Infection are the leading cause of intensive care unit (ICU) admission, yet conventional microbiological methods frequently fail to identify the causative pathogen. Metagenomic next-generation sequencing (mNGS) is an emerging, unbiased, pan-pathogen diagnostic tool. However, its real-world microbiological and clinical impact in the ICU remains poorly characterized. This study aimed to assess the microbiological yield and clinical impact of mNGS when implemented in routine ICU practice. This retrospective multicenter study was conducted across ten tertiary-care ICUs in the Greater Paris area between January 2018 and April 2024. All patients for whom an mNGS analysis was requested by clinicians from a microbiological sample were included. Any additional pathogens identified by mNGS were independently classified as causative, possibly causative, or non-causative by two reviewers. The independent reviewers also categorised therapeutic changes attributable to mNGS as escalation, de-escalation, discontinuation, or other decision support. Discrepancies were adjudicated by a third reviewer. A total of 144 mNGS analyses were performed in 132 critically ill patients (median age 55 years), 31

CONTEXT:While health-related carbon emissions are a recognizably increasing concern, the environmental impacts of choosing cefotaxime over ceftriaxone have yet to be assessed on a hospital-wide scale. METHODS:We collected data on antibiotic consumption from 38 university hospitals in 2023. Using the new Carebone® tool, the respective carbon footprints of antibiotics and medical devices were calculated by life cycle assessment. RESULTS:Daily cefotaxime administration (1 g q8h) generates 5.40 kgCO₂eq (±48%), costs €5.5, and produces 274 g of waste, compared with 1.78 kgCO₂eq (±48%), €1.4, and 88 g of waste from ceftriaxone (1 g q24h). Seven hospitals have already implemented policies replacing ceftriaxone with cefotaxime. Similar policies in all 38 hospitals participating in the survey would annually generate 392,543 kgCO₂eq, 20 tons of waste and an additional cost of €440,713. Conversely, replacing cefotaxime with ceftriaxone could save 436,579 kgCO₂e, 22 tons of waste and €490,154 annually. CONCLUSIONS:Policies favoring cefotaxime have environmental and economic costs that should be integrated into antibiotic stewardship recommendations alongside other factors (resistance selection, etc.).

BACKGROUND:Infective endocarditis (IE) is a severe infection requiring efficient, sometimes combined, antibiotic therapy. For β-lactam-susceptible Enteroccus spp., particularly Enterococcus faecalis (EFS), the combination of amoxicillin and ceftriaxone is currently recommended. However, limited data are available for ampicillin-susceptible E. faecium strains (EFM-S). OBJECTIVES:To characterize the in vitro synergy of amoxicillin/ceftriaxone combination against clinical isolates of EFM-S and evaluate its clinical relevance. METHODS:Twenty-six EFM-S and 10 EFS clinical isolates from the Henri Mondor Hospital (Créteil, France) were tested. EFM-S clades were previously determined by whole-genome sequencing. Checkerboard assays were performed to assess the MICs and synergy across a range of amoxicillin and ceftriaxone concentrations. The fractional inhibitory concentration (FIC) index was computed for each combination, with synergy defined as ΣFIC ≤ 0.5. RESULTS:Amoxicillin and ceftriaxone MIC distributions were comparable between EFM-S (amoxicillin, 0.06-2 mg/L; ceftriaxone, 1 to ≥1024 mg/L) and EFS (amoxicillin, 0.5-2 mg/L; ceftriaxone, 64 to ≥1024 mg/L). Synergy was observed in 21/26 EFM-S and all EFS strains. The five non-synergistic EFM-S strains had low ceftriaxone MICs (1-16 mg/L), probably limiting synergy detection. No difference was observed according to EFM clades. The minimal synergistic concentrations were consistently higher for EFM-S (median amoxicillin, 0.125 mg/L; ceftriaxone, 32 mg/L) compared to EFS (amoxicillin, 0.03 mg/L; ceftriaxone, 2 mg/L). CONCLUSIONS:Despite in vitro synergy, the amoxicillin/ceftriaxone combination is clinically irrelevant for EFM-S IE due to unachievable drug concentrations in vivo. These findings support clearer guidelines explicitly excluding this regimen for E. faecium, regardless of β-lactam susceptibility.

