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Nosocomial infections remain a major threat for patients and a burden on healthcare institutions, hampering the public health economy. In intensive care units (ICUs), the most common life-threatening nosocomial infection [...]

Panton-Valentine leukocidin (PVL) is a cytotoxin produced by some strains of Staphylococcus aureus. These strains are responsible for primary skin infections and necrotizing pneumonia. This rare entity is mainly described [...]

National and international guidelines were recently published regarding the treatment of Enterobacteriaceae resistant to third-generation cephalosporins infections. We aimed to assess the implementation of the French guidelines in critically ill patients suffering from extended-spectrum β-lactamase-producing Enterobacteriaceae bloodstream infection (ESBL-E BSI). We conducted a retrospective observational cohort study in the ICU of three French hospitals. Patients treated between 2018 and 2022 for ESBL-E BSI were included. The primary assessment criterion was the proportion of adequate empirical carbapenem prescriptions, defined as prescriptions consistent with the French guidelines. Among the 185 included patients, 175 received an empirical anti-biotherapy within 24 h of ESBL-E BSI onset, with a carbapenem for 100 of them. The proportion of carbapenem prescriptions consistent with the guidelines was 81%. Inconsistent prescriptions were due to a lack of prescriptions of a carbapenem, while it was recommended in 25% of cases. The only factor independently associated with adequate empirical carbapenem prescription was ESBL-E colonization (OR: 107.921 [9.303–1251.910], p = 0.0002). The initial empirical anti-biotherapy was found to be appropriate in 83/98 patients (85%) receiving anti-biotherapy in line with the guidelines and in 56/77 (73%) patients receiving inadequate anti-biotherapy (p = 0.06). Our results illustrate the willingness of intensivists to spare carbapenems. Promoting implementation of the guidelines could improve the proportion of initial appropriate anti-biotherapy in critically ill patients with ESBL-E BSI. [ABSTRACT FROM AUTHOR]

Simple Summary: Sepsis is a life-threatening infection usually resulting in admission to an Intensive Care Unit, and is responsible for 1 in 5 deaths worldwide. Muscle weakness is a common and early complication of sepsis that impairs short- and long-term prognoses. It is characterized by muscle fiber atrophy and mitochondrial dysfunction. In addition, sepsis induces a negative imbalance in energy homeostasis, also associated with hospital complications. However, whether this energy deficit disrupts the metabolism in skeletal muscle has never been studied. Our study compared three groups of mice (sepsis with a spontaneous energy deficit, control without an energy deficit, and control with an energy deficit) to investigate the impact of energy debt on skeletal muscle in the first 24 h of sepsis. We demonstrated that a sepsis-like energy deficit was not in itself sufficient to alter muscle fiber size or the mitochondrial population, in contrast with sepsis. Conversely, an energy deficit led to important metabolic adaptations that were not found in sepsis. 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. [ABSTRACT FROM AUTHOR]

Byline: Fabio Ferrari (1,2), Qin Lu (1,2), Cassio Girardi (3), Olivier Petitjean (4), Charles-Hugo Marquette (5), Frederic Wallet (6), Jean-Jacques Rouby (1,2) Keywords: Nebulization; Ceftazidime; Pneumonia; Pseudomonas aeruginosa; Mechanical ventilation; Treatment Abstract: Purpose Ventilator-associated pneumonia caused by Pseudomonas aeruginosa with impaired sensitivity to ceftazidime is frequent in critically ill patients. The aim of the study was to compare lung tissue deposition and antibacterial efficiency between nebulized and intravenous administrations of ceftazidime in ventilated piglets with pneumonia caused by Pseudomonas aeruginosa with impaired sensitivity to ceftazidime. Methods Ceftazidime was administered 24 h following the intra-bronchial inoculation of Pseudomonas aeruginosa (minimum inhibitory concentration = 16 ug ml.sup.-1), either by nebulization (25 mg kg.sup.-1 every 3 h, n = 6) or by continuous intravenous infusion (90 mg kg.sup.-1 over 24 h after an initial rapid infusion of 30 mg kg.sup.-1, n = 6). Four non-treated inoculated animals served as controls. All piglets were killed 48 h (intravenous and control groups) or 51 h (aerosol group) after inoculation. Lung tissue concentrations and lung bacterial burden were assessed on multiple post-mortem sub-pleural lung specimens [(lower limit of quantitation = 10.sup.2 colony forming unit (cfu g.sup.-1)]. Results Ceftazidime trough lung tissue concentrations following nebulization were greater than steady-state lung tissue concentrations following continuous intravenous infusion [median and interquartile range, 24.8 (12.6--59.6) ug g.sup.-1 vs. 6.1 (4.6--10.8) ug g.sup.-1] (p < 0.001). After 24 h of ceftazidime administration, 83% of pulmonary segments had bacterial counts Conclusion Nebulized ceftazidime provides more efficient bacterial killing in ventilated piglets with pneumonia caused by Pseudomonas aeruginosa with impaired sensitivity to ceftazidime. Author Affiliation: (1) Reanimation Polyvalente Pierre Viars, Departement d'Anesthesie-Reanimation, UPMC Univ Paris 06, Hopital Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris, 47-83 boulevard de l'Hopital, 75013, Paris, France (2) Polyvalent Intensive Care Unit Pierre Viars, La Pitie-Salpetriere Hospital, University Pierre et Marie Curie, Paris, France (3) Department of Anesthesiology, Federal University of Sao Paulo, Escola Paulista de Medicina, Sao Paulo, Brazil (4) Department of Pharmacology, Avicenne Hospital, Bobigny, France (5) DHURE and INSERM U 416, University of Medicine, Lille, France (6) Department of Bacteriology, University of Medicine, Lille, France Article History: Registration Date: 17/07/2009 Received Date: 03/03/2009 Accepted Date: 08/07/2009 Online Date: 04/08/2009

