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Background: This study aimed to describe documented infections associated with postinfusion fever after CAR T-cell therapy and to evaluate daily changes in vital signs, laboratory results, and the National Early Warning Score (NEWS) in patients with and without confirmed bacterial infections following fever onset, with the objective of assisting in antibiotic stewardship., Methods: This was a retrospective, observational study including all consecutive adult patients who received CAR T-cell therapy. Documented infection in the first fever episode after infusion, and clinical and analytic trend comparison of patients with bacterial documented infections and those without documented infections, are described., Results: Among 152 patients treated with CAR T-cell therapy, 87 (57.2%) had fever within 30 days of infusion, with a median time from infusion to fever of 3 (interquartile range, 2-5) days. Of these 87 patients, 82 (94.3%) received broad-spectrum antibiotics. Infection was documented in 9 (10.3%) patients and only 4 (4.6%) had bacterial infections. Clinical signs and biomarkers were similar in patients with bacterial documented infection and in those without documented infection at fever onset. Fever, tachycardia, and high C-reactive protein levels remained high during the first 3 days after CAR T-cell infusion, even when no infection was documented., Conclusions: Fever is a common symptom following CAR T-cell infusion and is largely treated with broad-spectrum antibiotics. However, confirmed bacterial documented infections after the first fever post-CAR T-cell infusion are very unusual. Because clinical parameters and biomarkers are not useful for identifying infectious fever, other methods should be assessed to ensure the proper use of antibiotics., Competing Interests: Potential conflicts of interest. C. G.-V. has received honoraria for talks on behalf of Gilead Sciences, MSD, Pfizer, Janssen, Novartis, Basilea, GSK, Shionogi, AbbVie, and Advanz Pharma, and grant support from Gilead Sciences, Pfizer, GSK, MSD, and Pharmamar. A. S. has received honoraria for talks on behalf of Merck Sharp and Dohme, Pfizer, Novartis, Angelini, Menarini, and Gilead Sciences as well as grant support from Pfizer and Gilead Sciences. J. M. has received honoraria for talks on behalf of Merck Sharp and Dohme, Pfizer, Novartis, and Angelini. O. P. has received honoraria for talks on behalf of BMS and Qiagen and consulting for Sanofi. C. F. d. L. declares receiving grants through his institution from BMS, Janssen, and Amgen; honoraria from Amgen, Janssen, BMS, GSK, and Sanofi; support for attending meetings or travel from Janssen, BMS, GSK, and Amgen; and participation in data and safety monitoring boards or advisory boards with Janssen, BMS, Amgen, Pfizer, and Sanofi. All other authors report no potential conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: We described the real-life epidemiology and causes of infections on the different therapy phases in patients undergoing chimeric antigen receptor (CAR) T-cells directed towards CD19+ or BCMA+ cells., Methods: All consecutive patients receiving CAR T-cell therapy at our institution were prospectively followed-up. We performed various comparative analyses of all patients and subgroups with and without infections., Results: Ninety-one adults mainly received CAR T-cell therapy for acute leukaemia (53%) and lymphoma (33%). We documented a total of 77 infections in 47 (52%) patients, 37 (48%) during the initial neutropenic phase and 40 (52%) during the non-neutropenic phase. Infections during the neutropenic phase were mainly due to bacterial (29, 78%): catheter infections (11 [38%] cases), endogenous source (5 [17%]), and Clostridioides difficile (5 [17%]). Patients receiving corticosteroids after CAR T-cell therapy had a higher risk of endogenous infection (100% vs. 16%; p = .006). During the non-neutropenic phase, bacterial infections remained very frequent (24, 60%), mainly with catheter source (8, 33%). Respiratory tract infections were common (17, 43%)., Conclusions: Infections after CAR T-cell therapy were frequent. During the neutropenic phase, it is essential to prevent nosocomial infections and balance the use of antibiotics to lower endogenous bacteraemia and Clostridial infection rates., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Clinical data on which artificial intelligence (AI) algorithms are trained and tested provide the basis to improve diagnosis or treatment of infectious diseases (ID). We aimed to identify important data for ID research to prioritise efforts being undertaken in AI programmes., Methods: We searched for 1,000 articlesfrom high-impact ID journals on PubMed, selecting 288 of the latest articles from 10 top journals. We classified them into structured or unstructured data. Variables were homogenised and grouped into the following categories: epidemiology, admission, demographics, comorbidities, clinical manifestations, laboratory, microbiology, other diagnoses, treatment, outcomes and other non-categorizable variables., Results: 4,488 individual variables were collected, from the 288 articles. 3,670 (81.8%) variables were classified as structured data whilst 818 (18.2%) as unstructured data. From the structured data, 2,319 (63.2%) variables were classified as direct-retrievable from electronic health records-whilst 1,351 (36.8%) were indirect. The most frequent unstructured data were related to clinical manifestations and were repeated across articles. Data on demographics, comorbidities and microbiology constituted the most frequent group of variables., Conclusions: This article identified that structured variables have comprised the most important data in research to generate knowledge in the field of ID. Extracting these data should be a priority when a medical centre intends to start an AI programme for ID. We also documented that the most important unstructured data in this field are those related to clinical manifestations. Such data could easily undergo some structuring with the use of semi-structured medical records focusing on a few symptoms., (©The Author 2023. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