OBJECTIVES:MSSA remains the leading cause of infective endocarditis (IE) and is responsible for significant mortality. While clinical factors tied to mortality are well documented, possible contributing strain-specific characteristics have not been extensively explored. This study investigates MSSA phenotypic and genotypic characteristics and medical-surgical data related to Day-90 mortality in IE. METHODS:We included all patients enrolled in a monocentric prospective cohort (2016-23), with definite or probable MSSA IE. Cefazolin and oxacillin MICs and inoculum effects were determined by broth microdilution. Genotyping analysis and BlaZ typing were obtained from WGS. Phenotypic and genotypic characteristics of strains and clinical risk factors were confronted with Day-90 mortality. RESULTS:Eighty-eight patients with MSSA IE were included. The most frequent clinical presentations were left-sided native valve IE (25/88), left-sided prosthetic valve IE (12/88) and right-sided IE (19/88). Day-90 mortality rate was 39% (34/88). Most patients were treated with antistaphylococcal penicillin as a primary antibiotic (60/88). The main MSSA clonal complexes identified were CC398 (17/88), CC30 (13/88) and CC5 (13/88). Cefazolin inoculum effect was observed in 18/88 strains, and oxacillin inoculum effect in 13/88. Overall, 15/88 isolates exhibited an inoculum effect on primary antibiotic therapy. Factors independently associated with improved outcomes included cardiac surgery [hazard ratio (HR) 0.34, 95% CI (0.13-0.89)] and source control [HR 0.21, 95% CI (0.03-0.53)]. Neither genetic background, blaZ carriage, nor in vitro inoculum effect to the primary antibiotherapy was associated with Day-90 mortality. CONCLUSIONS:This cohort of MSSA IE did not find any microbiological factors correlated with Day-90 mortality. Clinical features and infection management appear to be the main factors in the prognosis of MSSA IE.

OBJECTIVES:To evaluate the diagnostic performance of synovial fluid (SF) biochemical markers and assess the value of combining their measurements into a composite score for identifying septic arthritis (SA). METHODS:Patients who underwent arthrocentesis with SF biochemical analysis (proteins, glucose, lactate dehydrogenase (LDH), lactate) were included in the initial cohort (IC) (May 2018-May 2021) or the validation cohort (June 2021-March 2023). Using IC data, we compared marker levels in SA vs. non-SA and vs. crystal-related arthritis (C-rA) subgroup. Based on receiver operating characteristic (ROC) curves, we identified two thresholds (one optimizing sensitivity, the other specificity) to assign a score of 0-2 for each biomarker. We developed a composite score by combining the individual scores for discriminative biomarkers and assessed its diagnostic performance. RESULTS:We included 190 SF (170 patients) in the IC; 36 SF (18.9%) were septic. Glucose level was lower in SA than non-SA and C-rA, but lactate and LDH levels were higher (P<0.001). The composite score was developed with a 0-6 scale, with the following thresholds: glucose (≤7 and ≤1.5mmol/L), lactate (≥4.5 and ≥7.5mmol/L), and LDH (≥600 and ≥1200 UI/L). A composite score ≥3 had 100% sensitivity and 73.9% specificity for SA diagnosis in the IC cohort, and a score≥5 had 55.5% sensitivity and 97.8% specificity. These findings were consistent in the validation cohort. CONCLUSION:A combined score based on SF markers including glucose, LDH, and lactate may be an effective method for rapidly ruling out SA. A multicentric study is warranted to confirm these results.

