Favorable outcome without corticosteroids during post-artesunate delayed hemolysis with positive direct antiglobulin test in severe imported Plasmodium falciparum malaria, France.

OBJECTIVES: Positive direct antiglobulin tests (DATs) have been reported in cases of post-artesunate delayed hemolysis (PADH), but the causal role of auto-immune hemolysis remains unclear. We aimed to analyze a cohort of patients with PADH and DAT during severe malaria. METHODS: We describe PADH and DAT results in a 7-year multi-center retrospective cohort of patients receiving artesunate for severe imported malaria. RESULTS: Of 337 patients treated with artesunate, 46 (13.6%) had at least one DAT result within 30 days of treatment initiation, and 25/46 (54.3%) had at least one positive DAT. Among 40 patients with available data, 17 (42.5%) experienced PADH. Patient characteristics were similar for patients with a positive or negative DAT, and DAT positivity was not associated with PADH occurrence (P = 0.36). Among patients, 5/13 (38.5%) with a positive DAT after day 7 experienced PADH, compared to 10/13 (76.9%) of those with a negative DAT after day 7 (P = 0.11). Overall, 41% of patients required blood transfusions, and outcome was favorable without corticosteroids, even in cases of PADH. CONCLUSIONS: DAT does not appear to be a marker of PADH, but rather an indirect marker of an immune-mediated mechanism. DAT positivity should not lead to the administration of systemic corticosteroids during PADH.

Improvement in OCD symptoms associated with serotoninergic psychedelics: a retrospective online survey.

A renewed interest in the use of psychedelics for treating obsessive compulsive disorder (OCD) has emerged in the last 20 years. But pre-clinical and clinical evidence remain scarce, and little is known about the factor determining the magnitude and persistence of the therapeutic effect. We therefore designed a retrospective online survey to explore, in the general population using psychoactive drugs, their impact on OCD symptoms. We also assessed the attitude of the participants towards the substance in term of frequency of intakes. In a sample of 174 participants, classic psychedelics were reported as the only substances effective at reducing OCD symptoms. In classic psychedelics users, symptoms reduction was associated with the intensity of acute effects, itself correlated to the dose. Reports on the persistence of the therapeutic effect varied from weeks to months, but we could not find any predicting factor. Finally, the occurrence and frequency of subsequent intakes, which seemed to be limited in our sample, were predicted by the magnitude and persistence of the therapeutic effect, respectively. Our observations support the hypothesis of classic psychedelics efficacy in reducing OCD symptoms but a careful evaluation of the persistence of this effect is still needed.

Real-life temocillin use in Greater Paris area, effectiveness and risk factors for failure in infections caused by ESBL-producing Enterobacterales: a multicentre retrospective study.

Background: Temocillin is a ß-lactam that is not hydrolysed by ESBLs. Objectives: To describe the real-life use of temocillin, to assess its effectiveness in infections caused by ESBL-producing Enterobacterales, and to identify risk factors for treatment failure. Methods: Retrospective multicentric study in eight tertiary care hospitals in the Greater Paris area, including patients who received at least one dose of temocillin for ESBL infections from 1 January to 31 December 2018. Failure was a composite criterion defined within 28 day follow-up by persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment and/or death from infection. A logistic regression with univariable and multivariable analysis was performed to identify risks associated with failure. Results: Data on 130 infection episodes were collected; 113 were due to ESBL-producing Enterobacterales. Mean age was 65.2 ±â€Š15.7 years and 68.1% patients were male. Indications were mostly urinary tract infections (UTIs) (85.8%), bloodstream infections (11.5%), respiratory tract infections (RTIs) (3.5%) and intra-abdominal infections (3.5%). Bacteria involved were Escherichia coli (49.6%), Klebsiella pneumoniae (44.2%) and Enterobacter cloacae (8.8%). Polymicrobial infections occurred in 23.0% of cases. Temocillin was mostly used in monotherapy (102/113, 90.3%). Failure was found in 13.3% of cases. Risk factors for failure in multivariable analysis were: RTI (aOR 23.3, 95% CI 1.5-358.2) and neurological disease (aOR 5.3, 95% CI 1.5-18.6). Conclusions: The main use of temocillin was UTI due to ESBL-producing E. coli and K. pneumoniae, with a favourable clinical outcome. The main risk factor for failure was neurological disease.

Pneumococcal and influenza vaccination coverage among at-risk adults: A 5-year French national observational study.

