S. saprophyticus is a common pathogen of urinary tract infections, but bacteremia is rare. We report a case of S. saprophyticus infective endocarditis. A 77-year-old woman with aortic stenosis was admitted for abscessed diverticulitis: S. saprophyticus was isolated from a single blood culture and considered as contamination. Two months later, S. saprophyticus infective endocarditis was diagnosed. Very few cases are reported with a variety of sources ranging from gastrointestinal procedures, urinary tract infections, intravenous drug use and device-related infections. S. saprophyticus growth in only one blood culture does not automatically confirm a diagnosis of bacteremia, but can be significant in high-risk patients.

Endocan and its major catabolite cleaved endocan are reported as potential biomarkers of pneumonia in the setting of critical illness. However, very little is known about their accuracy to discriminate microbiologically confirmed ventilator-associated pneumonia (VAP) at the time of clinical suspicion. The objective of this study was to evaluate the performance of endocan and cleaved endocan for the early discrimination of microbiologically confirmed VAP. In a pre-planned ancillary analysis of the single-center prospective observational SOH-VAP cohort (NCT03434821) which was conducted at the University hospital of Lille from March 2018 to April 2022, patients presenting with a clinical suspicion of VAP leading to microbiological respiratory sampling were included. Endocan and cleaved endocan were measured on EDTA plasma collected on the day of VAP clinical suspicion. The performance of these biomarkers and of the endocan cleavage ratio (ECR) was determined by comparing values obtained in patients with microbiologically confirmed VAP to those without microbiological confirmation, and by establishing ROC curves. We enrolled 47 patients with microbiologically confirmed VAP and 67 patients without microbiological confirmation. No significant differences were found when comparing endocan, cleaved endocan, and ECR values between confirmed and non-confirmed VAP (median [IQR] = 5 [2.7; 9.6] ng/mL vs. 4.7 [2.5; 8.5] ng/mL, p = 0.86 for endocan; 1.2 [0; 2] ng/mL vs. 1 [0; 2] ng/mL, p = 0.71 for cleaved endocan; and 0.06 [0; 0.32] vs. 0.07 [0; 0.29], p = 0.94 for ECR). Areas under the ROC curves for differentiating confirmed and non-confirmed VAP were respectively calculated at 0.51 (95% CI: 0.4-0.62) for endocan, 0.52 (95% CI: 0.43-0.64) for cleaved endocan, and 0.52 (95% CI: 0.41-0.63) for ECR. Our results do not support the use of endocan nor cleaved endocan for the early detection of microbiologically confirmed VAP at the time of clinical suspicion.

We report the first French case of endocarditis due to Staphylococcus pasteuri in a 70-year-old male. S. pasteuri was isolated from several sets of blood cultures and identified using MALDI-TOF-MS enabling differentiation from Staphylococcus warneri. In the literature, isolates of S. pasteuri, frequently regarded as contaminants, have been associated with embolic complications in several reported cases.

We report the first French case of infective endocarditis due to Staphylococcus pasteuri in a 70-year-old male. S. pasteuri was isolated from several sets of blood cultures and identified using MALDI-TOF-MS enabling differentiation from Staphylococcus warneri. In the literature, isolates of S. pasteuri, frequently regarded as contaminants, have been associated with embolic complications in several reported cases.

Ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia requiring mechanical ventilation (vHAP) are frequent in intensive care units and require prompt diagnosis. The FilmArray Pneumonia Panel (FAPP) enables fast pathogen identification, but its clinical impact remains uncertain. To assess whether adding FAPP to conventional microbiology increases the rate of targeted antimicrobial therapy (AMT) in patients with suspected VAP or vHAP. Open-label, multicenter randomized-controlled trial in immunocompetent adults with suspected VAP or vHAP. Patients were randomized to management with FAPP plus conventional microbiology or conventional microbiology alone. The primary outcome was the proportion of patients receiving targeted AMT 24 h after inclusion. From June 2020 to September 2023, 156 patients were randomized; 146 were analyzed (74 intervention, 72 control), as 10 did not provide consent for continued participation. Median age was 58 years (interquartile range, 43–70), 67.8

Pseudomonas aeruginosa infections in cystic fibrosis (CF) often present therapeutic challenges due to acquired resistance. This study analyzed 178 strains from adult CF patients at a single French university hospital. High in vitro activity was observed for newer antibiotics such as ceftolozane-tazobactam (83% susceptibility), ceftazidime-avibactam (85% susceptibility), and cefiderocol (89% susceptibility). Delafloxacin also showed promising activity, with 93% of the isolates exhibiting MICs below the EUCAST epidemiological cut-off value. Results emphasize the potential utility of these agents.

