68 research outputs found
NLRP3 activation during S. aureus or E. coli bacteremia and in the course of SARS-CoV-2 infection
No full textA la phase précoce d’une infection bactérienne ou virale l’immunité innée est capable de détecter certains motifs microbiens conservés (PAMP) reconnus par des récepteurs dédiés à ces motifs (PRR) permettant ainsi d’amorcer la réaction pro-inflammatoire via différentes voies de signalisation. Les inflammasomes représentent une catégorie de PRR capable de transformer la pro-IL-1β et la pro-IL-18 en cytokines pro-inflammatoires actives ainsi que d’induire une mort cellulaire pro-inflammatoire nommée pyroptose. NLRP3 est l’inflammasome le plus étudié. De nombreuses bactéries et de nombreux virus ont été décrits comme pouvant soit activer soit inhiber l’inflammasome NLRP3 mais l’implication clinique de cette activation ou inhibition, reste pour le moment indéterminée. L’objectif de ma thèse était d’étudier l’implication de l’inflammasome NLRP3 au cours de la bactériémie chez l’homme. L’apparition de l’épidémie de COVID-19 nous a permis d’élargir cette étude à l’infection par le SARS-CoV-2. Le protocole NLRP3-BACT nous a permis de mettre en œuvre un test cellulaire à partir du sang total afin d’évaluer le niveau d’activation de la Caspase-1 dans les monocytes et polynucléaires neutrophiles (PNN) ainsi que le potentiel d’activation de l’inflammasome NLRP3 dans ces cellules chez des patients présentant une bactériémie à S. aureus ou E. coli via une analyse par cytométrie en flux (signal FAM-FLICA).Le protocole CoVinnate avait pour objectif l’utilisation du test cellulaire précédemment mentionné afin de décrire l’activation d’une partie du système immunitaire inné dans les différentes cellules myéloïdes circulantes des patients COVID-19 ainsi que l’évaluation de ce test en tant qu’outil pronostique.Pour NLRP3-BACT 22 patients ont été inclus depuis le début de de l’étude, 16 ont bénéficié d’une analyse cytométrique. Dans cette première série de patients inclus nous avons mis en évidence que les monocytes présentent un potentiel d’activation de la Caspase-1 par Nigéricine+LPS plus important que les donneurs sains. Par ailleurs, l’activation basale de cette caspase dans les monocytes est plus importante chez les patients de réanimation et ceux infectés par E. coli. Enfin la multiplication de la MFI du signal FAM-FLICA induite par Nigéricine+LPS est plus important pour les patients de médecine comparativement aux patients de réanimation.Pour CoVinnate, 66 patients COVID-19 et 24 donneurs sains ont été inclus durant la période de l’étude. Dans les cellules CD66b+ CD16dim nous avons observé une diminution significative du signal de la sonde FAM-FLICA chez les patients les plus sévères comparativement aux témoins. Au sein des granulocytes, l’activation de la Caspase-1 induite par la Nigéricine était altérée dans les granulocytes CD66b+ CD16dim selon le degré de sévérité des patients. Nous avons enregistré une augmentation de l’activation de NLRP3 induite par la Nigéricine dans les monocytes non-classiques isolés chez les patients les plus graves, cet effet était inversement corrélé au nombre total de monocytes non-classiques. Chez les patients les plus sévères on notait une augmentation du nombre de cellules CD66b+CD16dimCD15+CD10- correspondant à des neutrophiles immatures. Nous avons utilisé la diminution des monocytes non-classiques et le défaut d’activation de NLRP3 par la Nigéricine des granulocytes CD66b+ CD16dim pour construire un score pronostique. Nous avons mis en évidence une corrélation entre ce score et le rapport SpO2 / FiO2 le jour de l’inclusion ainsi que 48 heures plus tard. Nous avons également constaté une association significative de ces deux marqueurs avec l’évolution finale des patients. Mon travail a permis de mieux comprendre l’implication de l’inflammasome NLRP3 chez l’homme au cours de la bactériémie et durant l’infection à SARS-CoV-2. Nous envisageons d’utiliser ces travaux pour caractériser la réponse des patients aux traitements immunomodulateurs utilisés dans la COVID-19 notamment les corticoïdes.At the early phase of bacterial or viral infections, innate immunity is able to detect some conserved microbial motifs (PAMP) recognized by receptors dedicated to these motifs (PRR), thus making it possible to initiate the pro-inflammatory reaction via different signaling pathways. Inflammasomes represent a family of PRR able to transform pro-IL-1β and pro-IL-18 into active pro-inflammatory cytokines as well as inducing a pro-inflammatory cell death called pyroptosis. NLRP3 is the most studied inflammasome. Many bacteria and viruses have been described as being able to either activate or inhibit the NLRP3 inflammasome, but the clinical implication of this activation or inhibition, under the control of