We aimed to describe the characteristics and outcomes of biliary source bloodstream infections (BSIs) in oncological patients. Secondarily, we analyzed risk factors for recurrent BSI episodes. All episodes of biliary source BSIs in oncological patients were prospectively collected (2008-2019) and retrospectively analyzed. Logistic regression analyses were performed. A rule to stratify patients into risk groups for recurrent biliary source BSI was conducted. Four hundred biliary source BSIs were documented in 291 oncological patients. The most frequent causative agents were Escherichia coli (42%) and Klebsiella spp. (27%), and 86 (21.5%) episodes were caused by multidrug-resistant Gram-negative bacilli (MDR-GNB). The rates of MDR-GNB increased over time. Overall, 73 patients developed 118 recurrent BSI episodes. Independent risk factors for recurrent BSI episodes were prior antibiotic therapy (OR 3.781, 95% CI 1.906-7.503), biliary prosthesis (OR 2.232, 95% CI 1.157-4.305), prior admission due to suspected biliary source infection (OR 4.409, 95% CI 2.338-8.311), and BSI episode caused by an MDR-GNB (OR 2.857, 95% CI 1.389-5.874). With these variables, a score was generated that predicted recurrent biliary source BSI with an area under the receiver operating characteristic (ROC) curve of 0.819. Inappropriate empirical antibiotic treatment (IEAT) was administered in 23.8% of patients, and 30-d mortality was 19.5%. As a conclusion, biliary source BSI in oncological patients is mainly caused by GNB, with high and increasing MDR rates, frequent IEAT, and high mortality. Recurrent BSI episodes are frequent. A simple score to identify recurrent episodes was developed to potentially establish prophylactic strategies. IMPORTANCE This study shows that biliary source bloodstream infections (BSIs) in oncological patients are mainly caused by Gram-negative bacilli (GNB), with high and increasing rates of multidrug resistance. Importantly, recurrent biliary source BSI episodes were very frequent and associated with delays in chemotherapy, high rates of inappropriate empirical antibiotic therapy, and high 30-d mortality (19.5%). Using the variable independently associated with recurrent BSI episodes, a score was generated that predicted recurrent biliary source BSI with high accuracy. This score could be used to establish prophylactic strategies and lower the risk of relapsing episodes and the associated morbidity and mortality.

Background: There is no reliable microbiological marker to guide the indication and the response to antiviral treatment in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the dynamics of subgenomic RNA (sgRNA) in patients with COVID-19 before and after receiving treatment with remdesivir., Methods: We included consecutive patients admitted for COVID-19 who received remdesivir according to our institutional protocol and accepted to participate in the study. A nasopharyngeal swab for quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was collected at baseline and after 3 and 5 days of treatment with remdesivir. Genomic and sgRNA were analyzed in those samples and main comorbidities and evolution were collected for the analyses. The main outcomes were early discharge (≤10 days) and 30-day mortality., Results: A total of 117 patients were included in the study, of whom 24 had a negative sgRNA at baseline, with 62.5% (15/24) receiving early discharge (≤10 days) and no deaths in this group. From the 93 remaining patients, 62 had a negative sgRNA at day 5 with 37/62 (59.6%) with early discharge and a mortality rate of 4.8% (3/62). In the subgroup of 31 patients with positive sgRNA after 5 days of remdesivir, the early discharge rate was 29% (9/31) and the mortality rate was 16.1% (5/31). In multivariable analyses, the variables associated with early discharge were negative sgRNA at day 3 and not needing treatment with corticosteroids or intensive care unit admission., Conclusions: Qualitative sgRNA could help in monitoring the virological response in patients who receive remdesivir. Further studies are needed to confirm these findings., Competing Interests: Potential conflicts of interest. C. G.-V. has received support for attending meetings and/or travel and honoraria for talks on behalf of Gilead Sciences, Merck, Sharp and Dhome (MSD), Novartis, Pfizer, Janssen, and Lilly, as well as grants from Gilead Sciences and MSD. L. M. has received honoraria for talks on behalf of MSD; Pfizer; and Angelini. P. P.-A. has received honoraria for talks on behalf of Gilead Sciences and MSD. P. P.-A. also reports grants or contract from Rio Hortega (contract), Juan Rodes (contract), and a national competitive grant (to Instituto de Salud Carlos III); honoraria for lectures from Pfizer, Gilead S.A., ViiV Healthcare, and MSD; support for attending meetings and/or travel from Pfizer (National Congress), MSD (National Congress), and Gilead S.A. (International Congress); and participation on a Data Safety Monitoring Board or Advisory Board for Gilead S.A. (personal payment). M. T. has received grants from Janssen, Gilead, ViiV, and MSD; honoraria from Janssen, Gilead, ViiV, MSD, TheraTechnologies, and Shionogi for HIV and antimicrobial related presentations; and support for attending meetings and/or travel from ViiV and Gilead. J. M. has received honoraria for talks on behalf of MSD; Pfizer; Novartis; and Angelini. A. S. has received consulting fees and honoraria for talks on behalf of MSD; Pfizer; Novartis; Gilead; Shionogi; Menarini; and Angelini as well as grant support from Pfizer and Gilead, including support for attending meetings from Pfizer. D. S. reports support for attending meetings and/or travel from Pfizer (contribution to costs of events-registration fees). A. M. reports receipt of materials of laboratory from Gilead (reactive—IN-ES-540-6089). N. G.-P. reports support for attending meetings and/or travel from Gilead. R. A.