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Background: Immunosuppression at intensive care unit (ICU) admission has been associated with a higher incidence of ICU-acquired infections, some of them related to opportunistic pathogens. However, the association of immunosuppression with the incidence, microbiology and outcomes of ICU-acquired bacterial bloodstream infections (BSI) has not been thoroughly investigated. Methods: Retrospective single-centered cohort study in France. All adult patients hospitalized in the ICU of Lille University-affiliated hospital for > 48 h between January 1st and December 31st, 2020, were included, regardless of their immune status. Immunosuppression was defined as active cancer or hematologic malignancy, neutropenia, hematopoietic stem cell and solid organ transplants, use of steroids or immunosuppressive drugs, human immunodeficiency virus infection and genetic immune deficiency. The primary objective was to compare the 28-day cumulative incidence of ICU-acquired bacterial BSI between immunocompromised and non-immunocompromised patients. Secondary objectives were to assess the microbiology and outcomes of ICU-acquired bacterial BSI in the two groups. Results: A total of 1313 patients (66.9% males, median age 62 years) were included. Among them, 271 (20.6%) were immunocompromised at ICU admission. Severity scores at admission, the use of invasive devices and antibiotic exposure during ICU stay were comparable between groups. Both prior to and after adjustment for pre‐specified baseline confounders, the 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between immunocompromised and non-immunocompromised patients. The distribution of bacteria was comparable between groups, with a majority of Gram-negative bacilli (~ 64.1%). The proportion of multidrug-resistant bacteria was also similar between groups. Occurrence of ICU-acquired bacterial BSI was associated with a longer ICU length-of-stay and a longer duration of invasive mechanical ventilation, with no significant association with mortality. Immune status did not modify the association between occurrence of ICU-acquired bacterial BSI and these outcomes. Conclusion: The 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between patients with and without immunosuppression at ICU admission. [ABSTRACT FROM AUTHOR]

Introduction: Concern about Klebsiella pneumoniae (K. pneumoniae) bloodstream infections (KP-BSIs) is widespread because of their high incidence and lethality. The aim of this study was to investigate the clinical features of, and risk factors for mortality caused by KP-BSIs. Methodology: This was a single-center retrospective observational study performed between 1 January 2019 and 31 December 2021, at a tertiary hospital. All patients with KP-BSIs were enrolled and their clinical data were retrieved from electronic medical records. Results: A total of 145 patients were included (121 in the survival group and 24 in the non-survival group). There was a higher proportion of lower respiratory tract infections in the non-survival group than in the survival group (33.3% vs. 12.4%) (p < 0.05). There was a higher proportion of multi drug resistant (MDR) strains of K. pneumoniae in the non-survival group than in the survival group (41.7% vs. 16.5%) (p < 0.05). Multivariate analysis revealed that sequential organ failure assessment (SOFA) score > 6.5 (OR, 13.71; 95% CI, 1.05–179.84), admission to the intensive care unit (ICU) (OR, 2.27; 95% CI, 0.26–19.61) and gastrointestinal bleeding (OR, 19.97; 95% CI, 1.11–361.02) were independent risk factors for death in patients with KP-BSIs. Conclusions: Among all KP-BSIs, a high proportion of K. pneumoniae originated from lower respiratory tract infections, and a high proportion of K. pneumoniae were MDR; however, mortality was not influenced. SOFA score > 6.5, admission to the ICU, and gastrointestinal bleeding were independent risk factors for death in patients with KP-BSI. [ABSTRACT FROM AUTHOR]

Background A small proportion of Escherichia coli and Klebsiella pneumoniae demonstrate in vitro non-susceptibility to piperacillin/tazobactam but retain susceptibility to ceftriaxone. Uncertainty remains regarding how best to treat these isolates. Objectives We sought to compare clinical outcomes between patients with piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae bloodstream infection receiving definitive therapy with ceftriaxone versus an alternative effective antibiotic. Methods We retrospectively identified patients with a positive blood culture for piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae between 1 January 2013 and 31 December 2022. Patients were divided into one of two definitive treatment groups: ceftriaxone or alternative effective antibiotic. Our primary outcome was a composite of 90 day all-cause mortality, hospital readmission, or recurrence of infection. We used Cox proportional hazards models to compare time with the composite outcome between groups. Results Sixty-two patients were included in our analysis. Overall, median age was 63 years (IQR 49.5–71.0), the most common source of infection was intra-abdominal (25/62; 40.3%) and the median total duration of therapy was 12.0 days (IQR 9.0–16.8). A total of 9/22 (40.9%) patients in the ceftriaxone treatment group and 18/40 (45.0%) patients in the alternative effective antibiotic group met the composite endpoint. In an adjusted time-to-event analysis, there was no difference in the composite endpoint between groups (HR 0.67, 95% CI 0.30–1.50). The adjusted Bayesian posterior probability that the HR was less than or equal to 1 (i.e. ceftriaxone is as good or better than alternative therapy) was 85%. Conclusions These findings suggest that ceftriaxone can be used to effectively treat bloodstream infections with E. coli or K. pneumoniae that are non-susceptible to piperacillin/tazobactam but susceptible to ceftriaxone. [ABSTRACT FROM AUTHOR]

Background: Nosocomial bloodstream infections (nBSI) have emerged as a clinical concern for physicians treating COVID-19 patients. In this study, we aimed to evaluate the effectiveness of a multiplex ddPCR in detecting bacterial pathogens in the blood of COVID-19 critically ill patients. Methods: This prospective diagnostic study included RT-PCR-confirmed COVID-19 patients admitted to our hospital from December 2022 to February 2023. A multiplex ddPCR assay was used to detect common bacterial pathogens and AMR genes in blood samples of the patients, along with antimicrobial susceptibility testing (AST). The diagnostic performance of the ddPCR assay was evaluated by comparing the results with those obtained through blood culture and clinical diagnosis. Additionally, the ability of ddPCR in detecting bacterial resistance was compared with the AST results. Results: Of the 200 blood samples collected from 184 patients, 45 (22.5%) were positive using blood culture, while 113 (56.5%) were positive for bacterial targets using the ddPCR assay. The ddPCR assay outperformed blood culture in pathogen detection rate, mixed infection detection rate, and fungal detection rate. Acinetobacter baumannii and Klebsiella pneumoniae were the most commonly detected pathogens in COVID-19 critically ill patients, followed by Enterococcus and Streptococcus. Compared to blood culture, ddPCR achieved a sensitivity of 75.5%, specificity of 51.0%, PPV of 30.9%, and NPV of 87.8%, respectively. However, there were significant differences in sensitivity among different bacterial species, where Gram-negative bacteria have the highest sensitivity of 90.3%. When evaluated on the ground of clinical diagnosis, the sensitivity, specificity, PPV and NPV of ddPCR were 78.1%, 90.5%, 94.7%, and 65.5%, respectively. In addition, the ddPCR assay detected 23 cases of blaKPC, which shown a better consistent with clinical test results than other detected AMR genes. Compared to blaKPC, there were few other AMR genes detected, indicating that the application of other AMR gene detection in the COVID-19 critically ill patients was limited. Conclusion: The multiplex ddPCR assay had a significantly higher pathogen detection positivity than the blood culture, which could be an effective diagnostic tool for BSIs in COVID-19 patients and to improve patient outcomes and reduce the burden of sepsis on the healthcare system, though there is room for optimization of the panels used.- Adjusting the targets to include E. faecalis and E. faecium as well as Candida albicans and Candida glabrata could improve the ddPCR' s effectiveness. However, further research is needed to explore the potential of ddPCR in predicting bacterial resistance through AMR gene detection. [ABSTRACT FROM AUTHOR]

