Breakthrough COVID-19 in vaccinated patients with hematologic malignancies: results from the EPICOVIDEHA survey.

Limited data are available on breakthrough COVID-19 in patients with hematologic malignancy (HM) after anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Adult patients with HM, ≥1 dose of anti-SARS-CoV-2 vaccine, and breakthrough COVID-19 between January 2021 and March 2022 were analyzed. A total of 1548 cases were included, mainly lymphoid malignancies (1181 cases, 76%). After viral sequencing in 753 cases (49%), the Omicron variant was prevalent (517, 68.7%). Most of the patients received ≤2 vaccine doses before COVID-19 (1419, 91%), mostly mRNA-based (1377, 89%). Overall, 906 patients (59%) received COVID-19-specific treatment. After 30-day follow-up from COVID-19 diagnosis, 143 patients (9%) died. The mortality rate in patients with the Omicron variant was 7.9%, comparable to other variants, with a significantly lower 30-day mortality rate than in the prevaccine era (31%). In the univariable analysis, older age (P < .001), active HM (P < .001), and severe and critical COVID-19 (P = .007 and P < .001, respectively) were associated with mortality. Conversely, patients receiving monoclonal antibodies, even for severe or critical COVID-19, had a lower mortality rate (P < .001). In the multivariable model, older age, active disease, critical COVID-19, and 2-3 comorbidities were correlated with a higher mortality, whereas monoclonal antibody administration, alone (P < .001) or combined with antivirals (P = .009), was protective. Although mortality is significantly lower than in the prevaccination era, breakthrough COVID-19 in HM is still associated with considerable mortality. Death rate was lower in patients who received monoclonal antibodies, alone or in combination with antivirals.

Dexamethasone treatment for COVID-19 is related to increased mortality in hematologic malignancy patients: results from the EPICOVIDEHA Registry.

Not available.

Survival in multiple myeloma and SARS-COV-2 infection through the COVID-19 pandemic: Results from the EPICOVIDEHA registry.

Patients affected by multiple myeloma (MM) have an increased risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and subsequent coronavirus (20)19 disease (COVID-19)-related death. The changing epidemiological and therapeutic scenarios suggest that there has been an improvement in severity and survival of COVID-19 during the different waves of the pandemic in the general population, but this has not been investigated yet in MM patients. Here we analyzed a large cohort of 1221 patients with MM and confirmed SARS-CoV-2 infection observed between February 2020, and August 2022, in the EPICOVIDEHA registry from 132 centers around the world. Median follow-up was 52 days for the entire cohort and 83 days for survivors. Three-hundred and three patients died (24%) and COVID-19 was the primary reason for death of around 89% of them. Overall survival (OS) was significantly higher in vaccinated patients with both stable and active MM versus unvaccinated, while only a trend favoring vaccinated patients was observed in subjects with responsive MM. Vaccinated patients with at least 2 doses showed a better OS than those with one or no vaccine dose. Overall, according to pandemic waves, mortality rate decreased over time from 34% to 10%. In multivariable analysis, age, renal failure, active disease, hospital, and intensive care unit admission, were independently associated with a higher number of deaths, while a neutrophil count above 0.5 × 109 /L was found to be protective. This data suggests that MM patients remain at risk of SARS-CoV-2 infection even in the vaccination era, but their clinical outcome, in terms of OS, has progressively improved throughout the different viral phases of the pandemic.

Laboratory and clinical management capacity for invasive fungal infections: the Italian landscape.

