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Objectives: This study aims to identify infection etiology in febrile neutropenia (FN) is vital. This study explores different microbiological approaches and their impact on diagnosing infections in patients with hematologic malignancies and FN. Methods: This is a retrospective analysis conducted at the Hospital Clinic of Barcelona details microbiological testing strategies used to diagnose infections at FN onset between January 2020 and July 2022. Results: A total of 4520 microbiological tests were ordered in 462 FN episodes, achieving a 10% test positivity rate, with 200 (43.3%) episodes showing microbiological documentation of infection. Blood cultures (40.4%), non-culture blood tests (21.2%), and respiratory tract samples (16.2%) were the most requested. Blood cultures exhibited the highest (16.9%) test positivity rates, whereas non-culture blood tests showed the lowest (3.3%). Bacterial infections were present in 149 of 462 (32.3%) FN episodes. Viral infections (66 of 462, 14.3%)—notably, respiratory viruses—were also frequent. Mortality rate at 60 days was 9.1%; documented infections were associated with a higher risk (15%). Conclusions: In the current landscape of antimicrobial diagnostics, our findings revealed the highest reported rate of microbiologically documented infections at FN onset. Bacterial infections are common; however, our data reiterate the significance of viral infections in causing fever. Optimizing FN management during respiratory viral infections remains a challenge for antimicrobial de-escalation. The low positivity rates observed in certain diagnostic tests emphasize the need for cost-effective diagnostic stewardship.

Background: Rezafungin is an echinocandin approved in the US and EU to treat candidaemia and/or invasive candidiasis. This post-hoc, pooled analysis of the Phase 2 STRIVE and Phase 3 ReSTORE trials assessed rezafungin versus caspofungin in patients with candidaemia and/or invasive candidiasis (IC) in the intensive care unit (ICU) at randomisation. Methods: STRIVE and ReSTORE were randomised double-blind trials in adults with systemic signs and mycological confirmation of candidaemia and/or IC in blood or a normally sterile site ≤ 96 h before randomisation. Data were pooled for patients in the ICU at randomisation who received intravenous rezafungin (400 mg loading dose then 200 mg once weekly) or caspofungin (70 mg loading dose then 50 mg once daily) for ≤ 4 weeks. Outcomes were Day 30 all-cause mortality (primary outcome), Day 5 and 14 mycological eradication, time to negative blood culture, mortality attributable to candidaemia/invasive candidiasis, safety, and pharmacokinetics. Results: Of 294 patients in STRIVE/ReSTORE, 113 were in the ICU at randomisation (rezafungin n = 46; caspofungin n = 67). At baseline, ~ 30% of patients in each group had impaired renal function and/or an Acute Physiologic Assessment and Chronic Health Evaluation II score ≥ 20. One patient (in the caspofungin group) was neutropenic at baseline. Day 30 all-cause mortality was 34.8% for rezafungin versus 25.4% for caspofungin. Day 5 and 14 mycological eradication was 78.3% and 71.7% for rezafungin versus 59.7% and 65.7% for caspofungin, respectively. Median time to negative blood culture was 18 (interquartile range, 12.6–43.0) versus 38 (interquartile range, 15.9–211.3) h for rezafungin versus caspofungin (stratified log-rank P = 0.001; nominal, not adjusted for multiplicity). Candidaemia/IC-attributable deaths occurred in two rezafungin patients versus one caspofungin patient. Safety profiles were similar between groups. Overall, 17.4% (rezafungin) versus 29.9% (caspofungin) of patients discontinued due to treatment-emergent adverse events. Rezafungin exposure following the initial 400-mg dose was comparable between patients in the ICU at randomisation (n = 50) and non-ICU patients (n = 117). Conclusions: Rezafungin was well tolerated and efficacious in critically ill, mainly non-neutropenic patients with candidaemia and/or IC. This analysis provides additional insights into the efficacy and safety of rezafungin in the ICU population. [ABSTRACT FROM AUTHOR]