Bloodstream infections (BSI) caused by multidrug-resistant (MDR) bacteria, pose a major threat for patients, especially for those who are immunosuppressed. Rapid pathogen detection and characterization from positive blood cultures are crucial in the management of patients with BSI to enable an adequate and timely antimicrobial therapy. This study aimed to investigate the potential role of the Molecular Mouse system, a new CE IVD molecular test designed to rapidly detect the causative agents of bacteremia and their resistance determinants, in the management of the therapy in critically ill patients. Agreement between the results of the Molecular Mouse and the conventional routine method was also considered. Overall, 100 positive blood cultures were collected from septic critically ill patients from May 2023 to January 2024 and analyzed with Molecular Mouse and routine protocols. The new instrument consistently agreed with the routine protocols in the case of monomicrobial blood cultures, while some discrepancies were obtained in the polymicrobial samples. Antimicrobial resistance genes were detected in 35 samples, with vanA and CTX-M-1/9 groups being the most frequently detected targets. Therapy was adjusted in 42 critically ill patients confirming the importance of new rapid molecular tests in the management of positive blood cultures, to adjust empirical therapy and use new antibiotics accurately. [ABSTRACT FROM AUTHOR]

Bloodstream infections (BSIs) caused by multidrug-resistant bacteria are a critical life-threatening challenge which necessitates the urgency to trigger life-saving treatment in a timely manner. This study aimed to evaluate the time required for rapid detection of carbapenemase-producing Enterobacterales (CPE) directly from blood culture bottles to optimize empirical treatment of BSI, especially in pediatric and infant patients, using a cost-effective method. This study included 419 Gram-negative bacteria, of which Klebsiella pneumoniae and Escherichia coli were the most common CPE causing BSI in pediatric and neonatal patients. Phenotypic and genotypic resistance of the selected isolates (45 K. pneumoniae and 9 E. coli) were determined by VITEK-2 Compact system and PCR, respectively. BACT/ALERT bottles were spiked with isolates. Finally, colorimetric RESIST-BC assay and Vitek-2 compact system were evaluated for the rapid detection of carbapenem-resistant bacteria directly from positive blood culture bottles. All selected isolates were phenotypically resistant to carbapenems. PCR showed that bla NDM and bla OXA-48 were present in all isolates, bla VIM was present in 44.4%, while bla KPC and bla IMP were entirely absent. The RESIST-BC kit showed good agreement with PCR for bla NDM and bla OXA-48, demonstrating high sensitivity and specificity, but not with bla VIM. These findings point out that RESIST-BC assay demonstrated an exceptionally short detection time for CPE, completing all cases within the first hour after the blood culture bottles flagged positive. It is also superior in providing a clue for clinicians on antibiotic combinations that can be administered, depending on the type of β-lactamases detected, promptly and efficiently, with low expenses. [ABSTRACT FROM AUTHOR]

Background: Rapid antimicrobial susceptibility testing (AST) is urgently needed to provide safer treatment to counteract antimicrobial resistance. This is critical in septic patients, because resistance increases empiric therapy uncertainty and the risk of a poor outcome. We validate a novel 2h flow cytometry AST assay directly from positive blood cultures (PBC) by using a room temperature stable FASTgramneg and FASTgrampos kits (FASTinov® Porto, Portugal) in three sites: FASTinov (site-1), Hospital Ramon y Cajal, Madrid, Spain (site-2) and Centro Hospitalar S. João, Porto, Portugal (site-3). A total of 670 PBC were included: 333 spiked (site-1) and 337 clinical PBC (151 site-2 and 186 site-3): 367 gram-negative and 303 gram-positive. Manufacturer instructions were followed for sample preparation, panel inoculation, incubation (1h/37ºC) and flow cytometry analysis using CytoFlex (Site-1 and -2) or DxFlex (site-3) both instruments from Beckman-Coulter, USA. Results: A proprietary software (bioFAST) was used to immediately generate a susceptibility report in less than 2 h. In parallel, samples were processed according to reference AST methods (disk diffusion and/or microdilution) and interpreted with EUCAST and CLSI criteria. Additionally, ten samples were spiked in all sites for inter-laboratory reproducibility. Sensitivity and specificity were >95% for all antimicrobials. Reproducibility was 96.8%/95.0% for FASTgramneg and 95.1%/95.1% for FASTgrampos regarding EUCAST/CLSI criteria, respectively. Conclusion: FASTinov® kits consistently provide ultra-rapid AST in 2h with high accuracy and reproducibility on both Gram-negative and Gram-positive bacteria. This technology creates a new paradigm in bacterial infection management and holds the potential to significantly impact septic patient outcomes and antimicrobial stewardship. [ABSTRACT FROM AUTHOR]

The concentration of antimicrobial agents in environments like water and food has increased rapidly, which led to a rapid increase in antimicrobial resistance levels in the environment. Monitoring of bacterial resistance levels is considered as a necessary means to control the bacterial resistance. Reference standards are critical for antimicrobial susceptibility testing. CLSI M45 A3 standard defines pathogenic microorganisms that cause infections less frequently than those covered by CLSI M02, M07, and M100 as Infrequently Isolated or Fastidious Bacteria and specifies antimicrobial susceptibility testing methods. Our study investigated the epidemiology and antimicrobial susceptibility testing data of Infrequently Isolated or Fastidious Bacteria strains isolated from blood specimens in 70 hospitals in Guangdong Province between 2017 and 2021. We defined testing methods other than those specified in CLSI M45 A3 as "Non-Standardized." The proportion of standardized antimicrobial susceptibility testing for penicillin increased significantly (Corynebacterium spp. 17.4% vs. 50.0% p < 0.05; Micrococcus spp. 50.0% vs. 77.8% p < 0.05; Abiotrophia spp. and Granulicatella spp. 21.4% vs. 90.9% p < 0.001), while for cefotaxime (Corynebacterium spp. 0.0% vs. 45.2% p < 0.05; Abiotrophia spp. and Granulicatella spp. 0.0% vs. 14.3% p = 0.515) and vancomycin increased finitely. Non-standardized methods were used for all other antimicrobials. Due to limitations in the economic and medical environment, some clinical laboratories are unable to fully comply with CLSI M45 A3 standard. We recommend that CLSI should add breakpoints for disk diffusion method to improve the standardization of antimicrobial susceptibility testing. [ABSTRACT FROM AUTHOR]

Purpose: Data on the molecular epidemiology of methicillin-resistant Staphylococcus aureus isolates from patients with bacteraemia in Slovenia are lacking. The aim of this study was to phenotypically and genotypically investigate 82 MRSA strains isolated from patients with bloodstream infections in central Slovenia between 2019 and 2022. Methods: Whole-genome sequencing of selected strains was performed to characterize the strains based on sequence typing, antimicrobial resistance, toxin, and virulence factors genes. Results: Most MRSA carried SCCmec II (63.4%), followed by SCCmec IV (34.1%) and SCCmec V (2.5%). A high proportion of strains belonging to the ST225 lineage (45.1%) was observed, followed by ST97 (18.3%), ST2883 (15.9%), ST22 (9.8%), ST5 (3.7%), and the ST1, ST398 and ST45 lineages (2.4% each). Sixteen different spa types were identified, predominantly ST225-t003 (31.7%), ST97-t359 (15.9%), and ST2883-t4336 (14.6%). None of the strains carried Panton-Valentine leukocidin, exfoliative toxins, or toxic shock toxin. All MRSA strains were susceptible to linezolid, rifampicin, vancomycin, teicoplanin, and trimethoprim-sulfamethoxazole. MRSA strains were resistant to erythromycin, clindamycin, tetracycline and gentamicin, with a frequency of 74.4%, 74.4%, 8.5%, and 1.2%, respectively. Conclusion: This study demonstrates that bacteraemia in central Slovenia is caused by diverse MRSA lineages. Identification of newly emerged lineages should be followed in the future to detect changes in the molecular epidemiology of MRSA in our country. [ABSTRACT FROM AUTHOR]