a particular microorganism, remains undetermined at this time.The objective of my thesis was to study the involvement of the NLRP3 inflammasome during bacteremia in humans. The onset of the COVID-19 epidemic allowed us to expand this study to SARS-CoV-2 infection.The NLRP3-BACT protocol allowed us to implement a cellular test performed on whole blood to assess the level of Caspase-1 activation in monocytes and polymorphonuclear neutrophils (PMN) as well as the activation potential of the NLRP3 inflammasome in these cells in patients with S. aureus or E. coli bacteremia via flow cytometry (fluorescent inhibitor probe, FAM-FLICA).The objective of the CoVinnate protocol was to use the aforementioned cellular test to describe the activation of a part of the innate immune system in the various circulating myeloid cells of COVID-19 patients as well as the evaluation of this test as a prognostic tool.For NLRP3-BACT 22 patients have been included since the start of the study, 16 have undergone cytometric analysis. In this first series of patients included, we demonstrated that monocytes have a greater potential for Caspase-1 activation by Nigericin+LPS than healthy donors. In addition, basal activation of this caspase in monocytes is greater in intensive care patients and in those infected with E. coli compared to the ID ward and S. aureus respectively. Finally, the multiplication of the MFI of the FAM-FLICA signal induced by Nigericin + LPS is more important for medical patients compared to intensive care patients.For CoVinnate, 66 COVID-19 patients and 24 healthy donors were included during the study period. In CD66b+ CD16dim cells, we observed a significant decrease of the FAM-FLICA probe signal in the most severe patients compared to the controls. Within granulocytes, the activation of Caspase-1 induced by Nigericin was decreased in CD66b+ CD16dim cells according to the severity of the patients. We recorded an increase in Nigericin-induced activation of NLRP3 in non-classical monocytes isolated from the most severe patients, this effect was inversely correlated with the total number of non-classical monocytes. In the most severe patients there was an increase in the number of CD66b+CD16dimCD15+CD10- cells corresponding to immature neutrophils.We used the decreased number in non-classical monocytes and the failure of NLRP3 activation upon nigericin activation in CD66b + CD16dim granulocytes to build a prognostic score. We found a correlation between this score and the SpO2 / FiO2 ratio on the day of inclusion as well as 48 hours later. We also found a significant association of these two markers with the final outcome of the patients.My work has led to a better understanding of the involvement of the NLRP3 inflammasome in humans during bacteremia and during SARS-CoV-2 infection. We plan to use this work to characterize the response of patients to immunomodulatory treatments used in COVID-19, including corticosteroids
Activation de l’inflammasome NLRP3 au cours des bactériémies à E. coli ou S. aureus et durant l’infection à SARS-CoV-2
No full textAt the early phase of bacterial or viral infections, innate immunity is able to detect some conserved microbial motifs (PAMP) recognized by receptors dedicated to these motifs (PRR), thus making it possible to initiate the pro-inflammatory reaction via different signaling pathways. Inflammasomes represent a family of PRR able to transform pro-IL-1β and pro-IL-18 into active pro-inflammatory cytokines as well as inducing a pro-inflammatory cell death called pyroptosis. NLRP3 is the most studied inflammasome. Many bacteria and viruses have been described as being able to either activate or inhibit the NLRP3 inflammasome, but the clinical implication of this activation or inhibition, under the control of a particular microorganism, remains undetermined at this time.The objective of my thesis was to study the involvement of the NLRP3 inflammasome during bacteremia in humans. The onset of the COVID-19 epidemic allowed us to expand this study to SARS-CoV-2 infection.The NLRP3-BACT protocol allowed us to implement a cellular test performed on whole blood to assess the level of Caspase-1 activation in monocytes and polymorphonuclear neutrophils (PMN) as well as the activation potential of the NLRP3 inflammasome in these cells in patients with S. aureus or E. coli bacteremia via flow cytometry (fluorescent inhibitor probe, FAM-FLICA).The objective of the CoVinnate protocol was to use the aforementioned cellular test to describe the activation of a part of the innate immune system in the various circulating myeloid cells of COVID-19 patients as well as the evaluation of this test as a prognostic tool.For NLRP3-BACT 22 patients have been included since the start of the study, 16 have undergone cytometric analysis. In