Suppressive antibiotic therapy for infectious endocarditis.

OBJECTIVES: Suppressive antibiotic therapy (SAT) is a long-term antibiotic strategy at times applied when an indicated surgical management of infective endocarditis (IE) is not possible. Our aim was to describe the characteristics and outcomes of patients having received SAT for IE. METHODS: We conducted a retrospective, observational study at Strasbourg University Hospital, France between January 2020 and May 2023. We reviewed all medical files taken into consideration at weekly meetings of the local Multidisciplinary Endocarditis Team (MET) during the study period. We included patients having received SAT following the MET evaluation. The primary endpoint was all-cause mortality at most recent follow-up. Secondary endpoints included all-cause mortality at 3 and 6 months, infection relapse, and tolerance issues attributed to SAT. RESULTS: The MET considered 251 patients during the study time, among whom 22 (9 %) had received SAT. Mean age was 77.2 ± 12.3 years. Patients were highly comorbid with a mean Charlson index score of 6.6 ± 2.5. Main indication for SAT was surgery indicated but not performed or an infected device not removed (20/22). Fourteen patients had prosthetic valve IE, including 9 TAVIs. Six patients had IE affecting cardiac implantable electronic devices. Staphylococcus aureus and enterococci were the main bacteria involved (6/22 each). Median follow-up time was 249 days (IQR 95-457 days). Mortality at most recent follow-up was 23 % (5/22). Three patients (14 %) presented tolerance issues attributed to SAT, and two patients suffered late infectious relapse. CONCLUSION: Mortality at most recent follow-up was low and tolerance issues were rare for patients under SAT, which might be a palliative approach to consider when optimal surgery or device removal is not possible.

Incidence and Time-to-Onset of Carbapenemase-Producing Enterobacterales (CPE) Infections in CPE Carriers: a Retrospective Cohort Study.

This study aimed to assess the proportion of carbapenemase-producing Enterobacterales (CPE) infections among all infectious episodes in CPE carriers, compare the time-to-onset of CPE infections with that of other infections, assess the mortality of patients with CPE infections, and identify risk factors for CPE infections in CPE carriers. A retrospective cohort study was performed over a 10-year period in our University Hospital, and 274 CPE carriers were identified. All infectious episodes within the first 6 months following the diagnosis of CPE rectal carriage were considered. Risk factor analysis for CPE infections in CPE carriers was performed by univariate and multivariate analyses. This study revealed an incidence of 24.1% (66/274) of CPE infection within 6 months of CPE carriage diagnosis. The 28-day all-cause mortality due to CPE infections was 25.7%. CPE infections represented 52.6% (70/133) of all infectious episodes in CPE carriers in the first 6 months following CPE carriage detection, and these significantly occurred earlier than non-CPE infections, with a median time of 15 versus 51 days, respectively (P < 0.01). Based on the multivariate analysis, prior neurological disease was the only risk factor associated with CPE infections in CPE carriers. CPE infections have an early onset, accounting for a large proportion of infections in CPE carriers, and are associated with high mortality. IMPORTANCE Carbapenemase-producing Enterobacterales (CPE) infections are emerging infections and may represent a therapeutic challenge, while effective antibiotic therapy is likely to be delayed. We aimed to assess the proportion of CPE infections in CPE carriers and to identify risk factors of CPE infections among this population that could guide empirical antibiotic therapy. We showed that CPE infections are frequent in CPE carriers, have an early onset after CPE carriage diagnosis, and represent a significant proportion of all infectious episodes in CPE carriers. No significant risk factors for CPE infections could be identified. Overall, this study suggests that empirical antibiotic treatment covering CPE might be initiated in CPE carriers at least in the first month after its diagnosis and in severe infections due to the high frequency and early occurrence of CPE infections in these patients.

3D-printed simulator for nasopharyngeal swab collection for COVID-19.