-N. reports support for attending meetings and/or travel from Pfizer (contribution to costs of events-registrations fees). S. H. reports payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from MSD and Shire, and support for attending meetings and/or travel from Pfizer. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Assess the impact of viral load estimated by cycle threshold (Ct) of reverse transcription real time-polymerase chain reaction (rRT-PCR) and the days from symptoms onset on mortality in hospitalized patients with COVID19., Methods: Retrospective observational study of 782 patients with a positive rRT-PCR from a nasopharyngeal swab was performed within the first 24 h from admission. Demographic data, clinical manifestations and laboratory parameters were collected. Uni- and multivariate analyses were performed to identify factors associated with mortality at 60 days., Results: Ct was divided into three groups and the mortality rate decreased from 27.3 to 20.7% and 9.8% for Ct values of ≤ 20, 21-25 and > 25, respectively (P = 0.0001). The multivariate analysis identified as predictors of mortality, a Ct value < 20 (OR 3.13, CI 95% 1.38-7.10), between 21-25 (OR 2.47, CI 95% 1.32-4.64) with respect to a Ct value > 25. Days from symptoms onset is a variable associated with mortality as well (DSOA) ≤ 6 (OR 1.86, CI 95% 1.00-3.46), among other factors. Patients requiring hospital admission within 6 DSOA with a Ct value ≤ 25 had the highest mortality rate (28%)., Conclusions: The inclusion of Ct values and DSOA in the characterization of study populations could be a useful tool to evaluate the efficacy of antivirals., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Introduction: Increased mortality has been reported in the Latin American population. The objective is to compare the clinical characteristics and outcome of Latin American and Spanish populations in a cohort of patients hospitalized with COVID-19 during the first year of the pandemic., Methods: We retrospectively analysed all the Latin American patients (born in South or Central America) hospitalized in our centre from February 2020 to February 2021 and compared them with an age- and gender-matched group of Spanish subjects. Variables included were demographics, co-morbidities, clinical and analytical parameters at admission and treatment received. The primary outcomes were ICU admission and mortality at 60 days. A conditional regression analysis was performed to evaluate the independent baseline predictors of both outcomes., Results: From the 3216 patients in the whole cohort, 216 pairs of case-controls (Latin American and Spanish patients, respectively) with same age and gender were analysed. COPD was more frequent in the Spanish group, while HIV was more prevalent in the Latin American group. Other co-morbidities showed no significant difference. Both groups presented with similar numbers of days from symptom onset, but the Latin American population had a higher respiratory rate (21 vs. 20 bpm, P = 0.041), CRP (9.13 vs. 6.22 mg/dl, P = 0.001), ferritin (571 vs. 383 ng/ml, P = 0.012) and procalcitonin (0.10 vs. 0.07 ng/ml, P = 0.020) at admission and lower cycle threshold of PCR (27 vs. 28.8, P = 0.045). While ICU admission and IVM were higher in the Latin American group (17.1% vs. 13% and 9.7% vs. 5.1%, respectively), this was not statistically significant. Latin American patients received remdesivir and anti-inflammatory therapies more often, and no difference in the 60-day mortality rate was found (3.2% for both groups)., Conclusion: Latin American patients with COVID-19 have more severe disease than Spanish patients, requiring ICU admission, antiviral and anti-inflammatory therapies more frequently. However, the mortality rate was similar in both groups., (© 2022. The Author(s).)

Objectives: We described the current incidence and risk factors of bacterial co-infection in hospitalized patients with COVID-19., Methods: Observational cohort study was performed at the Hospital Clinic of Barcelona (February 2020-February 2021). All patients with COVID-19 who were admitted for >48 hours with microbiological sample collection and procalcitonin (PCT) determination within the first 48 hours were included., Results: A total of 1125 consecutive adults met inclusion criteria. Co-infections were microbiologically documented in 102 (9.1%) patients. Most frequent microorganisms were Streptococcus pneumoniae (79%), Staphylococcus aureus (6.8%), and Haemophilus influenzae (6.8%). Test positivity was 1% (8/803) for blood cultures, 10.1% (79/780) for pneumococcal urinary antigen test, and 11.4% (15/132) for sputum culture. Patients with PCT higher than 0.2, 0.5, 1, and 2 ng/mL had significantly more co-infections than those with lower levels (p=0.017, p=0.031, p<0.001, and p<0.001, respectively). In multivariate analysis, oxygen saturation ≤94% (OR 2.47, CI 1.57-3.86), ferritin levels <338 ng/mL (OR 2.63, CI 1.69-4.07), and PCT higher than 0.2 ng/mL (OR 1.74, CI 1.11-2.72) were independent risk factors for co-infection at hospital admission owing to COVID-19., Conclusions: Bacterial co-infection in patients hospitalized for COVID-19 is relatively common. However, clinicians could spare antibiotics in patients with PCT values <0.2, especially with high ferritin values and oxygen saturation >94%., Competing Interests: Declaration of Competing Interest CG-V has received honoraria for talks on behalf of Gilead Science, MSD, Novartis, Pfizer, Janssen, Lilly, as well as a grant from Gilead Science and MSD. AS has received honoraria for talks on behalf of Merck Sharp and Dohme, Pfizer, Novartis, Angellini, as well as grant support from Pfizer. PC has received honoraria for talks on behalf of Merck Sharp and Dohme, Pfizer, Gilead, and Alexion. JM has received honoraria for talks on behalf of Merck Sharp and Dohme, Pfizer, Novartis, and Angellini. PP-A has received honoraria for talks on behalf of Merck Sharp and Dohme, Lilly, ViiV Healthcare, and Gilead Science., (Copyright © 2022. Published by Elsevier Ltd.)

