulmonary embolism). When we compared patients who did not receive any “specific” treatment for AIHA other than antibiotic ± transfusion (n=31, 62%) with those treated with GC alone (n=14, 28%), we found that patients with GC had more severe cAIHA with a lower Hb nadir (6.4 [5.9-7.4] vs. 5 [5.7-5.9] g/dl, p=0.001), a greater number of packed RBC transfused (2 [0-2] vs. 1.25 [3.5-4.75], p=0.03), and a lower rate of complete remission of cAIHA (4/14 (28.6%) vs. (26/28 (92.9%), p=0.02). However, GC did not appear to improve neither the outcome nor the time to Hb normalization in patients with MP -associated cAIHA. Conclusion These data show that cAIHA associated with MP infection is not exceptional; and that although being often initially severe, with a high rate of venous thrombotic events, it has a good prognosis and recovers (either spontaneously or after transfusion) within few weeks in parallel with the bacterial infection. Based on our study, there is no evidence suggesting that GC, which were used for the management of the most severe cases, are helpful in this setting for reducing the duration of cAIHA.

OBJECTIVES:To describe the PHAGEinLYON Clinic programme, set up in 2022 to improve access to phage therapy in France using pharmaceutical-grade phages. METHODS:All phage therapy requests received during 2022 were collected prospectively, and reviewed retrospectively to analyse the decision and the patient care pathway (NCT05883995). RESULTS:Of 143 requests for phage therapy, the indication was confirmed at a multidisciplinary team meeting for 57 (40%) patients. Forty-four patients were infected with bacteria that could be targeted easily by phages in France. Finally, 33 patients were treated, including 26 at the study institution, through a compassionate access programme or in a clinical trial. The main indication were complex bone and joint infections, endovascular infection and lung infection. In order to manage these patients, 172 pharmaceutical phage cocktails targeting Staphylococcus aureus and/or Pseudomonas aeruginosa were prepared: 57 for local injection and 99 for intravenous injection. During follow-up, 18 (69%) patients showed a favourable clinical evolution, and six (23%) patients required subsequent phage therapy, either with the same phage with greater exposure, or with a different phage from elsewhere. CONCLUSIONS:Implementation of the PHAGEinLYON Clinic programme in 2022 was associated with groundbreaking access to phage therapy in France.

BACKGROUNDWeakly virulent environmental mycobacteria (EM) can cause severe disease in HLA-DRB1*15:02 or 16:02 adults harboring neutralizing anti-IFN-γ autoantibodies (nAIGAs). The overall prevalence of nAIGAs in the general population is unknown, as are the penetrance of nAIGAs in HLA-DRB1*15:02 or 16:02 individuals and the proportion of patients with unexplained, adult-onset EM infections carrying nAIGAs.METHODSThis study analyzed the detection and neutralization of anti-IFN-γ autoantibodies (auto-Abs) from 8,430 healthy individuals of the general population, 257 HLA-DRB1*15:02 or 16:02 carriers, 1,063 patients with autoimmune disease, and 497 patients with unexplained severe disease due to EM.RESULTSWe found that anti-IFN-γ auto-Abs detected in 4,148 of 8,430 healthy individuals (49.2%) from the general population of an unknown HLA-DRB1 genotype were not neutralizing. Moreover, we did not find nAIGAs in 257 individuals carrying HLA-DRB1* 15:02 or 16:02. Additionally, nAIGAs were absent in 1,063 patients with an autoimmune disease. Finally, 7 of 497 patients (1.4%) with unexplained severe disease due to EM harbored nAIGAs.CONCLUSIONThese findings suggest that nAIGAs are isolated and that their penetrance in HLA-DRB1*15:02 or 16:02 individuals is low, implying that they may be triggered by rare germline or somatic variants. In contrast, the risk of mycobacterial disease in patients with nAIGAs is high, confirming that these nAIGAs are the cause of EM disease.FUNDINGThe Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI095983 and U19AIN1625568), the National Center for Advancing Translational Sciences (NCATS), the NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), the French National Research Agency (ANR) under the "Investments for the Future" program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), ANR-GENMSMD (ANR-16-CE17-0005-01), ANR-MAFMACRO (ANR-22-CE92-0008), ANRSECTZ170784, the French Foundation for Medical Research (FRM) (EQU201903007798), the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), and ANR AI2D (ANR-22-CE15-0046) projects, the ANR-RHU program (ANR-21-RHUS-08-COVIFERON), the European Union's Horizon 2020 research and innovation program under grant agreement no. 824110 (EASI-genomics), the Square Foundation, Grandir - Fonds de solidarité pour l'enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the Battersea & Bowery Advisory Group, William E. Ford, General Atlantic's Chairman and Chief Executive Officer, Gabriel Caillaux, General Atlantic's Co-President, Managing Director, and Head of business in EMEA, and the General Atlantic Foundation, Institut National de la Santé et de la Recherche Médicale (INSERM) and of Paris Cité University. JR was supported by the INSERM PhD program for doctors of pharmacy (poste d'accueil INSERM). JR and TLV were supported by the Bettencourt-Schueller Foundation and the MD-PhD program of the Imagine Institute. MO was supported by the David Rockefeller Graduate Program, the Funai Foundation for Information Technology (FFIT), the Honjo International Scholarship Foundation (HISF), and the New York Hideyo Noguchi Memorial Society (HNMS).