Background Rezafungin, a novel, once-weekly echinocandin for the treatment of candidemia and/or invasive candidiasis (IC) was noninferior to caspofungin for day 30 all-cause mortality (ACM) and day 14 global cure in the phase 3 ReSTORE trial (NCT03667690). We conducted preplanned subgroup analyses for patients with a positive culture close to randomization in ReSTORE. Methods ReSTORE was a multicenter, double-blind, double-dummy, randomized trial in patients aged ≥18 years with candidemia and/or IC treated with once-weekly intravenous rezafungin (400 mg/200 mg) or once-daily intravenous caspofungin (70 mg/50 mg). This analysis comprised patients with a positive blood culture drawn between 12 hours before and 72 hours after randomization or a positive culture from another normally sterile site sampled between 48 hours before and 72 hours after randomization. Efficacy endpoints included day 30 ACM, day 14 global cure rate, and day 5 and 14 mycological response. Adverse events were evaluated. Results This analysis included 38 patients randomized to rezafungin and 46 to caspofungin. In the rezafungin and caspofungin groups, respectively, day 30 ACM was 26.3% and 21.7% (between-group difference [95% confidence interval], 4.6% [−13.7%, 23.5%]), day 14 global response was 55.3% and 50.0% (between-group difference, 5.3% [−16.1%, 26.0%]), and day 5 mycological eradication was 71.1% and 50.0% (between-group difference, 21.1% [−0.2%, 40.2%]). Safety was comparable between treatments. Conclusions These findings support the efficacy and safety of rezafungin compared with caspofungin for the treatment of candidemia and/or IC in patients with a positive culture close to randomization, with potential early treatment benefits for rezafungin. [ABSTRACT FROM AUTHOR]

Objectives To describe the management of haematological patients experiencing prolonged SARS-CoV-2 viral shedding, as the optimal management strategy for this condition remains undetermined. Methods We conducted a retrospective evaluation of our prospectively followed cohort of haematological patients treated with remdesivir for more than 10 days. Starting January 2023, upon COVID-19 diagnosis, the treatment strategy was based on symptoms and PCR cycle threshold (Ct) as follows: (i) when Ct was 25 or less or if the patient had symptoms, a course of remdesivir for at least 10 days, nirmatrelvir/ritonavir for 5 days (whenever possible) and convalescent plasma was administered; and (ii) when the patient was asymptomatic and had a PCR Ct of more than 25, when possible, a course of 5 days of nirmatrelvir/ritonavir was administered. The patient was considered to have achieved viral clearance and, thus, remdesivir was stopped, in either of these cases: (i) PCR negativity, or (ii) subgenomic RNA negativity. Results From January to November 2023, 18 patients benefited from a safe extended remdesivir administration, resulting in detection of SARS-CoV-2 viral clearance in a median time of 3.5 weeks (IQR 2.6–3.9) (min–max 1.6–8.0). No clinical or biological side effects were detected. No patient died or needed further treatment for their COVID-19 episode. Conclusions The extended course of remdesivir, combined with other active therapies for COVID-19 infection, was well tolerated. Cure and virus negativity were obtained in all these high-risk patients. [ABSTRACT FROM AUTHOR]

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]

Background: Ceftaroline fosamil is approved for the treatment of complicated skin and soft tissue infections (cSSTI) and community-acquired pneumonia (CAP); however, data on its real-world use and effectiveness in Europe and Latin America are currently limited. This retrospective observational study assessed ceftaroline fosamil use and treatment outcomes in adults hospitalized with cSSTI or CAP treated with ceftaroline fosamil in a usual care setting in Europe and Latin America. Results for patients with cSSTI are reported. Methods: Data from patients with cSSTI who received ≥ 4 consecutive intravenous ceftaroline fosamil doses up to May 31, 2019, were collected from sites in Brazil, Colombia, France, Greece, Italy, and Spain. Patient characteristics, clinical management, hospitalization information, microbiological diagnosis, and clinical responses were summarized descriptively. Healthcare resource use variables were evaluated by clinical response to ceftaroline fosamil. Results: Data for 132 patients were included (58.3% male; mean age 58.5 years). Most common lesions were cellulitis/fasciitis (62.1%), abscess (34.1%), and post-surgical wounds (19.7%). Pathogens most frequently identified were methicillin-resistant (18.2%) and methicillin-susceptible Staphylococcus aureus (17.4%). Median (range) ceftaroline fosamil treatment duration was 8 (2– 60) days (daily doses of 1200 [400– 2400] mg); 78 patients (59.1%) received monotherapy. In total, 75 (56.8%) patients had additional antibiotics after ceftaroline fosamil. Clinical response occurred in 118 (89.4%) patients. All-cause 30-day readmission occurred in 13 (9.8%) patients, and all-cause 30-day mortality in 7 (5.3%). Clinical response to ceftaroline was associated with > 25% shorter length of hospital and intensive care stay, and with ~40% lower hospital costs, versus non-responders. Conclusion: Ceftaroline fosamil was effective in treating adults with cSSTI and clinical response to ceftaroline fosamil was associated with reductions in healthcare resource use compared with non-responders, in Europe and Latin America. Clinicaltrials.gov Identifier: NCT04198571. [ABSTRACT FROM AUTHOR]