BACKGROUND:Although widely used, cefazolin efficacy for the treatment of meticillin-susceptible Staphylococcus aureus (MSSA) bacteraemia has not thus far been investigated in a clinical trial. In this study, we aimed to compare the efficacy and safety of cefazolin with that of cloxacillin in patients with MSSA bacteraemia. METHODS:We conducted an open-label, non-inferiority, randomised clinical trial in 21 university and non-university hospitals in France in adults (aged ≥18 years) with MSSA bacteraemia, without intravascular implant or suspicion of CNS infection. Participants were randomly assigned (1:1) to receive intravenously cefazolin (25-50 mg/kg every 8 h) or cloxacillin (25-50 mg/kg every 4-6 h) for the first 7 days of therapy using computer-generated blocks of various sizes and stratification on vascular-access associated bacteraemia and centre. Subsequent treatment was left to the choice of the investigator (total duration ≥14 days). The primary endpoint was a composite of sterile blood cultures at day 3 (day 5 for endocarditis) without relapse of bacteraemia, survival, and clinical success at day 90, and was assessed in the intention-to-treat population. A non-inferiority margin of 12% was chosen. This trial is registered on ClinicalTrials.gov (NCT03248063) and is complete. FINDINGS:Between Sept 5, 2018, and Nov 16, 2023, 315 participants were enrolled and assigned to cefazolin (n=158) or cloxacillin (n=157); 12 participants were excluded from analysis in the cefazolin group, and 11 in the cloxacillin group (final population of 146 in each group). Mean age was 62·7 years (SD 16·4), 215 (74%) participants were male, and race or ethnicity data were not collected. Median Pitt score was 0 (IQR 0-0). The primary endpoint was met in 109 (75%) of 146 participants in the cefazolin group versus 108 (74%) of 146 participants in the cloxacillin group (treatment difference -1%; 95% CI -11 to 9; p=0·012). At the end of study treatment, 22 (15%) of 146 participants assigned to cefazolin and 40 (27%) of 146 participants assigned to cloxacillin had had a serious adverse event (p=0·010). Acute kidney injury occurred more frequently in participants assigned to cloxacillin (15 [12%] of 128) than in those assigned to cefazolin (one [1%] of 134; p=0·0002). INTERPRETATION:Cefazolin constitutes an alternative to cloxacillin for the treatment of MSSA bacteraemia, offering non-inferior clinical efficacy and potentially enhanced tolerability. FUNDING:French Ministry of Health.

Objectives: The treatment of long-term intravenous catheter-related bloodstream infections (LTIVC-related BSI) often requires catheter removal or conservative treatment using intra-catheter locks, with a 50–60% success rate. We previously demonstrated the synergistic effect of a combination of gentamicin and ethylenediaminetetraacetic acid disodium salt (EDTA-Na2) against bacterial biofilms. We conducted a phase 1/2 clinical trial to assess the tolerance and efficacy of genta-EDTA-Na2 locks for the conservative treatment of LTIVC-related BSI. Methods: Prospective study including adult patients with monomicrobial, uncomplicated LTIVC-related BSI caused by gentamicin-susceptible coagulase-negative staphylococci, Enterobacterales, or Pseudomonas aeruginosa. Primary objective: assess the safety and efficacy at genta-EDTA-Na2 locks at day 40 (D40) by evaluating the frequency of clinical and microbiological cure 30 days after the end of treatment (D40). Results: Eight patients were included. Complete follow-up was obtained for seven patients, six of whom met the criteria for cure. The single patient with incomplete follow-up met all criteria for cure at D23. A single microbiological failure occurred (relapse of P. aeruginosa LTIVC-related BSI). Two patients experienced at least one serious adverse event; none were attributed to the genta-EDTA-Na2 locks. Conclusions: Genta-EDTA-Na2, used as intra-catheter locks, may be a promising anti-biofilm candidate for evaluation in a randomized controlled trial.

