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Key Points Measurement of NLRP3 inflammasome activation in the blood of patients reveals an impaired immature neutrophil response in severe COVID-19. Inflammasome signature analysis in circulating myeloid cells allows COVID-19 patients to be stratified and predicts evolution., Dysregulated immune response is the key factor leading to unfavorable coronavirus disease 2019 (COVID-19) outcome. Depending on the pathogen-associated molecular pattern, the NLRP3 inflammasome can play a crucial role during innate immunity activation. To date, studies describing the NLRP3 response during severe acute respiratory syndrome coronavirus 2 infection in patients are lacking. We prospectively monitored caspase-1 activation levels in peripheral myeloid cells from healthy donors and patients with mild to critical COVID-19. The caspase-1 activation potential in response to NLRP3 inflammasome stimulation was opposed between nonclassical monocytes and CD66b+CD16dim granulocytes in severe and critical COVID-19 patients. Unexpectedly, the CD66b+CD16dim granulocytes had decreased nigericin-triggered caspase-1 activation potential associated with an increased percentage of NLRP3 inflammasome impaired immature neutrophils and a loss of eosinophils in the blood. In patients who recovered from COVID-19, nigericin-triggered caspase-1 activation potential in CD66b+CD16dim cells was restored and the proportion of immature neutrophils was similar to control. Here, we reveal that NLRP3 inflammasome activation potential differs among myeloid cells and could be used as a biomarker of a COVID-19 patient’s evolution. This assay could be a useful tool to predict patient outcome. This trial was registered at www.clinicaltrials.gov as #NCT04385017., Visual Abstract

Objectives We aimed to evaluate the impact of an uninterrupted workflow regarding blood cultures on turnaround time and antibiotic prescription. Methods Monomicrobial episodes of bacteremia were retrospectively evaluated before and after a continuous 24/7 workflow was implemented in our clinical microbiology laboratory (pre- and post-intervention periods; PREIP and POSTIP). Primary outcome was the time from specimen collection to the first change in antibiotic therapy. Secondary outcomes included the time from specimen collection to effective antibiotic therapy and to antibiotic susceptibility testing results (or turnaround time), as well as hospital length of stay and all-cause mortality at 30 days. Results A total of 548 episodes of bacteremia were included in the final analysis. There was no difference in PREIP and POSTIP regarding patient characteristics and causative bacteria. In POSTIP, the mean time to the first change in antibiotic therapy was reduced by 10.4 h (p Conclusions Around the clock processing of blood cultures allows for a reduction in turnaround time, which in turn reduces the delay until effective antibiotic therapy prescription.

Bacillus cereus group species are widespread, Gram-positive, spore-forming environmental bacteria. B. cereus sensu stricto is one of the major causes of food poisoning worldwide. In high-risk individuals, such as preterm neonates, B. cereus infections can cause fatal infections. It is important to note that the phenotypic identification methods commonly used in clinical microbiology laboratories make no distinction between B. cereus sensu stricto and the other members of the group (Bacillus anthracis excluded). As a result, all the invasive infections attributed to B. cereus are not necessarily due to B. cereus sensu stricto but likely to other closely related species of the B. cereus group. Next-generation sequencing (NGS) should be used to characterize the whole genome of the strains belonging to the B. cereus group. This could confirm whether the strains involved in previously reported B. cereus invasive infections preferentially belong to formerly known or emerging individual species. Moreover, infections related to B. cereus group species have probably been overlooked, since their isolation in human bacteriological samples has for a long time been regarded as an environmental contaminant of the cultures. Recent studies have questioned the emergence or reemergence of B. cereus invasive infections in preterm infants. This review reports our current understanding of B. cereus infections in neonates, including taxonomical updates, microbiological characteristics, bacterial identification, clinical features, host-pathogen interactions, environmental sources of contamination, and antimicrobial resistance.

Clindamycin is an antibiotic with high bioavailability and appropriate bone diffusion, often proposed as an alternative in guidelines forA retrospective analysis was conducted at the University Hospital of Nice (France) between 2010 and 2019. We included patients with one shoulder implant surgical procedure and at least oneForty-eight SIJI were identified and 33 were treated with clindamycin, among which 25 were treated with monotherapy. The median duration of clindamycin antibiotherapy was 6 weeks. The average follow-up was 45 months; one patient was lost to follow-up. Twenty-seven patients out of 33 (82%) were cured with clindamycin, compared to 9/12 (75%) with other antibiotics. The rate of favorable outcomes increased to 27/31 (87%) with clindamycin and to 9/10 (90%) for other antibiotics when no septic revision strategies were excluded (The therapeutic strategy based on one- or two-stage revision associated with 6 weeks of clindamycin seems to be effective.