This document is a reply to a comment made by Paranhos-Baccalà et al. regarding a recent article published in the journal Diagnostics. The authors of the reply acknowledge the sensitivity controversy surrounding the Biofire Filmarray ME panel, specifically in relation to HSV-1. They discuss the limitations of their study and address concerns raised by Paranhos-Baccalà et al. regarding the representativeness of the samples studied. The authors emphasize the importance of clinical correlation in the diagnosis of meningoencephalitis and suggest that larger comparative studies are needed to confirm their findings. [Extracted from the article]

Background The first-line management strategy for acute periprosthetic joint infections (PJIs) is debridement, antibiotics, and implant retention (DAIR). Suppressive antibiotic therapy (SAT) after DAIR is proposed to improve outcomes, yet its efficacy remains under scrutiny. Methods We conducted a multicenter retrospective study in patients with acute PJI of the hip or knee who were treated with DAIR in centers from Europe and the United States. We analyzed the effect of SAT using a Cox model landmarked at 12 weeks. The primary covariate of interest was SAT, which was analyzed as a time-varying covariate. Patients who experienced treatment failure or were lost to follow-up within 12 weeks were excluded from the analysis. Results The study included 510 patients with 66 treatment failures with a median follow-up of 801 days. We did not find a statistically significant association between SAT and treatment failure (hazard ratio, 1.37; 95% CI,.79–2.39; P =.27). Subgroup analyses for joint, country cohort, and type of infection (early or late acute) did not show benefit for SAT. Secondary analysis of country cohorts showed a trend toward benefit for the US cohort (hazard ratio, 0.36; 95% CI,.11–1.15; P =.09), which also had the highest risk of treatment failure. Conclusions The utility of routine SAT as a strategy for enhancing DAIR's success in acute PJI remains uncertain. Our results suggest that SAT's benefits might be restricted to specific groups of patients, underscoring the need for randomized controlled trials. Identifying patients most likely to benefit from SAT should be a priority in future studies. [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]

