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Klebsiella pneumoniae (KP) is the most common cause of endogenous endophthalmitis (EE) in Asia, but data in Europe are scarce. We describe eight cases of KP EE compared to a cohort of EE in a French center. EE cases were retrospectively studied between January 2014 and January 2021. KP EE cases were analyzed to assess clinical, microbiological features, and outcome. Among the 33 EE cases identified, the first causative agent (24%, n = 8) was KP, mainly (7/8) with hypervirulent phenotype (hvKP). All but one of these cases occurred from December 2019 to January 2021. Contrary to non-KP patients, KP patients had multiple extraocular infective foci (p =.006), all presented with liver abscesses (p <.001), 50% had cerebral involvement (p =.13). Visual outcome was poor in both groups. KP is an emerging cause of EE in a French center, consistently associated with liver abscesses, frequent cerebral involvement, and predominance of hvKP strains. [ABSTRACT FROM AUTHOR]

To evaluate performances of the rapid multiplex PCR assay BioFire FilmArray Pneumonia Panel (FA-PP) for detection of bacterial pathogens and antibiotic resistance genes in sputum, endotracheal aspirate (ETA) and bronchoalveolar lavage (BAL) specimens. This prospective observational study was conducted in 11 French university hospitals (July to December 2018) and assessed performance of FA-PP by comparison with routine conventional methods. A total of 515 respiratory specimens were studied, including 58 sputa, 217 ETA and 240 BAL. The FA-PP detected at least one pathogen in 384 specimens, yielding an overall positivity rate of 74.6% (384/515). Of them, 353 (68.5%) specimens were positive for typical bacteria while eight atypical bacteria and 42 resistance genes were found. While identifying most bacterial pathogens isolated by culture (374/396, 94.4%), the FA-PP detected 294 additional species in 37.7% (194/515) of specimens. The FA-PP demonstrated positive percentage agreement and negative percentage agreement values of 94.4% (95% CI 91.7%–96.5%) and 96.0% (95% CI 95.5%–96.4%), respectively, when compared with culture. Of FA-PP false-negative results, 67.6% (46/68) corresponded to bacterial species not included in the panel. At the same semi-quantification level (in DNA copies/mL for FA-PP versus in CFU/mL for culture), the concordance rate was 43.4% (142/327) for culture-positive specimens with FA-PP reporting higher semi-quantification of ≥1 log 10 in 48.6% (159/327) of cases. Interestingly, 90.1% of detected bacteria with ≥106 DNA copies/mL grew significantly in culture. FA-PP is a simple and rapid molecular test that could complement routine conventional methods for improvement of diagnosis accuracy of pneumonia. [ABSTRACT FROM AUTHOR]

Reliable diagnostic methods are mandatory for effective management of Helicobacter pylori infection. Histology and culture are the most common invasive methods in current practice, even if molecular methods are gaining in importance. The performance of these conventional methods varies significantly. We conducted a retrospective study of 1540 adults and 504 children with gastric biopsies taken during endoscopy to assess the impact of bacterial load and the cagA virulence factor on the performance of H. pylori infection testing. The association between virulence and histology findings was also investigated. With 23S rRNA qPCR confirmed by glmM amplification as the gold standard, culture and histology had lower sensitivity, 74.4% and 73.3%, respectively. However, their sensitivity was enhanced (>90%) in biopsies with high bacterial load (qPCR Ct < 30). Positive cagA status of the strain was associated with high bacterial load (94.9%), thus resulting in more frequent positive culture (94.3%) and H. pylori histology detection (91.7%) and more severe lesions on histology (p < 0.001). Conversely, the cagA status of the strains was negative in 110/119 (92.4%) of biopsies with low bacterial load (qPCR Ct < 30), 82/90 (91.1%) with negative H. pylori histology detection and 119/131 (90%) with negative culture findings (p < 0.001). This study highlights the low sensitivity of conventional culture and histology that may lead to false negative diagnosis if used alone. H. pylori quantification associated with cagA genotyping in routine workflow are essential for a sensitive and reliable diagnosis, to identify patients at high risk and to manage eradication therapies. [ABSTRACT FROM AUTHOR]