Necrotizing soft tissue infections (NSTIs) are uncommon, yet rapidly progressive and potentially fatal conditions. However, evidence-based guidance on antibiotic therapy remains limited. Current recommendations emphasize the need for broad-spectrum empirical coverage, including gram-positive, gram-negative, anaerobes, and Streptococcus pyogenes when clinically indicated. We aimed at developing a practical, evidence-based framework for empirical antibiotic therapy in NSTIs. This narrative review is informed by a comprehensive literature search of PubMed, without date restrictions. We propose a structured decision-making algorithm for empirical antibiotic selection in NSTIs, integrating key clinical parameters: infection site, healthcare-associated versus community-acquired origin, risk factors for extended-spectrum β-lactamase-producing Enterobacterales and methicillin-resistant Staphylococcus aureus, and signs of sepsis or septic shock. Alternative regimens are provided for patients with severe β-lactam allergies. Special considerations for immunocompromised and other vulnerable host populations are also addressed. This review offers clinicians a pragmatic, stepwise approach to antibiotic therapy in NSTIs, while identifying critical knowledge gaps and priorities for future research.

IntroductionEnviron 15% des consommations d'antibiotiques en ville sont générées par des prescriptions hospitalières. Les indicateurs hospitalier de bon usage d'intègrent pas, à ce jour, cette dimension ambulatoire. Cette étude permettra d'évaluer la part d'antibiotiques ambulatoires prescrits aux urgences et d'en analyser la conformité vis-à-vis des recommandations de prise en charge.Matériels et méthodesL'étude était observationnelle multicentrique dans 15 services d'accueil des urgences (SAU). Les inclusions étaient effectuées un jour donné, répété 4 fois lors de la période d'étude de mai 2022 à avril 2023, prenant en compte la saisonnalité des infections. Etaient inclus les patients majeurs admis dans un SAU et rentrant à domicile sans hospitalisation. Le critère d'évaluation principal était l'adéquation aux recommandations locales des prescriptions d'antibiotiques (ATB). Cette adéquation était évaluée par un binôme infectiologue-urgentiste au sein de chaque centre d'étude selon deux critères : conformité de l'indication et conformité des modalités d'antibiothérapie (molécule, posologie, voie, durée).RésultatsOnt été recensés 8661 passages au SAU lors de l'étude (144 ± 2 par centre et par période). Parmi eux, 6260 (72,3 %) sont rentrés à domicile et ont été inclus dans l'étude. Le moyenne d'âge était de 45,9 ± 21 ans et la moitié étaient des femmes. Le taux de prescription d'ATB était de 7,5 % (n = 471 / 6260). Parmi les patients traités par ATB, 269 étaient des femmes (57,1 %), 18 étaient immunodéprimés (3,8 %). Le score de Charlson était de 0, 1 à 2 ou ≥ 5 dans 62,1 %, 20,5% et 8,3% des cas. Les antibiothérapies concernaient majoritairement une infection cutanée, urinaire, ORL ou pulmonaire (respectivement 34,8 %, 26,1 %, 18,7 % et 11,5 % des cas). Des monothérapies étaient prescrites pour 448 patients (95,7 %), la voie orale était privilégiée (96,6 %). L'ATB le plus prescrit était l'amoxicilline + acide clavulanique (49,1 %). Les prescripteurs étaient des internes dans un tiers des cas. L'indication à une antibiothérapie était adaptée dans 72,0 % des cas (44,7 à 100 % selon les centres). La conformité des modalités des prescriptions était adaptée dans 39,8 % des cas (12,5 à 67.9 %). Les causes de non-conformité étaient principalement la durée et le choix de la molécule (51,1 % et 62.1 % de conformité, respectivement). Les prescriptions étaient plus fréquemment conformes pour les infections urinaires (60,3%) que pour les autres sites infectieux (28,3 à 34,1 %). Seuls le type de centre (CHG vs. CHU) et le type d'infection étaient associés à un taux d'inadéquation supérieurs.ConclusionL'incidence des antibiothérapies pour des patients consultant au SAU et rentrant au domicile était estimé à 7,5%. Ces antibiothérapies sont majoritairement jugées conforme dans leur indication mais ne respectent les recommandations dans leurs modalités que dans moins de la moitié des cas. Cette étude permettra de mettre en place des plans d'actions locaux, principalement orientés sur les durées de traitements et les infections respiratoires ou digestives.Aucun lien d'intérêt