Background: The cryptic Aspegillus species are rare, these microorganisms are usually more resistant to common antifungal therapies. Therefore, a correct identification is important when evaluating the impact of such species in aspergillosis., Aims: We aimed to describe the frequency, clinical and microbiological characteristics, and the outcomes of those cases of aspergillosis caused by cryptic species in a tertiary hospital., Methods: We retrospectively identified all microbiologically documented cases of aspergillosis between January 2013 and December 2018. Definitive species identification of clinically significant isolates was achieved via sequencing methods. The polymerase chain reaction (PCR) products were sequenced, and the results obtained were compared to sequences deposited in GenBank. Antifungal susceptibility testing was performed using the Sensititre® YeastOne® panel., Results: A total of 679 Aspergillus isolates were recovered from 489 patients, of which 109 were clinically relevant. Ten (9.2%) isolates were identified as cryptic species: Aspergillus arcoverdensis (2), Aspergillus lentulus (2), Aspergillus ellipticus (2), Aspergillus alliaceus (1), Aspergillus nomius (1), Aspergillus tubingensis (1) and Aspergillus montevidensis (1). Most patients already suffered some type of immunosuppression. Half of these patients had required intensive care before the infection showed up, and most of them had a pulmonary infection. Mortality at the 100-day follow-up was 40%. Antifungal susceptibility testing was performed on three of the isolates (A. arcoverdensis, A. tubingensis and A. nomius), which showed high minimum inhibitory concentrations (MIC) for azoles and amphotericin B., Conclusions: The frequency of cryptic species in our centre was 9.2%. Most patients had some degree of immunosuppression, and the mortality rate was 40%., (Copyright © 2022 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Dexamethasone and tocilizumab have been associated with reduction in mortality, however, the beneficial effect is not for all patients and the impact on viral replication is not well defined. We hypostatized that C-reactive protein (CRP) could help in the identification of patients requiring anti-inflammatory therapy. Patients admitted for > 48 h in our hospital for a confirmed or suspected infection by SARS-CoV-2 from February 2020 to February 2021 were retrospectively evaluated. The primary outcome was mortality at 30 days. Demographics and the most relevant variables related with the outcome were included. CRP was stratified by percentiles. Univariate and multivariate analysis were performed. A total of 3218 patients were included with a median (IQR) age of 66 (74-78) years and 58.9% were males. The rate of intensive care unit admission was 24.4% and the 30-day mortality rate was 11.8%. Within the first 5 days from admission, 1018 (31.7%) patients received dexamethasone and 549 tocilizumab (17.1%). The crude analysis showed a mortality reduction in patients receiving dexamethasone when CRP was > 13.75 mg/dL and > 3.5 mg/dL for those receiving tocilizumab. Multivariate analysis identified the interaction of CRP > 13.75 mg/dL with dexamethasone (OR 0.57; CI 95% 0.37-0.89, P = 0014) and CRP > 3.5 mg/dL with tocilizumab (0.65; CI95%:0.44-0.95, P = 0.029) as independent predictors of mortality. Our results suggest that dexamethasone and tocilizumab are associated with a reduction in mortality when prescribed to patients with a certain inflammatory activity assessed by C-reactive protein., (© 2022. The Author(s).)

We documented a hematologic patient with prolonged SARS-CoV-2 viral replication in whom emergence of viral mutations was documented after the consecutive use of antivirals and convalescent plasma. The virus detected in the last of 12 clinical samples (day 237) had accumulated 22 changes in amino acids and 29 in nucleotides. Some of these changes, such as the E484Q, were mutations of concern as defined by WHO. This finding represents an enormous epidemiological threat and poses a major clinical challenge. Combined antiviral strategies, as well as specific strategies related to the diagnostic approach of prolonged infections for this specific population, may be needed., Competing Interests: CG-V has received honoraria for talks on behalf of Gilead Science, MSD, Novartis, Pfizer, Janssen, Lilly as well as a grant from Gilead Science and MSD. AS has received honoraria for talks on behalf of Merck Sharp and Dohme, Pfizer, Novartis, Angelini, as well as grant support from Pfizer. PP-A has received honoraria for talks on behalf of Merck Sharp and Dohme, Gilead, Lilly, ViiV Healthcare, and Gilead Science. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Garcia-Vidal, Iglesias-Caballero, Puerta-Alcalde, Mas, Cuesta-Chasco, Garcia-Pouton, Varona, Pozo, Vázquez-Morón, Marcos, Soriano and Casas.)