INTRODUCTION: The risk of developing pneumococcal infections increases with certain chronic conditions and in immunocompromised patients. We aimed to monitor pneumococcal vaccination coverage in at-risk patients and to examine factors associated with pneumococcal vaccination in France. MATERIAL AND METHODS: In this annual cross-sectional study, at-risk patients were extracted between 2014 and 2018 from the National Health Insurance's (NHI) General scheme's claims database with their vaccine reimbursements. Descriptive analyses and a logistic model were performed to assess the influence of healthcare use and medical and demographic factors on pneumococcal vaccination. RESULTS AND DISCUSSION: In 2018, 4.5% of 4,045,021 at-risk adults were up to date with their pneumococcal vaccination. During the study period, the number of patients with chronic medical conditions (86% of 4,045,021) increased by 10.1%, but vaccination coverage decreased from 12.9% to 2.9%. The population with immunocompromised status (14% of 4,045,021) increased by 16.2% and vaccination coverage from 10.3% to 18.8%. Influenza vaccination coverage was much higher and stable (around 45.0%). Factors associated with pneumococcal vaccination were: immunocompromised status vs. having a chronic medical condition (odds ratio [OR] 4.72), influenza vaccination (OR 2.36-3.42), hepatitis B vaccination (OR 2.82), DTPolio vaccination (OR 1.52), ≥5 specialist physicians' visits (OR 1.17), and age above 74 (OR 1.12). Pneumococcal vaccine dispensing was extremely low (median of 9per GP,1per specialist over 9 years) despite frequent healthcare visits. CONCLUSION: Pneumococcal and influenza vaccination coverage of adults at risk of pneumococcal disease fell well below public health expectations. Invitations for pneumococcal vaccination should be sent by the NHI to high-risk patients. Patient management protocols should include pneumococcal vaccination. Patients with multiple comorbidities are a high-priority population given the large potential health gains offered by pneumococcal vaccination. Commitment of both scientific societies and health authorities is urgently needed to increase vaccination coverage in at-risk populations.

Complete Remission After Immunotherapy-Induced Abdominal Tuberculosis in a Patient With Advanced NSCLC Treated With Pembrolizumab: A Case Report.

The use of immune checkpoint inhibitors (ICIs) has drastically transformed the therapeutic landscape in lung cancer. Special focus has been put on immune-related toxicity; however, infections can also seem during ICI treatment. Although rare, tuberculosis (TB) has been increasingly identified after ICIs, and it seems that the programmed cell death protein 1 and programmed death-ligand 1 pathway is directly involved in its pathophysiology. Here, we describe the case of a patient with advanced NSCLC who developed abdominal TB after 32 months of pembrolizumab and who remains in tumor remission 10 months after discontinuation of this drug. Routine screening for latent TB before ICI treatment is advised, with closer collaboration between infectious disease specialists and oncologists.

Four-Month Clinical Status of a Cohort of Patients After Hospitalization for COVID-19.

Importance: Little is known about long-term sequelae of COVID-19. Objective: To describe the consequences at 4 months in patients hospitalized for COVID-19. Design, Setting, and Participants: In a prospective uncontrolled cohort study, survivors of COVID-19 who had been hospitalized in a university hospital in France between March 1 and May 29, 2020, underwent a telephone assessment 4 months after discharge, between July 15 and September 18, 2020. Patients with relevant symptoms and all patients hospitalized in an intensive care unit (ICU) were invited for further assessment at an ambulatory care visit. Exposures: Survival of hospitalization for COVID-19. Main Outcomes and Measures: Respiratory, cognitive, and functional symptoms were assessed by telephone with the Q3PC cognitive screening questionnaire and a checklist of symptoms. At the ambulatory care visit, patients underwent pulmonary function tests, lung computed tomographic scan, psychometric and cognitive tests (including the 36-Item Short-Form Health Survey and 20-item Multidimensional Fatigue Inventory), and, for patients who had been hospitalized in the ICU or reported ongoing symptoms, echocardiography. Results: Among 834 eligible patients, 478 were evaluated by telephone (mean age, 61 years [SD, 16 years]; 201 men, 277 women). During the telephone interview, 244 patients (51%) declared at least 1 symptom that did not exist before COVID-19: fatigue in 31%, cognitive symptoms in 21%, and new-onset dyspnea in 16%. There was further evaluation in 177 patients (37%), including 97 of 142 former ICU patients. The median 20-item Multidimensional Fatigue Inventory score (n = 130) was 4.5 (interquartile range, 3.0-5.0) for reduced motivation and 3.7 (interquartile range, 3.0-4.5) for mental fatigue (possible range, 1 [best] to 5 [worst]). The median 36-Item Short-Form Health Survey score (n = 145) was 25 (interquartile range, 25.0-75.0) for the subscale "role limited owing to physical problems" (possible range, 0 [best] to 100 [worst]). Computed tomographic lung-scan abnormalities were found in 108 of 171 patients (63%), mainly subtle ground-glass opacities. Fibrotic lesions were observed in 33 of 171 patients (19%), involving less than 25% of parenchyma in all but 1 patient. Fibrotic lesions were observed in 19 of 49 survivors (39%) with acute respiratory distress syndrome. Among 94 former ICU patients, anxiety, depression, and posttraumatic symptoms were observed in 23%, 18%, and 7%, respectively. The left ventricular ejection fraction was less than 50% in 8 of 83 ICU patients (10%). New-onset chronic kidney disease was observed in 2 ICU patients. Serology was positive in 172 of 177 outpatients (97%). Conclusions and Relevance: Four months after hospitalization for COVID-19, a cohort of patients frequently reported symptoms not previously present, and lung-scan abnormalities were common among those who were tested. These findings are limited by the absence of a control group and of pre-COVID assessments in this cohort. Further research is needed to understand longer-term outcomes and whether these findings reflect associations with the disease.