In recent years, incidence and severity of invasive group A Streptococcus infections (iGAS) has increased in Europe and worldwide (1). The Centers for Disease Control and Prevention surveillance reports attest [...]

Bacterial infections of the respiratory tract constitute a major cause of death worldwide. Given the constant rise in bacterial resistance to antibiotics, treatment failure is increasingly frequent. In this context, innovative therapeutic strategies are urgently needed. Stimulation of innate immune cells in the respiratory tract [via activation of Toll-like receptors (TLRs)] is an attractive approach for rapidly activating the body's immune defenses against a broad spectrum of microorganisms. Previous studies of the TLR5 agonist flagellin in animal models showed that standalone TLR stimulation does not result in the effective treatment of pneumococcal respiratory infection but does significantly improve the therapeutic outcome of concomitant antibiotic treatment. Here, we investigated the antibacterial interaction between antibiotic and intranasal flagellin in a mouse model of pneumococcal respiratory infection. Using various doses of orally administered amoxicillin or systemically administered cotrimoxazole, we found that the intranasal instillation of flagellin (a dose that promotes maximal lung pro-inflammatory responses) induces synergistic rather than additive antibacterial effects against antibiotic–susceptible pneumococcus. We next set up a model of infection with pneumococcus that is resistant to multiple antibiotics in the context of influenza superinfection. Remarkably, the combination of amoxicillin and flagellin effectively treated superinfection with the amoxicillin-resistant pneumococcus since the bacterial clearance was increased by more than 100-fold compared to standalone treatments. Our results also showed that, in response to flagellin, the lung tissue generated an innate immune response even though it had been damaged by the influenza virus and pneumococcal infections. In conclusion, we demonstrated that the selective boosting of lung innate immunity is a conceptually advantageous approach for improving the effectiveness of antibiotic treatment and fighting antibiotic-resistant bacteria. [ABSTRACT FROM AUTHOR]

Starting from an approach that mobilizes a plural definition of proximity -- institutional, organizational and geographical -- in the aim of endogenizing the space in economic analysis, this article seeks to understand the dynamics of local economic spaces through a re-reading of the concept of local governance. Thus, it stresses the importance of institutional compromise-building processes in explaining the trajectories and the diversity of spatialized forms of economic coordination, and it tackles these by giving an operational definition to the concept of local governance. More precisely, it considers the mechanisms that explain the dynamics of local governance through the distinction between endogenous and exogenous dynamics, a distinction that accounts for the linkages between local governance and macro-economic regulation. Then, in the second part, these theoretical and methodological principles are tested in an analysis of the evolution of local governance in relation to the process of industrial conversion in the aerospace-defence industrial centre located in the Bordeaux conurbation.

To the Editor: Vibrio metschnikovii is a gram-negative, oxidase-negative bacillus. This species was isolated in 1981 from blood culture of an 82-year-old diabetic woman with cholecystitis (1). It was previously [...]

