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Significant variations in the variables collected in clinical studies focusing on bacteraemia lead to inconsistency in the evaluation of risk factors for mortality. We aimed to define a minimum set of risk factors that should be assessed and reported in all studies assessing survival in bacteraemia. We conducted a systematic review including observational prospective and retrospective cohort studies that assessed all-cause mortality among patients with bacteraemia. We included only studies computing an adjusted analysis for mortality, with >500 participants. Independently significant risk factors for all-cause, preferably 30-day, mortality. PubMed was used to identify eligible studies published between 2000 and 2020. A Delphi survey among experts was used to evaluate and prioritize the factors identified by the systematic review. SIGN checklist complemented by risk of bias assessment of the adjusted analysis. Definite universal risk factors were defined as those assessed in >50% of all included studies and significant in >50% of those. Potential universal risk factors were defined as those significant in >50% of studies evaluating the factor and a subgroup analysis was performed for studies of Staphylococcus aureus bacteraemia. We included in the systematic review 62 studies, comprising more than 300,000 patients, from which a list of 17 risk factors was derived, whose association with all-cause mortality was statistically significant in most studies. The factors address baseline patient variables, the setting of infection acquisition, factors associated with the specific infection, the inflammatory response at onset of sepsis and management parameters where relevant. There were 14 risk factors for S. aureus bacteraemia. We identified a minimum set of universal factors to be collected, reported, and assessed, in all future studies evaluating factors associated with mortality in bacteraemia to improve study quality and harmonization. [ABSTRACT FROM AUTHOR]

To evaluate the risk of recurrent Clostridioides difficile infection (CDI) in solid-organ transplant (SOT) recipients. Retrospective multicenter study including SOT recipients with a first CDI episode in the year after transplantation (Jan 2017-June 2020). The primary outcome measure was recurrence, defined as a new CDI ≤56 days from the first episode. A competing risk analysis was performed using the sub-distribution hazard model multivariable analysis. 191 SOT recipients were included: 101 (52.9%) were kidney, 66 (34.6%) liver, 11 (5.8%) lung, 8 (4.2%) simultaneous pancreas-kidney, 4 (2.1%) heart and 1 (0.5%) pancreas alone recipients. Treatment for the first CDI were: vancomycin (n = 114,59.7%), vancomycin+metronidazole (n = 39,20.4%), metronidazole (n = 26,13.6%), fidaxomicin (n = 9,4.7%), 3 patients did not receive any therapy. After the first CDI, 17/191 (8.9%) patients died within 56-day mortality without having a recurrence, while 23/191 (12%) patients had a recurrence. Among patients with recurrent CDI, 56-day mortality rate was 30.4% (7/23 patients). On multivariable analysis, severe CDI (sHR4.01, 95% CI 1.77–9.08, p <.001) and metronidazole monotherapy (sHR 3.65, 95% CI 1.64–8.14, p =.001) were factors independently associated with recurrence. Metronidazole monotherapy is associated with increased risk of recurrent CDI in SOT recipients. Therapeutic strategies aimed to reduce the risk of recurrence should be implemented in this setting. [Display omitted] • The risk of recurrent CDI in SOT recipients after the first CDI episode is about 12%. • Metronidazole monotherapy is associated with increased risk of recurrent CDI. • Approaches to reduce the risk of recurrence should be applied in this population. [ABSTRACT FROM AUTHOR]

• Long-COVID is a major problem for physicians and health care policy makers. • SARS-CoV-2 RNAemia is associated with worse quality of life. • SARS-CoV-2 RNAemia is associated with more long-COVID symptoms. • SARS-CoV-2 RNAemia was not associated with any specific long-COVID symptom. [ABSTRACT FROM AUTHOR]