We report here the complete genome sequences of three Bacillus cereus group strains isolated from blood cultures from premature and immunocompromised infants hospitalized in intensive care units in three French hospitals. These complete genome sequences were obtained from a combination of Illumina HiSeq X Ten short reads and Oxford Nanopore MinION long reads.

Dalbavancin is a glycopeptide antibiotic with a long half-life, recently marketed in Europe for skin and soft-tissue infections (SSTIs), but its real-life use is not well known. The aim of this study was to describe all first prescriptions in France over an 16-month period. A retrospective study on all adult patients receiving at least one dose of dalbavancin from 1 June 2017 to 31 September 2018 was performed (75 patients from 29 French hospitals). Data were collected via a standard questionnaire. Failure was defined as persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment, and/or death from infection. The main indications were bone and joint infection (BJI) (64.0%), endocarditis (25.3%), and SSTI (17.3%). The main bacteria involved were Staphylococcus aureus (51.4%), including methicillin-resistant S. aureus (MRSA) (19.4%), and coagulase-negative staphylococci (44.4%). Median minimum inhibitory concentrations (MICs) for staphylococci to vancomycin and dalbavancin ranged from 0.875-2.0 mg/L and 0.032-0.064 mg/L, respectively. Dalbavancin was used after a mean of 2.3 ± 1.2 lines of antimicrobial treatment. The main treatment regimens for dalbavancin were a two-dose regimen (1500 mg each) in 38 cases (50.7%) and a single-dose regimen (1500 mg) in 13 cases (17.3%). Overall, at the patient's last visit, clinical cure was observed in 54/68 patients, whilst failure was observed in 14/68 patients. First use of dalbavancin in France was mostly off-label. Most were due to BJI, often as rescue therapy for severe infections. Even in off-label situations, dalbavancin appears safe and effective.

Nocardiopsis species are aerobic, gram-positive, non-acid fast rods isolated from soil, waters, and animals. They are opportunistic human pathogens, but very few cases have been published so far. We report the first case of fatal pulmonary infection related to Nocardiopsis dassonvillei in an immunocompetent patient with chronic obstructive pulmonary disease.

We describe here the first case of catheter-related bloodstream infection due to Pantoea eucrina in a 23-year-old female patient with colon adenocarcinoma and congenital hypogammaglobulinemia. In May 2018, she was admitted for fever and abdominal pain. Blood cultures withdrawn from peripheral inserted central catheter and periphery revealed the presence of Pantoea eucrina, with differential time of positivity in favor of catheter-related bloodstream infection. Catheter was removed and antibiotic started, with rapid recovery. Species of genus Pantoea are mainly environmental strains and plant pathogens, rarely responsible for human infection. Patient’s comorbid conditions and gut microbiota imbalance could have been responsible for such bacteremia. Identification of Pantoea eucrina was performed using the MALDI-TOF technique. Infections due to Pantoea eucrina were probably until recently underestimated, as older methods such as Phoenix frequently lead to false identification.

We propose the main characteristics of a new bacterium species named Nissabacter archeti strain 2134 (CSURP3445 = LT631518), isolated from pustule scalp of a 29-year-old man at hospital Archet 2, Nice, south of France.

Matrix-assisted laser desorption ionization–time of flight mass spectrometry is not widely used to identify bacteria directly from positive blood culture bottles (BCBs) because of overlong protocols. The objective of this work was to develop and evaluate a simple extraction protocol for reliable identification from BCBs. The 10-min protocol was applied over a 5-month period. Direct identifications on day 0 were compared with those obtained from colonies on day 1 [log(score) of ≥2]. We evaluated a range of seven log(score) thresholds on day 0 from 1.4 to 2.0 to find the lower confidence score that provides the higher percentage of direct identifications without loss of accuracy. With a log(score) threshold of ≥1.5 at day 0, our protocol allowed us to identify 80% of bacteria in 632 BCBs (96% of Enterobacteriaceae, 95% of Staphylococcus aureus, 92% of enterococci, and 62% of streptococci). At least one bacterial species of the mixture was identified in 77% of the polymicrobial samples. The rapidity and reliability of the protocol were factors in its adoption for routine use, allowing us to save up to 24 h in identifying 80% of the bacteria in the BCBs and, thus, to supply useful information to adapt antibiotic therapy when necessary. We currently provide reliable daily direct identifications of staphylococci, enterococci, Enterobacteriaceae, Pseudomonas aeruginosa, and beta-hemolytic streptococci.