Nocardiosis is a serious infection in immunosuppressed patients, especially transplant recipients. The slow-growing phenotype of the bacterium and the variety of symptoms complicate diagnosis and delay antimicrobial therapy, resulting in high mortality rates despite effective treatments. A further complication is that some nocardiosis patients test positive in fungal diagnostics that detect (1,3)-β-D-glucan (the Fungitell assay), but the basis for this cross-reactivity remains unknown. We demonstrate that nocardial cell wall arabinogalactan is a cryptic antigen responsible for cross-reactivity in the Fungitell assay and that this antigen is revealed in vivo following bacterial cell lysis. We further show that the reactivity results from a β-glucose substitution of the galactan domain, a modification specific to nocardia, and identify the optimal antigen as a tetramer of the trisaccharide repeating unit. By providing structural evidence for Fungitell cross-reactivity during nocardiosis, this work paves the way for developing specific diagnostic tools that are currently lacking.

Streptococcus pneumoniae infection is considered an uncommon cause of arthritis in adults. To determine the clinical and microbiological characteristics of pneumococcal septic arthritis, we retrospectively studied a large series of cases among adult patients during the 2010-2018 conjugate vaccine era in France. We identified 110 patients (56 women, 54 men; mean age 65 years), and cases included 82 native joint infections and 28 prosthetic joint infections. Most commonly affected were the knee (50/110) and hip (25/110). Concomitant pneumococcal infections were found in 37.2% (38/102) and bacteremia in 57.3% (55/96) of patients, and underlying conditions were noted for 81.4% (83/102). Mortality rate was 9.4% (8/85). The proportion of strains not susceptible to penicillin was 29.1% (32/110). Of the 55 serotyped strains, 31 (56.4%) were covered by standard pneumococcal vaccines; however, several nonvaccine serotypes (mainly 23B, 24F, and 15A) had emerged, for which susceptibility to β-lactams was low.

BACKGROUND:Sepsis survivors often experience sustained muscle weakness, leading to physical disability, with no pharmacological treatments available. Despite these well-documented long-term clinical consequences, research exploring the cellular and molecular mechanisms is sorely lacking. METHODS:Bioinformatic analysis was performed in the vastus lateralis transcriptome of human ICU survivors 7 days after ICU discharge (D7), 6 months (M6) and age- and sex-matched controls. Enrichment analysis using Gene Ontology (GO) terms and Mitocarta3.0 was performed at D7 and M6 on differentially expressed genes (DEGs) and modules identified by weighted gene co-expression network analysis (WGCNA). Using a murine model of resuscitated sepsis induced by caecal slurry injection, pathways identified by the bioinformatics analysis were explored in 18- to 24-week-old sepsis-surviving (SS) mice at Day 10. Autophagy flux was investigated both in vivo and in vitro with chloroquine, a lysosomal inhibitor and urolithin A (UA), an autophagy inducer. Systemic metabolism was evaluated with indirect calorimetry, muscle phenotype with in situ and ex vivo contractility, muscle mass, myofibre cross-sectional area and typing and mitochondrial population with transmission electron microscopy (TEM), as well as mitochondrial function with high-resolution respirometry. Autophagic vacuole (AV) level was monitored using LC3B-II and P62 protein expression and TEM. RESULTS:Pathways related to 'mitochondrion' were the only ones whose deregulation persisted between D7 and M6 (p < 0.05) and characterized WGCNA modules correlated with muscle mass, strength and physical function. Shared mitochondrial DEGs between D7 and M6 encoded matrix mitochondrial proteins related to 'metabolism' and 'mitochondrial dynamics'. SS mice exhibited reduced complex I-driven oxygen consumption (CI-JO2) (-45%), increased S-nitrosylation of complex I, damaged (+35%) and oxidized (+51%) mitochondria and AV accumulation (5 vs. 50 AVs/mm2) compared with sham pair-fed mice (p < 0.05) despite no differences in mitochondrial size or number. Autophagy flux was reduced in SS mice due to decreased AV degradation ratio (p < 0.05). UA restored a balanced autophagy flux (turnover ratio 0.96 vs. -0.17) by increasing AVs formation and degradation ratio (p < 0.05). UA also improved CI-JO2 (81 vs. 106 pmol/s/mg), tetanic force (215 vs. 244 mN/mm2) and hindlimb muscle weight in SS mice (p < 0.05). CONCLUSION:Mitochondrial and autophagy disruption contributes to long-term muscle dysfunction in human and mouse sepsis survivors. We demonstrate for the first time that sepsis induces an autophagy flux blockade. Urolithin A prevents mitochondrial and muscle impairments both in vivo and in vitro by improving autophagy flux.