Objectives: To identify global differences in the use of suppressive antimicrobial therapy (SAT) in the management of prosthetic joint infection (PJI)., Methods: An online survey was designed to investigate clinician's approach to SAT for PJI, including indications, preferred antimicrobial drugs, dosing, treatment duration and follow-up. The survey was distributed to members of four international (bone and joint) infection societies and study groups., Results: Respondents comprised 330 physicians (204 infectious diseases specialists, 110 orthopedic surgeons, 23 clinical microbiologists) from 43 different countries (Europe, n = 134, 41%; Oceania n = 112, 34%; North America, n = 51, 16%; other, n = 33, 10%; total response rate 20%). After debridement, antibiotics and implant retention (DAIR) or one-stage revision, SAT would be initiated often or almost always by 38% of respondents from North America, but only in 6% from Europe and 7% from Oceania. First choices of SAT for staphylococcal PJI were oral cephalosporins (39%) and tetracyclines (31%) in North America; tetracyclines (27%) and anti-staphylococcal penicillins (22%) in Europe; and anti-staphylococcal penicillins (55%) in Oceania. There was no global or regional preferred SAT regimen for Gram-negative PJI. Of all respondents, dosage of SAT was never lowered (n = 126, 38%), lowered for specific antibiotics (n = 125, 38%) or lowered for all antibiotics (n = 79, 24%). SAT was prescribed for a lifelong duration (n = 43, 13%), a fixed duration (range 6 months-3 years) (n = 104, 32%) or for an undetermined duration (n = 154, 47%)., Conclusions: Approach to SAT in PJI is highly regional, with no consensus regarding the indication, selection, dose, or duration of SAT between physicians worldwide. This reflects the paucity of data and need for high quality studies to define the optimal use of SAT in the treatment of patients with PJI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The study aimed to describe the epidemiology of multidrug-resistant (MDR) bacteria among solid cancer (SC) patients with bloodstream infections (BSIs), evaluating inappropriate empiric antibiotic treatment (IEAT) use and mortality trends over a 25-year period. All BSI occurrences in adult SC patients at a university hospital were analyzed across five distinct five-year intervals. MDR bacteria were classified as extended-spectrum beta-lactamases (ESBL)-producing and/or Carbapenem-resistant Enterobacterales, non-fermenting Gram-negative bacilli (GNB) resistant to at least three antibiotic classes, methicillin-resistant Staphylococcus aureus (MRSA), and Vancomycin-resistant Enterococci . A multivariate regression model identified the risk factors for MDR BSI. Of 6,117 BSI episodes, Gram-negative bacilli (GNB) constituted 60.4% (3,695/6,117), being the most common are Escherichia coli with 26.8% (1,637/6,117), Klebsiella spp. with 12.4% (760/6,117), and Pseudomonas aeruginosa with 8.6% (525/6,117). MDR-GNB accounted for 644 episodes (84.8% of MDR or 644/759), predominantly ESBL-producing strains (71.1% or 540/759), which escalated significantly over time. IEAT was administered in 24.8% of episodes, mainly in MDR BSI, and was associated with higher mortality (22.9% vs. 14%, P < 0.001). Independent factors for MDR BSI were prior antibiotic use [odds ratio (OR) 2.93, confidence interval (CI) 2.34-3.67], BSI during antibiotic treatment (OR 1.46, CI 1.18-1.81), biliary (OR 1.84, CI 1.34-2.52) or urinary source (OR 1.86, CI 1.43-2.43), admission period (OR) 1.28, CI 1.18-1.38, and community-acquired infection (OR 0.57, CI 0.39-0.82). The study showed an increase in MDR-GNB among SC patients with BSI. A quarter received IEAT, which was linked to increased mortality. Improving risk assessment for MDR infections and the judicious prescription of empiric antibiotics are crucial for better outcomes., Importance: Multidrug-resistant (MDR) bacteria pose a global public health threat as they are more challenging to treat, and they are on the rise. Solid cancer patients are often immunocompromised due to their disease and cancer treatments, making them more susceptible to infections. Understanding the changes and trends in bloodstream infections in solid cancer patients is crucial, to help physicians make informed decisions about appropriate antibiotic therapies, manage infections in this vulnerable population, and prevent infection. Solid cancer patients often require intensive and prolonged treatments, including surgery, chemotherapy, and radiation therapy. Infections can complicate these treatments, leading to treatment delays, increased healthcare costs, and poorer patient outcomes. Investigating new strategies to combat MDR infections and researching novel antibiotics in these patients is of paramount importance to avoid these negative impacts., Competing Interests: C.G.-V. has received honoraria for talks on behalf of Gilead Sciences, MSD, Novartis, Pfizer, Janssen, and Lilly, as well as a grant from Gilead Sciences, Pfizer, and MSD. P.P.-A. has received honoraria for talks on behalf of Merck Sharp & Dohme, Gilead, Lilly, ViiV Healthcare, and Gilead Sciences. A.S. has received honoraria for talks on behalf of Merck Sharp & Dohme, Pfizer, Novartis, Angelini, Menarini, and Gilead Sciences, as well as grant support from Pfizer and Gilead Sciences. O.P. has received honoraria for talks on behalf of MSD, Qiagen, and expertise for Sanofi.