We analyzed risk factors for mortality in febrile neutropenic patients with bloodstream infections (BSI) presenting with septic shock and assessed the impact of empirical antibiotic regimens. A multicenter retrospective study (2010 to 2019) of two prospective cohorts compared BSI episodes in patients with or without septic shock. Multivariate analysis was performed to identify independent risk factors for mortality in episodes with septic shock. Of 1,563 patients with BSI, 257 (16%) presented with septic shock. Those patients with septic shock had higher mortality than those without septic shock (55% versus 15%, P  < 0.001). Gram-negative bacilli caused 81% of episodes with septic shock, Gram-positive cocci caused 22%, and Candida species caused 5%. Inappropriate empirical antibiotic treatment (IEAT) was administered in 17.5% of septic shock episodes. Empirical β-lactam combined with other active antibiotics was associated with the lowest mortality observed. When amikacin was the only active antibiotic, mortality was 90%. Addition of empirical specific Gram-positive coverage had no impact on mortality. Mortality was higher when IEAT was administered (76% versus 51%, P  = 0.002). Age of >70 years (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.2 to 4.7), IEAT for Candida spp. or Gram-negative bacilli (OR, 3.8; 95% CI, 1.3 to 11.1), acute kidney injury (OR, 2.6; 95% CI, 1.4 to 4.9), and amikacin as the only active antibiotic (OR, 15.2; 95% CI, 1.7 to 134.5) were independent risk factors for mortality, while the combination of β-lactam and amikacin was protective (OR, 0.32; 95% CI, 0.18 to 0.57). Septic shock in febrile neutropenic patients with BSI is associated with extremely high mortality, especially when IEAT is administered. Combination therapy including an active β-lactam and amikacin results in the best outcomes.

Hospitalized patients with coronavirus disease 2019 (COVID-19) experiencing respiratory symptoms have different complications (inflammatory, co-infection, and thrombotic) that are identifiable by analytics patterns. Personalized treatment decisions decreased early mortality (odds ratio [OR] .144; 95% confidence interval [CI] .03-.686; P = .015). Increasing age (OR 1.06; P = .038) and therapeutic effort limitation (OR 9.684; P < .001) were associated with higher mortality., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The use of remdesivir has demonstrated a significant reduction in the time to recovery in patients with COVID-19. However, the impact on mortality is still controversial. Therefore, it is necessary to evaluate whether there is a specific subgroup of patients in whom an active antiviral therapy also reduces the mortality., Methods: Patients admitted for >48 h in our hospital for a SARS-CoV-2 confirmed or suspected infection from February 2020 to February 2021 were retrospectively analysed. The primary outcome of the study was mortality at 30 days. Univariate and multivariate analyses were performed to identify predictors of mortality., Results: In total, 2607 patients (438 receiving remdesivir and 2169 not) were included with a median (IQR) age of 65 (54-77) years and 58% were male. Four hundred and seventy-six were admitted to the ICU (18.3%) and 264 required invasive mechanical ventilation (10.1%). The global 30 day mortality rate was 10.7%. Pre-admission symptom duration of 4-6 days and ≤3 days was associated with a 1.5- and 2.5-fold increase in the mortality rate, respectively, in comparison with >6 days and treatment with remdesivir was independently associated with a lower mortality rate (OR = 0.382, 95% CI = 0.218-0.671). The analysis showed that the major difference was among patients with shorter pre-admission symptom duration (<6 days)., Conclusions: Patients with ≤3 days and 4-6 days from symptom onset to admission are associated with a 2.5- and 1.5-fold higher risk of death, respectively. Remdesivir was associated with 62% reduced odds of death versus standard-of-care and its survival benefit increased with shorter duration of symptoms., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Invasive fungal infection often complicates patients with severe viral infection, especially those admitted to critical care units. Severe SARS-CoV-2 infection has been no exception and a significant association with Aspergillus spp. has been documented, resulting in high patient mortality. In this summary we describe the clinical presentation, the underlying diseases most commonly linked with this association, radiological manifestations and therapeutic management of CAPA.