this first series of patients included, we demonstrated that monocytes have a greater potential for Caspase-1 activation by Nigericin+LPS than healthy donors. In addition, basal activation of this caspase in monocytes is greater in intensive care patients and in those infected with E. coli compared to the ID ward and S. aureus respectively. Finally, the multiplication of the MFI of the FAM-FLICA signal induced by Nigericin + LPS is more important for medical patients compared to intensive care patients.For CoVinnate, 66 COVID-19 patients and 24 healthy donors were included during the study period. In CD66b+ CD16dim cells, we observed a significant decrease of the FAM-FLICA probe signal in the most severe patients compared to the controls. Within granulocytes, the activation of Caspase-1 induced by Nigericin was decreased in CD66b+ CD16dim cells according to the severity of the patients. We recorded an increase in Nigericin-induced activation of NLRP3 in non-classical monocytes isolated from the most severe patients, this effect was inversely correlated with the total number of non-classical monocytes. In the most severe patients there was an increase in the number of CD66b+CD16dimCD15+CD10- cells corresponding to immature neutrophils.We used the decreased number in non-classical monocytes and the failure of NLRP3 activation upon nigericin activation in CD66b + CD16dim granulocytes to build a prognostic score. We found a correlation between this score and the SpO2 / FiO2 ratio on the day of inclusion as well as 48 hours later. We also found a significant association of these two markers with the final outcome of the patients.My work has led to a better understanding of the involvement of the NLRP3 inflammasome in humans during bacteremia and during SARS-CoV-2 infection. We plan to use this work to characterize the response of patients to immunomodulatory treatments used in COVID-19, including corticosteroids.A la phase précoce d’une infection bactérienne ou virale l’immunité innée est capable de détecter certains motifs microbiens conservés (PAMP) reconnus par des récepteurs dédiés à ces motifs (PRR) permettant ainsi d’amorcer la réaction pro-inflammatoire via différentes voies de signalisation. Les inflammasomes représentent une catégorie de PRR capable de transformer la pro-IL-1β et la pro-IL-18 en cytokines pro-inflammatoires actives ainsi que d’induire une mort cellulaire pro-inflammatoire nommée pyroptose. NLRP3 est l’inflammasome le plus étudié. De nombreuses bactéries et de nombreux virus ont été décrits comme pouvant soit activer soit inhiber l’inflammasome NLRP3 mais l’implication clinique de cette activation ou inhibition, reste pour le moment indéterminée. L’objectif de ma thèse était d’étudier l’implication de l’inflammasome NLRP3 au cours de la bactériémie chez l’homme. L’apparition de l’épidémie de COVID-19 nous a permis d’élargir cette étude à l’infection par le SARS-CoV-2. Le protocole NLRP3-BACT nous a permis de mettre en œuvre un test cellulaire à partir du sang total afin d’évaluer le niveau d’activation de la Caspase-1 dans les monocytes et polynucléaires neutrophiles (PNN) ainsi que le potentiel d’activation de l’inflammasome NLRP3 dans ces cellules chez des patients présentant une bactériémie à S. aureus ou E. coli via une analyse par cytométrie en flux (signal FAM-FLICA).Le protocole CoVinnate avait pour objectif l’utilisation du test cellulaire précédemment mentionné afin de décrire l’activation d’une partie du système immunitaire inné dans les différentes cellules myéloïdes circulantes des patients COVID-19 ainsi que l’évaluation de ce test en tant qu’outil pronostique.Pour NLRP3-BACT 22 patients ont été inclus depuis le début de de l’étude, 16 ont bénéficié d’une analyse cytométrique. Dans cette première série de patients inclus nous avons mis en évidence que les monocytes présentent un potentiel d’activation de la Caspase-1 par Nigéricine+LPS plus important que les donneurs sains. Par ailleurs, l’activation basale de cette caspase dans les monocytes est plus importante chez les patients de réanimation et ceux infectés par E. coli. Enfin la multiplication de la MFI du signal FAM-FLICA induite par Nigéricine+LPS est plus important pour les patients de médecine comparativement aux patients de réanimation.Pour CoVinnate, 66 patients COVID-19 et 24 donneurs sains ont été inclus durant la période de l’étude. Dans les cellules CD66b+ CD16dim nous avons observé une diminution significative du signal de la sonde FAM-FLICA chez les patients les plus sévères comparativement aux témoins. Au sein des granulocytes, l’activation de la Caspase-1 induite par la Nigéricine était altérée dans les granulocytes CD66b+ CD16dim selon le degré de sévérité des patients. Nous avons enregistré une augmentation de l’activation de NLRP3 induite