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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. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) and machine learning (ML) have the potential to revolutionize the management of febrile neutropenia (FN) and drive progress toward personalized medicine. In this review, we detail how the collection of a large number of high-quality data can be used to conduct precise mathematical studies with ML and AI. We explain the foundations of these techniques, covering the fundamentals of supervised and unsupervised learning, as well as the most important challenges, e.g. data quality, 'black box' model interpretation and overfitting. To conclude, we provide detailed examples of how AI and ML have been used to enhance predictions of chemotherapy-induced FN, detection of bloodstream infections (BSIs) and multidrug-resistant (MDR) bacteria, and anticipation of severe complications and mortality. There is promising potential of implementing accurate AI and ML models whilst managing FN. However, their integration as viable clinical tools poses challenges, including technical and implementation barriers. Improving global accessibility, fostering interdisciplinary collaboration, and addressing ethical and security considerations are essential. By overcoming these challenges, we could transform personalized care for patients with FN. [ABSTRACT FROM AUTHOR]

Background: We aimed to describe a cohort of hematologic patients with COVID‐19 treated with antivirals early. Methods: Non‐interventional chart review study. Comparison of baseline characteristics and outcomes in high‐risk hematologic patients treated with remdesivir between December 2021 and April 2022 versus those treated with nirmatrelvir/ritonavir between May and August 2022. Results: Eighty‐three patients were analyzed. Forty‐two received remdesivir, and 41 nirmatrelvir/ritonavir. Patients with remdesivir were younger, vaccinated with lower number of doses, and received prior corticosteroids less frequently and sotrovimab, hyperimmune plasma and corticosteroids more often. Viral shedding median (IQR) duration was 18 (13–23) and 11 (8–21) days in the remdesivir and nirmatrelvir/ritonavir groups, respectively (p = 0.004). Median (IQR) Ct values before treatment were similar in both groups. Within 5 days of treatment, median (IQR) Ct values were 26 (23–29) and 33 (30–37) in the remdesivir and nirmatrelvir/ritonavir groups, respectively (p < 0.0001). All patients were hospitalized for remdesivir administration and only four (9.8%) in the nirmatrelvir/ritonavir group. The overall outcomes in this cohort of COVID‐19 patients with Omicron variant was good, as no patient needed oxygen or ICU admission. One patient in remdesivir group died from septic shock. No severe adverse event was recorded in both treatment groups. Conclusions: Patients with hematologic malignancies and non‐severe COVID‐19 who received nirmatrelvir/ritonavir experienced faster decrease in viral load and shorter viral shedding. Furthermore, besides the advantage of oral administration, nirmatrelvir/ritonavir administration reduced the need of hospital admission. [ABSTRACT FROM AUTHOR]

Background Our aim in this study was to evaluate the clinical and prognostic impact of communicating microbiological information in real time for adult patients with bloodstream infections (BSIs). Methods We retrospectively reviewed 6225 clinical episodes of bacteremia in a teaching hospital from January 2013 to December 2019. Bacteremia-associated mortality was compared when blood culture results were relayed to the infectious diseases specialist (IDS) in real time and periods when results were relayed the following morning. The impact of information availability using mortality at 30 days was used as the main outcome of the study. Results The initial analysis (all microorganisms included) did not show an association of mortality and information delay to the IDS (odds ratio [OR], 1.18; 95% confidence interval [CI],.99–1.42). However, information delay of BSIs caused by fast-growing microorganisms such as Enterobacterales was associated with a significant increase in the odds of death at 30 days both in the univariate (OR, 1.76; 95% CI, 1.30–2.38) and multivariate analysis (OR, 2.22; 95% CI, 1.50–3.30). Similar results were found with mortality at 14 days and 7 days in the univariate (OR, 1.54; 95% CI, 1.08–2.20 and OR, 1.56; 95% CI, 1.03–2.37, respectively) and the multivariate analysis (OR, 2.05; 95% CI, 1.27–3.32 and OR, 1.92; 95% CI, 1.09–3.40, respectively). Conclusions Information delivered in real time has prognostic relevance and is likely to improve survival of patients with documented BSIs. Future studies should address the prognostic impact of adequate resource allocation (microbiologist/IDS with 24/7 coverage) in BSIs. [ABSTRACT FROM AUTHOR]