Background In vitro–in vivo discordance in β-lactams' activities against metallo-ß-lactamase (MBL)-producing Enterobacterales has been described. We aimed to assess whether this discordance is attributed to the supra-physiologic zinc concentration in in vitro testing media. Methods A clinical and microbiological observational study of patients with bloodstream infections due to New Delhi metallo-ß-lactamase-producing Klebsiella pneumoniae was performed. Outcomes of patients treated empirically with non-MBL-active β-lactam therapy (carbapenems and ceftazidime/avibactam) and MBL-active β-lactam therapy (ceftazidime/avibactam + aztreonam) were documented. The patients' isolates were used to induce septicemia in mice, and survival upon meropenem treatment was recorded. Meropenem minimum inhibitory concentrations (MICs) were determined in standard media and in the presence of physiological zinc concentrations. Results Twenty-nine patients receiving empiric non-MBL-active β-lactams (median duration, 4 days) were compared with 29 receiving MBL-active β-lactams. The 14-day mortality rates were 21% and 14%, respectively. In the murine septicemia model, meropenem treatment resulted in protection from mortality (P <.0001). Meropenem MICs in the physiologic zinc concentration broth were 1- to >16-fold lower vs MICs in zinc-unadjusted broth (≥64 mg/L). Conclusions Our data provide foundational support to establish pharmacokinetic/pharmacodynamic relationships using MICs derived in physiologic zinc concentration, which may better predict β-lactam therapy outcome. [ABSTRACT FROM AUTHOR]

A retrospective study at the 4th Military Clinical Hospital in Wroclaw, Poland, assessed PCR testing alongside blood cultures to guide antimicrobial therapy decisions in hospitalized patients, to determine how much time the results of the molecular tests preceded conventional methods. Among 118 patients, Staphylococcus aureus (37%) and Escherichia coli (21%) were the most common bloodstream infection agents. Blood cultures utilized the BacT/ALERT 3D system, and molecular diagnostics were conducted using the FilmArray platform with the BIOFIRE BCID2 panel. Methicillin susceptibility was observed in 66% of S. aureus strains, while 26% of Gram-negative bacilli exhibited an ESBL phenotype. Therapeutic decisions based on molecular test results were often incorrect for S. aureus infections, particularly MSSA (64.5%), but generally accurate for Gram-negative bacilli. The median times from positive blood culture to BCID2 and pathogen identification/susceptibility were 10 h and 52 h, respectively. Molecular diagnostics facilitated faster initiation of appropriate antibiotic therapy, highlighting the need to educate medical staff on proper interpretation. Consulting within an antimicrobial stewardship program (ASP) could enhance the benefits of implementing molecular methods in bloodstream infection diagnostics. [ABSTRACT FROM AUTHOR]

Medical devices such as venous catheters (VCs) and urinary catheters (UCs) are widely used in the hospital setting. However, the implantation of these devices is often accompanied by complications. About 60 to 70% of nosocomial infections (NIs) are linked to biofilms. The main complication is the ability of microorganisms to adhere to surfaces and form biofilms which protect them and help them to persist in the host. Indeed, by crossing the skin barrier, the insertion of VC inevitably allows skin flora or accidental environmental contaminants to access the underlying tissues and cause fatal complications like bloodstream infections (BSIs). In fact, 80,000 central venous catheters—BSIs (CVC-BSIs)—mainly occur in intensive care units (ICUs) with a death rate of 12 to 25%. Similarly, catheter-associated urinary tract infections (CA-UTIs) are the most commonlyhospital-acquired infections (HAIs) worldwide.These infections represent up to 40% of NIs.In this review, we present a summary of biofilm formation steps. We provide an overview of two main and important infections in clinical settings linked to medical devices, namely the catheter-asociated bloodstream infections (CA-BSIs) and catheter-associated urinary tract infections (CA-UTIs), and highlight also the most multidrug resistant bacteria implicated in these infections. Furthermore, we draw attention toseveral useful prevention strategies, and advanced antimicrobial and antifouling approaches developed to reduce bacterial colonization on catheter surfaces and the incidence of the catheter-related infections. [ABSTRACT FROM AUTHOR]

With blood stream infections (BSIs) representing a major cause of mortality and morbidity worldwide, blood cultures play a crucial role in diagnosis, but their clinical application is dampened by the long turn-around time and the detection of only culturable pathogens. In this study, we developed and validated a shotgun metagenomics next-generation sequencing (mNGS) test directly from positive blood culture fluid, allowing for the identification of fastidious or slow growing microorganisms more rapidly. The test was built based on previously validated next-generation sequencing tests, which rely on several key marker genes for bacterial and fungal identification. The new test utilizes an open-source metagenomics CZ-ID platform for the initial analysis to generate the most likely candidate species, which is then used as a reference genome for downstream, confirmatory analysis. This approach is innovative because it takes advantage of an open-source software's agnostic taxonomic calling capability while still relying on the more established and previously validated marker gene-based identification scheme, increasing the confidence in the final results. The test showed high accuracy (100%, 30/30) for both bacterial and fungal microorganisms. We further demonstrated its clinical utility especially for anaerobes and mycobacteria that are either fastidious, slow growing, or unusual. Although applicable in only limited settings, the Positive Blood Culture mNGS test provides an incremental improvement in solving the unmet clinical needs for the diagnosis of challenging BSIs.

ABSTRACT 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.IMPORTANCEMultidrug-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.

ABSTRACT The use of rapid disk diffusion or modified automated antimicrobial susceptibility testing (AST) system approaches demonstrates excellent performance for gram-negative organisms directly from blood cultures. In a recent study, S. Khan, A. Das, A. Mishra, A. Vidyarthi, et al. (Microbiol Spectr 12:e03081-23, 2024, https://doi.org/10.1128/spectrum.03081-23) compared the performance of three direct-from-blood AST methods against standard of care disk diffusion and automated AST. The results demonstrated high categorical agreements and low error rates across three protocols. The study suggests that locally validated direct-from-blood AST protocols offer reliable and fast results, particularly for resource-limited settings. However, local context and workflows should be considered prior to implementing rapid AST protocols, and more research is needed on the performance of rapid AST protocols for gram-positive organisms.

ABSTRACT Delayed time to antimicrobial susceptibility results can impact patients’ outcomes. Our study evaluated the impact of susceptibility turnaround time (TAT) and inadequate empiric antibacterial therapy (IET) in patients with bloodstream infections (BSI) caused by Enterobacterales (ENT) species on in-hospital mortality and length of stay (LOS). This retrospective, multicenter investigation which included 29,570 blood ENT-positive admissions across 161 US healthcare facilities evaluated the association between antimicrobial susceptibility testing (AST) TAT, carbapenem susceptibility, and empiric therapy on post-BSI in-hospital mortality and LOS following an ENT BSI event in adult patients. After adjusting for outcomes covariates, post-BSI in-hospital mortality was significantly higher for patients in the IET vs adequate empiric therapy (AET) group [odds ratio (OR): 1.61 (95% CI: 1.32, 1.98); P < 0.0001], and when AST TAT was >63 h [OR:1.48 (95% CI: 1.16, 1.90); P = 0.0017]. Patients with carbapenem non-susceptible (carb-NS) ENT BSI had significantly higher LOS (16.6 days, 95% CI: 15.6, 17.8) compared to carbapenem susceptible (carb-S, 12.2 days, 95% CI: 11.8, 12.6), (P < 0.0001). Extended AST TAT was significantly associated with longer LOS for TAT of 57–65 h and >65 h (P = 0.005 and P< 0.0001, respectively) compared to TAT ≤42 h (reference). Inadequate empiric therapy (IET), carb-NS, and delayed AST TAT are significantly associated with adverse hospital outcomes in ENT BSI. Workflows that accelerate AST TAT for ENT BSIs and facilitate timely and adequate therapy may reduce post-BSI in-hospital mortality rate and LOS.IMPORTANCEFor patients diagnosed with bloodstream infections (BSI) caused by Enterobacterales (ENT), delayed time to antimicrobial susceptibility (AST) results can significantly impact in-hospital mortality and hospital length of stay. However, this relationship between time elapsed from blood culture collection to AST results has only been assessed, to date, in a limited number of publications. Our study focuses on this important gap using retrospective data from 29,570 blood ENT-positive admissions across 161 healthcare facilities in the US as we believe that a thorough understanding of the dynamic between AST turnaround time, adequacy of empiric therapy, post-BSI event mortality, and hospital length of stay will help guide effective clinical management and optimize outcomes of patients with ENT infections.