BACKGROUND: We assessed the laboratory diagnosis and treatment of invasive fungal disease (IFD) in Italy to detect limitations and potential for improvement. METHODS: The survey was available online at www.clinicalsurveys.net/uc/IFI management capacity/, and collected variables such as (a) institution profile, (b) perceptions of IFD in the respective institution, (c) microscopy, (d) culture and fungal identification, (e) serology, (f) antigen detection, (g) molecular tests, (h) susceptibility testing and (i) therapeutic drug monitoring (TDM). RESULTS: The laboratory capacity study received responses from 49 Italian centres, with an equitable geographical distribution of locations. The majority of respondents (n = 36, 73%) assessed the occurrence of IFD as moderate-high, with Aspergillus spp. being the pathogen of highest concern, followed by Candida spp. and Mucorales. Although 46 (94%) of the institutions had access to microscopy, less than half of them performed direct microscopy on clinical specimens always when IFD was suspected. Cultures were available in all assessed laboratories, while molecular testing and serology were available in 41 (83%), each. Antigen detection tests and antifungal drugs were also generally accessible (> 90%) among the participating institutions. Nevertheless, access to TDM was limited (n = 31, 63%), with a significant association established between therapeutic drug monitoring availability and higher gross domestic product per capita. CONCLUSIONS: Apart from TDM, Italy is adequately prepared for the diagnosis and treatment of IFD, with no significant disparities depending on gross domestic product. Future efforts may need to focus on enhancing the availability and application of direct microscopic methods, as well as TDM, to promote optimal treatment and better patient outcomes.

Challenges in assessing the immunization status of adults in Germany-lessons from a population-based VACCELERATE survey on polio vaccination.

PURPOSE: Considering the re-emergence of poliomyelitis (PM) in non-endemic regions, it becomes apparent that vaccine preventable diseases can rapidly develop epi- or even pandemic potential. Evaluation of the current vaccination status is required to inform patients, health care providers and policy makers about vaccination gaps. METHODS: Between October 28 2022 and November 23 2022, 5,989 adults from the VACCELEREATE Volunteer Registry completed an electronic case report form on their previous PM vaccine doses including number, types/-valencies and the time of administration based on their vaccination records. A uni-/multivariable regression analysis was performed to assess associations in participant characteristics and immunization status. RESULTS: Among German volunteers (n = 5,449), complete PM immunization schedule was found in 1,981 (36%) participants. Uncertain immunization, due to unknown previous PM vaccination (n = 313, 6%), number of doses (n = 497, 9%), types/-valencies (n = 1,233, 23%) or incoherent immunization schedule (n = 149, 3%) was found in 40% (n = 2,192). Out of 1,276 (23%) participants who reported an incomplete immunization schedule, 62 (1%) never received any PM vaccine. A total of 5,074 (93%) volunteers reported having been vaccinated at least once and 2,087 (38%) indicated that they received vaccination within the last ten years. Female sex, younger age, as well as availability of first vaccination record were characteristics significantly associated with complete immunization (p < 0.001). CONCLUSION: Full PM immunization schedule was low and status frequently classified as uncertain due to lack of details on administered doses. There is an obviousneed for improved recording to enable long-term access to detailed vaccination history in the absence of a centralized immunization register.

Questioning the 14-day dogma in candidemia treatment duration.

The growing threat of antimicrobial resistance (AMR) is a global concern. With AMR directly causing 1.27 million deaths in 2019 and projections of up to 10 million annual deaths by 2050, optimising infectious disease treatments is imperative. Prudent antimicrobial use, including treatment duration, can mitigate AMR emergence. This is particularly critical in candidemia, a severe condition with a 45% crude mortality rate, as the 14-day minimum treatment period has not been challenged in randomised comparison. A comprehensive literature search was conducted in August 2023, revealing seven original articles and two case series discussing treatment durations of less than 14 days for candidemia. No interventional trials or prospective observational studies assessing shorter durations were found. Historical studies showed varying candidemia treatment durations, questioning the current 14-day minimum recommendation. Recent research observed no significant survival differences between patients receiving shorter or longer treatment, emphasising the need for evidence-based guidance. Treatment duration reduction post-blood culture clearance could decrease exposure to antifungal drugs, limiting selection pressure, especially in the context of emerging multiresistant Candida species. Candidemia's complexity, emerging resistance and potential for shorter in-hospital stays underscore the urgency of refining treatment strategies. Evidence-driven candidemia treatment durations are imperative to balance efficacy with resistance prevention and ensure the longevity of antifungal therapies. Further research and clinical trials are needed to establish evidence-based guidelines for candidemia treatment duration.

Multicentric Study on the Clinical Mycology Capacity and Access to Antifungal Treatment in Portugal.