Thyroid nocardiosis: Case report and review of the literature.

Disseminated nocardiosis is a rare but growing concern in immunocompromised patients. Typical localizations include the lung, brain and/or soft tissues, but laboratory confirmation of nocardiosis usually requires sampling of infected organs by invasive procedures such as bronchoalveolar lavage or brain biopsy. We report a case of disseminated nocardiosis occurring in a hematopoietic stem-cell transplant recipient, with clinical lung and brain localizations. Examination of the thyroid gland was suggestive of a unilateral abscess. A culture of thyroid pus sampled by fine-needle aspiration was positive for Nocardia farcinica and therefore avoided a more invasive procedure. The patient recovered after a six-month antibiotic therapy without thyroid surgery. We reviewed other ten cases of thyroid nocardiosis published in the medical literature. Among the ten cases of disseminated nocardiosis established during the patient's lifetime including ours, six (60%) were asymptomatic and seven (70%) were confirmed by culture of the aspiration of thyroid pus. When disseminated nocardiosis is suspected, systematic examination for a thyroid abscess may help establish a microbiological diagnosis and prevent further invasive procedures.

Susceptibility Testing Is Key for the Success of Cefiderocol Treatment: A Retrospective Cohort Study.

Cefiderocol is a novel siderophore cephalosporin, which has proven in vitro activity against carbapenem-resistant (CR) Gram-negative pathogens and stability towards all carbapenemases. The aim of this study was to describe the first cases of prescriptions and the efficacy of cefiderocol for compassionate use in the 2 months following its access in France. We performed a national retrospective study of all patients who received at least one dose of cefiderocol from 2 November 2018 to 5 November 2019. We collected clinical characteristics and outcome through a standard questionnaire. Bacterial isolates from 12 patients were centralized and analyzed in the French National Reference Center for Antimicrobial Resistance, and sequenced using Illumina technology. Finally, 13 patients from 7 French university hospitals were included in the study. The main type of infection treated by cefiderocol was respiratory tract infections (RTI, n = 10). The targeted bacteria were Pseudomonas aeruginosa (n = 12), including carbapenemase-producing P. aeruginosa (n = 9), Acinetobacter baumannii (n = 2), Klebsiella pneumoniae (n = 1), and Enterobacter hormaechei (n = 1). Overall, of the 12 patients whose samples were analyzed, 5 P. aeruginosa strains were not susceptible to cefiderocol (4 categorized as resistant and 1 as intermediate) according to Clinical and Laboratory Standards Institute (CLSI) breakpoints. If considering susceptible strains, the cure rate was 6/7, while being 0/5 among not-susceptible strains. This study underlines the necessity to test strains in adequate conditions.

Clinical recurrences of COVID-19 symptoms after recovery: Viral relapse, reinfection or inflammatory rebound?

For the first 3 months of COVID-19 pandemic, COVID-19 was expected to be an immunizing non-relapsing disease. We report a national case series of 11 virologically-confirmed COVID-19 patients having experienced a second clinically- and virologically-confirmed acute COVID-19 episode. According to the clinical history, we discuss either re-infection or reactivation hypothesis. Larger studies including further virological, immunological and epidemiologic data are needed to understand the mechanisms of these recurrences.

Early and delayed post-pneumonectomy empyemas: Microbiology, management and prognosis.

INTRODUCTION: Post-pneumonectomy empyema (PPE) is the most severe complication of pneumonectomy. Microbiology and its impact on management and prognosis have rarely been reported METHODS: We retrospectively reviewed the files of a series of 37 consecutive patients with PPE over a 10-year period with a special focus on microbiology, means used to treat empyema and prognosis. RESULTS: PPE occurred within 14 days of pneumonectomy in 17 cases (early PPE) and after postoperative day 16 in 20 patients (delayed PPE). PPE was monomicrobial in 57% of cases. The most frequent pathogens were Staphylococcus sp. and Streptococcus sp. Polymicrobial empyema was more frequent in patients with early PPE than delayed PPE (65% vs 25%; P = .02). Video-assisted thoracoscopic approach for cavity lavage was performed in 22 patients without broncho-pleural fistulae (BPF), associated with antimicrobial therapy and drainage, and was successful in 13 cases (59%). Seventeen patients (46%) underwent an open window thoracostomy. Overall 90-day post empyema mortality was 19%, with 6 deaths because of empyema in the early PPE group (35%), versus one (5%) in the delayed PPE group (P = .02). CONCLUSION: We distinguished 2 different PPE presentations: an early occurrence, mostly with polymicrobial cultures, including Gram-negative bacteria, and associated with a high mortality rate. By contrast, delayed PPEs were mostly monomicrobial with Gram-positive bacteria and associated with a better prognosis. VATS approach was successful in the majority of cases without BPF, even if some patients required secondary thoracostomy. PPE was associated with an excess of mortality especially when occurring in the early course after pneumonectomy.