Staphylococcus argenteus is a novel species within the Staphylococcus aureus complex and can cause serious bloodstream infections (BSIs) in humans, which have been mainly reported in adults, especially the elderly. In this study, we analyzed the molecular characterization of a strain of S. argenteus (22WJ8192) isolated from the peripheral vein blood sample of a seven-month-old female infant in Eastern China. The 22WJ8192 belonged to sequence type (ST)2250 and harbored six antibiotic-resistance genes and 53 virulence genes and was resistant to penicillin. Additionally, we conducted a comparative analysis of the molecular characteristics of S. argenteus sourced from various origins within the dataset, predominantly from the National Center for Biotechnology Information Collection (NCBI) genome database. Antibiotic-resistance genes blaR1, blaI_of_Z, blaZ, fosB-Saur, tet(L), aph(3”)-IIIa, mecA, and dfrG were more prevalent among the strains of human origin. Virulence genes lukF-PV, sak, sdrE, scn, sdrC, and sdrD were more prevalent among strains of human origin. The presence of antibiotic-resistance genes blaR1, blaI_of_Z, blaZ, fosB-Saur, and aph(3”)-IIIa in strain 22WJ8192 was also more common among strains of human origin in the dataset. Conversely, the antibiotic-resistance genes tet(L), mecA, and dfrG, typically found in strains of human origin, were not detected in 22WJ8192. Additionally, virulence genes lukF-PV, sak, sdrE, scn, sdrC, and sdrD present in 22WJ8192 exhibited a higher prevalence among strains of human origin in the dataset. In conclusion, this study emphasizes the potential of S. argenteus ST2250 to induce severe bloodstream infections in infants, shedding light on the molecular characteristics of this strain.

BackgroundBloodstream infections caused by Candida species are responsible for significant morbidity and mortality worldwide, with an ever-changing epidemiology. We conducted this study to assess trends in the epidemiologic features, risk factors and Candida species distribution in candidemia patients in Alameda County, California.MethodsWe analyzed data collected from patients in Alameda County, California between 2017 and 2020 as part of the California Emerging Infections Program (CEIP). This is a laboratory-based, active surveillance program for candidemia. In our study, we included incident cases only.ResultsDuring the 4-year period from January 1st, 2017, to December 31st, 2020, 392 incident cases of candidemia were identified. The mean crude annual cumulative incidence was 5.9 cases per 100,000 inhabitants (range 5.0-6.5 cases per 100,000 population). Candida glabrata was the most common Candida species and was present as the only Candida species in 149 cases (38.0%), followed by Candida albicans, 130 (33.2%). Mixed Candida species were present in 13 patients (3.3%). Most of the cases of candidemia occurred in individuals with one or more underlying conditions. Multivariate regression models showed that age ≥ 65 years (RR 1.66, CI 1.28-2.14), prior administration of systemic antibiotic therapy, (RR 1.84, CI 1.06-3.17), cirrhosis of the liver, (RR 2.01, CI 1.51-2.68), and prior admission to the ICU (RR1.82, CI 1.36-2.43) were significant predictors of mortality.ConclusionsNon-albicans Candida species currently account for the majority of candidemia cases in Alameda County.

Background: Candidaemia is a life‐threatening disease that is associated with high mortality, especially in intensive care units (ICUs). The number of comprehensive studies dealing with the epidemiologic characteristics of biofilm‐related properties is limited. Objective: This study evaluated the clinical characteristics of candidaemia, to assess the biofilm‐forming properties of isolates, and to identify the risk factors of mortality. Patients and Methods: A total of 149 candidaemia episodes from the University of Debrecen, Clinical Centre, between January 2020 and December 2023 were investigated retrospectively. The susceptibility of Candida isolates to fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin was evaluated and compared to the susceptibility of 1‐day‐old biofilms. Multivariate logistic regression analysis was applied to identify the independent predictors of 30‐day mortality rate. Results: The most common Candida species was Candida albicans (41%), followed by C. parapsilosis (20%), C. glabrata (14%), C. tropicalis (13%), rare Candida species (7%), and C. krusei (5%). Sixty‐six percent of Candida isolates were biofilm formers and 44% had high metabolic activity. The 30‐day mortality rate was 52%, which was higher in ICUs (65%). The logistic regression analysis revealed several factors significantly influencing mortality including ICU admission (odds ratio [OR] 2.99, 95% confidence interval [CI] 1.17–8.04, p = 0.025), fluconazole treatment (OR 4.12, 95% CI 1.62–11.42, p =.004), and pneumonia (OR 0.261, 95% CI 0.1–0.67, p =.006). Conclusions: This comprehensive analysis supports the better characterisation of candidaemia in healthcare settings, which ultimately may reduce mortality among patients. [ABSTRACT FROM AUTHOR]

Background and Objectives: Candidemia is the most common serious fungal infection in critically ill patients in intensive care units (ICU). It series fourth among bloodstream infectious agents. In this study, candidemia risk analysis was examined in COVID 19 and non-COVID 19 patients during the pandemic period. Materials and Methods: COVID 19 and non-COVID 19 cases who were followed up with candidemia in the ICU of our hospital were retrospectively screened. Demographic data, intubation, central venous catheter (CVC), medications, and total parenteral nutrition (TPN) status were evaluated in terms of risk between the two groups. Isolated Candida species and susceptibilty were evaluated. Results: When age, gender, medication, intubation, TPN and CVC were evaluated, no difference was seen in terms of risk. Differences were detected in terms of comorbidities. While the most frequently identified Candida species was C. albicans, the most frequently detected species in the COVID19 patient group was C. parapsilosis. Conclusion: There was no difference in candidemia incidence and risk factors between the two groups. Since candidemias were evaluated in terms of comorbidities, it was determined that Diabetes Mellitus (DM) and chronic obstructive pulmoner disease (COPD) were more common in patients with COVID 19 and less common in coronary artery disease (CAD) and malignancy. [ABSTRACT FROM AUTHOR]

Adolescent and young adults (AYAs) belong to a unique category of patients diagnosed with acute lymphoblastic leukaemia (ALL). Bloodstream infection (BSI) is a leading cause of treatment‐related mortality in ALL patients. However, the epidemiology and risk factors for mortality from BSIs in AYA patients remain unclear. In this study, we analysed these aspects in AYAs patients and compared similarities and differences with children (<15 years old) and older adults (>39 years old). We analysed the pathogenic epidemiology, antibiotic resistance and BSI risk factors of 73 children, 180 AYAs, and 110 older adults with ALL in three comprehensive hospitals from January 2010 to August 2021. The data on BSIs in AYAs were compared to that of the other two groups. In this study, the epidemiology of BSIs in AYAs was similar to that of older adult patients. Concerning clinical characteristics, most AYAs and older adults with BSIs were in a relapsed or uncontrolled state (34.5% vs. 35.4%, p = 0.861). In terms of pathogen distribution, Gram‐negative bacteria (GNB) were the most common causative pathogens in AYAs and older adult groups. Extended‐spectrum beta‐lactamase (ESBL)‐producing bacteria were more commonly found in AYAs than in children (32.8% vs. 16.4%, p = 0.09). Regarding risk factors, the length of hospitalization (>14 days) and renal inadequacy (creatinine ≥ 177 μmol/L) were influencing factors for 30‐day mortality in AYAs patients with BSIs. In our study, AYA patients with BSIs showed clinical characteristics and pathogen distributions similar to those of older adult patients but quite different from those of children. [ABSTRACT FROM AUTHOR]