• EE is associated with: 64% extra-ocular foci, 19% ICU management, 8% mortality. • EE is associated with: 49% final VA <20/400, 23% bulbar phthisis, 8% enucleation. • Initial VA, bacterial origin and vitrectomy are determinants of ocular outcomes. • We propose a management plan to improve diagnosis and medical management. To describe the clinical and microbiological characteristics of patients with endogenous endophthalmitis (EE), determine factors associated with outcome and propose a management plan for EE. Retrospective case series in two tertiary referral centers from 2010 to 2022. Sixty-four eyes of 53 patients were included. Bilateral involvement occurred for 11/53 patients (21%). Ocular symptoms were the only first manifestation of the disease in 36/53 (68%) of cases; signs of sepsis were evident in 17/53 (32%). Imaging tests detected at least one extraocular focus of infection in 34/53 patients (64%), with contrast-enhanced thoraco-abdominopelvic computed tomography showing relevant findings in 28/50 (56%) of cases. EE was microbiologically confirmed in 43/53 patients (81%); the organisms involved were: Gram-positive bacteria (19/53, 36%), Gram-negative bacteria (13/53, 25%) and Candida sp. (11/53, 21%). Klebsiella pneumoniae was the most common bacteria (10/32, 31%). Blood cultures were positive in 28/53 patients (53%) and eye samples in 11/41 eyes (27%). All patients were treated with systemic antimicrobial therapy, 39/64 eyes (61%) received anti-infective intravitreal injection(s) and 17/64 eyes (27%) underwent vitrectomy. Four patients (8%) died due to uncontrolled systemic infection. Final visual acuity (VA) was < 20/400 in 28/57 eyes (49%) and ocular structural loss (bulbar phthisis or enucleation/evisceration) was reported in 18/64 eyes (28%). In multivariate analysis, initial VA was the only parameter associated with visual and/or structural loss of the eye (OR = 24.44 (4.33-228.09) and 5.44 (1.33-26.18) respectively). EE remains a severe infection with a poor ocular outcome. We propose a standard protocol to improve diagnosis and medical management. [Display omitted] [ABSTRACT FROM AUTHOR]

IFN-gamma treatment led to a fast increase in HLA-DR SP high sp monocytes in all but one patient with rapidly fatal septic shock (patient #3). Patients were assessed for mHLA-DR expression and were then administered interferon (IFN)-gamma to restore activated monocytes and thereby improve lung defense. IFN-gamma treatment was based on mHLA-DR expression, a reliable biomarker of post-aggressive immune suppression, thereby accounting for a good example of personalized medicine in critically ill patients. [Extracted from the article]