par la Nigéricine dans les monocytes non-classiques isolés chez les patients les plus graves, cet effet était inversement corrélé au nombre total de monocytes non-classiques. Chez les patients les plus sévères on notait une augmentation du nombre de cellules CD66b+CD16dimCD15+CD10- correspondant à des neutrophiles immatures. Nous avons utilisé la diminution des monocytes non-classiques et le défaut d’activation de NLRP3 par la Nigéricine des granulocytes CD66b+ CD16dim pour construire un score pronostique. Nous avons mis en évidence une corrélation entre ce score et le rapport SpO2 / FiO2 le jour de l’inclusion ainsi que 48 heures plus tard. Nous avons également constaté une association significative de ces deux marqueurs avec l’évolution finale des patients. Mon travail a permis de mieux comprendre l’implication de l’inflammasome NLRP3 chez l’homme au cours de la bactériémie et durant l’infection à SARS-CoV-2. Nous envisageons d’utiliser ces travaux pour caractériser la réponse des patients aux traitements immunomodulateurs utilisés dans la COVID-19 notamment les corticoïdes
Bacterial infections in solid organ transplant recipients
No full textPurpose of review: Bacteria are the leading cause of infections in solid organ transplant (SOT) recipients, significantly impacting patient outcome. Recently detailed and comprehensive epidemiological data have been published.
Recent finding: This literature review aims to provide an overview of bacterial infections affecting different types of SOT recipients, emphasizing underlying risk factors and pathophysiological mechanisms.
Summary: Lung transplantation connects two microbiotas: one derived from the donor's lower respiratory tract with one from the recipient's upper respiratory tract. Similarly, liver transplantation involves a connection to the digestive tract and its microbiota through the bile ducts. For heart transplant recipients, specific factors are related to the management strategies for end-stage heart failure based with different circulatory support tools. Kidney and kidney-pancreas transplant recipients commonly experience asymptomatic bacteriuria, but recent studies have suggested the absence of benefice of routine treatment. Bloodstream infections (BSI) are frequent and affect all SOT recipients. Nonorgan-related risk factors as age, comorbidity index score, and leukopenia contribute to BSI development. Bacterial opportunistic infections have become rare in the presence of efficient prophylaxis. Understanding the epidemiology, risk factors, and pathophysiology of bacterial infections in SOT recipients is crucial for effective management and improved patient outcomes.</p
Patients with community-acquired bacteremia of unknown origin: clinical characteristics and usefulness of microbiological results for therapeutic issues: a single-center cohort study
No full textAbstract Bacteremia of unknown origin (BUO) are associated with increased mortality compared to those with identified sources. Microbiological data of those patients could help to characterize an appropriate empirical antibiotic treatment before bloodcultures results are available during sepsis of unknown origin. Based on the dashboard of our ward that prospectively records several parameters from each hospitalization, we report 101 community-acquired BUO selected among 1989 bacteremic patients from July 2005 to April 2016, BUO being defined by the absence of clinical and paraclinical infectious focus and no other microbiological samples retrieving the bacteria isolated from blood cultures. The in-hospital mortality rate was 9%. We retrospectively tested two antibiotic associations: amoxicillin–clavulanic acid + gentamicin (AMC/GM) and 3rd generation cephalosporin + gentamicin (3GC/GM) considered as active if the causative bacteria was susceptible to at least one of the two drugs. The mean age was 71 years with 67% of male, 31 (31%) were immunocompromised and 52 (51%) had severe sepsis. Eleven patients had polymicrobial infections. The leading bacterial species involved were Escherichia coli 25/115 (22%), group D Streptococci 12/115 (10%), viridans Streptococci 12/115 (10%) and Staphylococcus aureus 11/115 (9%). AMC/GM displayed a higher rate of effectiveness compared to 3GC/GM: 100/101 (99%) vs 94/101 (93%) (p = 0.04): one Enterococcus faecium strain impaired the first association, Bacteroides spp. and Enterococcus spp. the second. In case of community-acquired sepsis of unknown origin, AMC + GM should be considered
Managing ESBL-producing Enterobacteriaceae-related urinary tract infection in primary care: a tool kit for general practitioners
No full textCefoxitin-based antibiotic therapy for extended-spectrum β-lactamase-producing Enterobacteriaceae prostatitis: a prospective pilot study