Introduction: The study aim was to assess the influence of inflammatory response modifiers, including anti-interleukin-6 (IL-6) biologics and corticosteroids, on the incidence of hospital-acquired infections in patients with coronavirus disease 2019 (COVID-19)., Methods: Case-control study performed at a university hospital from February 26 to May 26, 2020. Cases were defined as patients with COVID-19 who developed hospital-acquired infections. For each case, two controls were selected among patients without infections. Cases and controls were matched obeying three criteria in a hierarchical sequence: length of hospital stay up until the first infection; comorbidity; and need for Intensive care unit (ICU) admission. Conditional logistic regression analysis was used to estimate the association of exposures with being a case., Results: A total of 71 cases and 142 controls were included. Independent predictors for acquiring a hospital infection were chronic liver disease [odds ratio (OR) 16.56, 95% CI 1.87-146.5, p = 0.012], morbid obesity (OR 6.11, 95% CI 1.06-35.4, p = 0.043), current or past smoking (OR 4.15, 95% CI 1.45-11.88, p = 0.008), exposure to hydroxychloroquine (OR 0.2, 95% CI 0.041-1, p = 0.053), and invasive mechanical ventilation (OR 61.5, 95% CI 11.08-341, p ≤ 0.0001)., Conclusions: Inflammatory response modifiers had no influence on acquisition of nosocomial infections in admitted patients with COVID-19. Hospital-acquired infections primarily occurred in the critically ill and invasive mechanical ventilation was the main exposure conferring risk., (© 2021. The Author(s).)

Introduction: We aimed to assess risk factors for multidrug-resistant Gram-negative bacilli (MDR-GNB) from a large amount of data retrieved from electronic health records (EHRs) and determine whether machine learning (ML) may be useful in assessing the risk of MDR-GNB infection at febrile neutropenia (FN) onset., Methods: Retrospective study of almost 7 million pieces of structured data from all consecutive episodes of FN in hematological patients in a tertiary hospital in Barcelona (January 2008-December 2017). Conventional multivariate analysis and ML algorithms (random forest, gradient boosting machine, XGBoost, and GLM) were done., Results: A total of 3235 episodes of FN in 349 patients were documented; MDR-GNB caused 180 (5.6%) infections in 132 patients. The most frequent MDR-GNBs were MDR-Pseudomonas aeruginosa (53%) and extended-spectrum beta-lactamase-producing Enterobacterales (46%). According to conventional logistic regression analysis, independent factors associated with MDR-GNB infection were age older than 45 years (OR 2.07; 95% CI 1.31-3.24), prior antibiotics (2.62; 1.39-4.92), first-ever FN in this hospitalization (2.94; 1.33-6.52), prior hospitalizations for FN (1.72; 1.02-2.89); at least 15 prior hospital visits (2.65; 1.31-5.33), high-risk hematological diseases (3.62; 1.12-11.67), and hospitalization in a room formerly occupied by patients with MDR-GNB isolation (1.69; 1.20-2.38). ML algorithms achieved the following AUC and F1 score for MDR-GNB prediction: random forest, 0.79-0.9711; GMB, 0.79-0.9705; XGBoost, 0.79-0.9670; and GLM, 0.78-0.9716., Conclusion: Data generated in EHRs proved useful in assessing risk factors for MDR-GNB infections in patients with FN. The great number of analyzed variables allowed us to identify new factors related to MDR infection, as well as to train ML algorithms for infection predictions. This information may be used by clinicians to make better clinical decisions.

In recent years, important epidemiologic changes have been described in hematopoietic stem cell transplantation (HSCT) recipients with bloodstream infection (BSI), with increases in gram-negative bacilli and multidrug resistant (MDR) gram-negative bacilli. These changes have been linked to a worrisome increase in mortality. We aimed to define the risk factors for mortality of HSCT patients experiencing BSI. All episodes of BSI in patients with HSCT between 2008 and 2017 were prospectively collected. Multivariate analyses were performed. A total of 402 BSI episodes were documented in 293 patients who had undergone HSCT (75.4% allogenic, 32.3% autologous, 19.3% second HSCT). The median time from HSCT to BSI was 62 days (interquartile range, 9 to 182 days). Gram-positive cocci accounted for 56.7% of the episodes; gram-negative bacilli, for 42%. The most common microorganisms were coagulase-negative staphylococci (30.6%) and Pseudomonas aeruginosa (15.9%). MDR gram-negative bacilli caused 11.9% of all episodes. Clinical characteristics, source of BSI, etiology, and outcomes changed depending on time since HSCT. Globally, 26.6% of episodes were treated with inappropriate empiric antibiotic therapy, more frequently in BSI episodes caused by P. aeruginosa, MDR P. aeruginosa, and MDR gram-negative bacilli. The 30-day mortality was 19.2%. Independent risk factors for mortality were BSI occurring ≥30 days after HSCT (odds ratio [OR], 11.21; 95% confidence interval [CI], 4.63 to 27.19), shock (OR, 7.10; 95% CI, 2.98 to 16.94), BSI caused by MDR P. aeruginosa (OR, 4.45; 95% CI, 1.12 to 17.72), and inappropriate empiric antibiotic therapy for gram-negative bacilli or Candida spp. (OR, 3.73; 95% CI, 1.27 to 10.89). HSCT recipients experiencing BSI have high mortality related to host and procedure factors, causative microorganism, and empiric antibiotic therapy. Strategies to identify HSCT recipients at risk of MDR P. aeruginosa and reducing inappropriate