Enterocytozoon bieneusi Microsporidiosis in Stem Cell Transplant Recipients Treated with Fumagillin

Enterocytozoon bieneusi microsporidiosis is an emerging disease in immunocompromised patients. We report 2 cases of this disease in allogeneic hematopoietic stem cell transplant patients successfully treated with fumagillin. Thrombocytopenia occurred but without major adverse events. Modifications of immunosuppression could be avoided when E. bieneusi is rapidly identified and fumagillin therapy is started promptly.

Delayed-onset hemolytic anemia in patients with travel-associated severe malaria treated with artesunate, France, 2011-2013.

Artesunate is the most effective treatment for severe malaria. However, delayed-onset hemolytic anemia has been observed in ≈20% of travelers who receive artesunate, ≈60% of whom require transfusion. This finding could discourage physicians from using artesunate. We prospectively evaluated a cohort of 123 patients in France who had severe imported malaria that was treated with artesunate; our evaluation focused on outcome, adverse events, and postartesunate delayed-onset hemolysis (PADH). Of the 123 patients, 6 (5%) died. Overall, 97 adverse events occurred. Among the 78 patients who received follow-up for >8 days after treatment initiation, 76 (97%) had anemia, and 21 (27%) of the 78 cases were recorded as PADH. The median drop in hemoglobin levels was 1.3 g/dL; 15% of patients with PADH had hemoglobin levels of <7 g/dL, and 1 required transfusion. Despite the high incidence of PADH, the resulting anemia remained mild in 85% of cases. This reassuring result confirms the safety and therapeutic benefit of artesunate.

High Rate of Acquisition but Short Duration of Carriage of Multidrug-Resistant Enterobacteriaceae After Travel to the Tropics.

BACKGROUND: Multidrug-resistant Enterobacteriaceae (MRE) are widespread in the community, especially in tropical regions. Travelers are at risk of acquiring MRE in these regions, but the precise extent of the problem is not known. METHODS: From February 2012 to April 2013, travelers attending 6 international vaccination centers in the Paris area prior to traveling to tropical regions were asked to provide a fecal sample before and after their trip. Those found to have acquired MRE were asked to send fecal samples 1, 2, 3, 6, and 12 months after their return, or until MRE was no longer detected. The fecal relative abundance of MRE among all Enterobacteriaceae was determined in each carrier. RESULTS: Among 824 participating travelers, 574 provided fecal samples before and after travel and were not MRE carriers before departure. Of these, 292 (50.9%) acquired an average of 1.8 MRE. Three travelers (0.5%) acquired carbapenemase-producing Enterobacteriaceae. The acquisition rate was higher in Asia (142/196 [72.4%]) than in sub-Saharan Africa (93/195 [47.7%]) or Latin America (57/183 [31.1%]). MRE acquisition was associated with the type of travel, diarrhea, and exposure to ß-lactams during the travel. Three months after return, 4.7% of the travelers carried MRE. Carriage lasted longer in travelers returning from Asia and in travelers with a high relative abundance of MRE at return. CONCLUSIONS: MRE acquisition is very frequent among travelers to tropical regions. Travel to these regions should be considered a risk factor of MRE carriage during the first 3 months after return, but not beyond. CLINICAL TRIALS REGISTRATION: NCT01526187.

No booster dose for yellow fever vaccination: what are the consequences for the activity of vaccination in travel clinics?

In April 2013, the Strategic Advisory Group of Experts (SAGE) on immunization stated that a single dose of yellow fever (YF) vaccine is sufficient in the general population to confer a lifelong protection against YF. When the period of validity of the International Certificate of Vaccination (ICV) will be extended to a lifetime in June 2016, no booster dose will be needed. The objective of this prospective study was to determine the potential impact of the SAGE recommendations on the vaccination activity of our travel clinics. We showed that among 1,037 subjects seen in our three travel clinics for a YF vaccination in 2013, about 32.3% went for a booster dose that is no longer useful according to the SAGE. A drop in vaccination activity has to be expected by travel clinics in the next years, and changes in daily exercise have to be anticipated, as YF vaccination is a large part of the regular work of many healthcare providers specialized in travel medicine.