• Data on antibiotic de-escalation in sepsis associated with bloodstream infection caused by Enterobacterales are scarce. • Neutropenia, central catheter use, and extended-spectrum β-lactamase were negatively associated with de-escalation in sepsis. • De-escalation was not associated with mortality in patients with sepsis and bloodstream infection. Data about antibiotic de-escalation in sepsis associated with the bloodstream and caused by Enterobacterales are scarce. The objectives of this study are to identify factors associated with early de-escalation and to analyse the impact of de-escalation on mortality in patients with Enterobacterales bloodstream infection (BSI) with a Sequential Organ Failure Assessment (SOFA) score ≥ 2. A prospective, multicentre cohort study was performed including episodes of BSI due to Enterobacterales and a SOFA score ≥ 2 who were receiving an active antipseudomonal β-lactam; the isolate should be susceptible to at least 1 narrower-spectrum antibiotic. Variables associated with de-escalation were identified using logistic binary regression. The association of de-escalation with 30-day mortality was investigated. Confounding was controlled by calculating a propensity score used as covariate, as matching variable, and for inverse probability treatment weighting. Of the 582 patients included, de-escalation was performed in 311 (53.4%). Neutropenia (adjusted odds ratio [aOR] = 0.37; 95% confidence interval [95% CI] = 0.18–0.75), central venous catheter (aOR = 0.52; 95% CI = 0.32–0.83), and extended-spectrum β-lactamase (ESBL)–producing isolate (aOR = 0.28; 95% CI = 0.17–0.48) were negatively associated with de-escalation, and urinary tract source was positively associated (aOR = 2.27; 95% CI = 1.56–3.33). The 30-day mortality was 6.8% (21 patients) in de-escalated patients and 14.4% (39) in not de-escalated patients (relative risk, 0.63; 95% CI = 0.44–0.89). In multivariate analysis including the propensity score, de-escalation was not associated with mortality (AOR = 0.98; 95% CI = 0.39–2.47) and was protective in the case of urinary or biliary tract source (AOR = 0.31, 95% CI = 0.09–1.06). Matched and inverse probability treatment weighting analysis showed similar results. These results suggest that early de-escalation from antipseudomonal β-lactams is safe in patients with Enterobacterales bacteremia and SOFA ≥ 2. [Display omitted] [ABSTRACT FROM AUTHOR]

Rapid and widespread increases in carbapenem resistance (CR) necessitate identification of risk factors to guide appropriate interventions. We aimed to identify risk factors for CR Gram-negative infection through a systematic literature review. We searched MEDLINE (via OvidSP and PubMed) and Embase (via OvidSP) databases and the Cochrane Central Register of Controlled Trials. Prospective or retrospective cohort and case–control studies reporting quantitative data on risk factors associated with infections due to CR Gram-negative pathogens in hospitalized patients were eligible. Studies included hospitalized patients with CR infection caused by Gram-negative bacterial pathogens (Enterobacterales and non-fermenters). Searches were conducted in January 2018/December 2019 to identify studies published since 2007. Risk factor data were extracted and grouped by factor. The primary metric was proportion of studies reporting a significant association with CR infection for each factor. In total, 92 studies were identified. Risk factors most frequently reported as significantly associated with CR infection (>10 studies) were previous antibiotic use (91.1%; 72/79 studies); previous carbapenem use (82.6%; 57/69); previous colonization (72.7%; 8/11); mechanical ventilation (66.7%; 36/54); previous intensive care unit stay (64.4%; 38/59); dialysis (61.1%; 11/18); catheter (58.0%; 40/69); length of stay in hospital (54.5%; 30/55); comorbidities (52.7%; 39/74); APACHE II (51.7%; 15/29); and intubation (51.4%; 18/35). Risk factors were mostly consistent across different species and sites of infection. Several variables, particularly previous antibiotic use, are strong risk factors for CR infection. Interventions to mitigate against CR infection should target these factors. [ABSTRACT FROM AUTHOR]

• HBV could be reactivated in HBcAb-positive and HBsAg-negative patients treated with direct-acting antivirals. • Periodic monitoring of viral load of HBV during direct-acting antivirals treatment has been proposed in this review. • HIV patients with HBcAb-positive should be treated with nucleoside/nucleotide analogous to avoid possible reactivations. [ABSTRACT FROM AUTHOR]