Little is known about localized osteoarticular Scedosporiosis (LOS). Most data come from case reports and small case series. Here we present an ancillary study of the nationwide French Scedosporiosis Observational Study (SOS), describing 15 consecutive cases of LOS diagnosed between January 2005 and March 2017. Adult patients diagnosed with LOS defined by osteoarticular involvement without distant foci reported in SOS were included. Fifteen LOS were analyzed. Seven patients had underlying disease. Fourteen patients had prior trauma as potential inoculation. Clinical presentation was arthritis (n = 8), osteitis (n = 5), and thoracic wall infection (n = 2). The most common clinical manifestation was pain (n = 9), followed by localized swelling (n = 7), cutaneous fistulization (n = 7), and fever (n = 5). The species involved were Scedosporium apiospermum (n = 8), S. boydii (n = 3), S. dehoogii (n = 1), and Lomentospora prolificans (n = 3). The species distribution was unremarkable except for S. boydii, which was associated with healthcare-related inoculations. Management was based on medical and surgical treatment for 13 patients. Fourteen patients received antifungal treatment for a median duration of 7 months. No patients died during follow-up. LOS exclusively occurred in the context of inoculation or systemic predisposing factors. It has a non-specific clinical presentation and is associated with an overall good clinical outcome, provided there is a prolonged course of antifungal therapy and adequate surgical management. Lay Summary Localized osteoarticular scedosporiosis mostly occurs following direct inoculation. Management was most often based on voriconazole therapy and concomitant surgery. Unlike other invasive scedosporiosis, no patient died during follow-up.

Bone and joint infections (BJI) are one of the most difficult-to-treat bacterial infection, especially in the era of antimicrobial resistance. Lytic bacteriophages (phages for short) are natural viruses that can selectively target and kill bacteria. They are considered to have a high therapeutic potential for the treatment of severe bacterial infections and especially BJI, as they also target biofilms. Here we report on the management of a patient with a pandrug-resistant Pseudomonas aeruginosa spinal abscess who was treated with surgery and a personalized combination of phage therapy that was added to antibiotics. As the infecting P. aeruginosa strain was resistant to the phages developed by private companies that were contacted, we set up a unique European academic collaboration to find, produce and administer a personalized phage cocktail to the patient in due time. After two surgeries, despite bacterial persistence with expression of small colony variants, the patient healed with local and intravenous injections of purified phages as adjuvant therapy.

The pharmacokinetics of ceftolozane-tazobactam (TOL-TAZ) and ceftazidime-avibactam (CEF-AVI) is influenced by renal function. Application of recommended dosages in patients with renal impairment requires the use of fractions of the full dose, as only one dosage is available for both antibiotics.