The success of the clinical management of invasive fungal diseases (IFD) is highly dependent on suitable tools for timely and accurate diagnosis for effective treatment. An in-depth analysis of the ability of European institutions to promptly and accurately diagnose IFD was previously conducted to identify limitations and aspects to improve. Here, we evaluated and discussed the specific case of Portugal, for which, to our knowledge, there are no reports describing the national mycological diagnostic capacity and access to antifungal treatment. Data from 16 Portuguese medical institutions were collected via an online electronic case report form covering different parameters, including institution profile, self-perceived IFD incidence, target patients, diagnostic methods and reagents, and available antifungals. The majority of participating institutions (69%) reported a low-very low incidence of IFD, with Candida spp. indicated as the most relevant fungal pathogen, followed by Aspergillus spp. and Cryptococcus spp. All institutions had access to culture and microscopy, whereas 94 and 88% were able to run antigen-detection assays and molecular tests, respectively. All of the institutions capable of providing antifungal therapy declared to have access to at least one antifungal. However, echinocandins were only available at 85% of the sites. Therapeutic drug monitoring (TDM) was reported to remain a very restricted practice in Portugal, being available in 19% of the institutions, with the TDM of itraconazole and posaconazole performed in only 6% of them. Importantly, several of these resources are outsourced to external entities. Except for TDM, Portugal appears to be well-prepared concerning the overall capacity to diagnose and treat IFD. Future efforts should focus on promoting the widespread availability of TDM and improved access to multiple classes of antifungals, to further improve patient outcomes.

The Cologne ECMM Excellence Center: A Two-Year Analysis of External Consultation Service for Invasive Fungal Infections.

The European Confederation of Medical Mycology (ECMM), formed due to the surge in invasive fungal infections (IFI), initiated the Excellence Centers program in 2016 to guide stakeholders to leading medical mycology sites. This report focuses on the Cologne ECMM Excellence Center, recognized with Diamond status for active global involvement in 2017. The center offers free consultation via email and phone, responding within 24 h for life-threatening IFI, collecting data on origin, pathogens, infection details, and more. Over two years, 189 requests were received globally, predominantly from Germany (85%), mainly involving Aspergillus spp., Mucorales, and Candida spp. Fungal mixed infections occurred in 4% of cases. The center's service effectively addresses IFI challenges, advocating for a comprehensive study encompassing all ECMM Excellence Centers to enhance global mycological care. Proactive expansion of consultancy platforms is crucial, with future analyses needed to assess expert advice's impact on patient outcomes.

COVID-19 in adult acute myeloid leukemia patients: a long-term follow-up study from the European Hematology Association survey (EPICOVIDEHA).

Patients with acute myeloid leukemia (AML) are at high risk of dying from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients diagnosed with COVID-19 between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the preceding 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with better survival when AML treatment could be delayed (80%; P<0.001). Overall survival in patients with a diagnosis of COVID-19 between January 2020 and August 2020 was significantly lower than that in patients diagnosed between September 2020 and February 2021 and between March 2021 and September 2021 (39.8% vs. 60% vs. 61.9%, respectively; P=0.006). COVID-19 in AML patients was associated with a high mortality rate and modifications of therapeutic algorithms. The best approach to improve survival was to delay AML treatment, whenever possible.

The Argentinian landscape of mycological diagnostic capacity and treatment accessibility.

Immunosuppressed patients, transplant recipients, and those with acute or chronic respiratory disease are at increased risk for invasive fungal infections in Argentina. Although the national public system guarantees universal access to health care for all citizens, little is known about the quality of available diagnostic and treatment armamentaria for invasive fungal infections in the country. Between June and August 2022, infectious disease clinicians from each of the 23 provinces and the Autonomous City of Buenos Aires were contacted to describe local access to fungal diagnostic tools and antifungal agents. The information collected included different aspects such as hospital characteristics, patients admitted and wards, access to diagnostic tools, estimated infection incidence, and treatment capacity. Thirty responses were collected from facilities throughout Argentina. Most institutions were governmental (77%). A mycology department was available in 83% of them. Histopathology was available in almost 93% of the sites, while automated methods and galactomannan tests were available in 57%, each; 53% of the sites had access to MALDI-TOF-MS through regional reference laboratories, and PCR was present in 20% of the sites. Susceptibility testing was available in 63% of the laboratories. Candida spp. (24%), Cryptococcus spp. (20%), Aspergillus spp. (18%), and Histoplasma spp. (16%) were described as the main pathogens. Fluconazole was the only antifungal agent available in all institutions. This was followed by amphotericin B deoxycholate (83%) and itraconazole (80%). If an antifungal agent was not available onsite, then 60% of the patients could receive adequate antifungal treatment within the first 48 h upon request. Although there are no significant differences in access to diagnostic and clinical management of invasive fungal infections among the Argentinean centres studied, national awareness-raising initiatives led by policymakers could help to improve their general availability.