Background: The optimal duration of antibiotic treatment for extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) bloodstream infections (BSI) in intensive care unit (ICU) is not established. We aim to evaluate the frequency and clinical outcomesof a short appropriate antibiotic treatment (≤7 days) (SAT) for ESBL-E BSI acquired in the ICU. We specifically assessed the rate of ESBL-E BSI relapse, and in-ICU mortality. Method: All patients who acquired ESBL-E BSI in three ICU in Northern France between January 2011 and June 2022 were included in a multicenter retrospective cohort study. The factors associated with prescribing short (SAT, ≤7 days) versus long (LAT, >7 days) antibiotic treatment were analyzed. To evaluate the impact of SAT on mortality in the ICU, an estimation was applied using a Cox model with a time-dependent co-variable adjusted by inverse weighting of the propensity score. Results: In total, 379 patients were included. The proportion of patients receiving a SAT was 40% in the entire cohort and 25% in survivors beyond 7 days. In bivariate analysis, the factors associated with prescribing a SAT in survivors were shorter pre-bacteremia ICU stay (p = 0.005), lower proportion of chronic renal failure history (p = 0.034), cancer (p = 0.042), or transplantation (p = 0.025), less frequent exposure to carbapenem within 3 months (p = 0.015). There was a higher proportion of septic shock (p = 0.017) or bacteremia secondary to pneumonia (p = 0.003) in the group of survivors receiving a LAT. After adjustment, no difference in survival was found between the two groups (HR: 1.65, 95%CI: 0.91–3.00, p = 0.10). Conclusion: In our cohort, one quarter of patients with ESBL-E bacteremia acquired in the ICU surviving beyond 7 days were treated with a SAT. SAT did not appear to affect survival. Patients who could benefit from a SAT need to be better identified.

Susceptibility of delafloxacin on 199 osteoarticular levofloxacin-resistant staphylococci strains was reported in 49% and 1% using SSTI S. aureus breakpoint (0.25 mg/L) and general S. aureus breakpoint (0.016 mg/L) respectively. Fifty percents levofloxacin-resistant staphylococci showed resistance to delafloxacin using CA-SFM/EUCAST recommendations. Microbiological societies should define new breakpoints especially for CoNS.

Abstract Background Immunosuppression at intensive care unit (ICU) admission has been associated with a higher incidence of ICU-acquired infections, some of them related to opportunistic pathogens. However, the association of immunosuppression with the incidence, microbiology and outcomes of ICU-acquired bacterial bloodstream infections (BSI) has not been thoroughly investigated. Methods Retrospective single-centered cohort study in France. All adult patients hospitalized in the ICU of Lille University-affiliated hospital for > 48 h between January 1st and December 31st, 2020, were included, regardless of their immune status. Immunosuppression was defined as active cancer or hematologic malignancy, neutropenia, hematopoietic stem cell and solid organ transplants, use of steroids or immunosuppressive drugs, human immunodeficiency virus infection and genetic immune deficiency. The primary objective was to compare the 28-day cumulative incidence of ICU-acquired bacterial BSI between immunocompromised and non-immunocompromised patients. Secondary objectives were to assess the microbiology and outcomes of ICU-acquired bacterial BSI in the two groups. Results A total of 1313 patients (66.9% males, median age 62 years) were included. Among them, 271 (20.6%) were immunocompromised at ICU admission. Severity scores at admission, the use of invasive devices and antibiotic exposure during ICU stay were comparable between groups. Both prior to and after adjustment for pre‐specified baseline confounders, the 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between immunocompromised and non-immunocompromised patients. The distribution of bacteria was comparable between groups, with a majority of Gram-negative bacilli (~ 64.1%). The proportion of multidrug-resistant bacteria was also similar between groups. Occurrence of ICU-acquired bacterial BSI was associated with a longer ICU length-of-stay and a longer duration of invasive mechanical ventilation, with no significant association with mortality. Immune status did not modify the association between occurrence of ICU-acquired bacterial BSI and these outcomes. Conclusion The 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between patients with and without immunosuppression at ICU admission.

