Uniform distribution of three Candida albicans microsatellite markers in two French ICU populations supports a lack of nosocomial cross-contamination

BACKGROUND: The nosocomial acquisition of Candida albicans is a growing concern in intensive care units (ICUs) and understanding the route of contamination is relevant for infection control guidelines. METHODS: To analyze whether there is a specific ecology for any given hospital, we genotyped C. albicans isolates of the ICU of Versailles hospital (Hospital A) and compared the results with those previously obtained in another ICU in Henri Mondor hospital (Hospital B) using three polymorphic microsatellite markers (PMM). RESULTS: Among 36 patients with at least one positive culture for C. albicans, 26 had a specific multilocus genotype, two shared a common multilocus genotype, and 8 had the most common multilocus genotype found in the general population. The time interval between periods of hospitalization between patients with common genotypes differed by 13 to 78 days, thus supporting a lack of direct contamination. To confirm this hypothesis, the multilocus genotypic distributions of the three PMM were compared between the two hospitals. No statistically significant difference was observed. Multiple correspondences analysis did not indicate the association of a multilocus genotypic distribution with any given hospital. CONCLUSION: The present epidemiological study supports the conclusions that each patient harbours his/her own isolate, and that nosocomial transmission is not common in any given ICU. This study also supports the usefulness and practicability of PMM for studying the epidemiology of C. albicans

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Analyse statistique comparative des CMI obtenues par quatre méthodes d'antifongigramme sur 43 souches isolées de candidémies issues d'une étude multicentrique française réalisée en octobre 2004

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Diagnostic et épidémiologie des infections à Candida sp. en réanimation

Le diagnostic des infections profondes à Candida sp. est difficile, car les hémocultures ne sont positives que dans 40 à 60% des cas. La sensibilité d'autres méthodes diagnostiques comme l'antigénémie mannane (Mn), les IgM, les anticorps totaux anti-Candida, la procalcitonine et la PCR sérique ont été évaluées. Mn et les IgM ont une spécificité de 100% et détectent les patients infectés mais manquent de sensibilité. Mn pourrait être plus sensible que la PCR sérique, mais ces résultats méritent d'être confirmés. La procalcitonine >0,75 ng/ml différencie les infections fongiques et bactériennes des infections virales. Durant l'étude conduite durant deux ans en réanimation à l'hôpital de Versailles, l'index de colonisation (IC), défini comme le ratio des sites colonisés à Candida sp./ sites prélevés, et les tests sérologiques précédemment décrit ont été réalisés. Seul IC a une sensibilité de 100% chez les patients chirurgicaux. Ensuite l'épidémiologie de C. albicans a été explorée chez ces patients en utilisant 3 marqueurs microsatellites et nous avons comparé les résultats obtenus avec une étude préalablement réalisée à l'hôpital de Créteil. Si la distribution des génotypes avait été différente, ceci aurait pu être lié au fait qu'une transmission nosocomiale avait eu lieu ou que les populations de patients étaient différentes. Les patients sont porteurs du même isolat au cours du temps et quelque soit le site. Ceci confirme le fait qu'il n'y a pas eu d'infection croisée. Si certains génotypes sont plus fréquents, cela est lié au caractère clonal de C. albicans. Les populations des 2 hôpitaux sont similaires selon 3 tests statistiques : " genic differentiation ", " genotypic differentiation " et l'analyse factorielle des correspondances. Pour étudier l'épidémiologie de C. glabrata, deuxième espèce impliquée en réanimation, 3 marqueurs microsatellitesThe diagnosis of deep-seated Candida infections is difficult because bloodstream cultures are often negative. The sensitivity of other diagnostic methods such as mannan (Mn) antigenemia, IgM, total anti-Candida antibodies, procalcitonin and PCR were evaluated. Mn and IgM have a specificity of 100% and detect infected patients but lack sensitivity. Mn would be more sensitive than the serum PCR, but these results warrant confirmation. Procalcitonin >0,75 ng/ml differentiate fungal and bacterial infections from viral ones. During a 2-year study of the patients of the intensive care unit of the Versailles hospital, index of colonization (IC), defined as the ratio of Candida sp. colonized anatomical sites / tested sites, and the serological tests mentioned above were performed. Only IC had a 100% sensitivity in surgical patients. Then, we explored the epidemiology of C. albicans among these patients using 3 polymorphic microsatellite markers and we compared the results with a study already performed at Créteil hospital. If the C. albicans genotype's distribution had been different, that could have resulted from a nosocomial transmission or to the fact that the populations of patients were different. The patients harboured their own isolate whatever the anatomical site sampled and kept it over the study period. This confirms that there was no crossed transmission. Some genotypes were more frequent due to the fact that C. albicans is clonal. The populations of the 2 hospitals are similar using 3 statistical tests : " genic differentiation ", " genotypic differentiation " and factorial correspondence analysis. To study the epidemiology of C. glabrata, the second leading yeast species in intensive care units, three polymorphic microsatellite markers were characterized.PARIS12-CRETEIL BU Multidisc. (940282102) / SudocSudocFranceF