Increasing influenza vaccination coverage in healthcare workers: analysis of an intensified on-site vaccination campaign during the COVID-19 pandemic.

PURPOSE: Influenza infections have substantial impact on healthcare institutions. While vaccination is the most effective preventive measure against influenza infection, vaccination coverage in healthcare workers is low. The study investigates the impact of an intensified influenza vaccination campaign in a maximum-care hospital on influenza vaccination coverage in healthcare workers during the COVID-19 pandemic in 2020/21. METHODS: Building on findings from our previously published review Schumacher et al. (Infection 49(3): 387, 2021), an intensified influenza vaccination campaign comprising a mobile vaccination team providing on-site vaccination and vaccination at a recurring central vaccination site in addition to promotional measures was performed and analysed regarding vaccination coverage. A survey querying vaccination motivation was performed. Campaign strategies and vaccination coverage of influenza seasons between 2017/18 and 2019/20 were analysed. RESULTS: The influenza vaccination campaign 2020/21 led to a significant 2.4-fold increase yielding an overall vaccination coverage of 40% among healthcare workers. A significant increase in vaccination coverage was observed across all professional fields; especially among nurses, a 2.7-fold increase, reaching a vaccination coverage of 48%, was observed. The COVID-19 pandemic positively influenced vaccination decision in 72% of first time ever or first time in over ten years influenza vaccinees. Vaccination coverage during prior vaccination campaigns focusing on educational measures did not exceed 17%. CONCLUSION: A mobile vaccination team providing on-site vaccination and vaccinations at a central vaccination site in addition to promotional measures can be implemented to increase influenza vaccination coverage in healthcare workers. Our concept can inform influenza and other vaccination campaigns for healthcare workers.

A pilot surveillance report of SARS-CoV-2 rapid antigen test results among volunteers in Germany, 1st week of July 2022.

PURPOSE: We hypothesized that SARS-CoV-2 infection numbers reported by governmental institutions are underestimated due to high dark figures as only results from polymerase chain reaction (PCR) tests are incorporated in governmental statistics and testing capacities were further restricted as of July, 2022. METHODS: A point prevalence investigation was piloted by rapid antigen testing (RAT) among participants of the VACCELERATE volunteer registry. 2400 volunteers were contacted, of which 500 received a RAT including instructions for self-testing in the first week of July, 2022. Results were self-reported via e-mail. RESULTS: 419 valid RAT results were collected until July 7th, 2022. Between July-1 and July-7, 2022, 7/419 (1.67%) tests were positive. Compared to reports of the German Federal Government, our results suggest a more than twofold higher prevalence. Three out of seven positive individuals did not have a PCR test and are therefore likely not to be displayed in governmental statistics. CONCLUSION: Our findings imply that the actual prevalence of SARS-CoV-2 may be higher than detected by current surveillance systems, so that current pandemic surveillance and testing strategies may be adapted.

The Austrian landscape of diagnostic capacity and access to treatment for invasive fungal infections.

INTRODUCTION: Immunosuppression after chemotherapy, stem cell transplantation or solid organ transplantation are the main risk factors for invasive fungal infections in Austria. Here, we aim to describe the status of laboratory mycology and the access to antifungal treatment in Austria. METHODS: Between October and November 2021, hospitals were contacted to participate in our online survey: www.clinicalsurveys.net/uc/IFI_management_capacity/. Centres were required to provide information on their institutional profile; self-assessment of burden of invasive fungal infections; access to microscopy, culture, serology, antigen detection and molecular testing; and availability of antifungal agents and therapeutic drug monitoring. RESULTS: Responses were collected from university hospitals and laboratories in Graz, Innsbruck, Linz and Vienna. The four hospitals can provide tertiary care and were highly specialised, including management of patients with severe immunosuppression. All sites consider the incidence of invasive fungal infections to be moderate. Access to microscopy, culture, serology, antigen detection and molecular testing is provided regardless of laboratory. The maximum capacity to identify fungi varies from institution to institution. All currently marketed antifungal agents are available at the four sites. CONCLUSION: Austria is currently well equipped to deal with the emerging threat of invasive fungal infections. However, hospitals may consider preparing for the potential endemicity of certain infections in the near future.