Background: Most available information on carbapenemase-producing Enterobacteriaceae (CPE) is usually associated with specific types of infection or patient or with descriptions of outbreaks. The aim of this study was to comprehensively analyse the clinical epidemiology, clinical features and outcomes of colonisation and infections due to CPE in Spain.Methods: A multicentre prospective cohort study was carried out in 34 Spanish hospitals from February to May 2013. All new patients testing positive for CPE in clinical samples were included. Logistic regression was used to identify predictors of mortality.Results: Overall, 245 cases were included. The most frequent organism was Klebsiella pneumoniae (74%) and the carbapenemases belonged to the OXA-48 (74%), metallo-β-lactamase (MBL) (24%) and KPC (2%) groups. Acquisition was nosocomial in 145 cases (60%) and healthcare-associated (HCA) in 91 (37%); 42% of the latter were nursing home residents, in whom OXA-48-producing K. pneumoniae ST405 predominated. MBLs and OXA-48 predominated in ICU and medical patients, respectively. Overall, 67% of patients had infections. The most frequent infections identified in this study were urinary tract (43%) and skin structure (21%) infections, and 10% of infections were bacteraemic. Crude mortality was 20%. Inappropriate antibiotic therapy was independently associated with an increased risk of death (OR = 3.30; 95% CI: 1.34-8.11).Conclusions: We found some differences in the epidemiology of CPE depending on the type of carbapenemase produced. Although a low proportion of CPE infections were bacteraemic, active antibiotic therapy was a protective factor for reducing mortality. [ABSTRACT FROM AUTHOR]

Interferon-β is an attractive drug for repurposing and use in the treatment of COVID-19, based on its in vitro antiviral activity and the encouraging results from clinical trials. The aim of this study was to analyze the impact of early interferon-β treatment in patients admitted with COVID-19 during the first wave of the pandemic. This post hoc analysis of a COVID-19@Spain multicenter cohort included 3808 consecutive adult patients hospitalized with COVID-19 from 1 January to 17 March 2020. The primary endpoint was 30-day all-cause mortality, and the main exposure of interest was subcutaneous administration of interferon-β, defined as early if started ≤ 3 days from admission. Multivariate logistic and Cox regression analyses were conducted to identify the associations of different variables with receiving early interferon-β therapy and to assess its impact on 30-day mortality. A propensity score was calculated and used to both control for confounders and perform a matched cohort analysis. Overall, 683 patients (17.9%) received early interferon-β therapy. These patients were more severely ill. Adjusted HR for mortality with early interferon-β was 1.03 (95% CI, 0.82–1.30) in the overall cohort, 0.96 (0.82–1.13) in the PS-matched subcohort, and 0.89 (0.60–1.32) when interferon-β treatment was analyzed as a time-dependent variable. In this multicenter cohort of admitted COVID-19 patients, receiving early interferon-β therapy after hospital admission did not show an association with lower mortality. Whether interferon-β might be useful in the earlier stages of the disease or specific subgroups of patients requires further research. [Display omitted] • Interferon-β is an attractive drug to be repurposed for COVID-19. • This study analyzes the impact of early interferon-β treatment. • Interferon-β was not associated with lower mortality in hospitalized patients. • It might be useful in earlier disease stages or specific patients' subgroups. [ABSTRACT FROM AUTHOR]

To assess the mortality attributable to infections caused by carbapenem-resistant Enterobacterales (CRE) and to investigate the effect of clinical management on differences in observed outcomes in a multinational matched cohort study. A prospective matched-cohorts study (NCT02709408) was performed in 50 European hospitals from March 2016 to November 2018. The main outcome was 30-day mortality with an active post-discharge follow-up when applied. The CRE cohort included patients with complicated urinary tract infections, complicated intra-abdominal infections, pneumonia, or bacteraemia from other sources because of CRE. Two control cohorts were selected: patients with infection caused by carbapenem-susceptible Enterobacterales (CSE) and patients without infection. Matching criteria included type of infection for the CSE group, hospital ward of CRE detection, and duration of hospital admission up to CRE detection. Multivariable and stratified Cox regression was applied. The cohorts included 235 patients with CRE infection, 235 patients with CSE infection, and 705 non-infected patients. The 30-day mortality (95% CI) was 23.8% (18.8–29.6), 10.6% (7.2–15.2), and 8.4% (6.5–10.6), respectively. The difference in 30-day mortality rates between patients with CRE infection when compared with patients with CSE infection was 13.2% (95% CI, 6.3–20.0), (HR, 2.57; 95% CI, 1.55–4.26; p < 0.001), and 15.4% (95% CI, 10.5–20.2) when compared with non-infected patients (HR, 3.85; 95% CI, 2.57–5.77; p < 0.001). The population attributable fraction for 30-day mortality for CRE vs. CSE was 19.28%, and for CRE vs. non-infected patients was 9.61%. After adjustment for baseline variables, the HRs for mortality were 1.87 (95% CI, 0.99–3.50; p 0.06) and 3.65 (95% CI, 2.29–5.82; p < 0.001), respectively. However, when treatment-related time-dependent variables were added, the HR of CRE vs. CSE reduced to 1.44 (95% CI, 0.78–2.67; p 0.24). CRE infections are associated with significant attributable mortality and increased adjusted hazard of mortality when compared with CSE infections or patients without infection. Underlying patient characteristics and a delay in appropriate treatment play an important role in the CRE mortality. [ABSTRACT FROM AUTHOR]

