Anecdotal evidence rapidly accumulated during March 2020 from sites around the world that sudden hyposmia and hypogeusia are significant symptoms associated with the SARS-CoV-2 pandemic. Our ...objective was to describe the prevalence of hyposmia and hypogeusia and compare it in hospitalized and non-hospitalized COVID-19 patients to evaluate an association of these symptoms with disease severity. We performed a cross-sectional survey during 5 consecutive days in March 2020, within a tertiary referral center, associated outpatient clinic, and two primary care outpatient facilities in Paris. All SARS-CoV-2-positive patients hospitalized during the study period and able to be interviewed (
n
= 198), hospital outpatients seen during the previous month (
n
= 129), and all COVID-19-highly suspect patients in two primary health centers (
n
= 63) were included. Hospitalized patients were significantly more often male (64 vs 40%) and older (66 vs 43 years old in median) and had significantly more comorbidities than outpatients. Hyposmia and hypogeusia were reported by 33% of patients and occurred significantly less frequently in hospitalized patients (12% and 13%, respectively) than in the health centers’ outpatients (33% and 43%, respectively) and in the hospital outpatients (65% and 60%, respectively). Hyposmia and hypogeusia appeared more frequently after other COVID-19 symptoms. Patients with hyposmia and/or hypogeusia were significantly younger and had significantly less respiratory severity criteria than patients without these symptoms. Olfactory and gustatory dysfunction occurs frequently in COVID-19, especially in young, non-severe patients. These symptoms might be a useful tool for initial diagnostic work-up in patients with suspected COVID-19.
Increasing numbers of pyelonephritis-associated uropathogenic Escherichia coli (UPEC) are exhibiting high resistance to antibiotic therapy. They include a particular clonal group, the ...CTX-M-15-producing O25b:H4-ST131 clone, which has been shown to have a high dissemination potential. Here we show that a representative isolate of this E. coli clone, referred to as TN03, has enhanced metabolic capacities, acts as a potent intestine- colonizing strain, and displays the typical features of UPEC strains. In a modified streptomycin-treated mouse model of intestinal colonization where streptomycin was stopped 5 days before inoculation, we show that TN03 outcompetes the commensal E. coli strains K-12 MG1655, IAI1, and ED1a at days 1 and 7. Using an experimental model of ascending UTI in C3H/HeN mice, we then show that TN03 colonized the urinary tract. One week after the transurethral inoculation of the TN03 isolates, the bacterial loads in the bladder and kidneys were significantly greater than those of two other UPEC strains (CFT073 and HT7) belonging to the same B2 phylogenetic group. The differences in bacterial loads did not seem to be directly linked to differences in the inflammatory response, since the intrarenal expression of chemokines and cytokines and the number of polymorphonuclear neutrophils attracted to the site of inflammation was the same in kidneys colonized by TN03, CFT073, or HT7. Lastly, we show that in vitro TN03 has a high maximum growth rate in both complex (Luria-Bertani and human urine) and minimum media. In conclusion, our findings indicate that TN03 is a potent UPEC strain that colonizes the intestinal tract and may persist in the kidneys of infected hosts.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim of this multi-centre French retrospective study was to identify severe, i.e. crusted and profuse, scabies patients. Records were retrieved from 22 Dermatology or Infectious Diseases ...departments in the Ile-de-France from January 2009 to January 2015 to characterize epidemiology, demography, diagnosis, contributing factors, treatment features, and outcomes in severe scabies. A total of 95 inpatients (57 crusted and 38 profuse) were included. A higher number of cases was observed among elderly patients (>75 years), mostly living in institutions. Thirteen patients (13.6%) reported a history of previously treated scabies. Sixty-three patients (66.3%) had been seen by a previous practitioner for the current episode (up to 8 previous visits). Initial misdiagnosis (e.g. eczema, prurigo, drug-related eruptions, psoriasis) was documented in 41 patients (43.1%). Fifty-eight patients (61%) had already received 1 or more previous treatments for their current episode. Forty percent received corticosteroids or acitretin for an initial diagnosis of eczema or psoriasis. Median time from the onset of symptoms to the diagnosis of severe scabies was 3 months (range 0.3-22). Itch was present in all patients at diagnosis. Most patients (n=84, 88.4%) had comorbidities. Diagnostic and therapeutic approaches varied. Complications occurred in 11.5% of cases. To date, there is no consensus for diagnosis and treatment, and future standardization of is required for optimal management.