OBJECTIVES: Diagnosis of COVID-19 is essential to prevent the spread of SARS-CoV-2. Nasopharyngeal swabs (NPS) remain the gold standard in screening, although associated with false negative results (up to 30%). We developed a 3D simulator of the nasal and pharyngeal cavities for the learning and improvement of NPS collection. PATIENTS AND METHODS: Simulator training sessions were carried out in 11 centers in France. A questionnaire assessing the simulator was administered at the end of the sessions. The study population included both healthcare workers (HCW) and volunteers from the general population. RESULTS: Out of 589 participants, overall satisfaction was scored 9.0 [8.9-9.1] on a scale of 0 to 10 with excellent results in the 16 evaluation items of each category (HCWs and general population, NPS novices and experienced). The simulator was considered very realistic (95%), easy to use (97%), useful to understand the anatomy (89%) and NPS sampling technique (93%). This educational tool was considered essential (93%). Participants felt their future NPS would be more reliable (72%), less painful (70%), easier to perform (88%) and that they would be carried out more serenely (90%). The mean number of NPS conducted on the simulator to feel at ease was two; technical fluency with the simulator can thus be acquired quickly. CONCLUSION: Our simulator, whose 3D printing can be reproduced freely using a permanent open access link, is an essential educational tool to standardize the learning and improvement of NPS collection. It should enhance virus detection and thus contribute to better pandemic control.

Factors associated with treatment failure after advice from infectious disease specialists.

OBJECTIVE: Risk factors associated with treatment failure after the infectious disease specialist's (IDS) advice remain unknown. We aimed to identify these risk factors. METHODS: We included patients hospitalized in our tertiary care center who consulted an infectious disease specialist between January 2013 and April 2015. Treatment failure was defined by a composite criterion: signs of sepsis beyond Day 3, ICU admission, or death. Treatment success was defined by the patient's sustained clinical improvement. RESULTS: A total of 240 IDS recommendations were made. Diagnosis was changed for 64 patients (26.7%) and 50 patients experienced treatment failure after the IDS advice. In multivariate analysis, compliance with the IDS advice was associated with a higher rate of success (OR=0.09, 95%CI [0.01-0.67]). Variables associated with treatment failure in the multivariate analysis were Charlson comorbidity score at admission (OR=1.24, 95%CI [1.03-1.50]), a history of infection or colonization with multidrug-resistant bacteria (OR=8.27, 95%CI [1.37-49.80]), and deterioration of the patient's status three days after the IDS advice (OR=12.50, 95%CI [3.16-49.46]). CONCLUSION: Reassessing IDS recommendations could be interesting for specific patients to further adapt and improve them.

[Mesenteric lymph node cavitation in celiac disease: Report of four cases and literature review]. / Le syndrome de cavitation ganglionnaire mésentérique, complication rare de la maladie cœliaque de l'adulte : à propos de quatre cas et revue de la littérature.

INTRODUCTION: Mesenteric lymph node cavitation is an exceptional complication of celiac disease. We report four original observations of this syndrome, completed by a literature review. DISCUSSION: The analysis of 38 cases showed that this complication occurred exclusively in adults, with a mean age at diagnosis of 54 years. It revealed the celiac disease in the majority of cases. Hyposplenism was almost systematically associated. The risk of lymphoma appeared higher, especially enteropathy-associated T-cell lymphoma. The prognosis was poor with nearly 50% mortality and seemed related to the clinical response to the gluten-free diet. CONCLUSION: The severity of this complication deserves to be known and should lead to its research in celiac patients, especially in cases diagnosed in adulthood or in case of refractory disease.

[Neurosyphilis: A retrospective study of 13 cases at Strasbourg University Hospital]. / La neurosyphilis, étude rétrospective de 13 cas survenus aux hôpitaux universitaires de Strasbourg.

OBJECTIVE: After a decade of constant decline, the number of syphilis cases has been steadily increasing since the 2000s, particularly in HIV infected patients. Neurosyphilis is a rare manifestation of this sexually transmitted disease for which we performed a retrospective study and analyzed clinical manifestations. PATIENTS AND METHODS: We reviewed retrospectively all the neurosyphilis cases admitted to Strasbourg University Hospital between 2004 and 2014. We included and analyzed 13 patients admitted during this period who met the diagnostic criteria for neurosyphilis. RESULTS: Nine of 13 patients had isolated visual manifestations; three (23.1%) experienced posterior uveitis, two (15.4%), panuveitis, and 4 (30.8%) had papillitis. Out of five patients (38.5%) who were HIV positive, three (60%) had a CD4 cell count above 400/mm3 at the time of diagnosis of neurosyphilis. All patients received parenteral penicillin G or cephalosporin, and 5/13 (38.5%) received systemic corticotherapy. CONCLUSION: Ophthalmologists appear as key players in the identification, management and follow-up of neurosyphilis, since ocular findings are key diagnostic features in these patients.

VISLISI trial, a prospective clinical study allowing identification of a new metalloprotease and putative virulence factor from Staphylococcus lugdunensis.