Objective: Lung tissue deposition of intravenous ceftazidime administered either continuously or intermittently was compared in ventilated piglets with experimental bronchopneumonia.Design: Prospective experimental studyAnimals: Eighteen anesthetized and ventilated pigletsInterventions: Bronchopneumonia was produced by the intrabronchial inoculation of Pseudomonas aeruginosa characterized by an impaired sensitivity to ceftazidime (MIC 16 mg/l). Ceftazidime was administered either through a continuous infusion of 90 mg/kg per 24 h after a bolus of 30 mg/kg or by an intermittent infusion of 30 mg/kg per 8 h.Measurements and Results: Piglets were killed 24 h after the initiation of continuous ceftazidime (n = 6), and 1 h (peak, n = 6) and 8 h (trough, n = 6) after the third dose following intermittent administration. Lung tissue concentrations of ceftazidime, measured by HPLC, and lung bacterial burden were assessed on multiple postmortem lung specimens. During continuous administration ceftazidime lung tissue concentrations were 9.7 +/- 3.8 microg/g. Following intermittent administration peak and trough lung tissue concentrations were, respectively, 7.1 +/- 2.4 microg/g and 0.6 +/- 1 microg/g. Lung bacterial burden was different after continuous and intermittent administration (median 7.10(3) vs. 4.10(2) cfu/g).Conclusions: Continuous infusion of ceftazidime maintained higher tissue concentrations than intermittent administration. [ABSTRACT FROM AUTHOR]

Objectives: Evaluation of the efficacy of empirical aminoglycoside in critically ill patients with bloodstream infections caused by extended-spectrum β-lactamase producing Enterobacteriaceae (ESBL-E BSI). Methods: Patients treated between 2011 and 2018 for ESBL-E BSI in the ICU of six French hospitals were included in a retrospective observational cohort study. The primary endpoint was mortality on day 30. Results: Among 307 patients, 169 (55%) were treated with empirical aminoglycoside. Death rate was 40% (43% with vs. 39% without aminoglycoside, p = 0.55). Factors independently associated with death were age ≥70 years (OR: 2.67; 95% CI: 1.09–6.54, p = 0.03), history of transplantation (OR 5.2; 95% CI: 1.4–19.35, p = 0.01), hospital acquired infection (OR 8.67; 95% CI: 1.74–43.08, p = 0.008), vasoactive drugs >48 h after BSI onset (OR 3.61; 95% CI: 1.62–8.02, p = 0.001), occurrence of acute respiratory distress syndrome (OR 2.42; 95% CI: 1.14–5.16, p = 0.02), or acute renal failure (OR 2.49; 95% CI: 1.14–5.47, p = 0.02). Antibiotherapy appropriateness was more frequent in the aminoglycoside group (91.7% vs. 77%, p = 0.001). Rate of renal impairment was similar in both groups (21% vs. 24%, p = 0.59). Conclusions: In intensive care unit (ICU) patients with ESBL-E BSI, empirical treatment with aminoglycoside was frequent. It demonstrated no impact on mortality, despite increasing treatment appropriateness. [ABSTRACT FROM AUTHOR]

Two published unrelated case reports, one in France and one in Italy, describe infections due to Bacillus subtilis strains resistant to erythromycin and penicillin. While the Italian isolate was correlated to a national probiotic, the French strain differed from the probiotic available in France. 16S rRNA sequencing of the two clinical isolates and the respective probiotics revealed 100% identity of both clinical isolates to the Italian probiotic and classified the strains as Bacillus clausii, while the French probiotic was found to be Bacillus thuringiensis. The present report raises the difficulty of confirming strain identities and thus causal links between probiotic or alimentary microorganisms and strains isolated from immuno-suppressed hosts. [ABSTRACT FROM AUTHOR]

Among the coagulase-negative staphylococci, Staphylococcus sciuri has rarely been described as the aetiology of continuous ambulatory peritoneal dialysis (CAPD) peritonitis. It has been reported in 1 case of endocarditis and has been isolated from peritoneal dialysis fluid in 2 patients. The case reported here describes CAPD peritonitis due to S. sciuri shortly after a previous episode due to S. aureus, showing the necessity to identify coagulase-negative staphylococci to find new species that cause CAPD peritonitis. [ABSTRACT FROM AUTHOR]

Human infections with Pasteurella multocida are frequently attributed to transmission from animals. Although some cases of prosthetic implant infections have been described few gynecological cases have been reported. We describe a case of intrauterine device endometritis due to P. multocida. [ABSTRACT FROM AUTHOR]