Introduction: Dialysis catheter-associated bacteremia in Intensive Care Units (ICUs) increases morbidity and mortality, prolongs hospital admission and increases admission costs. Taurolidine-Citrate-Heparin Locking Solution (TCHLS) is a catheter-locking solution with a broad antimicrobial activity against gram-positive and gram-negative bacteria and fungi. The aim of this study was to analyze the effect of systematic sealing of hemodialysis catheters in the ICUs of the Hospital Clínic de Barcelona on the incidence of hemodialysis catheter-related blood stream infections (CRBSI)., Material and Methods: CRBSI episodes of patients who underwent intermittent hemodialysis (IHD) during ICU admission were reviewed. TCHLS was established as a routine dialysis catheter sealing solution in the hospital ICUs in 2015. As a control group an historic pre-TCHLS group from 2010 to 2014 was used. The post-TCHLS period comprised from 2015 to 2018., Results: A total of 243 and 266 patients required IHD in the pre- and post TCHLS periods, respectively. The number of CRBSI in the pre-TCHLS period was 18 (7.43%) as compared to 9 (3.38%) in the post-TCHLS period ( p  = 0.043). All infections were from percutaneous catheters except for three catheters that were tunneled. There was no association between the location of the catheter and the incidence of CRBSI. The most frequent isolated microorganisms were Gram positive bacteria (48.38%), with a global predominance of Staphylococcus epidermidis (32.25%). There were no significant differences in the median days from the start of hemodialysis to the onset of bacteremia (23.5 days in pre-TCHLS group vs 21 days in the post-TCHLS). There were also no significant differences between the days of ICU stay in the CRBSI in both groups or in mortality, being the overall mortality of 65.9%., Conclusions: In our population, the systematic application of TCHLS in the sealing of dialysis catheters in critically ill patients reduces the incidence of CRBSI in ICUs., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Ultraviolet- C (UV-C) light is effective for reducing environmental bioburden in hospitals, and the use of robots to deliver it may be advantageous., Aim: To evaluate the feasibility and clinical efficacy of an autonomous programmable UV-C robot in surgical and intensive care unit (ICU) rooms of a tertiary hospital., Method: During ten consecutive months, the device was used in six theatres where cardiac, colorectal and orthopaedic surgeries were performed, and in the rooms previously occupied by patients subjected to contact precautions of a 14-bed ICU. Surgical site infection (SSI) rates of procedures performed in the UV-cleaned theatres were compared with those of the previous year. Incidence in clinical samples of ICU-acquired multiple-drug resistant (MDR) microorganisms was compared with that of the same period of the previous year. An UV-C exposure study done by semi-quantitative dosimeters and a survey of the bioburden on surfaces were carried out., Findings: SSI rates in the pre- and post-intervention periods were 8.67% (80/922) and 7.5% (61/813), respectively (p=0.37). Incidence of target microorganisms in clinical samples remained unchanged (38.4 vs. 39.4 per 10,000 patient-days, p=0.94). All the dosimeters exposed to ≤1 meter received ≥500 mJ/cm 2 . The bacterial load on surfaces decreased after the intervention, particularly in ICU rooms (from 4.57±7.4 CFU to 0.27±0.8 CFU, p<0.0001)., Conclusion: Deployment of an UV-C robot in surgical and ICU rooms is feasible, ensures adequate delivery of germicidal UV-C light and reduces the environmental bacterial burden. Rates of surgical site infections or acquisition of MDR in clinical samples of critically-ill patients remained unchanged., (© 2024 The Authors.)

Background: Prosthetic joint infection (PJI) caused by Candida spp is a severe complication of arthroplasty. We investigated the outcomes of Candida PJI., Methods: This was a retrospective observational multinational study including patients diagnosed with Candida-related PJI between 2010 and 2021. Treatment outcome was assessed at 2-year follow-up., Results: A total of 269 patients were analyzed. Median age was 73.0 (interquartile range [IQR], 64.0-79.0) years; 46.5% of patients were male and 10.8% were immunosuppressed. Main infection sites were hip (53.0%) and knee (43.1%), and 33.8% patients had fistulas. Surgical procedures included debridement, antibiotics, and implant retention (DAIR) (35.7%), 1-stage exchange (28.3%), and 2-stage exchange (29.0%). Candida spp identified were Candida albicans (55.8%), Candida parapsilosis (29.4%), Candida glabrata (7.8%), and Candida tropicalis (5.6%). Coinfection with bacteria was found in 51.3% of cases. The primary antifungal agents prescribed were azoles (75.8%) and echinocandins (30.9%), administered for a median of 92.0 (IQR, 54.5-181.3) days. Cure was observed in 156 of 269 (58.0%) cases. Treatment failure was associated with age >70 years (OR, 1.811 [95% confidence interval {CI}: 1.079-3.072]), and the use of DAIR (OR, 1.946 [95% CI: 1.157-3.285]). Candida parapsilosis infection was associated with better outcome (OR, 0.546 [95% CI: .305-.958]). Cure rates were significantly different between DAIR versus 1-stage exchange (46.9% vs 67.1%, P = .008) and DAIR versus 2-stage exchange (46.9% vs 69.2%, P = .003), but there was no difference comparing 1- to 2-stage exchanges (P = .777)., Conclusions: Candida PJI prognosis seems poor, with high rate of failure, which does not appear to be linked to immunosuppression, use of azoles, or treatment duration., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)