OBJECTIVE: Staphylococcus lugdunensis is a coagulase-negative staphylococcus that displays an unusually high virulence rate close to that of Staphylococcus aureus. It also shares phenotypic properties with S. aureus and several studies found putative virulence factors. The objective of the study was to describe the clinical manifestations of S. lugdunensis infections and investigate putative virulence factors. METHOD: We conducted a prospective study from November 2013 to March 2016 at the University Hospital of Strasbourg. Putative virulence factors were investigated by clumping factor detection, screening for proteolytic activity, and sequence analysis using tandem nano-liquid chromatography-mass spectrometry. RESULTS: In total, 347 positive samples for S. lugdunensis were collected, of which 129 (37.2%) were from confirmed cases of S. lugdunensis infection. Eighty-one of these 129 patients were included in the study. Bone and prosthetic joints (PJI) were the most frequent sites of infection (n=28; 34.6%) followed by skin and soft tissues (n=23; 28.4%). We identified and purified a novel protease secreted by 50 samples (61.7%), most frequently associated with samples from deep infections and PJI (pr 0.97 and pr 0.91, respectively). Protease peptide sequencing by nano-liquid chromatography-mass spectrometry revealed a novel protease bearing 62.42% identity with ShpI, a metalloprotease secreted by Staphylococcus hyicus. CONCLUSION: This study confirms the pathogenicity of S. lugdunensis, particularly in bone and PJI. We also identified a novel metalloprotease called lugdulysin that may contribute to virulence.

Feedback on difficulties raised by the interpretation of serological tests for the diagnosis of Lyme disease.

OBJECTIVES: We had for objectives: i) to evaluate the accuracy of serologic testing for Lyme borreliosis performed in a private medical laboratory (PML); ii) to evaluate the impact of these tests on the practices of infectious diseases specialists (IDS). PATIENTS AND METHOD: This study was performed in two steps: i) retrospective study of patients followed in a university hospital infectious diseases outpatient clinic for suspected Lyme borreliosis, tested (ELISA and Western blot) by both the PML and the National Reference Center (NRC); ii) national survey on IDS practices concerning patients consulting for suspected Lyme borreliosis. RESULTS: Between July 2008 and July 2011, 128 patients consulting for suspected Lyme borreliosis were tested by both laboratories. Serological tests came back positive in 91% of cases from the PML versus 8% of cases from the NRC. Lyme borreliosis was the IDS's final diagnosis for 3.6% of patients. The survey on practices revealed that: i) the modal duration of consultation for suspected Lyme borreliosis was 30-60 minutes; ii) for 33% of patients, serologic test results performed at the PML were the only reason to suspect Lyme borreliosis; iii) 60% of patients had no indication for antibiotics. CONCLUSION: The serological test performed in the PML were positive most of the time, but were not confirmed by tests performed at the NRC. This discrepancy lead to multiple and prolonged consultations in infectious diseases clinics, and discordance in the indications for antibiotics.

Squeezed quadrature fluctuations in a gravitational wave detector using squeezed light.

Squeezed states of light are an important tool for optical measurements below the shot noise limit and for optical realizations of quantum information systems. Recently, squeezed vacuum states were deployed to enhance the shot noise limited performance of gravitational wave detectors. In most practical implementations of squeezing enhancement, relative fluctuations between the squeezed quadrature angle and the measured quadrature (sometimes called squeezing angle jitter or phase noise) are one limit to the noise reduction that can be achieved. We present calculations of several effects that lead to quadrature fluctuations, and use these estimates to account for the observed quadrature fluctuations in a LIGO gravitational wave detector. We discuss the implications of this work for quantum enhanced advanced detectors and even more sensitive third generation detectors.

Optimal alignment sensing of a readout mode cleaner cavity.

Critically coupled resonant optical cavities are often used as mode cleaners in optical systems to improve the signal-to-noise ratio (SNR) of a signal that is encoded as an amplitude modulation of a laser beam. Achieving the best SNR requires maintaining the alignment of the mode cleaner relative to the laser beam on which the signal is encoded. An automatic alignment system that is primarily sensitive to the carrier field component of the beam will not, in general, provide optimal SNR. We present an approach that modifies traditional dither alignment sensing by applying a large amplitude modulation on the signal field, thereby producing error signals that are sensitive to the signal sideband field alignment. When used in conjunction with alignment actuators, this approach can improve the detected SNR; we demonstrate a factor of 3 improvement in the SNR of a kilometer-scale detector of the Laser Interferometer Gravitational-Wave Observatory. This approach can be generalized to other types of alignment sensors.