Breakthrough invasive mold infections (IMIs) that occur during posaconazole or voriconazole prophylaxis are rare complications for which epidemiological data are lacking. This retrospective analysis comparing 24 microbiologically documented breakthrough with 66 nonbreakthrough IMIs shows a shift towards non-Aspergillus molds with a significantly increased proportion of rare multidrug-resistant molds.
Background: Candidemia is an opportunistic infection associated with high morbidity and mortality in patients hospitalized both inside and outside intensive care units (ICUs). Identification of patients at risk is crucial to ensure prompt antifungal therapy. We sought to assess risk factors for candidemia and death, both outside and inside ICUs. Methods: This prospective multicenter matched case-control study involved six teaching hospitals in Switzerland and France. Cases were defined by positive blood cultures for Candida sp. Controls were matched to cases using the following criteria: age, hospitalization ward, hospitalization duration, and, when applicable, type of surgery. One to three controls were enrolled by case. Risk factors were analyzed by univariate and multivariate conditional regression models, as a basis for a new scoring system to predict candidemia. Results: One hundred ninety-two candidemic patients and 411 matched controls were included. Forty-four percent of included patients were hospitalized in ICUs, and 56% were hospitalized outside ICUs. Independent risk factors for candidemia in the ICU population included total parenteral nutrition, acute kidney injury, heart disease, prior septic shock, and exposure to aminoglycoside antibiotics. Independent risk factors for candidemia in the non-ICU population included central venous catheter, total parenteral nutrition, and exposure to glycopeptides and nitroimidazoles. The accuracy of the scores based on these risk factors is better in the ICU than in the non-ICU population. Independent risk factors for death in candidemic patients included septic shock, acute kidney injury, and the number of antibiotics to which patients were exposed before candidemia. Discussion: While this study shows a role for known and novel risk factors for candidemia, it specifically highlights important differences in their distribution according to the hospital setting (ICU versus non-ICU). Conclusion: This study provides novel risk scores for candidemia accounting for the hospital setting and recent progress in patients' management strategies and fungal epidemiology.
Background Serological immunoassays that can identify protective immunity against SARS‐CoV‐2 are needed to adapt quarantine measures, assess vaccination responses, and evaluate donor plasma. To date, however, the utility of such immunoassays remains unclear. In a mixed‐design evaluation study, we compared the diagnostic accuracy of serological immunoassays that are based on various SARS‐CoV‐2 proteins and assessed the neutralizing activity of antibodies in patient sera. Methods Consecutive patients admitted with confirmed SARS‐CoV‐2 infection were prospectively followed alongside medical staff and biobank samples from winter 2018/2019. An in‐house enzyme‐linked immunosorbent assay utilizing recombinant receptor‐binding domain (RBD) of the SARS‐CoV‐2 spike protein was developed and compared to three commercially available enzyme‐linked immunosorbent assays (ELISAs) targeting the nucleoprotein (N), the S1 domain of the spike protein (S1) and a lateral flow immunoassay (LFI) based on full‐length spike protein. Neutralization assays with live SARS‐CoV‐2 were performed. Results One‐thousand four‐hundred and seventy‐seven individuals were included comprising 112 SARS‐CoV‐2 positives (defined as a positive real‐time PCR result; prevalence 7.6%). IgG seroconversion occurred between day 0 and day 21. While the ELISAs showed sensitivities of 88.4% for RBD, 89.3% for S1, and 72.9% for N protein, the specificity was above 94% for all tests. Out of 54 SARS‐CoV‐2 positive individuals, 96.3% showed full neutralization of live SARS‐CoV‐2 at serum dilutions ≥1:16, while none of the 6 SARS‐CoV‐2 negative sera revealed neutralizing activity. Conclusions ELISAs targeting RBD and S1 protein of SARS‐CoV‐2 are promising immunoassays which shall be further evaluated in studies verifying diagnostic accuracy and protective immunity against SARS‐CoV‐2.
BACKGROUND SARS-CoV-2/COVID-19, which emerged in China in late 2019, rapidly spread across the world with several million victims in 213 countries. Switzerland was severely hit by the virus, with 43,000 confirmed cases as of 1 September 2020. AIM In cooperation with the Federal Office of Public Health, we set up a surveillance database in February 2020 to monitor hospitalised patients with COVID-19, in addition to their mandatory reporting system. METHODS Patients hospitalised for more than 24 hours with a positive polymerase chain-reaction test, from 20 Swiss hospitals, are included. Data were collected in a customised case report form based on World Health Organisation recommendations and adapted to local needs. Nosocomial infections were defined as infections for which the onset of symptoms was more than 5 days after the patient’s admission date. RESULTS As of 1 September 2020, 3645 patients were included. Most patients were male (2168, 59.5%), and aged between 50 and 89 years (2778, 76.2%), with a median age of 68 (interquartile range 54–79). Community infections dominated with 3249 (89.0%) reports. Comorbidities were frequently reported, with hypertension (1481, 61.7%), cardiovascular diseases (948, 39.5%) and diabetes (660, 27.5%) being the most frequent in adults; respiratory diseases and asthma (4, 21.1%), haematological and oncological diseases (3, 15.8%) were the most frequent in children. Complications occurred in 2679 (73.4%) episodes, mostly respiratory diseases (2470, 93.2% in adults; 16, 55.2% in children), and renal (681, 25.7%) and cardiac (631, 23.8%) complications for adults. The second and third most frequent complications in children affected the digestive system and the liver (7, 24.1%). A targeted treatment was given in 1299 (35.6%) episodes, mostly with hydroxychloroquine (989, 76.1%). Intensive care units stays were reported in 578 (15.8%) episodes. A total of 527 (14.5%) deaths were registered, all among adults. CONCLUSION The surveillance system has been successfully initiated and provides a robust set of data for Switzerland by including about 80% (compared with official statistics) of SARS-CoV-2/COVID-19 hospitalised patients, with similar age and comorbidity distributions. It adds detailed information on the epidemiology, risk factors and clinical course of these cases and, therefore, is a valuable addition to the existing mandatory reporting.
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