Predictors for Prolonged Hospital Stay Solely to Complete Intravenous Antifungal Treatment in Patients with Candidemia: Results from the ECMM Candida III Multinational European Observational Cohort Study.

BACKGROUND: To date, azoles represent the only viable option for oral treatment of invasive Candida infections, while rates of azole resistance among non-albicans Candida spp. continue to increase. The objective of this sub-analysis of the European multicenter observational cohort study Candida III was to describe demographical and clinical characteristics of the cohort requiring prolonged hospitalization solely to complete intravenous (iv) antifungal treatment (AF Tx). METHODS: Each participating hospital (number of eligible hospitals per country determined by population size) included the first ~ 10 blood culture proven adult candidemia cases occurring consecutively after July 1st, 2018, and treating physicians answered the question on whether hospital stay was prolonged only for completion of intravenous antifungal therapy. Descriptive analyses as well as binary logistic regression was used to assess for predictors of prolonged hospitalization solely to complete iv AF Tx. FINDINGS: Hospital stay was prolonged solely for the completion of iv AF Tx in 16% (100/621) of candidemia cases by a median of 16 days (IQR 8 - 28). In the multivariable model, initial echinocandin treatment was a positive predictor for prolonged hospitalization to complete iv AF Tx (aOR 2.87, 95% CI 1.55 - 5.32, p < 0.001), while (i) neutropenia, (ii) intensive care unit admission, (iii) catheter related candidemia, (iv) total parenteral nutrition, and (v) C. parapsilosis as causative pathogen were found to be negative predictors (aOR 0.22 - 0.45; p < 0.03). INTERPRETATION: Hospital stays were prolonged due to need of iv AF Tx in 16% of patients with candidemia. Those patients were more likely to receive echinocandins as initial treatment and were less severely ill and less likely infected with C. parapsilosis.

Prognostic Impact of Bronchoalveolar Lavage Fluid Galactomannan and Aspergillus Culture Results on Survival in COVID-19 Intensive Care Unit Patients: a Post Hoc Analysis from the European Confederation of Medical Mycology (ECMM) COVID-19-Associated Pulmonary Aspergillosis Study.

Critically ill patients with coronavirus disease 2019 (COVID-19) may develop COVID-19-associated pulmonary aspergillosis (CAPA), which impacts their chances of survival. Whether positive bronchoalveolar lavage fluid (BALF) mycological tests can be used as a survival proxy remains unknown. We conducted a post hoc analysis of a previous multicenter, multinational observational study with the aim of assessing the differential prognostic impact of BALF mycological tests, namely, positive (optical density index of ≥1.0) BALF galactomannan (GM) and positive BALF Aspergillus culture alone or in combination for critically ill patients with COVID-19. Of the 592 critically ill patients with COVID-19 enrolled in the main study, 218 were included in this post hoc analysis, as they had both test results available. CAPA was diagnosed in 56/218 patients (26%). Most cases were probable CAPA (51/56 [91%]) and fewer were proven CAPA (5/56 [9%]). In the final multivariable model adjusted for between-center heterogeneity, an independent association with 90-day mortality was observed for the combination of positive BALF GM and positive BALF Aspergillus culture in comparison with both tests negative (hazard ratio, 2.53; 95% CI confidence interval [CI], 1.28 to 5.02; P = 0.008). The other independent predictors of 90-day mortality were increasing age and active malignant disease. In conclusion, the combination of positive BALF GM and positive BALF Aspergillus culture was associated with increased 90-day mortality in critically ill patients with COVID-19. Additional study is needed to explore the possible prognostic value of other BALF markers.

Invasive Trichoderma spp. infections: clinical presentation and outcome of cases from the literature and the FungiScope® registry.