Background In recent years, Acinetobacter baumannii-calcoaceticus complex (ABC) infections have attracted attention, mainly because of the impact of carbapenem-resistant isolates in hospital-acquired infections. However, acute community-acquired ABC infections are not uncommon in warm and humid countries, where they are responsible for community-acquired infections with specific clinical features. To date, such infection has not been reported in France. Case presentation We report the case of a 55-year-old non-immunocompromised patient living in France with no known risk factors for community-acquired ABC infections who presented pneumonia with bloodstream infection due to wild-type A. pittii . The outcome was favorable after 7 days of antibiotic treatment with cefepime. We confirmed bacterial identification with whole-genome sequencing, and we examined the A. pitii core-genome phylogeny for genomic clusters. Conclusions This situation is uncommon in Europe and occurred after a heat wave in France with temperatures above 38 °C. Herein, we discuss the possibility that this pneumonia may be emerging in the current context of global warming.

Background and objectives: Cefiderocol approved dosages are based on a prolonged infusion (PI) of 3 h that may not be adequate in all settings The objective of this study was to identify alternative cefiderocol dosage regimens based on short infusion (SI) or continuous infusion (CI). Methods: We performed 1000-patient pharmacokinetic/pharmacodynamic (PK/PD) simulations based on a reference population model. Drug penetration into the epithelial lining fluid (ELF) was considered for pneumonia. For various stages of creatinine clearance (CLCR), we simulated the recommended PI as well as various SI (1h-infusion) and CI regimens. The PK/PD targets were set at 75% or 100% of the dosing interval during which the free concentration of cefiderocol was above the MIC (fT > MIC) in plasma and ELF. The PTAs were computed considering the cefiderocol MIC breakpoint (2 mg/L). Results: In plasma, all recommended PI regimens were associated with a PTA >= 90%. Some SI regimens also showed acceptable PTAs. CI regimens were associated with high PTAs, even for doses as low as 2 g over 24 h and in patients with high CLCR. Recommended dosages failed to achieve acceptable PTAs in ELF for the 100% fT > MIC target in patients with CLCR >= 90 mL/min. CI regimens showed the highest PTAs for the high target, but high doses of 6 to 8 g over 24 h were required in patients with CLCR >= 90 mL/min. Conclusions: We identified SI and CI regimens of cefiderocol that may be useful alternatives to the PI regimens in some patients. Continuous administration of cefiderocol may be especially relevant for patients with pneumonia. However, further clinical evaluation is necessary.

Objective: This study aimed to analyze the outcomes and challenges associated with surgical redo procedures following aortic valve replacement for acute infective endocarditis. While transcatheter aortic valve implantation is growing in terms of its utilization for degenerative bioprostheses failure, valve-in-valve procedures are limited in acute aortic endocarditis. Surgical interventions for aortic prosthesis endocarditis carry a significant risk, with a higher mortality and morbidity, often requiring concomitant complex procedures. Methods: This was a retrospective, monocentric, observational study. We identified 352 patients with infective endocarditis from the institutional database. After applying the inclusion and exclusion criteria, 54 patients who underwent surgical re-operation between 2016 and 2023 were included. Endpoints included early and late mortality, complications, and major adverse cardiac and cerebrovascular events (MACCEs). Results: From the cohort, predominantly male and with an average age of 71.9 ± 12.1 years old (79.6%), the following notable findings were derived: isolated aortic valve replacement was feasible only in 34 patients (63%) while more complex procedures were demanded in the other cases; the overall 30-day mortality rate was 18.5%, post-operative ECMO occurred in 9.3% of cases, and post-operative new stroke in 2.7%; the 5-year overall survival rate was 58.3 ± 18.6%, while freedom from MACCEs was 41.7 ± 19.7%. Another re-intervention was required in three patients during follow-up, with one case attributed to re-endocarditis. Conclusions: Despite advancements in surgical and perioperative care, redo procedures for acute infective endocarditis pose significant risks, as evidenced by the high 30-day mortality rate. However, the 5-year survival suggests a relatively acceptable outcome, underscoring the complexities and challenges inherent in managing this condition surgically.