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]

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: Despite the advanced laboratory technologies available today, blood culture is the gold standard method in the diagnosis of bloodstream infections. Automated blood culture devices give blood culture results for laboratories approximately in 2 - 3 days up to 7 days. Moreover, some microorganisms like nonreproducible bacteria, fungi or viruses cannot be produced in culture. Among all samples taken for blood culture on suspicion of infection approximately 10% are determined as positive whereas the false positive rate due to contamination is 5%. Especially in life-threatening severe conditions such as sepsis early diagnosis and prompt treatment are crucial. Based on this the aim of this study is to investigate complete blood count parameters as potential early markers in Escherichia coli, Staphylococcus aureus and Candida albicans bloodstream infections using an ex vivo whole blood model. Methods: Blood samples collected from healthy donors (n = 10) were treated with suspensions containing a certain concentration of microorganisms (107 CFU/mL for both E. coli ATCC 25922 and S. aureus ATCC 29213, 106 CFU/mL for C. albicans ATCC 14053). After bacteremia and candidemia were induced, complete blood count parameters were analyzed hourly in the samples until the end of the 4th hour with a Mindray BC-6800 hematology analyzer. Statistical analysis was performed by Tukey-Kramer post-hoc multiple comparison test and statistical significance was accepted as p < 0.05. Results: When platelet derived parameter baseline values were compared to hourly values in E. coli and S. aureus induced whole blood samples, it was found that the decrease in PLT, P-LCC and the increase in IPF% was significant from the first hour whereas the increase in IMG% was found to be significant only from the 3rd hour onward. In the experiments with C. albicans, it was observed that the increase in IPF% and IMG% was significant from the 2nd and 3rd hour onward, respectively. There was no relationship between MPV, P-LCR, and NLR baseline and hourly results in any microorganism induced model. Conclusions: IPF% can guide clinicians in the early diagnosis and management of treatment of infections caused by S. aureus, E. coli, and C. albicans. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to develop and validate a nomogram for predicting the risk of bloodstream infections (BSI) in critically ill patients based on their admission status to the Intensive Care Unit (ICU). Patients and methods: Patients' data were extracted from the Medical Information Mart for Intensive Care--IV (MIMIC--IV) database (training set), the Beijing Friendship Hospital (BFH) database (validation set) and the eICU Collaborative Research Database (eICU--CRD) (validation set). Univariate logistic regression analyses were used to analyze the influencing factors, and lasso regression was used to select the predictive factors. Model performance was assessed using area under receiver operating characteristic curve (AUROC) and Presented as a Nomogram. Various aspects of the established predictive nomogramwere evaluated, including discrimination, calibration, and clinical utility. Results: The model dataset consisted of 14930 patients (1444 BSI patients) from the MIMIC-IV database, divided into the training and internal validation datasets in a 7:3 ratio. The eICU dataset included 2100 patients (100 with BSI) as the eICU validation dataset, and the BFH dataset included 419 patients (21 with BSI) as the BFH validation dataset. The nomogram was constructed based on Glasgow Coma Scale (GCS), sepsis related organ failure assessment (SOFA) score, temperature, heart rate, respiratory rate, white blood cell (WBC), red width of distribution (RDW), renal replacement therapy and presence of liver disease on their admission status to the ICU. The AUROCs were 0.83 (CI 95%:0.81-0.84) in the training dataset, 0.88 (CI 95%:0.88-0.96) in the BFH validation dataset, and 0.75 (95%CI 0.70-0.79) in the eICU validation dataset. The clinical effect curve and decision curve showed that most areas of the decision curve of this model were greater than 0, indicating that this model has a certain clinical effectiveness. Conclusion: The nomogram developed in this study provides a valuable tool for clinicians and nurses to assess individual risk, enabling them to identify patients at a high risk of bloodstream infections in the ICU. [ABSTRACT FROM AUTHOR]

To prioritize healthcare investments, ranking of infections caused by antibiotic-resistant bacteria should be based on accurate incidence data. We performed a systematic review to estimate frequency measures of antimicrobial resistance for six key bacteria causing bloodstream infections (BSI) in European countries. We searched PubMed, Web of Science, Embase databases, and the ECRAID-Base Epidemiological-Network platform. We included studies and surveillance systems assessing resistance-percentage, prevalence, or incidence-density of BSI because of carbapenem-resistant Pseudomonas aeruginosa , Acinetobacter baumannii , Klebsiella pneumoniae , and Escherichia coli , third-generation cephalosporins-resistant E. coli and K. pneumoniae , vancomycin-resistant Enterococcus faecium , and methicillin-resistant Staphylococcus aureus. Reviewers independently assessed published data and evaluated study quality with the modified Joanna Briggs Institute critical appraisal tool. Pooled estimates were determined using random effects meta-analysis. Consistency of data was assessed using random effects meta-regression (Wald test, p > 0.05). We identified 271 studies and 52 surveillance systems from 32 European countries. Forty-five studies (16%) reported on BSI, including 180 frequency measures most commonly as resistance-percentage (88, 48.9%). Among 309 frequency measures extracted from 24 (46%) surveillance systems, 278 (89%) were resistance-percentages. Frequency measures of methicillin-resistant S. aureus and vancomycin-resistant E. faecium BSI were more frequently reported from Southern Europe and Western Europe (80%), whereas carbapenem-resistant P. aeruginosa BSI from Northern Europe and Western Europe (88%). Highest resistance-percentages were detected for carbapenem-resistant A. baumannii (66% in Central Eastern Europe) and carbapenem-resistant K. pneumoniae (62.8% in Southern Europe). Pooled estimates showed lower resistance-percentages in community versus healthcare-associated infections and in children versus adults. Estimates from studies and surveillance systems were mostly consistent among European regions. The included data was of medium quality. Pathogen-specific frequency measures of antimicrobial resistance in BSI are insufficient to inform antibiotic stewardship and research and development strategies. Improving data collection and standardization of frequency measures is urgently needed. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is a global threat, which requires novel intervention strategies, for which priority pathogens and settings need to be determined. We evaluated pathogen-specific excess health burden of drug-resistant bloodstream infections (BSIs) in Europe. A systematic review and meta-analysis. MEDLINE, Embase, and grey literature for the period January 1990 to May 2022. Studies that reported burden data for six key drug-resistant pathogens: carbapenem-resistant (CR) Pseudomonas aeruginosa and Acinetobacter baumannii , third-generation cephalosporin or CR Escherichia coli and Klebsiella pneumoniae , methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Excess health outcomes compared with drug-susceptible BSIs or uninfected patients. For MRSA and third-generation cephalosporin E. coli and K. pneumoniae BSIs, five or more European studies were identified. For all others, the search was extended to high-income countries. Paediatric and adult patients diagnosed with drug-resistant BSI. Not applicable. An adapted version of the Joanna-Briggs Institute assessment tool. Random-effect models were used to pool pathogen-specific burden estimates. We screened 7154 titles, 1078 full-texts and found 56 studies on BSIs. Most studies compared outcomes of drug-resistant to drug-susceptible BSIs (46/56, 82.1%), and reported mortality (55/56 studies, 98.6%). The pooled crude estimate for excess all-cause mortality of drug-resistant versus drug-susceptible BSIs ranged from OR 1.31 (95% CI 1.03–1.68) for CR P. aeruginosa to OR 3.44 (95% CI 1.62–7.32) for CR K. pneumoniae. Pooled crude estimates comparing mortality to uninfected patients were available for vancomycin-resistant Enterococcus and MRSA BSIs (OR of 11.19 [95% CI 6.92–18.09] and OR 6.18 [95% CI 2.10–18.17], respectively). Drug-resistant BSIs are associated with increased mortality, with the magnitude of the effect influenced by pathogen type and comparator. Future research should address crucial knowledge gaps in pathogen- and infection-specific burdens to guide development of novel interventions. [ABSTRACT FROM AUTHOR]