BACKGROUND Necrotizing external otitis (NEO) is a severe infection of the skull base that occurs generally in the elderly and/or in diabetic recipients. There are few data in the literature about the therapeutic management of this complex bone infection. OBJECTIVES To analyse relapses after NEO treatment completion, and to describe the clinical features of NEO. METHODS We performed a retrospective cohort study in the Lyon regional reference centre for the management of complex bone and joint infections. Consecutive cases of NEO from 1 January 2006 to 31 December 2018 were included. The primary outcome was the relapse of NEO. Variables were analysed using Cox regression survival analysis with adjusted hazard ratio (aHR) and Kaplan-Meier curve. RESULTS Sixty-six patients were included. Median age was 75 (IQR 69-81) years and 46 (70%) patients were diabetic. Eleven patients (17%) had temporomandibular arthritis, 10 (15%) cranial nerve paralysis, 2 (3%) cerebral thrombophlebitis, and 2 (3%) contiguous abscess. Microbiological documentation was obtained in 56 patients and revealed Pseudomonas aeruginosa in 44/56 patients (79%). Nine (14%) cases had no microbiological documentation. Antibiotic therapy was dual for 63 (95%) patients. During a median follow-up of 27 (IQR 12-40) months, 16 out of 63 (25%) patients experienced a relapse. Fungal infection was significantly associated with relapse [aHR 4.1 (95% CI 1.1-15); P = 0.03]. CONCLUSIONS NEO is a severe bone infection, mainly (but not exclusively) caused by P. aeruginosa, which occurs in elderly and diabetic recipients. Fungal infections at baseline significantly impact the outcome.

ObjectiveOur aim was to assess the real‐world effectiveness of immune checkpoint inhibitors for treatment of patients with progressive multifocal leukoencephalopathy (PML).MethodsWe conducted a multicenter survey compiling retrospective data from 79 PML patients, including 38 published cases and 41 unpublished cases, who received immune checkpoint inhibitors as add‐on to standard of care. One‐year follow‐up data were analyzed to determine clinical outcomes and safety profile. Logistic regression was used to identify variables associated with 1‐year survival.ResultsPredisposing conditions included hematological malignancy (n = 38, 48.1%), primary immunodeficiency (n = 14, 17.7%), human immunodeficiency virus/acquired immunodeficiency syndrome (n = 12, 15.2%), inflammatory disease (n = 8, 10.1%), neoplasm (n = 5, 6.3%), and transplantation (n = 2, 2.5%). Pembrolizumab was most commonly used (n = 53, 67.1%). One‐year survival was 51.9% (41/79). PML–immune reconstitution inflammatory syndrome (IRIS) was reported in 15 of 79 patients (19%). Pretreatment expression of programmed cell death‐1 on circulating T cells did not differ between survivors and nonsurvivors. Development of contrast enhancement on follow‐up magnetic resonance imaging at least once during follow‐up (OR = 3.16, 95% confidence interval = 1.20–8.72, p = 0.02) was associated with 1‐year survival. Cerebrospinal fluid JC polyomavirus DNA load decreased significantly by 1‐month follow‐up in survivors compared to nonsurvivors (p < 0.0001). Thirty‐two adverse events occurred among 24 of 79 patients (30.4%), and led to treatment discontinuation in 7 of 24 patients (29.1%).InterpretationIn this noncontrolled retrospective study of patients with PML who were treated with immune checkpoint inhibitors, mortality remains high. Development of inflammatory features or overt PML‐IRIS was commonly observed. This study highlights that use of immune checkpoint inhibitors should be strictly personalized toward characteristics of the individual PML patient. ANN NEUROL 2023;93:257–270

Introduction: Few studies have investigated the management of COVID-19 cases from the operational perspective of the emergency department (ED), We sought to compare the management and outcome of COVID-19 positive and negative patients who presented to French EDs. Methods: We conducted a prospective, multicenter, observational study in four EDs. Included in the study were adult patients (≥18 years) between March 6–May 10, 2020, were hospitalized, and whose presenting symptoms were evocative of COVID-19. We compared the clinical features, management, and prognosis of patients according to their confirmed COVID-19 status. Results: Of the 2,686 patients included in this study, 760 (28.3%) were COVID-19 positive. Among them, 364 (48.0%) had hypertension, 228 (30.0%) had chronic cardiac disease, 186 (24.5%) had diabetes, 126 (16.6%) were obese, and 114 (15.0%) had chronic respiratory disease. The proportion of patients admitted to intensive care units (ICU) was higher among COVID-19 positive patients (185/760, 24.3%) compared to COVID-19 negative patients (206/1,926, 10.7%; P <0.001), and they required mechanical ventilation (89, 11.9% vs 37, 1.9%; P <0.001) and high-flow nasal cannula oxygen therapy (135, 18.1% vs 41, 2.2%; P < 0.001) more frequently. The in-hospital mortality was significantly higher among COVID-19 positive patients (139, 18.3% vs 149, 7.7%; P <0.001). Conclusion: Emergency departments were on the frontline during the COVID-19 pandemic and had to manage potential COVID-19 patients. Understanding what happened in the ED during this first outbreak is crucial to underline the importance of flexible organizations that can quickly adapt the bed capacities to the incoming flow of COVID-19 positive patients.