Introduction Les collections intra-abdominales (CIA) sont définies par l'accumulation dans la cavité péritonéale de liquide infecté, limitée par du tissu inflammatoire. Elles sont fréquentes, compliquant infections et/ou chirurgies digestives. Leur traitement repose habituellement sur un drainage associé à une antibiothérapie. Les modalités optimales de prise en charge ne sont pas connues et il n'existe aujourd'hui aucune recommandation. L'objectif de cette étude était d'évaluer les pratiques en France en 2024. Matériels et méthodes Nous avons mené une enquête nationale de pratique pluridisciplinaire. Les participants devaient répondre à 48 questions à choix multiples ou ouvertes à réponse courte correspondant à 5 vignettes cliniques représentatives de la pratique. Une analyse statistique était effectuée à l'aide du logiciel XLSTAT. Résultats Entre juillet 2023 et février 2024, 275 médecins ont répondu au questionnaire : 56.0% d'infectiologues (154/275), 16.4% de chirurgiens viscéraux (45/275), 13.5% d'anesthésistes (37/275), 4.3% d'internistes (12/275), 3.2% de réanimateurs (9/275), 2.5% de radiologues (7/275) et 4.0% d'autres spécialités (11/275). Parmi eux, 55.3% de praticiens hospitaliers (152/275), 15.6% d'internes (43/275), 16.0% de chefs de clinique (44/275), 13.1% de maitres de conférences des universités ou professeurs des universités (36/275) ; 47.6% travaillaient en Ile de France (131/275), 8.4% en Nouvelle Aquitaine (23/275), 6.2% en Auvergne (17/275), 5.1% dans la région Grand Est (14/275) et 32.7% d'autres régions (90/275). L'âge médian était de 37 ans (min: 26 ; max: 68), 49.8% étaient de sexe masculin.Pour les CIA <4 cm, l'indication à un drainage était retenue dans 17.8 % des cas. Dans cette situation, 74.3% des participants proposaient un drainage percutané. Les durées médianes d'antibiothérapie préconisées étaient de 7 jours (min: 0, max: 28) en cas de drainage radiologique, 7 jours (min: 0, max: 21) en cas de drainage chirurgical, 14 jours sans drainage (min: 4, max: 54).Pour les CIA de >4 cm, l'indication à un drainage était retenue dans 84.3 % des cas. Dans cette situation, 60.7 % des participants proposaient un drainage percutané. Les durées médianes d'antibiothérapie préconisées étaient de 7 jours (min: 2, max: 42) en cas de drainage radiologique, 7 jours (min: 1, max: 48) en cas de drainage chirurgical, 21 jours sans drainage (min: 4, max: 90).En analyse univariée, les facteurs influençant la durée de traitement des CIA était : la spécialité « chirurgie viscérale » (p=0.025), un âge >40 ans (p=0.003) étaient associés une prescription antibiotique plus courte. Conclusion Ce travail objective une forte prévalence de l'indication de drainage pour les CIA de plus >4 cm. La durée médiane d'antibiothérapie préconisée était de 7 jours post drainage quelle que soit la taille initiale ou le mode de drainage. En l'absence de drainage, les durées médianes étaient de 14 jours pour les CIA de <4 cm et 21 jours pour celles de >4 cm. Des facteurs ont été identifiés comme influençant la durée de prescription antibiotique. Cette étude constitue une base pour des recherches futures afin de rationaliser les durées de prescription antibiotique et proposer une uniformisation nationale des pratiquesAucun lien d'intérêt