Centers for Medicare and Medicaid Services imparts financial penalties for central line-associated bloodstream infections (CLABSIs) and other healthcare-acquired infections. Data for this purpose is obtained from the Centers for Disease Control and Prevention (CDC)'s National Health Safety Network. We present examples of misclassification of bloodstream infections into CLABSI by the CDC's definition and present the financial implications of such misclassification and potential long-term implications. [ABSTRACT FROM AUTHOR]

Introduction We aimed to conduct a systematic review of the epidemiology of Escherichia coli in bloodstream infections (BSI) of hematopoietic stem cell transplantation patients. Methods For a comprehensive search of studies that reported the prevalence of E. coli and antibiotic resistance in bloodstream infections from 2000 to January 1, 2024, databases such as PubMed, EMBASE, Google Scholar, Scopus, and Web of Science were searched. The main keywords used were: Escherichia coli, epidemiology, bloodstream infection, microbial resistance, antibiotic resistance, hematopoietic malignancy, hematopoietic stem cell transplantation. After applying eligibility criteria, and quality assessment of studies, data analysis was done by comprehensive meta-analysis (CMA) software. Results The prevalence of bacterial bloodstream infections amongst different studies varied between 8-51%. Also, bloodstream infections caused by E. coli varied between 2.5-57%. Prevalence of extendedspectrum β-lactamases (ESBLs) of Escherichia coli in bloodstream infections varied between 15-80%. As well, the mortality rate caused by Escherichia coli strains in bloodstream infection varied between 6.7- 27.3%. Resistance to ciprofloxacin, cefepime, third- and fourth-generation cephalosporins, was reported to be the highest (prevalence of 100%), and the lowest was against amikacin, with a prevalence between 13-38%. Conclusions The high prevalence of Escherichia coli-related BSI, and subsequent mortality, especially by multidrug resistance and ESBL strains, in patients undergoing hematopoietic stem cell transplantation, requires essential measures to prevent the spread of microbial resistance. [ABSTRACT FROM AUTHOR]

Objective This study aimed to evaluate the impact of short-term incubation (STI) protocol on clinical outcomes of bloodstream infection (BSI) patients. Methods A total of 1363 positive blood culture records from January 2019 to December 2021 were included. The main clinical outcomes included pathogen identification turnaround time (TAT), antimicrobial susceptibility testing (AST) TAT, and length of total hospital stay. Results The TAT of pathogen identification and AST significantly decreased after implementing the STI protocol (2.2 vs 1.4 days and 3.4 vs 2.5 days, respectively, with P <.001 for both). Moreover, for patients with Gram-negative bacteria (GNB)–infected BSIs, the length of total hospital stay decreased from 31.9 days to 27.1 days, indicating that these patients could be discharged 5 days earlier after implementing the STI protocol (P <.01). Conclusion The protocol led to a significant reduction in TAT and improved clinical outcomes, particularly for GNB organisms. The findings suggest that the STI protocol can improve patient outcomes and hospital resource utilization in the management of BSIs. [ABSTRACT FROM AUTHOR]

Background: Bloodstream infections (BSI) caused by a wide range of bacterial and fungal pathogens are associated with high rates of morbidity and mortality. Based on an estimate in 2017, the number of BSI incidences in Ontario is 150 per 100,000 population. The epidemiology of BSIs may be affected by many factors, including the social and travel restrictions and increased rates of hospitalizations in Ontario during the coronavirus disease 2019 (COVID-19) pandemic. Objectives: This study aimed to assess the changes in the microbiology of BSIs in Ontario during the COVID-19 pandemic compared to the pre-pandemic period. Methods: Retrospective blood culture data (n=189,106) from LifeLabs Ontario (July 2018 to December 2021) were analyzed. Blood culture positivity rates for common bacterial pathogens were compared between pre-COVID-19 (July 2018 to March 2020) and COVID-19 (April 2020 to December 2021) periods in community and hospital settings, using the chi-square test for significance. Results: During the COVID-19 period, blood culture positivity rates in the community remained the same, while hospital rates increased by approximately threefold (p=0.00E-00). In the community, the isolation rates of most bacterial species remained unchanged, except for an increase in Enterococcus spp. and a decrease in Salmonella spp. The rates of antibiotic-resistant organisms (AROs) also significantly decreased in the community. In hospitals, all bacterial species, including AROs, showed significant increases in isolation rates during the COVID-19 period. Conclusion: The study revealed shifts in the microbiology of BSIs and suggests changes in the epidemiology of BSIs during the COVID-19 pandemic in Ontario, both in hospitals and in the community. [ABSTRACT FROM AUTHOR]

Background: The drug resistance of carbapenem-resistant Acinetobacter baumannii bloodstream infections (CRAB-BSI), especially hospital-acquired infections, has promoted their rapid and vast spread. It is necessary to use reliable methods to establish better prediction models. According to Cox proportional hazards regression, a nomogram was established. Methods: A retrospective cohort study among patients who were diagnosed with CRAB-BSI was performed from January 2020 to December 2022. Univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors regarding CRAB-BSI. Then, nomograms were used to calculate the area under the curve (AUC), C-index, and calibration curve to determine the predictive accuracy and discriminability. Decision curve analysis (DCA) was employed to further confirm the clinical effectiveness of the nomogram. Results: A total of 98 cases were included in the comparison between the 28-day mortality group consisting of 32 patients and the 28-day survival group with 66 patients. The use of cefoperazone-sulbactam was significantly higher among patients who survived than among those who died. Univariable analysis revealed that factors such as primary diagnosis, time to inadequate antimicrobial therapy, and high serum creatinine and procalcitonin (PCT) levels were more prevalent in the mortality group. However, only primary diagnosis, time to inadequate antimicrobial therapy, and high PCT levels emerged as statistically significant risk factors for death in multivariate analysis and were used to construct the nomogram. The nomogram validation exhibited excellent performance. Conclusions: The nomogram was sufficiently accurate to predict the risk and prognostic factors of CRAB-BSI, allowing for individualized clinical decisions for future clinical work. The cefoperazone-sulbactam did have an effect, but more studies are needed to interpret it. [ABSTRACT FROM AUTHOR]

Background: Both critically ill patients with coronavirus disease 2019 (COVID-19) and patients receiving extracorporeal membrane oxygenation (ECMO) support exhibit a high incidence of healthcare-associated infections (HAI). However, data on incidence, microbiology, resistance patterns, and the impact of HAI on outcomes in patients receiving ECMO for severe COVID-19 remain limited. We aimed to report HAI incidence and microbiology in patients receiving ECMO for severe COVID-19 and to evaluate the impact of ECMO-associated infections (ECMO-AI) on in-hospital mortality. Methods: For this study, we analyzed data from 701 patients included in the ECMOSARS registry which included COVID-19 patients supported by ECMO in France. Results: Among 602 analyzed patients for whom HAI and hospital mortality data were available, 214 (36%) had ECMO-AI, resulting in an incidence rate of 27 ECMO-AI per 1000 ECMO days at risk. Of these, 154 patients had bloodstream infection (BSI) and 117 patients had ventilator-associated pneumonia (VAP). The responsible microorganisms were Enterobacteriaceae (34% for BSI and 48% for VAP), Enterococcus species (25% and 6%, respectively) and non-fermenting Gram-negative bacilli (13% and 20%, respectively). Fungal infections were also observed (10% for BSI and 3% for VAP), as were multidrug-resistant organisms (21% and 15%, respectively). Using a Cox multistate model, ECMO-AI were not found associated with hospital death (HR = 1.00 95% CI [0.79–1.26], p = 0.986). Conclusions: In a nationwide cohort of COVID-19 patients receiving ECMO support, we observed a high incidence of ECMO-AI. ECMO-AI were not found associated with hospital death. Trial registration number NCT04397588 (May 21, 2020). [ABSTRACT FROM AUTHOR]