Background: The 2011 4th European Conference on Infections in Leukemia (ECIL4) guidelines recommend antibiotics de-escalation/discontinuation in selected febrile neutropenia (FN) patients. We aimed to assess the impact of an antimicrobial stewardship (AMS) program based on these guidelines on antibiotics use and clinical outcomes in high-risk FN patients. Methods: We conducted an observational study in the hematology department of Cochin University Hospital in Paris, France. An ECIL4-based antibiotics de-escalation and discontinuation strategy was implemented jointly by the hematologists and the AMS team. The pre-intervention (January–October 2018) and post-intervention (January-October 2019) periods were compared. We retrospectively collected clinical and microbiological data. We compiled antibiotics consumptions via hospital pharmacy data and standardized them by calculating defined daily doses per 1000 patient-days. We analyzed the two-monthly antibiotic consumption using an interrupted time series method and built a composite endpoint for clinical outcomes based on transfer to the intensive care unit (ICU) and/or hospital death. Results: Overall, 273 hospital stays (164 patients) in the pre-intervention and 217 (148 patients) in the post-intervention periods were analyzed. Patients were mainly hospitalized for intensive chemotherapy for acute leukemia or autologous stem-cell transplant for myeloma. Patients were slightly younger in the pre-intervention compared to the post-intervention period (median age 60.4 vs 65.2 years, p = 0.049), but otherwise comparable. After implementation of the AMS program, glycopeptide and carbapenem use decreased by 85% (p = 0.03) and 72% (p = 0.04), respectively. After adjustment on confounders, the risk of transfer to the ICU/death decreased significantly after implementation of the AMS program (post-intervention period: odds-ratio = 0.29, 95% Confidence Interval: 0.15–0.53, p < 0.001). Conclusion: Implementation of a multidisciplinary AMS program for high-risk neutropenic patients was associated with lower carbapenem and glycopeptide use and improved clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Mass indoor gatherings were banned in early 2020 to prevent the spread of SARS-CoV-2. We aimed to assess, under controlled conditions, whether infection rates among attendees at a large, indoor gathering event would be similar to those in non-attendees, given implementation of a comprehensive prevention strategy including antigen-screening within 3 days, medical mask wearing, and optimised ventilation.Methods: The non-inferiority, prospective, open-label, randomised, controlled SPRING trial was done on attendees at a live indoor concert held in the Accor Arena on May 29, 2021 in Paris, France. Participants, aged 18-45 years, recruited via a dedicated website, had no comorbidities, COVID-19 symptoms, or recent case contact, and had had a negative rapid antigen diagnostic test within 3 days before the concert. Participants were randomly allocated in a 2:1 ratio to the experimental group (attendees) or to the control group (non-attendees). The allocation sequence was computer-generated by means of permuted blocks of sizes three, six, or nine, with no stratification. The primary outcome measure was the number of patients who were SARS-CoV-2-positive by RT-PCR test on self-collected saliva 7 days post-gathering in the per-protocol population (non-inferiority margin <0·35%). This trial is registered with ClinicalTrials.gov, NCT04872075.Findings: Between May 11 and 25, 2021, 18 845 individuals registered on the dedicated website, and 10 953 were randomly selected for a pre-enrolment on-site visit. Among 6968 who kept the appointment and were screened, 6678 participants were randomly assigned (4451 were assigned to be attendees and 2227 to be non-attendees; median age 28 years; 59% women); 88% (3917) of attendees and 87% (1947) of non-attendees complied with follow-up requirements. The day 7 RT-PCR was positive for eight of the 3917 attendees (observed incidence, 0·20%; 95% CI 0·09-0·40) and three of the 1947 non-attendees (0·15%; 0·03-0·45; absolute difference, 95% CI -0·26% to 0·28%), findings that met the non-inferiority criterion for the primary endpoint.Interpretation: Participation in a large, indoor, live gathering without physical distancing was not associated with increased SARS-CoV-2-transmission risk, provided a comprehensive preventive intervention was implemented.Funding: French Ministry of Health.Translation: For the French translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Rapid identification of SARS-CoV-2-infected individuals is a cornerstone for the control of virus spread. The sensitivity of SARS-CoV-2 RNA detection by RT-PCR is similar in saliva and nasopharyngeal swabs. Rapid molecular point-of-care tests in saliva could facilitate, broaden and speed up the diagnosis. We conducted a prospective study in two community COVID-19 screening centers to evaluate the performances of a CE-marked RT-LAMP assay (EasyCoV) designed for the detection of SARS-CoV2 RNA from fresh saliva samples, compared to nasopharyngeal RT-PCR, to saliva RT-PCR and to nasopharyngeal antigen testing. Overall, 117 of the 1718 participants (7%) tested positive with nasopharyngeal RT-PCR. Compared to nasopharyngeal RT-PCR, the sensitivity and specificity of the RT-LAMP assay in saliva were 34% and 97%, respectively. The Ct values of nasopharyngeal RT-PCR were significantly lower in the 40 true positive subjects with saliva RT-LAMP (Ct 25.9) than in the 48 false negative subjects with saliva RT-LAMP (Ct 28.4) (p = 0.028). Considering six alternate criteria for reference tests, including saliva RT-PCR and nasopharyngeal antigen, the sensitivity of saliva RT-LAMP ranged between 27 and 44%. The detection of SARS-CoV-2 in crude saliva samples with an RT-LAMP assay had a lower sensitivity than nasopharyngeal RT-PCR, saliva RT-PCR and nasopharyngeal antigen testing. Registration number: NCT04578509. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori (H pylori) is responsible for various diseases including cancer It co‐evolved with humans, and human migrations shaped the expansion and the diversity of strains around the world. The risk of developing a disease depends on virulence factors, mainly the cytotoxin‐associated gene A protein (CagA). The aim of this study was to determine the cagA status in H pylori strains from Mauritanian patients and to search for a relationship with endoscopic and histologic findings. Material and methods: H pylori was searched in gastric biopsies taken during endoscopy in patients with gastro‐duodenal symptoms. RT‐PCR was used for the diagnosis and resistance to clarithromycin. The cagA status was determined with PCR and the EPIYA‐cagA polymorphism with sequencing. Results: At all, 76/78 (97.4%) biopsies were positive. The rate of clarithromycin resistance was 4/76 (5.26%) due to the A2143G mutation, with a mixed population in 2 cases. The cagA gene was present in 23/76 (30.26%) biopsies, and the EPIYA motif was ABC in 21 (91.3%). High bacterial load and inflammation were significantly associated with cagA‐positive status (P <.01). Phylogenetic analysis of the glmM and hspA genes highlighted a mixture of African and European genes in strains of H pylori isolated from patients of Moor origin. Conclusion: We report a high prevalence of H pylori infection in Mauritanian patients, a low rate of clarithromycin resistance (5.26%) and high bacterial load and inflammation associated with cagA‐positive status. The phylogenetic analysis highlights the mix of different populations leading to the Moor ethnicity. [ABSTRACT FROM AUTHOR]