BACKGROUND:Staphylococcus aureus bloodstream infection is treated with at least 14 days of intravenous antimicrobials. We assessed the efficacy and safety of an early switch to oral therapy in patients at low risk for complications related to S aureus bloodstream infection. METHODS:In this international, open-label, randomised, controlled, non-inferiority trial done in 31 tertiary care hospitals in Germany, France, the Netherlands, and Spain, adult patients with low-risk S aureus bloodstream infection were randomly assigned after 5-7 days of intravenous antimicrobial therapy to oral antimicrobial therapy or to continue intravenous standard therapy. Randomisation was done via a central web-based system, using permuted blocks of varying length, and stratified by study centre. The main exclusion criteria were signs and symptoms of complicated S aureus bloodstream infection, non-removable foreign devices, and severe comorbidity. The composite primary endpoint was the occurrence of any complication related to S aureus bloodstream infection (relapsing S aureus bloodstream infection, deep-seated infection, and mortality attributable to infection) within 90 days, assessed in the intention-to-treat population by clinical assessors who were masked to treatment assignment. Adverse events were assessed in all participants who received at least one dose of study medication (safety population). Due to slow recruitment, the scientific advisory committee decided on Jan 15, 2018, to stop the trial after 215 participants were randomly assigned (planned sample size was 430 participants) and to convert the planned interim analysis into the final analysis. The decision was taken without knowledge of outcome data, at a time when 126 participants were enrolled. The new sample size accommodated a non-inferiority margin of 10%; to claim non-inferiority, the upper bound of the 95% CI for the treatment difference (stratified by centre) had to be below 10 percentage points. The trial is closed to recruitment and is registered with ClinicalTrials.gov (NCT01792804), the German Clinical trials register (DRKS00004741), and EudraCT (2013-000577-77). FINDINGS:Of 5063 patients with S aureus bloodstream infection assessed for eligibility, 213 were randomly assigned to switch to oral therapy (n=108) or to continue intravenous therapy (n=105). Mean age was 63·5 (SD 17·2) years and 148 (69%) participants were male and 65 (31%) were female. In the oral switch group, 14 (13%) participants met the primary endpoint versus 13 (12%) in the intravenous group, with a treatment difference of 0·7 percentage points (95% CI -7·8 to 9·1; p=0·013). In the oral switch group, 36 (34%) of 107 participants in the safety population had at least one serious adverse event compared with 27 (26%) of 103 participants in the intravenous group (p=0·29). INTERPRETATION:Oral switch antimicrobial therapy was non-inferior to intravenous standard therapy in participants with low-risk S aureus bloodstream infection. However, it is necessary to carefully assess patients for signs and symptoms of complicated S aureus bloodstream infection at the time of presentation and thereafter before considering early oral switch therapy. FUNDING:Deutsche Forschungsgemeinschaft. TRANSLATIONS:For the German, Spanish, French and Dutch translations of the abstract see Supplementary Materials section.