Abstract Background The impact of the variant of concern (VOC) Alpha on the severity of COVID-19 has been debated. We report our analysis in France. Methods We conducted an exposed/unexposed cohort study with retrospective data collection, comparing patients infected by VOC Alpha to contemporaneous patients infected by historical lineages. Participants were matched on age (± 2.5 years), sex and region of hospitalization. The primary endpoint was the proportion of hospitalized participants with severe COVID-19, defined as a WHO-scale > 5 or by the need of a non-rebreather mask, occurring up to day 29 after admission. We used a logistic regression model stratified on each matched pair and accounting for factors known to be associated with the severity of the disease. Results We included 650 pairs of patients hospitalized between Jan 1, 2021, and Feb 28, 2021, in 47 hospitals. Median age was 70 years and 61.3% of participants were male. The proportion of participants with comorbidities was high in both groups (85.0% vs 90%, p = 0.004). Infection by VOC Alpha was associated with a higher odds of severe COVID-19 (41.7% vs 38.5%—aOR = 1.33 95% CI [1.03–1.72]). Conclusion Infection by the VOC Alpha was associated with a higher odds of severe COVID-19.

Malaria diagnosis based on microscopy is impaired by the gradual disappearance of experienced microscopists in non-endemic areas. Aside from the conventional diagnostic methods, fluorescence flow cytometry technology using Sysmex XN-31, an automated haematology analyser, has been registered to support malaria diagnosis. The aim of this prospective, monocentric, non-interventional study was to evaluate the diagnostic accuracy of the XN-31 for the initial diagnosis or follow-up of imported malaria cases compared to the reference malaria tests including microscopy, loop mediated isothermal amplification, and rapid diagnostic tests. Over a one-year period, 357 blood samples were analysed, including 248 negative and 109 positive malaria samples. Compared to microscopy, XN-31 showed sensitivity of 100% (95% CI: 97.13–100) and specificity of 98.39% (95% CI: 95.56–100) for the initial diagnosis of imported malaria cases. Moreover, it provided accurate species identification asfalciparumor non-falciparumand parasitaemia determination in a very short time compared to other methods. We also demonstrated that XN-31 was a reliable method for patient follow-up on days 3, 7, and 28. Malaria diagnosis can be improved in non-endemic areas by the use of dedicated haematology analysers coupled with standard microscopy or other methods in development, such as artificial intelligence for blood slide reading. Given that XN-31 provided an accurate diagnosis in 1 min, it may reduce the time interval before treatment and thus improve the outcome of patient who have malaria.

Modified vaccinia virus Ankara vaccine (MVA-BN; Bavarian Nordic) is recommended to contacts of mpox cases up to 14 days post-exposure but the effectiveness of this strategy is unknown. Among 108 adults (≥ 18 years old) who received one dose of MVA-BN after exposure to mpox, 11 (10%) cases of breakthrough mpox were observed. Sexual exposure was associated with the risk of breakthrough mpox (p = 0.0179). Samples taken from vaccinated breakthrough mpox cases had similar rates of infectious virus isolation than unvaccinated mpox cases.

The optimal treatment for osteoarticular infection due to multidrug-resistant tuberculosis strains (MDR-OATB) remains unclear. This study aims to evaluate the diagnosis, management and outcome of MDR-OATB in France. We present a case series of MDR-OATB patients reviewed at the French National Reference Center for Mycobacteria between 2007 and 2018. Medical history and clinical, microbiological, treatment and outcome data were collected. Twenty-three MDR-OATB cases were reported, representing 3% of all concurrent MDR-TB cases in France. Overall, 17 were male, and the median age was 32 years. Six patients were previously treated for TB, including four with first-line drugs. The most frequently affected site was the spine (n = 16). Bone and joint surgery were required in 12 patients. Twenty-one patients (91%) successfully completed the treatment with a regimen containing a mean of four drugs (range, 2–6) for a mean duration of 20 months (range, 13–27). Overall, high rates of treatment success were achieved following WHO MDR-TB treatment guidelines and individualized patient management recommendations by the French National TB Consilium. However, the optimal combination of drugs, duration of treatment and role of surgery in the management of MDR-OATB remains to be determined.