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background: COVID-19 has become pandemic and can impact individuals with autism as well. Here, we report a case series admitted to a neurobehavioral unit dedicated to challenging behaviors in ...patients with autism. Methods: We describe 16 patients (mean age 20.8 years; range 12–43 years; 76% male) with autism hospitalized between March 2020 and mid-April 2020 for challenging behaviors, for which COVID-19 disease has been suspected and who needed both psychiatric and medical care. A close cooperation with the Infectious and Tropical Diseases Department was organized to limit viral spread and training sessions (e.g., hygiene, clinical COVID-19 monitoring, virus testing) were given to staff members. Results: Most patients had severe autism and severe/moderate intellectual disability. Eleven patients were already in the unit when it was hit by the pandemic, and five were admitted from the community. Based on a virus search via reverse transcriptase polymerase chain reaction (RT-PCR) or serology at the 2-month follow-up, we had 11 confirmed COVID-19 cases. The main COVID-19 symptoms included benign upper respiratory infection signs (N = 9, 81.8%), diarrhea (N = 7, 63.6%), fatigue (N = 7, 63.6%), and respiratory signs (N = 5, 45.5%), including one patient who needed oxygen therapy. Three patients remained asymptomatic and COVID-19-free (including two under immunosuppressive treatments). Among the symptomatic patients, five showed atypical behaviors that we understood as idiosyncratic manifestations (e.g., irrepressible licking behavior). On day 14, only one patient with respiratory dysfunction still had a positive RT-PCR SARS-CoV-2 test. Conclusions: Organizing a COVID+ unit for patients with autism is realistic and requires close collaboration with infectologists. We believe that this initiative should be promoted to limit both the spread of the virus and the ostracism of patients with autism and challenging behaviors.
Cefiderocol is a siderophore cephalosporin antibiotic active against Gram-negative bacteria, including extended-spectrum beta-lactamase and carbapenemase-producing strains. The pharmacokinetics of ...cefiderocol has been studied in healthy subjects and particularly in phase II and III studies. This retrospective study investigated intravenous cefiderocol population pharmacokinetics in adult patients treated by cefiderocol.
We studied 55 consecutive patients hospitalized in an intensive care unit. Cefiderocol plasma samples were obtained on different occasions during treatment. Plasma concentration was assayed using mass spectrometry. Data analysis was performed using a non-linear mixed-effect approach via Monolix 2020R1.
A total of 205 plasma samples were obtained from 55 patients. Eighty percent of patients received cefiderocol for ventilator-associated pneumonia due to carbapenem-resistant
infection. Cefiderocol concentration time-courses were best fit to a two-compartment open model with first-order elimination. Elimination clearance was positively related to renal function (estimated by the CKD formula). Adding albumin plasma binding in the model significantly improved the model assuming a ~40% unbound drug fraction given a ~40 g/L albuminemia. The final model included CKD plus cefiderocol plasma binding effects. Fat-free mass was better than total body weight to influence, via the allometric rule, clearance and volume terms, but this effect was negligible. The final clearance based on free circulating drug (CL
) for a typical patient, CKD = 90, was 7.38 L/h relative standard error, RSE, 22% with a between-subject variability of 0.47 RSE 10% (exponential distribution).
This study showed that albumin binding and CKD effects were significant predictors of unbound and total plasma cefiderocol concentrations. Our results indicate that individual adjustment of cefiderocol can be used to reach high minimum inhibitory concentrations based on an estimation of unbound drug concentration and optimize therapeutic efficacy.
Infectious and tropical diseases (ID) physicians are needed now more than ever to tackle existing and emerging global threats. However, in many countries, ID is not recognized as a qualifying ...specialty. The creation of ID residency in 2017 in France offers the opportunity to know how and why the specialty is chosen by medical students.
We first analyzed the choice of specialty of all French medical students in 2017 and 2018 according to their rank at the national exam that ends medical studies. A web questionnaire was then sent in January 2019 to all ID residents in France (n = 100) to assess the factors influencing their choice of specialty and their career plan.
We analyzed the choice of 17,087 medical students. ID was the first-chosen specialty with a median national rank of 526/8539, followed by plastic surgery and ophthalmology. The questionnaire was completed by 90% of the French ID residents (n = 100). The most encouraging factors to choose ID were the multi-system approach of the specialty, the importance of diagnostic medicine and having done an internship in ID during medical school. The potential deterrents were the work-life balance, the workload and the salary.
The recent recognition of ID as a qualifying specialty in France can be considered a success insofar as the specialty is the most popular among all medical and surgical specialties. Individuals who choose ID are attracted by the intellectual stimulation of the specialty but express concerns about the working conditions and salaries.