ASPERGILLOSE INVASIVE EN HEMATOLOGIE : DE L ENVIRONNEMENT AU PATIENT (à propos de l'étude épidémiologique et clinique des cas d'aspergillose invasive observés en unité de soins intensifs d'hématologie au centre hospitalier de Versailles)

L Aspergillose invasive (AI) est une maladie grave, dont la létalité est importante chez les patients d hématologie. La précocité du diagnostic influe sur la stratégie thérapeutique et de fait le pronostic. Deux études ont été réalisées au Centre Hospitalier de Versailles en 2009 et 2010. La première s est intéressée aux outils diagnostiques, le plus utilisé étant la détection de l antigène Galactomannane. Les faux positifs en Galactomannane sont connus tels que l association Pipéracilline-Tazobactam (PT), principal antibiotique utilisé en hématologie. L étude a été conduite chez la totalité des patients en aplasie hospitalisés en Soins Intensifs d hématologie (USI) et en unité d hématologie conventionnelle. Ce travail suggère que l association entre faux-positifs en GM et PT n est plus systématique, mais peut encore exister selon le laboratoire fournisseur, en effet 1 des 3 laboratoires avait une association statistique. Elle confirme également l intérêt de teste les lots de PT in vitro. La seconde étude a porté sur les patients hospitalisés uniquement en USI sur les deux années. Nous avons étudié de façon quasi-expérimentale, l impact de l épuration de l air d une part sur l environnement et d autre part sur l incidence des AI dans l USI d hématologie du Centre Hospitalier de Versailles. En effet, la mise en place des PlasmairsTM s est divisée en deux phases, la première en 2009, et la seconde en 2011-2012. Nous avons pu, de ce fait, comparer, dans le même temps et dans le même lieu, les prélèvements environnementaux des chambres équipées et non équipées, et l incidence des AI selon les séjours en chambre équipée ou non. Pour les patients ayant été hospitalisés dans une chambre ne comportant pas de système de traitement de l air de type Plasmair , le risque de développer une aspergillose invasive est multiplié par 4,3 par comparaison avec les patients protégés (p=0,03). Nos données apportent un argumentaire très important en faveur de l efficacité et de l importance des mesures environnementales sur la contamination aérienne fungique et surtout pour la première fois à notre connaissance en dehors du contexte de la greffe de moelle osseuse, démontrent que ces mesures ont un impact direct sur le risque pour les patients aplasiques de développer une aspergillose invasiveInvasive aspergillosis (IA) is an opportunistic disease associated with a high death rate in patients with hemtological malignancy. Early diagnosis influences the therapeutic strategy and the prognosis. Two studies were conducted at the Centre Hospitalier de Versailles in 2009 and 2010. The first investigated the diagnostic value of the detection of galactomannan antigen. False postive galactomannan are known to be associated with the administration of piperacillin-tazobactam (PT), the main antibiotic used in hemtology. We tested all patients, in aplasia, hospitalized in the unit. Our results suggest that the association between a false positive GM and PT administration is not a systematic finding, but can be related to the laboratory supplier. This observation confirms the need to test the batches of PT in vitro before their use in the clinic. The second study conducted during a two years period and focused on patients hospitalized in the ICU. We had the opportunity to compare, during the same period of time and in the same unit, the impact of air purification on the contamination of the patient's room and the relationship between air purification and the incidence of AI. Patients hospitalized in a room having no system of air-purification (plasmair TM), had a relative the risk of developing invasive as high as 4.3 compared with protecte patient (p=0.03). Our study demonstrated the effectiveness of environmental measures on the fungal contamination of air in an hematologic ICU outside the bone marrow transplant setting Moreover, we established that these measures had a direct impact on the risk of developing invasive aspergillosis in neutropenic patientsST QUENTIN EN YVELINES-BU (782972101) / SudocSudocFranceF

Use of microsatellite markers and gene dosage to quantify gene copy numbers in Candida albicans