Abstract A pandrug-resistant P. aeruginosa spinal abscess was treated with surgery and personalized phage therapy that was added to cefiderocol and colistin. After a 2-stage approach, despite bacterial persistence with expression of small colony variants, the patient cured with local and intravenous injections of purified bacteriophages as part of the treatment.

Background To describe the clinical characteristics, management, and outcome of patients admitted in French emergency departments (EDs) for COVID-19 suspicion. Methods A prospective, multicenter, observational study was conducted in 4 EDs. Adult patients (≥18 years) admitted in EDs between March 6, 2020 and May 10, 2020, hospitalized, and who were presenting symptoms evocative of COVID-19 were included. The clinical features, management, and prognosis of patients was compared according to their confirmed COVID-19 status. Results A total of 2,686 patients were included, among them 760 (28.3%) were COVID-19 positive. Among the latter, the mean ± SD age was 71.5 ± 16.5 years. A total of 364 (48.0%) positive patients had hypertension, 228 (30.0%) had chronic cardiac disease, 186 (24.5%) had diabetes, 126 (16.6%) were obese, and 114 (15.0%) had chronic respiratory disease. The proportion of patients admitted in intensive care units (ICU) was higher among COVID-19 positive patients (185, 24.3%) compared to COVID-19 negative patients (206, 10.7%; p<0.001) and they required mechanical ventilation more frequently (89, 11.9% vs 37, 1.9%; p<0.001). The median [IQR] length of hospital stay was longer among COVID-19-positive patients (10 [6-15] vs 6 [2-11] days; p<0.001). The in-hospital mortality was significantly higher among COVID-19 positive patients (139, 18.3% vs 149, 7.7%; p<0.001). Conclusions This study suggests that among the COVID-19 suspected patients admitted in EDs and requiring a hospitalization, the management was different according to the confirmed COVID-19 status and required different resources in terms of ICU beds and ventilator support.

Exebacase, a recombinantly produced lysin has recently (i) reported proof-of-concept data from a phase II study in S. aureus bacteremia and (ii) demonstrated antibiofilm activity in vitro against S. epidermidis . In patients with relapsing multidrug-resistant (MDR) S. epidermidis prosthetic knee infection (PKI), the only surgical option is prosthesis exchange. In elderly patients who have undergone several revisions, prosthesis explantation could be associated with definitive loss of function and mortality. In our BJI reference regional center, arthroscopic debridement and implant retention with local administration of exebacase (LysinDAIR) followed by suppressive tedizolid as salvage therapy is proposed for elderly patients with recurrent MDR S. epidermidis PKI with no therapeutic option or therapeutic dead end (for whom revision or transfemoral amputation is not feasible and no other oral option is available). Each use was decided in agreement with the French health authority and in accordance with the local ethics committee. A written consent was obtained for each patient. Exebacase (75 mg/mL; 30 mL) was administered directly into the joint during arthroscopy. Four patients (79–89 years old) were treated with the LysinDAIR procedure. All had several previous prosthetic knee revisions without prosthesis loosening. Three had relapsing PKI despite suppressive antibiotics following open DAIR. Two had clinical signs of septic arthritis; the two others had sinus tract. After the LysinDAIR procedure, no adverse events occurred during arthroscopy; all patients received daptomycin 8 mg/kg and linezolid 600 mg bid (4–6 weeks) as primary therapy, followed by tedizolid 200 mg/day as suppressive therapy. At 6 months, recurrence of the sinus tract occurred in the two patients with sinus tract at baseline. After >1 year follow up, the clinical outcome was favorable in the last two patients with total disappearance of clinical signs of septic arthritis even if microbiological persistence was detected in one of them. Exebacase has the potential to be used in patients with staphylococci PKI during arthroscopic DAIR as salvage therapy to improve the efficacy of suppressive antibiotics and to prevent major loss of function.