Background: 18F-fluorodeoxyglucose positron emission tomography–CT (FDG-PET/CT) is useful for identifying infective endocarditis (IE) but also the detection of other concomitant septic foci. Previously, we found that FDG-PET/CT identified an osteoarthritic septic graft (OASG) in 19.1% of IE patients, frequently asymptomatic. These preliminary results encouraged us to extend our analyses to a larger population, including all patients initially explored for suspected IE, to assess the prevalence, characteristics, and OASG locations brought out by FDG-PET/CT and to identify predictive factors. Methods: From a single-center cohort of patients referred for a clinical and/or biological suspicion of IE, we included all patients who underwent FDG-PET/CT, mainly performed to confirm a prosthesis heart valve or a foreign cardiac device infection. We excluded those who did not meet the 2015 modified Duke Criteria and those for whom another infectious diagnosis was finally retained or for whom all bacterial samples were negative. Demographic, clinical, bacteriological, imaging, and therapeutic data were collected. FDG-PET/CT images were retrospectively analyzed by three blinded nuclear medicine specialists to identify OASGs. Results: We identified 72 distinct OASG locations by FDG-PET/CT in 48 of 174 patients (27.6%), mainly located in the spine (21 OASGs in 20 patients); 14 patients (8.0%) had several OASG locations. In total, 43.8% of OASG locations were asymptomatic. In multivariate analysis, the presence of OASGs was associated with musculoskeletal pain (p < 0.001) and tricuspid valve involvement (p = 0.002). Conclusions: FDG-PET/CT is useful for identifying OASGs in patients with suspected IE, especially those with tricuspid IE or musculoskeletal pain. The identification of OASGs could impact antibiotic therapy and would allow adapted orthopedic management to be proposed.

A 44-year-old woman treated with corticosteroids and methotrexate for mixed connective tissue disease was hospitalized for lower limb edema and chest pain. Imaging studies revealed a large pericardial abscess with spondylodiscitis. Blood cultures were positive for methicillin-sensitive Staphylococcus aureus (MSSA). Pairwise genomes comparison done on both the responsible strain and an MSSA strain isolated 3 months earlier in a context of catheter-related infraclinical blood stream infection revealed identical patterns, highlighting the probable silent evolution of an incompletely treated infection in a patient receiving corticosteroids.

BACKGROUND:It remains unclear today whether risk scores created specifically to predict early mortality after cardiac operations for infective endocarditis (IE) outperform or not the European System for Cardiac Operative Risk Evaluation II (EuroSCORE II). METHODS:Perioperative data and outcomes from a European multicenter series of patients undergoing surgery for definite IE were retrospectively reviewed. Only the cases with known pathogen and without missing values for all considered variables were retained for analyses. A comparative validation of EuroSCORE II and 5 specific risk scores for early mortality after surgery for IE-(1) STS-IE (Society of Thoracic Surgeons for IE); (2) PALSUSE (Prosthetic valve, Age ≥70, Large intracardiac destruction, Staphylococcus spp, Urgent surgery, Sex (female), EuroSCORE ≥10); (3) ANCLA (Anemia, New York Heart Association class IV, Critical state, Large intracardiac destruction, surgery on thoracic Aorta); (4) AEPEI II (Association pour l'Étude et la Prévention de l'Endocardite Infectieuse II); (5) APORTEI (Análisis de los factores PROnósticos en el Tratamiento quirúrgico de la Endocarditis Infecciosa)-was carried out using calibration plot and receiver-operating characteristic curve analysis. Areas under the curve (AUCs) were compared 1:1 according to the Hanley-McNeil's method. The agreement between APORTEI score and EuroSCORE II of the 30-day mortality prediction after surgery was also appraised. RESULTS:A total of 1,012 patients from 5 European university-affiliated centers underwent 1,036 cardiac operations, with a 30-day mortality after surgery of 9.7%. All IE-specific risk scores considered achieved better results than EuroSCORE II in terms of calibration; AEPEI II and APORTEI score showed the best performances. Despite poor calibration, EuroSCORE II overcame in discrimination every specific risk score (AUC, 0.751 vs 0.693 or less, P = .01 or less). For a higher/lesser than 20% expected mortality, the agreement of prediction between APORTEI score and EuroSCORE II was 86%. CONCLUSION:EuroSCORE II discrimination for 30-day mortality after surgery for IE was higher than 5 established IE-specific risk scores. AEPEI II and APORTEI score showed the best results in terms of calibration.