Objectives We aimed to describe the clinical outcomes and duration of viral shedding in high-risk patients with haematological malignancies hospitalized with COVID-19 during Omicron variant predominance who received early treatment with antivirals. Methods We conducted a prospective observational study on high-risk haematological patients admitted in our hospital between December 2021 and March 2022. We performed detection techniques on viral subgenomic mRNAs until negative results were obtained to document active, prolonged viral replication. Results This analysis included 60 consecutive adults with high-risk haematological malignancies and COVID-19. All of these patients underwent early treatment with remdesivir. Thirty-two (53%) patients received combined antiviral strategies, with sotrovimab or hyperimmune plasma being added to remdesivir. The median length of viral replication—as measured by real-time RT-PCR and/or subgenomic RNA detection—was 20 (IQR 14–28) days. Prolonged viral replication (6 weeks after diagnosis) was documented in six (10%) patients. Only two patients had prolonged infection for more than 2 months. Overall mortality was 5%, whereas COVID-19-related mortality was 0%. Conclusions Current outcomes of high-risk patients with haematological malignancies hospitalized with COVID-19 during Omicron variant predminance are good with the use of early antiviral strategies. Persistent viral shedding is uncommon. [ABSTRACT FROM AUTHOR]

We aimed to describe the current epidemiology of both hosts with invasive fungal infections (IFIs) and causative fungi. And, detail outcomes of these infections at 12 weeks in a real-life cohort of hospitalized patients. The study was retrospective and observational to describe IFI diagnosed in a tertiary hospital (February 2017–December 2021). We included all consecutive patients meeting criteria for proven or probable IFI according to EORTC-MSG and other criteria. A total of 367 IFIs were diagnosed. 11.7% were breakthrough infections, and 56.4% were diagnosed in the intensive care unit. Corticosteroid use (41.4%) and prior viral infection (31.3%) were the most common risk factors for IFI. Lymphoma and pneumocystis pneumonia were the most common baseline and fungal diseases. Only 12% of IFI occurred in patients with neutropenia. Fungal cultures were the most important diagnostic tests (85.8%). The most frequent IFIs were candidemia (42.2%) and invasive aspergillosis (26.7%). Azole-resistant Candida strains and non- fumigatus Aspergillus infections represented 36.1% and 44.5% of the cases, respectively. Pneumocystosis (16.9%), cryptococcosis (4.6%), and mucormycosis (2.7%) were also frequent, as well as mixed infections (3.4%). Rare fungi accounted for 9.5% of infections. Overall, IFI mortality at 12 weeks was 32.2%; higher rates were observed for Mucorales (55.6%), Fusarium (50%), and mixed infections (60%). We documented emerging changes in both hosts and real-life IFI epidemiology. Physicians should be aware of these changes to suspect infections and be aggressive in diagnoses and treatments. Currently, outcomes for such clinical scenarios remain extremely poor. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Gram-negative bacilli are intrinsically resistant to many antibiotics due to the low permeability of their outer membrane. The most effective strategy to solve this problem has been the design of antibiotics that cross the membrane using specific transport systems. This is the case of cefiderocol, which, unlike cefepime or ceftazidime, has a chlorocatechol group at the end of the C-3 side chain. This group is recognized by transporters located in the outer membrane that allow cefiderocol to accumulate in the periplasmic space. Furthermore, cefiderocol is not a substrate for efflux pumps and the configuration of the side chains at C-7 and in particular at C-3 confer it a high stability against hydrolysis by most beta-lactamases of clinical interest including class A (KPC, BLEEs), C (ampC) or D (OXA-48) serine beta-lactamases and metallo-betalactamases (NDM, VIM. IMP). In order to better understand the mechanism of action of cefiderocol, the importance of iron in bacterial metabolism and the competition for iron between bacteria and host are reviewed. [ABSTRACT FROM AUTHOR]

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