BACKGROUND: Trichoderma spp. are filamentous fungi causing invasive fungal diseases in patients with haematological malignancies and in peritoneal dialysis patients. OBJECTIVES: To analyse clinical presentation, predisposing factors, treatment and outcome of Trichoderma infections. METHODS: A systematic literature review was conducted for published cases of invasive Trichoderma infection in PubMed until December 2021 and by reviewing the included studies' references. Cases from the FungiScope® registry were added to a combined analysis. RESULTS: We identified 50 invasive infections due to Trichoderma species, including 11 in the FungiScope® registry. The main underlying conditions were haematological malignancies in 19 and continuous ambulatory peritoneal dialysis (CAPD) in 10 cases. The most prevalent infection sites were lung (42%) and peritoneum (22%). Systemic antifungal therapy was administered in 42 cases (84%), mostly amphotericin B (n = 27, lipid-based formulation 13/27) and voriconazole in 15 cases (30%). Surgical interventions were performed in 13 cases (26%). Overall mortality was 48% (n = 24) and highest for allogeneic HSCT and solid organ transplantation (SOT) recipients [80% (4/5) and 77% (7/9), respectively]. In patients treated with amphotericin B, voriconazole and caspofungin, mortality was 55% (15/27), 46% (7/15) and 28% (2/7), respectively. Three out of four patients treated with a combination therapy of voriconazole and caspofungin survived. CONCLUSIONS: Despite treatment with antifungal therapies and surgery, invasive Trichoderma infections are life-threatening complications in immunocompromised patients, especially after HSCT and SOT. In addition, Trichoderma spp. mainly affect the lungs in patients with haematological malignancies and the peritoneum in CAPD patients.

Harmonized procedure coding system for surgical procedures and analysis of surgical site infections (SSI) of five European countries.

BACKGROUND: The use of routine data will be essential in future healthcare research. Therefore, harmonizing procedure codes is a first step to facilitate this approach as international research endeavour. An example for the use of routine data on a large scope is the investigation of surgical site infections (SSI). Ongoing surveillance programs evaluate the incidence of SSI on a national or regional basis in a limited number of procedures. For example, analyses by the European Centre for Disease Prevention (ECDC) nine procedures and provides a mapping table for two coding systems (ICD9, National Healthcare Safety Network [NHSN]). However, indicator procedures do not reliably depict overall SSI epidemiology. Thus, a broader analysis of all surgical procedures is desirable. The need for manual translation of country specific procedures codes, however, impedes the use of routine data for such an analysis on an international level. This project aimed to create an international surgical procedure coding systems allowing for automatic translation and categorization of procedures documented in country-specific codes. METHODS: We included the existing surgical procedure coding systems of five European countries (France, Germany, Italy, Spain, and the United Kingdom [UK]). In an iterative process, country specific codes were grouped in ever more categories until each group represented a coherent unit based on method of surgery, interventions performed, extent and site of the surgical procedure. Next two ID specialist (arbitrated by a third in case of disagreement) independently assigned country-specific codes to the resulting categories. Finally, specialist from each surgical discipline reviewed these assignments for their respective field. RESULTS: A total number of 153 SALT (Staphylococcus aureus Surgical Site Infection Multinational Epidemiology in Europe) codes from 10 specialties were assigned to 15,432 surgical procedures. Almost 4000 (26%) procedure codes from the SALT coding system were classified as orthopaedic and trauma surgeries, thus this medical field represents the most diverse group within the SALT coding system, followed by abdominal surgical procedures with 2390 (15%) procedure codes. CONCLUSION: Mapping country-specific codes procedure codes onto to a limited number of coherent, internally and externally validated codes proofed feasible. The resultant SALT procedure code gives the opportunity to harmonize big data sets containing surgical procedures from international centres, and may simplify comparability of future international trial findings. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov under NCT03353532 on November 27th, 2017.

Attributable mortality of candidemia at a German tertiary hospital from 1997 to 2001 before the introduction of echinocandins.