empiric antibiotic therapy are paramount to reduce mortality., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Introduction: We aimed to compare the clinical characteristics and outcomes of bloodstream infections (BSI) in cancer patients presenting febrile neutropenia with and without HIV infection, and analyze the prognostic factors for mortality., Methods: BSI episodes in febrile neutropenic patients following chemotherapy were prospectively collected (1997-2018). A case (HIV-infected)-control (non-HIV-infected) sub-analysis was performed (1:2 ratio), matching patients by age, gender, baseline disease, and etiological microorganism., Results: From 1755 BSI episodes in neutropenic cancer patients, 60 (3.4%) occurred in those with HIV. HIV characteristics: 51.7% were men who have sex with men; 58.3% had < 200 CD4; 51.7% had a detectable HIV-1 RNA viral load before the BSI episode; 70.0% met AIDS-defining criteria; and 93.3% were on antiretroviral therapy, with a protease inhibitor-based regimen being the most common (53.0%). HIV-infected patients were younger, more frequently male and more commonly presenting chronic liver disease (p < 0.001 for all). BSI due to Enterococcus spp. was significantly more frequent among patients with HIV (p = 0.017) with no differences in other pathogens. HIV-infected patients with cancer presented with shock more frequently (p = 0.014) and had higher mortality (31.7% vs. 18.1%, p = 0.008). In the case-control analysis, cases (HIV-infected) had chronic liver disease (p = 0.003) more frequently, whereas acute leukemia (p = 0.013) and hematopoietic stem-cell transplant (p = 0.023) were more common among controls. There was a non-significant trend for cases to have higher mortality (p = 0.084). However, in multivariate analysis, HIV infection was not associated with mortality (p = 0.196)., Conclusion: HIV-infected patients with cancer developing febrile neutropenia and BSI have different epidemiological and clinical profiles, and experience higher mortality. However, HIV infection by itself was not associated with mortality.

Objective: Controversial results on remdesivir efficacy have been reported. We aimed to report our real-life experience with the use of remdesivir from its availability in Spain., Methods: We performed a descriptive study of all patients admitted for ≥48 hours with confirmed COVID-19 who received remdesivir between the 1st of July and the 30th of September 2020., Results: A total of 123 patients out of 242 admitted with COVID-19 at our hospital (50.8%) received remdesivir. Median age was 58 years, 61% were males and 56.9 % received at least one anti-inflammatory treatment. No adverse events requiring remdesivir discontinuation were reported. The need of intensive care unit admission, mechanical ventilation and 30-days mortality were 19.5%, 7.3% and 4.1%, respectively., Conclusions: In our real-life experience, the use of remdesivir in hospitalized patients with COVID-19 was associated with a low mortality rate and good safety profile., (©The Author 2021. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Background: We aimed to describe changes in characteristics and treatment strategies of hospitalised patients with COVID-19 and detail the mortality trend over time., Methods: Observational cohort study of all consecutive patients admitted ≥ 48 h to Hospital Clinic of Barcelona for COVID-19 (1 March-30 September 2020)., Findings: A total of 1645 consecutive patients with COVID-19 were assessed over a 7-month period. Overall mortality (≤30 days) was 9.7% (159 patients), 7.7% in patients hospitalised in regular wards and 16.7 % in patients requiring ICU admission. Overall mortality decreased from 11.6% in the first month to 1.4% in the last month, reflecting a progressive, significant downward trend ( p for trend <0.001). Patients' age changed over time, peaking in June. Most changes in the use of antivirals and anti-inflammatory treatments were documented. Age (OR 1.1, CI 1.1-1.12), chronic heart disease, (OR 1.7, CI 1.1-2.9), D-dimer>700 ng/mL (OR 2.3, CI 1.3-4.1), ferritin>489 ng/mL (OR 1.9; CI 1.5-3.2), C-RP>7 mg/dL (OR 2.6; CI 1.5-4.6), and shorter duration from symptom onset to hospital admission (OR 1.11; CI 1.04-1.17) were factors associated with 30-day mortality at hospital admission. Conversely, hospital admission in the last months (OR 0.80; CI 0.65-0.98) was significantly associated with lower mortality., Interpretation: In-hospital mortality has decreased in patients with COVID-19 over the last, few months, even though main patient characteristics remain similar. Several changes made when managing patients may explain this decreasing trend. Our study provides current data on mortality of patients hospitalised with COVID-19 that might be useful in establishing quality of standard of care., Funding: EIT Health, European Union´s Horizon 2020 Research and Innovation Programme), EDRD. PPA [CM18/00132], NGP [FI19/00133], and CGV [FIS PI18/01061], have received grants from Ministerio de Sanidad y Consumo, ISCIII., Competing Interests: This research is part of an activity that has received funding from EIT Health. EIT Health is supported by the European Institute of Innovation and Technology (EIT), a body of the European Union that receives support from the European Union´s Horizon 2020 Research and Innovation Programme. This study has been co-funded by the European Regional Development Fund (EDRD). All authors report grants from EIT Health and the European Regional Development