No full textFast track consultation in the infectious diseases department of a French university hospital: evaluation of the service delivered to the general practitioner
No full textTime-to-detection in culture of Mycobacterium tuberculosis: performance for assessing index cases contact-positivity
No full textObjectives: Time-to-detection (TTD) in culture on liquid media is inversely correlated to bacillary load and should be a contributing factor for assessing tuberculosis transmission. We wanted to assess if TTD was a better alternative than smear status to estimate transmission risk. Methods: From October 2015 to June 2022, we retrospectively studied a cohort of index cases (IC) with pulmonary tuberculosis (tuberculosis disease [TD]) from which samples were culture-positive before treatment. We studied the correlation between TTD and contact-positivity (CP) of IC contacts: CP was defined as CP = 1 (CP group) in case of TD or latent tuberculosis infection (LTI) in at least one screened contact of an IC, and CP = 0 otherwise (contact-negativity [CN] group). Univariate and multivariable analyses (logistic regression) were done. Results: Of the 185 IC, 122 were included, generating 846 contact cases of which 705 were assessed. A transmission event (LTI or TD) was identified in 193 contact cases (transmission rate: 27%). At day 9, 66% and 35% of the IC had their sample positive in culture for CP and CN groups, respectively. Age and TTD ≤9 days were independent criteria of CP (odds ratio 0.97, confidence interval [0.95-0.98], P = 0.002 and odds ratio 3.52, confidence interval [1.59-7.83], P = 0.001, respectively). Conclusion: TTD was a more discriminating parameter than smear status to evaluate the transmission risk of an IC with pulmonary tuberculosis. Therefore, TTD should be considered in the contact-screening strategy around an IC
Clindamycin Efficacy for Cutibacterium acnes Shoulder Device-Related Infections
No full textClindamycin is an antibiotic with high bioavailability and appropriate bone diffusion, often proposed as an alternative in guidelines for C. acnes prosthetic joint infections. We aimed to evaluate the efficacy of clindamycin in the treatment of C. acnes shoulder implant joint infections (SIJI). Methods: A 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 one C. acnes positive sample. We selected the C. acnes SIJI according to French and international recommendations. The primary endpoint was favorable outcome of C. acnes SIJI treatment after at least 1-year follow-up in the clindamycin group compared to another therapeutic group. Results: Forty-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 (P = 1.00). Conclusions: The therapeutic strategy based on one- or two-stage revision associated with 6 weeks of clindamycin seems to be effective
What Place Is There for Long-Acting Antibiotics in the Management of Gram-Positive Infections? A Qualitative Cross-Sectional Study
No full textObjectives. To identify the current practices with long half-life lipoglycopeptides (LGPs) and potential use/position of oritavancin. Results. Despite their indication being limited to skin and soft tissue infections (SSTIs), long half-life lipoglycopeptides are mainly used off-label to treat bone and joint infections (BJIs) and infective endocarditis. Oritavancin and dalbavancin are both semisynthetic lipoglycopeptide antibiotics with activity against Gram-positive organisms. The game-changing property of these two antibiotics is their one-time dosing. Due to its shorter half-life, oritavancin might have an advantage over dalbavancin for a treatment duration of less than 2 weeks, as it could be used both in prolonged treatments of complicated patients in BJIs or administered as a single-dose treatment for Gram-positive cocci infections usually treated by a 5- to 10-day antibiotic course. These infections include urinary tract infections, bacteremias, catheter-related infections, etc. In addition to the possibility of being used as an end-of-treatment injection, oritavancin could be used as an empiric therapy treatment in the postoperative period in the context of device-associated especially prosthetic joint infections to allow for the early discharge of the patient. Methods. A qualitative survey was conducted in March 2022 including sixteen infectiologists, one internist, five hospital pharmacists, and one pharmacologist. Conclusion. Long half-life lipoglycopeptides contribute to changing the paradigm in the management of acute bacterial infections, as infectiologists now consider a range of indications and patient profiles for one single drug. Oritavancin strengthens the therapeutic arsenal in numerous infections from BJIs to urinary tract infections and could help to manage specific clinical situations, on top of providing potential benefits for the hospital’s budget
- …