OBJECTIVES: The relevance of candidemia has increased over the last decades due to higher incidence rates in an ageing society. Studies on amphotericin B and fluconazole have shown high attributable mortality rates of 38% and 49% in the United States. Incidence rates and locational factors might have an impact on the mortality rates at the University Hospital of Cologne (UHC), Germany. METHODS: We performed a matched case-control study including 57 patients with candidemia, hospitalised at the UHC between 1 July 1997 and 30 June 2001. Controls were matched by age, sex, admission date, treatment on intensive care unit (ICU), number of days at risk, underlying diseases, surgical procedures and the Charlson Comorbidity Index. RESULTS: The incidence of candidemia was 3.5 per 10 000 admissions. For cases and controls, we observed in-hospital-mortality rates of 33.3% and 11.8%, and a 30-day mortality of 23.5% and 7.8% respectively. The attributable mortality rate to candidemia was 21.5%, and at 30 days, it was 15.7%. Underlying conditions were more frequent in cases than in controls, especially central venous catheter (80% vs 33%, P < .001), chronic cardiovascular disease (39.2% vs 25.5%, P = .138), treatment on ICU (31.4% vs 13.7%, P = .033) and chronic liver disease (21.6% vs 0%, P < .001). CONCLUSIONS: The attributable mortality of candidemia at the UHC between 1997 and 2001 was lower compared to studies performed in the United States with a similar design. Contributing factors might be lower incidence rates and less comorbidities in our study.

Impact of single-room contact precautions on acquisition and transmission of vancomycin-resistant enterococci on haematological and oncological wards, multicentre cohort-study, Germany, January-December 2016.

BackgroundEvidence supporting the effectiveness of single-room contact precautions (SCP) in preventing in-hospital acquisition of vancomycin-resistant enterococci (haVRE) is limited.AimWe assessed the impact of SCP on haVRE and their transmission.MethodsWe conducted a prospective, multicentre cohort study in German haematological/oncological departments during 2016. Two sites performed SCP for VRE patients and two did not (NCP). We defined a 5% haVRE-risk difference as non-inferiority margin, screened patients for VRE, and characterised isolates by whole genome sequencing and core genome MLST (cgMLST). Potential confounders were assessed by competing risk regression analysis.ResultsWe included 1,397 patients at NCP and 1,531 patients at SCP sites. Not performing SCP was associated with a significantly higher proportion of haVRE; 12.2% (170/1,397) patients at NCP and 7.4% (113/1,531) patients at SCP sites (relative risk (RR) 1.74; 95% confidence interval (CI): 1.35-2.23). The difference (4.8%) was below the non-inferiority margin. Competing risk regression analysis indicated a stronger impact of antimicrobial exposure (subdistribution hazard ratio (SHR) 7.46; 95% CI: 4.59-12.12) and underlying disease (SHR for acute leukaemia 2.34; 95% CI: 1.46-3.75) on haVRE than NCP (SHR 1.60; 95% CI: 1.14-2.25). Based on cgMLST and patient movement data, we observed 131 patient-to-patient VRE transmissions at NCP and 85 at SCP sites (RR 1.76; 95% CI: 1.33-2.34).ConclusionsWe show a positive impact of SCP on haVRE in a high-risk population, although the observed difference was below the pre-specified non-inferiority margin. Importantly, other factors including antimicrobial exposure seem to be more influential.

COVID-19-Associated Pulmonary Aspergillosis, March-August 2020.

Pneumonia caused by severe acute respiratory syndrome coronavirus 2 emerged in China at the end of 2019. Because of the severe immunomodulation and lymphocyte depletion caused by this virus and the subsequent administration of drugs directed at the immune system, we anticipated that patients might experience fungal superinfection. We collected data from 186 patients who had coronavirus disease-associated pulmonary aspergillosis (CAPA) worldwide during March-August 2020. Overall, 182 patients were admitted to the intensive care unit (ICU), including 180 with acute respiratory distress syndrome and 175 who received mechanical ventilation. CAPA was diagnosed a median of 10 days after coronavirus disease diagnosis. Aspergillus fumigatus was identified in 80.3% of patient cultures, 4 of which were azole-resistant. Most (52.7%) patients received voriconazole. In total, 52.2% of patients died; of the deaths, 33.0% were attributed to CAPA. We found that the cumulative incidence of CAPA in the ICU ranged from 1.0% to 39.1%.