The aim of the study was to build a machine learning-based predictive model to discriminate between hospitalized patients at low risk and high risk of bloodstream infection (BSI). A Data Mart including all patients hospitalized between January 2016 and December 2019 with suspected BSI was built. Multivariate logistic regression was applied to develop a clinically interpretable machine learning predictive model. The model was trained on 2016–2018 data and tested on 2019 data. A feature selection based on a univariate logistic regression first selected candidate predictors of BSI. A multivariate logistic regression with stepwise feature selection in five-fold cross-validation was applied to express the risk of BSI. A total of 5660 hospitalizations (4026 and 1634 in the training and the validation subsets, respectively) were included. Eleven predictors of BSI were identified. The performance of the model in terms of AUROC was 0.74. Based on the interquartile predicted risk score, 508 (31.1%) patients were defined as being at low risk, 776 (47.5%) at medium risk, and 350 (21.4%) at high risk of BSI. Of them, 14.2% (72/508), 30.8% (239/776), and 64% (224/350) had a BSI, respectively. The performance of the predictive model of BSI is promising. Computational infrastructure and machine learning models can help clinicians identify people at low risk for BSI, ultimately supporting an antibiotic stewardship approach. [ABSTRACT FROM AUTHOR]

Background Despite the availability of antimicrobial therapies, gram-negative bacteremia remains a significant cause of morbidity and mortality on a global level. Recent randomized controlled trials support shorter antibiotic treatment duration for individuals with uncomplicated gram-negative bacteremia. The target trial framework using the cloning approach utilizes real-world data but eliminates the issue of immortal time bias seen in observational studies by emulating the analysis of randomized trials with full adherence. Method A hypothetical target trial allocating individuals with gram-negative bacteremia to either short antibiotic treatment duration (5–7 days) or longer antibiotic treatment duration (8–14 days) was specified and emulated using the cloning, censoring, and weighting approach. The primary outcome was 90-day all-cause mortality. Secondary outcome was a composite endpoint of clinical and microbiological relapse. The emulated trial included individuals from four hospitals in Copenhagen from 2018 through 2021. Results In sum, 1040 individuals were included. The median age of the cohort was 76 years, the majority were male (54%), had community-acquired gram-negative bacteremia (86%), urinary tract infection as the source of the infection (78%), and Escherichia coli as the pathogen of the infection (73%). The adjusted 90-day risk difference in all-cause mortality was 1.3% (95% confidence interval [CI]: −.7, 3.3), and the risk ratio was 1.12 (95% CI:.89, 1.37). The adjusted 90-day risk difference in relapse was 0.7% (95% CI: −2.3, 3.8), and the risk ratio was 1.07 (95% CI:.71, 1.45). Conclusions We found comparative outcomes for shorter treatment duration compared to longer treatment duration in patients with gram-negative bacteremia. [ABSTRACT FROM AUTHOR]

Background: Metagenomic next-generation sequencing (mNGS) of plasma cell-free DNA (cfDNA) shows promising application for complicated infections that cannot be resolved by conventional microbiological tests (CMTs). The criteria for cfDNA sequencing are currently in need of agreement and standardization. Methods: We performed a retrospective cohort observation of 653 patients who underwent plasma cfDNA mNGS, including 431 with suspected bloodstream infections (BSI) and 222 with other suspected systemic infections. Plasma mNGS and CMTs were performed simultaneously in clinical practice. The diagnostic efficacy of plasma mNGS and CMTs in the diagnosis of blood-borne and other systemic infections was evaluated using receiver operating characteristic (ROC) curves. The sensitivity and specificity of the two methods were analyzed based on the final clinical outcome as the gold standard. Results: The mNGS test showed an overall positive rate of 72.3% (472/653) for detecting microorganisms in plasma cfDNA, with a range of 2 to 6 different microorganisms detected in 171 patient specimens. Patients with positive mNGS results were more immunocompromised and had a higher incidence of severe disease (P<0·05). The sensitivity of mNGS was higher for BSI (93·5%) and other systemic infections (83·6%) compared to CMTs (37·7% and 14·3%, respectively). The mNGS detected DNA from a total of 735 microorganisms, with the number of microbial DNA reads ranging from 3 to 57,969, and a higher number of reads being associated with clinical infections (P<0·05). Of the 472 patients with positive mNGS results, clinical management was positively affected in 203 (43%) cases. Negative mNGS results led to a modified clinical management regimen in 92 patients (14.1%). The study also developed a bacterial and fungal library for plasma mNGS and obtained comparisons of turnaround times and detailed processing procedures for rare pathogens. Conclusion: Our study evaluates the clinical use and analytic approaches of mNGS in predicting bloodstream and local infections in clinical practice. Our results suggest that mNGS has higher positive predictive values (PPVs) for BSI and systemic infections compared to CMTs, and can positively affect clinical management in a significant number of patients. The standardized wholeprocess management procedure for plasma mNGS developed in this study will ensure improved pre-screening probabilities and yield clinically valuable data. [ABSTRACT FROM AUTHOR]

Objectives To assess the impact of piperacillin/tazobactam MICs on in-hospital 30 day mortality in patients with third-generation cephalosporin-resistant Escherichia coli bloodstream infection treated with piperacillin/tazobactam, compared with those treated with carbapenems. Methods A multicentre retrospective cohort study was conducted in three large academic hospitals in Italy between 2018 and 2022. The study population comprised patients with monomicrobial third-generation cephalosporin-resistant E. coli bloodstream infection, who received either piperacillin/tazobactam or carbapenem therapy within 48 h of blood culture collection. The primary outcome was in-hospital 30 day all-cause mortality. A propensity score was used to estimate the likelihood of receiving empirical piperacillin/tazobactam treatment. Cox regression models were performed to ascertain risk factors independently associated with in-hospital 30 day mortality. Results Of the 412 consecutive patients included in the study, 51% received empirical therapy with piperacillin/tazobactam, while 49% received carbapenem therapy. In the propensity-adjusted multiple Cox model, the Pitt bacteraemia score [HR 1.38 (95% CI, 0.85–2.16)] and piperacillin/tazobactam MICs of 8 mg/L [HR 2.35 (95% CI, 1.35–3.95)] and ≥16 mg/L [HR 3.69 (95% CI, 1.86–6.91)] were significantly associated with increased in-hospital 30 day mortality, while the empirical use of piperacillin/tazobactam was not found to predict in-hospital 30 day mortality [HR 1.38 (95% CI, 0.85–2.16)]. Conclusions Piperacillin/tazobactam use might not be associated with increased mortality in treating third-generation cephalosporin-resistant E. coli bloodstream infections when the MIC is <8 mg/L. [ABSTRACT FROM AUTHOR]

Introduction: Improper antibiotic use triggers outbreaks of hospital-acquired VRE infections. Relevant studies were gathered from Scopus, and PubMed. Over two decades, prevalence of VRE in humans and animals grew from 0.05 % to 99.0 % globally and from 1.0 % to 45.6 % in India. Identifying VRE at the species level helps identify acquired/intrinsic resistance. Results and conclusion: VRE infections, especially bloodstream infections, inflict significant mortality (60-70%-global; 23%-India) and economic burden ($539 million). Linezolid and daptomycin are frequently used without adequate clinical trial evidence. India lacks studies on prevalence, mortality and cost, which needs political will, public-private partnership, and prioritizing public health.