International audienceWith microsatellite marker typing, the number of alleles must be known for calculation of allelic frequencies in the diploid Candida albicans for a given locus. We describe a gene dosage with a double real-time PCR. Such a dosage should also be useful in exploring the loss of heterozygosity in C. albicans

Invasive Aspergillosis associated with Covid-19: A word of caution

International audienceIntroduction: Invasive pulmonary aspergillosis is a well-known complication of acute respiratory distress syndrome, the most serious manifestation of COVID-19. Four recent studies have reported its incidence among ICU COVID-19 patients. However, they do not share the same case definition, and have provided conflicting results. In this paper we have aimed at reported the incidence of invasive pulmonary aspergillosis for COVID-19 patients in our ICU, and at comparing the different definitions in order to assess their respective relevance. Methods: Retrospective cohort study of critically ill patients with severe COVID-19 requiring ICU management between 1st March and 30th April 2020. Results: Our results showed significantly lower incidence of invasive pulmonary aspergillosis (1.8%;1/53), compared to three out of four previous studies, and wide variation in the numbers of cases with regard to the different definitions. Conclusion: Large-scale studies are needed for a better definition and a more accurate estimation of invasive pulmonary aspergillosis coinfection during COVID-19

Severity of self-reported symptoms and psychological burden 6-months after hospital admission for COVID-19: a prospective cohort study

International audienceOBJECTIVES: Few studies have reported clinical COVID-19 sequelae six months (M6) after hospital discharge, but none has studied symptom severity. METHODS: Prevalence and severity of 7 symptoms were estimated until M6 using the self-administered influenza severity scale in COVID-19 hospitalized patients enrolled in the French COVID cohort. Factors associated with severity were assessed by logistic regression. Anxiety, depression and health-related quality of life (HRQL) were also assessed. RESULTS: At M6, among the 324 patients (median age 61 years, 63% men, 19% admitted to intensive care during the acute phase), 187/324 (58%) reported at least one symptom mostly fatigue (47%) and myalgia (23%). Symptom severity was scored, at most, mild in 125 (67%), moderate in 44 (23%) and severe in 18 (10%). Female gender was the sole factor associated with moderate/severe symptom reporting (OR = 1.98, 95%CI=1.13-3.47). Among the 225 patients with psychological assessment, 24 (11%) had anxiety, 18 (8%) depressive symptoms, and their physical HRQL was significantly poorer than the general population (p=0.0005). CONCLUSION: Even if 58% of patients reported ≥1 symptom at M6, less than 7% rated any symptom as severe. Assessing symptoms severity could be helpful to identify patients requiring appropriate medical care. Women may require special attention

Active Surveillance Program to Increase Awareness on Invasive Fungal Diseases: the French RESSIF Network (2012 to 2018)

The French National Reference Center for Invasive Mycoses and Antifungals leads an active and sustained nationwide surveillance program on probable and proven invasive fungal diseases (IFDs) to determine their epidemiology in France. Between 2012 and 2018, a total of 10,886 IFDs were recorded. The incidence increased slightly over time (2.16 to 2.36/10,000 hospitalization days, P = 0.0562) in relation with an increase of fungemia incidence (1.03 to 1.19/10,000, P = 0.0023), while that of other IFDs remained stable. The proportion of ≥65-year-old patients increased from 38.4% to 45.3% (P < 0.0001). Yeast fungemia (n = 5,444) was due mainly to Candida albicans (55.6%) with stable proportions of species over time. Echinocandins became the main drug prescribed (46.7% to 61.8%), but global mortality rate remained unchanged (36.3% at 1 month). Pneumocystis jirovecii pneumonia (n = 2,106) was diagnosed mostly in HIV-negative patients (80.7%) with a significantly higher mortality than in HIV-positive patients (21.9% versus 5.4% at 1 month, P < 0.0001). Invasive aspergillosis (n = 1,661) and mucormycosis (n = 314) were diagnosed mostly in hematology (>60% of the cases) with a global mortality rate of 42.5% and 59.3%, respectively, at 3 months and significant changes in diagnosis procedure over time. More concurrent infections were also diagnosed over time (from 5.4% to 9.4% for mold IFDs, P = 0.0115). In conclusion, we observed an aging of patients with IFD with a significant increase in incidence only for yeast fungemia, a trend toward more concurrent infections, which raises diagnostic and therapeutic issues. Overall, global survival associated with IFDs has not improved despite updated guidelines and new diagnostic tools