A significant increased risk of complications and mortality in immunocompromised patients affected by COVID-19 has been described. However, the impact of COVID-19 in solid organ transplant (SOT) recipients is an issue still under debate, due to conflicting evidence that has emerged from different observational studies. We performed a systematic review with a meta-analysis to assess the clinical outcome in SOT recipients with COVID-19 compared with the general population. PubMed-MEDLINE and Scopus were independently searched until 13 October 2021. Prospective or retrospective observational studies comparing clinical outcome in SOT recipients versus general populations affected by COVID-19 were included. The primary endpoint was 30-day mortality. Participants were patients with confirmed COVID-19. Interventions reviewed were SOTs. The quality of the included studies was independently assessed with the Risk of Bias in Non-randomized Studies of Interventions tool for observational studies. The meta-analysis was performed by pooling ORs retrieved from studies providing adjustment for confounders using a random-effect s model with the inverse variance method. Multiple subgroups and sensitivity analyses were conducted to investigate the source of heterogeneity. A total of 3501 articles were screened, and 31 observational studies (N = 590 375; 5759 SOT recipients vs. 584 616 general population) were included in the meta-analyses. No difference in 30-day mortality rate was found in the primary analysis, including studies providing adjustment for confounders (N = 17; 3752 SOT recipients vs. 159 745 general population; OR: 1.13; 95% CI, 0.94–1.35; I2 = 33.9%). No evidence of publication bias was reported. A higher risk of intensive care unit admission (OR: 1.56; 95% CI, 1.03–2.63) and occurrence of acute kidney injury (OR: 2.50; 95% CI, 1.81–3.45) was found in SOT recipients. No increased risk in mortality was found in SOT recipients affected by COVID-19 compared with the general population when adjusted for demographic and clinical features and COVID-19 severity. [ABSTRACT FROM AUTHOR]

• Data regarding the use of isavuconazole in non-neutropenic IFI patients is scarce. • Our study positions isavuconazole as a safe treatment for these patients. • Isavuconazole could be used in patients with QT elongation. • Mortality and clinical response are comparable to other antifungals. • Isavuconazole could replace other triazoles as reference treatment. Information is scarce on clinical experiences with non-neutropenic patients with invasive fungal infection (IFI) receiving isavuconazole. We aimed to report the safety and effectiveness of this drug as a first-line treatment or rescue in real life. A retrospective, observational multicentric study of non-neutropenic patients who received isavuconazole as an IFI treatment at 12 different university hospitals (January 2018-2022). All patients met criteria for proven, probable or possible IFI according to EORTC-MSG. A total of 238 IFIs were treated with isavuconazole during the study period. Combination therapy was administered in 27.7% of cases. The primary IFI was aspergillosis (217, 91.2%). Other IFIs treated with isavuconazole were candidemia (n = 10), mucormycosis (n = 8), histoplasmosis (n = 2), cryptococcosis (n = 2), and others (n = 4). Median time of isavuconazole treatment was 29 days. Only 5.9% (n = 14) of cases developed toxicity, mainly hepatic-related (10 patients, 4.2%). Nine patients (3.8%) had treatment withdrawn. Successful clinical response at 12 weeks was documented in 50.5% of patients. Isavuconazole is an adequate treatment for non-neutropenic patients with IFIs. Toxicity rates were low and its effectiveness was comparable to other antifungal therapies previously reported. [Display omitted] [ABSTRACT FROM AUTHOR]