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,
= 10). The targeted bacteria were
(
= 12), including carbapenemase-producing
(
= 9),
(
= 2),
(
= 1), and
(
= 1). Overall, of the 12 patients whose samples were analyzed, 5
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.
Incubation for 14 days is recommended for the culture of microorganisms from osteoarticular infections (OAI), but there are no recommendations for postoperative antibiotic stewardship concerning ...empirical antimicrobial therapy (EAT), while prolonging broad-spectrum EAT results in adverse effects. The aim of this study was to describe the local OAI epidemiology with consideration of bacterial growth times to determine which antibiotic stewardship intervention should be implemented in cases of negative culture after 2 days of incubation. We performed a 1-year, single-center, noninterventional cohort study at the Pitié-Salpêtrière hospital OAI reference center. Samples were taken as part of the local standard of care protocol for adult patients who underwent surgery for OAI (native or device related) and received EAT (i.e., piperacillin-tazobactam plus daptomycin PTD) following surgery. The time to culture positivity was monitored daily. Overall, 147 patients were recruited, accounting for 151 episodes of OAI, including 112 device-related infections. Microbiological cultures were positive in 144 cases, including 42% polymicrobial infections. Overall, a definitive microbiological result was obtained within 48 h in 118 cases (78%) and within 5 days in 130 cases (86%). After 5 days, only Gram-positive bacteria were recovered, especially Cutibacterium acnes, Staphylococcus spp., and Streptococcus spp. Overall, 90% of culture-positive OAI were correctly treated with the locally established EAT. EAT guidance for OAI was in agreement with our local epidemiology. Our results supported antibiotic stewardship intervention consisting of stopping piperacillin-tazobactam treatment at day 5 in cases of negative culture.
Osteoarticular infections (OAI) remain challenging to diagnose and to treat. One of the issues concerns postoperative empirical antimicrobial therapy (EAT), which is usually a combination of broad-spectrum antibiotics. This EAT is maintained up to 2 weeks, until the availability of the microbiological results (identification and drug susceptibility testing of the microorganisms responsible for the OAI). Our results provide new data that will help to improve OAI management, especially EAT. Indeed, we have shown that antibiotic stewardship intervention consisting of stopping the antibiotic targeting Gram-negative bacteria included in the EAT could be implemented in cases where culture is negative after 5 days of incubation. The benefits of such an antibiotic stewardship plan include improved patient outcomes, reduced adverse events (including Clostridioides difficile infection), improvement in rates of susceptibilities to targeted antibiotics, and optimization of resource utilization across the continuum of care.
Adaptive processes in chronic bacterial infections are well described, but much less is known about the processes at play during acute infections. Here, by sequencing seven randomly selected isolates ...per patient, we analyzed
populations from three acute extraintestinal infections in adults (meningitis, pyelonephritis, and peritonitis), in which a high-mutation-rate isolate or mutator isolate was found. The isolates of single patients displayed between a few dozen and more than 200 independent mutations, with up to half being specific to the mutator isolate. Multiple signs of positive selection were evidenced: a high ratio of nonsynonymous to synonymous mutations (
/
ratio) and strong mutational convergence within and between patients, some of them at loci well known for their adaptive potential, such as
,
,
, and
For all patients, the mutator isolate was likely due to a large deletion of a methyl-directed mismatch repair gene, and in two instances, the deletion extended to genes involved in some genetic convergence, suggesting potential coselection. Intrinsic extraintestinal virulence assessed in a mouse model of sepsis showed variable patterns of virulence ranging from non-mouse killer to mouse killer for the isolates from single patients. However, genomic signature and gene inactivation experiments did not establish a link between a single gene and the capacity to kill mice, highlighting the complex and multifactorial nature of the virulence. Altogether, these data indicate that
isolates are adapting under strong selective pressure when colonizing an extraintestinal site.
Little is known about the dynamics of adaptation in acute bacterial infections. By sequencing multiple isolates from monoclonal extraintestinal
infections in several patients, we were able to uncover traces of selection taking place at short time scales compared to chronic infection. High genomic diversity was observed in the patient isolates, with an excess of nonsynonymous mutations, and the comparison within and between different infections showed patterns of convergence at the gene level, both constituting strong signs of adaptation. The genes targeted were coding mostly for proteins involved in global regulation, metabolism, and adhesion/motility. Moreover, virulence assessed in a mouse model of sepsis was variable among the isolates of single patients, but this difference was left unexplained at the molecular level. This work gives us clues about the
lifestyle transition between commensalism and pathogenicity.
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