Fund (for themselves or their institution), during the conduct of the study. PPA [CM18/00132], NGP [FI19/00133], and CGV [FIS PI18/01061] have received research grants from the Ministerio de Sanidad y Consumo and Instituto de Salud Carlos III. No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. CGV has received honoraria for talks on behalf of Gilead Science, MSD, Novartis, Pfizer, Janssen, and Lilly, as well as a grant from Gilead Science and MSD. PPA has received honoraria for talks on behalf of Gilead Science and MSD. JM has received honoraria for talks on behalf of Merck Sharp and Dohme, Pfizer, Novartis, and Angellini. AS has received honoraria for talks on behalf of Merck Sharp and Dohme, Pfizer, Novartis, and Angellini, as well as grant support from Pfizer. Other authors do not declare conflict of interest outside the submitted work. Hospital Clinic of Barcelona COVID-19 Researchers: Infectious Diseases’ Research Group: Albiach L, Agüero D, Ambrosioni J, Blanco JL, De la Mora L, González-Cordón A, Inciarte A, Jordan C, Laguno M, Leal L, Lopera C, Macaya I, Mallolas J, Martínez E, Martínez M, Miró JM, Moreno A, Rojas J, Solá M, Torres B, Torres M, and all the staff members. Medical Intensive Care Unit: Adrian Téllez, Sara Fernández, and all the staff members. Department of International Health: Daniel Camprubi Ferrer, Maria Teresa de Alba, Marc Fernandez, Elisabet Ferrer, Berta Grau, Helena Marti, Magdalena Muelas, Maria Jesus Pinazo, Natalia Rodríguez, Montserrat Roldan, Carme Subira, Isabel Vera, Nana Williams, Jose Muñoz, and all the staff members. Department of Internal Medicine: Aldea A, Camafort M, Calvo J, Capdevila A, Cardellach F, Carbonell I, Coloma E, Foncillas A, Estruch R, Feliu M, Fernández-Solá J, Fuertes I, Gabara C, Grafia I, Ladino A, López-Alfaro R, López-Soto A, Masanés F, Matas A, Navarro M, Marco-Hernández J, Miguel L, Milisenda J, Moreno P, Naval J, Nicolás D, Oberoi H, Padrosa J, Prieto-González S, Pellicé M, Ribot J, Rodríguez-Núnez O, Sacanella E, Seguí F, Sierra C, Tomé A, Ugarte A, Ventosa H, Zamora-Martínez C, and all the staff members. Department of Microbiology: M. Almela, M. Alvarez, J. Bosch, C. Casals, J. Costa, G. Cuesta, M. Fernandez, B. Fidalgo, J. Gonzàlez, J.C. Hurtado, F. Marco, M.A. Marcos, M. Martínez, M. Mosquera, S. Narvaez, C. Pitart, E. Rubio, A. Vergara, M.E.Valls, J. Vila, Y. Zboromyrska and all the staff members. Department of Farmacy: E. López, D. Soy, M. Tuset and all the staff members. Data sharing statement: All data will be available under request after manuscript acceptance., (© 2021 Published by Elsevier Ltd.)

Objectives: To describe the burden, epidemiology and outcomes of co-infections and superinfections occurring in hospitalized patients with coronavirus disease 2019 (COVID-19)., Methods: We performed an observational cohort study of all consecutive patients admitted for ≥48 hours to the Hospital Clinic of Barcelona for COVID-19 (28 February to 22 April 2020) who were discharged or dead. We describe demographic, epidemiologic, laboratory and microbiologic results, as well as outcome data retrieved from electronic health records., Results: Of a total of 989 consecutive patients with COVID-19, 72 (7.2%) had 88 other microbiologically confirmed infections: 74 were bacterial, seven fungal and seven viral. Community-acquired co-infection at COVID-19 diagnosis was uncommon (31/989, 3.1%) and mainly caused by Streptococcus pneumoniae and Staphylococcus aureus. A total of 51 hospital-acquired bacterial superinfections, mostly caused by Pseudomonas aeruginosa and Escherichia coli, were diagnosed in 43 patients (4.7%), with a mean (SD) time from hospital admission to superinfection diagnosis of 10.6 (6.6) days. Overall mortality was 9.8% (97/989). Patients with community-acquired co-infections and hospital-acquired superinfections had worse outcomes., Conclusions: Co-infection at COVID-19 diagnosis is uncommon. Few patients developed superinfections during hospitalization. These findings are different compared to those of other viral pandemics. As it relates to hospitalized patients with COVID-19, such findings could prove essential in defining the role of empiric antimicrobial therapy or stewardship strategies., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The use of artificial intelligence (AI) to support clinical medical decisions is a rather promising concept. There are two important factors that have driven these advances: the availability of data from electronic health records (EHR) and progress made in computational performance. These two concepts are interrelated with respect to complex mathematical functions such as machine learning (ML) or neural networks (NN). Indeed, some published articles have already demonstrated the potential of these approaches in medicine. When considering the diagnosis and management of pneumonia, the use of AI and chest X-ray (CXR) images primarily have been indicative of early diagnosis, prompt antimicrobial therapy, and ultimately, better prognosis. Coupled with this is the growing research involving empirical therapy and mortality prediction, too. Maximizing the power of NN, the majority of studies have reported high accuracy rates in their predictions. As AI can handle large amounts of data and execute mathematical functions such as machine learning and neural networks, AI can be revolutionary in supporting the clinical decision-making processes. In this review, we describe and discuss the most relevant studies of AI in pneumonia.