Healthcare-associated infections (HAI) are among the most common adverse events of medical care. Surveillance of HAI is a key component of successful infection prevention programmes. Conventional surveillance – manual chart review – is resource intensive and limited by concerns regarding interrater reliability. This has led to the development and use of automated surveillance (AS). Many AS systems are the product of in-house development efforts and heterogeneous in their design and methods. With this roadmap, the PRAISE network aims to provide guidance on how to move AS from the research setting to large-scale implementation, and how to ensure the delivery of surveillance data that are uniform and useful for improvement of quality of care. The PRAISE network brings together 30 experts from ten European countries. This roadmap is based on the outcome of two workshops, teleconference meetings and review by an independent panel of international experts. This roadmap focuses on the surveillance of HAI within networks of healthcare facilities for the purpose of comparison, prevention and quality improvement initiatives. The roadmap does the following: discusses the selection of surveillance targets, different organizational and methodologic approaches and their advantages, disadvantages and risks; defines key performance requirements of AS systems and suggestions for their design; provides guidance on successful implementation and maintenance; and discusses areas of future research and training requirements for the infection prevention and related disciplines. The roadmap is supported by accompanying documents regarding the governance and information technology aspects of implementing AS. Large-scale implementation of AS requires guidance and coordination within and across surveillance networks. Transitions to large-scale AS entail redevelopment of surveillance methods and their interpretation, intensive dialogue with stakeholders and the investment of considerable resources. This roadmap can be used to guide future steps towards implementation, including designing solutions for AS and practical guidance checklists. [ABSTRACT FROM AUTHOR]

Surveillance of healthcare-associated infections (HAI) is increasingly automated by applying algorithms to routine-care data stored in electronic health records. Hitherto, initiatives have mainly been confined to single healthcare facilities and research settings, leading to heterogeneity in design. The PRAISE network – Providing a Roadmap for Automated Infection Surveillance in Europe – designed a roadmap to provide guidance on how to move automated surveillance (AS) from the research setting to large-scale implementation. Supplementary to this roadmap, we here discuss the governance aspects of automated HAI surveillance within networks, aiming to support both the coordinating centres and participating healthcare facilities as they set up governance structures and to enhance involvement of legal specialists. This article is based on PRAISE network discussions during two workshops. A taskforce was installed that further elaborated governance aspects for AS networks by reviewing documents and websites, consulting experts and organizing teleconferences. Finally, the article has been reviewed by an independent panel of international experts. Strict governance is indispensable in surveillance networks, especially when manual decisions are replaced by algorithms and electronically stored routine-care data are reused for the purpose of surveillance. For endorsement of AS networks, governance aspects specifically related to AS networks need to be addressed. Key considerations include enabling participation and inclusion, trust in the collection, use and quality of data (including data protection), accountability and transparency. This article on governance aspects can be used by coordinating centres and healthcare facilities participating in an AS network as a starting point to set up governance structures. Involvement of main stakeholders and legal specialists early in the development of an AS network is important for endorsement, inclusivity and compliance with the laws and regulations that apply. [ABSTRACT FROM AUTHOR]

The study aim was to assess predictors of negative antibody response (AbR) in solid organ transplant (SOT) recipients after the first booster of SARS-CoV-2 vaccination. Solid organ transplant recipients receiving SARS-CoV-2 vaccination were prospectively enrolled (March 2021–January 2022) at six hospitals in Italy and Spain. AbR was assessed at first dose (t 0), second dose (t 1), 3 ± 1 month (t 2), and 1 month after third dose (t 3). Negative AbR at t 3 was defined as an anti-receptor binding domain titre <45 BAU/mL. Machine learning models were developed to predict the individual risk of negative (vs. positive) AbR using age, type of transplant, time between transplant and vaccination, immunosuppressive drugs, type of vaccine, and graft function as covariates, subsequently assessed using a validation cohort. Overall, 1615 SOT recipients (1072 [66.3%] males; mean age±standard deviation [SD], 57.85 ± 13.77) were enrolled, and 1211 received three vaccination doses. Negative AbR rate decreased from 93.66% (886/946) to 21.90% (202/923) from t 0 to t 3. Univariate analysis showed that older patients (mean age, 60.21 ± 11.51 vs. 58.11 ± 13.08), anti-metabolites (57.9% vs. 35.1%), steroids (52.9% vs. 38.5%), recent transplantation (<3 years) (17.8% vs. 2.3%), and kidney, heart, or lung compared with liver transplantation (25%, 31.8%, 30.4% vs. 5.5%) had a higher likelihood of negative AbR. Machine learning (ML) algorithms showing best prediction performance were logistic regression (precision-recall curve-PRAUC mean 0.37 [95%CI 0.36–0.39]) and k-Nearest Neighbours (PRAUC 0.36 [0.35–0.37]). Almost a quarter of SOT recipients showed negative AbR after first booster dosage. Unfortunately, clinical information cannot efficiently predict negative AbR even with ML algorithms. [ABSTRACT FROM AUTHOR]