Drug poisoning frequently leads to admission to intensive care units, often resulting in aspiration, a potentially life-threatening condition if not properly managed. Aspiration can manifest as either bacterial aspiration pneumonia (BAP) or aspiration pneumonitis (AP), which are challenging to distinguish potentially leading to overprescription of antibiotics and the emergence of multidrug-resistant bacteria. This study aims to assess the accuracy of the Infectious Diseases Society of America (IDSA) and British Thoracic Society (BTS) criteria in differentiating BAP from AP in comatose ventilated patients following drug poisoning. This cross-sectional study included 95 patients admitted for drug poisoning at the Lille University Hospital intensive care department, between 2013 and 2017, requiring mechanical ventilation and receiving antibiotics for aspiration. Patients were categorized as having bacterial complications if tracheal sampling yielded positive culture results, and if they were otherwise considered to have chemical complications. The sensitivity, specificity, positive predictive value, and negative predictive value of IDSA and BTS criteria in identifying patients with bacterial complications were evaluated. Among the patients, 34 (36%) experienced BAP. The IDSA criteria demonstrated a sensitivity of 62% and specificity of 33%, while the BTS criteria showed a sensitivity of 50% and specificity of 38%. Both the IDSA and BTS criteria exhibited poor sensitivity and specificity in identifying microbiologically confirmed pneumonia in comatose ventilated patients following drug poisoning.

Objective: Carbapenem resistance is increasing worldwide. Earlier detection of this resistance, combined with appropriate treatment, could improve the prognosis of bloodstream infection. This study aims to evaluate the detection of carbapenemase-producing Gram-negative bacteria directly from positive blood cultures to quickly adapt antibiotic therapy before the results of antibiotic susceptibility testing are available. Methods: A prospective single-centre study was conducted over a 5-month period at Lille University Hospital. Carbapenemase detection by immunochromatographic testing was performed directly from positive blood cultures with Gram-negative rods of 35 patients previously colonized with carbapenemase-producing bacteria. Results: Among these 35 positive blood cultures, 15 carbapenemase-producing strains were directly detected, mainly OXA-48 and NDM. This rapid procedure provided results in less than 1 h, compared to several hours for conventional methods. Of the patients with infections caused by carbapenemase-producing isolates, 67% (10 patients) received inappropriate empiric treatment, highlighting the potential of the rapid test to adjust antibiotic therapy sooner. Conclusions: Carbapenemase detection by immunochromatographic testing directly on blood culture pellets is reliable and can lead to early adaptation of antibiotic therapy in these severe infections.

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Novel therapeutic strategies are urgently needed to combat pneumonia caused by Streptococcus pneumoniae strains resistant to standard-of-care antibiotics. Previous studies have shown that targeted stimulation of lung innate immune defenses through intranasal administration of the Toll-like receptor 5 agonist flagellin improves the treatment of pneumonia when combined with antibiotics. To promote translation to the clinic application, this study assessed the direct delivery of flagellin to the airways through nebulization using a vibrating mesh nebulizer in mice. Intranasal delivery achieved approximately 40% lung deposition of the administered flagellin dose, whereas nebulization yielded less than 1%. Despite these differences, nebulized flagellin induced transient activation of lung innate immunity characterized by cytokine/chemokine production and neutrophil infiltration into airways analogous to intranasal administration. Furthermore, inhalation by nebulization resulted in an accelerated resolution of systemic pro-inflammatory responses. Lastly, adjunct therapy combining nebulized flagellin and amoxicillin proved effective against antibiotic-resistant pneumococcal pneumonia in mice. We posit that flagellin aerosol therapy represents a safe and promising approach to address bacterial pneumonia within the context of antimicrobial resistance.