International audience; Clostridium indolis is an anaerobic spore-forming Gram-positive bacillus belonging to the Clostridium saccharolyticum group. Its clinical significance in human remains poorly known. We describe the first case of osteitis related to C. indolis, identified by MALDI-TOF mass spectrometry and provide a literature review of human infections related to C. saccharolyticum group species.

International audience

The E3 ubiquitin ligase HACE1 is a potent tumor suppressor that controls cell proliferation and ubiquitylates the small GTPase Rac1 to target it to proteasomal degradation. Whether and how the activity of HACE1 is regulated by the N-terminal ankyrin (ANK) and the middle (MID) domains is ill defined. Here, we identified in the version 64 of the Catalogue of Somatic Mutations in Cancer (COSMIC) 13 missense mutations of hace1 located outside the HECT domain, and found that all lead to defective control of cell proliferation. In addition, several mutations located in the ankyrin domain displayed a dramatic reduction in Rac1 ubiquitylation associated with a decrease of colony formation in soft agar. 3D structure modelling of the 7 ankyrin-repeats coupled to functional analysis identified a surface epitope centered on one of the mutated residue, Gly-175, which is critical for controlling Rac1 binding and ubiquitylation. We also identified a role for the MID domain in conferring the specificity of association of HACE1 to the active form of Rac1. Our study of the functional interplay between HACE1 and Rac1 in cancer thus sheds a new light on the molecular mechanism of Rac1 ubiquitylation by HACE1 and the impact of its cancer-associated mutations in cell proliferation.

International audience; no abstract

The genus Actinotignum contains three species, Actinotignum schaalii (formerly Actinobaculum schaalii), Actinotignum urinale and Actinotignum sanguinis. A. schaalii is the species most frequently involved in human infections, with 172 cases, mostly urinary tract infections (UTIs), reported so far. Invasive infections have also been described. This facultative anaerobic Gram-positive rod is part of the urinary microbiota of healthy patients. It is responsible for UTIs, particularly in elderly men and young children. A. schaalii is an underestimated cause of UTIs because of its fastidious growth on usual media and difficulties associated with its identification using phenotypic methods. Indeed, this slow-growth bacterium requires blood-enriched media and an incubation time of 48 hours under anaerobic or 5% CO2 atmosphere. Furthermore, only matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) or molecular-based methods allow the accurate identification of this bacteria. MALDI-TOF using Microflex LT with the Biotyper database (Bruker Daltonics, Bremen, Germany) is the most reliable technology for the routine identification of A. schaalii. The identification of this uropathogen is all the more important because it is resistant to trimethoprim/sulfamethoxazole and second-generation quinolones that are widely used in the treatment of UTIs. Antimicrobial therapy using β-lactams prolonged for up to 2 weeks is the most efficient treatment and should be recommended. Microbiologists should assess the presence of A. schaalii in urine using appropriate culture and identification methods in the case of a direct examination that is positive for small coccoid rods, a negative nitrite urinary stick associated with leukocyturia, treatment failure with trimethoprim/sulfamethoxazole or fluoroquinolones, or undocumented, repeated UTIs.

We report here a rare case of chronic lumbar discitis caused by Clostridium perfringens in an elderly patient that was treated with a combination of β-lactams and clindamycin. Molecular analysis performed on the strain revealed an unusual toxin gene pattern.

We describe here a rare case of bladder wall necrosis associated with Actinobaculum schaalii in a 72-year-old patient with non-muscle-invasive bladder cancer (NMIBC). A. schaalii microbiological diagnosis requires high index of suspicion and accurate identification methods such as 16S rDNA sequencing or MALDI-TOF Mass spectrometry.