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

A 16-year old girl consulted for repeated axillary abscesses. The bacteriological culture yielded monomicrobial Staphylococcus aureus. Faced with these recurrent abscesses in an immunocompetent patient playing a close contact sport, the biologist suspected the strain to harbor a virulence factor explaining these recurrences.

Sepsis-induced myopathy is characterized by muscle fiber atrophy, mitochondrial dysfunction, and worsened outcomes. Whether whole-body energy deficit participates in the early alteration of skeletal muscle metabolism has never been investigated. Three groups were studied: "Sepsis" mice, fed ad libitum with a spontaneous decrease in caloric intake (n = 17), and "Sham" mice fed ad libitum (Sham fed (SF), n = 13) or subjected to pair-feeding (Sham pair fed (SPF), n = 12). Sepsis was induced by the intraperitoneal injection of cecal slurry in resuscitated C57BL6/J mice. The feeding of the SPF mice was restricted according to the food intake of the Sepsis mice. Energy balance was evaluated by indirect calorimetry over 24 h. The tibialis anterior cross-sectional area (TA CSA), mitochondrial function (high-resolution respirometry), and mitochondrial quality control pathways (RTqPCR and Western blot) were assessed 24 h after sepsis induction. The energy balance was positive in the SF group and negative in both the SPF and Sepsis groups. The TA CSA did not differ between the SF and SPF groups, but was reduced by 17% in the Sepsis group compared with the SPF group (p < 0.05). The complex-I-linked respiration in permeabilized soleus fibers was higher in the SPF group than the SF group (p < 0.05) and lower in the Sepsis group than the SPF group (p < 0.01). Pgc1α protein expression increased 3.9-fold in the SPF mice compared with the SF mice (p < 0.05) and remained unchanged in the Sepsis mice compared with the SPF mice; the Pgc1α mRNA expression decreased in the Sepsis compared with the SPF mice (p < 0.05). Thus, the sepsis-like energy deficit did not explain the early sepsis-induced muscle fiber atrophy and mitochondrial dysfunction, but led to specific metabolic adaptations not observed in sepsis.

A bloodstream infection (BSI) is a severe ICU-acquired infection. A growing proportion is caused by multidrug-resistant bacteria (MDRB). COVID-19 was reported to be associated with a high rate of secondary infections. However, there is a lack of data on the relationship between COVID-19 and the incidence of MDRB ICU-acquired BSI. The aim of this study was to evaluate the relationship between COVID-19 and ICU-acquired BSI related to MDRB. This retrospective study was conducted in a single-center ICU during a one-year period. All adult patients admitted for more than 48 h were included. The cumulative incidence of ICU-acquired BSI related to MDRB was estimated using the Kalbfleisch and Prentice method. The association of COVID-19 status with the risk of ICU-acquired BSI related to MDRB was assessed using cause-specific Cox’s proportional hazard model. Among the 1320 patients included in the analysis, 497 (37.65%) had COVID-19. ICU-acquired BSI related to MDRB occurred in 50 patients (36 COVID patients (7%) and 14 non-COVID patients (1.6%)). Extended-spectrum beta-lactamase Enterobacteriacae (46%) and carbapenem-resistant Acinetobacter baumannii (30%) were the most commonly isolated MDRB. COVID-19 was significantly associated with a higher risk of MDRB ICU-acquired BSI (adjusted cHR 2.65 (1.25 to 5.59) for the whole study period). However, this relationship was only significant for the period starting at day 15 after ICU admission. ICU-acquired BSI related to MDRB was significantly associated with ICU mortality (HR (95%CI) 1.73 (1–3)), although COVID-19 had no significant impact on this association (p het 0.94). COVID-19 is significantly associated with an increased risk of ICU-acquired BSI related to MDRB, mainly during the period starting at day 15 after ICU admission.