Escherichia coli is one of the most important pathogens causing bloodstream infections (BSIs) throughout the world. We sought to characterize the phylogroup classification, major human sequence types (STs), antimicrobial resistance, presence of selected antimicrobial resistance and virulence genes, and genetic diversity of E. coli isolated from patients with BSIs at the University Hospital in Iran. A total of 100 E. coli bloodstream isolates were collected between December 2020 and June 2022. This study used PCR to investigate phylogenetic groups (A, B1, B2, C, D, E, and F), four major STs (ST69, ST73, ST95, and ST131), antibiotic resistance genes (ARGs), virulence-associated genes (VAGs), and pathogenicity islands (PAIs). Antimicrobial susceptibility testing was done by disk diffusion method. Genetic diversity was analyzed by repetitive element sequence-based PCR (REP-PCR). The phylogenetic group B2 (32%) predominated, followed by phylogenetic group E (25%). ST131 (28%) was the most prevalent ST and the majority of these isolates (89.3%) were of serotype O25b. Most of E. coli isolates (75%) were categorized as multidrug resistant (MDR) with high rates of resistance (>55%) to ampicillin, trimethoprim-sulfamethoxazole, ciprofloxacin, cefazolin, and ceftriaxone. The most frequent ARGs were blaTEM (66%), sul1 (57%), and sul2 (51%). The most prevalent VAGs and PAIs were fimH (type 1 fimbriae adhesin; 85%), aer (iucC) (aerobactin; 79%), traT (serum resistance; 77%), iutA (aerobactin siderophore receptor; 69%), and PAI IV536 (75%), respectively. The highest rate of ARGs and VAGs was observed in the ST131 isolates. REP-PCR analysis showed high diversity among the studied isolates. The high prevalence of MDR septicemic E. coli with different types of ARGs, VAGs and genotypes is an extremely worrisome sign of BSIs treatment and poses a major threat for hospitalized patients. Active surveillance, stringent prescribing policies, increasing the awareness of ARGs among clinicians and re-defining the infection control measures are essential to curb the dissemination of these strains.

Marie Kempf,1,2 Francis F Arhin,3 Alona Kuraieva,4 Eric Utt5 1Laboratory of Bacteriology, University Hospital Angers, Angers, France; 2INCIT, Inserm, CHU Angers, Univ Angers, Nantes Université, Angers, F-49000, France; 3Pfizer Inc, Kirkland, Quebec, Canada; 4Pfizer Inc, New York, NY, USA; 5Pfizer Inc, Groton, CT, USACorrespondence: Eric Utt, Pfizer Inc, Gorton, CT, 06340, USA, Tel +1 860 9174808, Email eric.a.utt@pfizer.comPurpose: To assess the in vitro activity of ceftaroline and a panel of comparator agents against isolates of Gram-positive bacteria, including Staphylococcus aureus, Streptococcus pneumoniae, β-hemolytic streptococci, and coagulase-negative staphylococci (CoNS) from blood collected in Africa and Middle East (AfME), Asia Pacific (APAC), Europe, Latin America (LATAM), and North America from 2017 to 2020 as a part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program.Methods: Susceptibility and minimum inhibitory concentration were determined using broth microdilution for all antimicrobial agents by a central reference laboratory according to the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines.Results: Ceftaroline showed good activity (susceptibility ≥ 89.8%, MIC90 0.008– 2 mg/L) against all Gram-positive isolates tested. All isolates of methicillin-susceptible S. aureus, penicillin-susceptible S. pneumoniae, S. agalactiae, S. dysgalactiae, and S. pyogenes were susceptible to ceftaroline (MIC90 0.008– 0.25 mg/L). Ceftaroline susceptibility for MRSA isolates was 89.8% globally (MIC90 2 mg/L). Among the comparator agents, all isolates were susceptible to vancomycin, except S. epidermis (susceptibility, 99.9%). Among other agents, daptomycin, linezolid, and tigecycline showed potent activity (susceptibility ≥ 97.9%, MIC90 0.03– 2 mg/L) against all isolates tested.Conclusion: Ceftaroline showed potent in vitro activity against global bloodstream isolates of Gram-positive bacteria collected between 2017 and 2020. Monitoring and surveillance of global as well as regional longitudinal trends of resistance rates among Gram-positive isolates causing bloodstream infections are important to limit the spread of AMR, establish stewardship measures, and manage and appropriately treat infections.Keywords: ATLAS, bloodstream infections, ceftaroline, Gram-positive bacteria, surveillance

Abstract Background At some point in their lives, many people will require major heart surgery (MHS). Patients are generally older adults with various risk factors for infection. However, the incidence of infection after MHS is poorly known, as reported infection data are frequently biased due to different factors like the surgical procedure, postoperative timing, and infectious syndromes or etiologic agents, among others. In addition, most patient data are retrospectively obtained. Purpose and methods Data were prospectively collected regarding the incidence of all nosocomial infections produced from the time of surgery to hospital discharge in a cohort of 800 adults consecutively undergoing a MHS procedure. Results During postoperative hospitalization, 124 of the 800 participants developed one or more infections (15.5%): during their ICU stay in 68 patients (54.8%), during their stay on the general ward post ICU in 50 (40.3%), and during their stay in both wards in 6 (4.8%). The most common infections were pneumonia (related or not to mechanical ventilation), surgical site and bloodstream. As etiological agents, 193 pathogens were isolated: mostly Gram-negative bacilli (54.4%), followed by Gram-positive bacteria (30%), viruses (4.6%) and fungi (1.5%). In our cohort, all-cause mortality was recorded in 33 participants (4.1%) and 9 infection-related deaths (1.1%) were produced. Among subjects who developed infections, overall mortality was 13.7% and in those who did not, this was only 2.3%. Conclusion Infection following MHS remains frequent and severe. Our data suggest that hospital-acquired infection studies should consider episodes of infection in all populations during their entire hospital stay and not only those related to specific clinical syndromes or acquired while the patient is in intensive care.

Background/Objectives: ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pose a serious public health threat as they are resistant to multiple antimicrobial agents. Bloodstream infections (BSIs) caused by ESKAPE bacteria have high mortality rates due to the limited availability of effective antimicrobials. This study aimed to evaluate the prevalence and susceptibility of ESKAPE pathogens causing BSIs over three years in a large tertiary hospital in Salerno. Methods: Conducted at the Clinical Microbiology Laboratory of San Giovanni di Dio e ‘‘Ruggi D’Aragona’’ Hospital from January 2020 to December 2022, blood culture samples from different departments were incubated in the BD BACTEC™ system for 5 days. Species identification was performed using MALDI-TOF MS, and antimicrobial resistance patterns were determined by the VITEK2 system. Results: Out of 3197 species isolated from positive blood cultures, 38.7% were ESKAPE bacteria. Of these, 59.9% were found in blood culture samples taken from men, and the most affected age group was those aged >60 years. (70.6%). Staphylococcus aureus was the main BSI pathogen (26.3%), followed by Klebsiella pneumoniae (15.8%). Significant resistance rates were found, including 35% of Staphylococcus aureus being resistant to oxacillin and over 90% of Acinetobacter baumannii being resistant to carbapenems. Conclusions: These results highlight the urgent need for antimicrobial stewardship programs to prevent incurable infections.

Staphylococcus aureus is an opportunistic pathogen and a leading cause of bloodstream infections, with its capacity to acquire antibiotic resistance genes posing significant treatment challenges. This pilot study characterizes the genomic profiles of S. aureus isolates from patients with bloodstream infections in KwaZulu-Natal, South Africa, to gain insights into their resistance mechanisms, virulence factors, and clonal and phylogenetic relationships. Six multidrug-resistant (MDR) S. aureus isolates, comprising three methicillin-resistant S. aureus (MRSA) and three methicillin-susceptible S. aureus (MSSA), underwent whole genome sequencing and bioinformatics analysis. These isolates carried a range of resistance genes, including blaZ, aac(6′)-aph(2″), ant(9)-Ia, ant(6)-Ia, and fosB. The mecA gene, which confers methicillin resistance, was detected only in MRSA strains. The isolates exhibited six distinct spa types (t9475, t355, t045, t1265, t1257, and t7888) and varied in virulence gene profiles. Panton–Valentine leukocidin (Luk-PV) was found in one MSSA isolate. Two SCCmec types, IVd(2B) and I(1B), were identified, and the isolates were classified into four multilocus sequence types (MLSTs), with ST5 (n = 3) being the most common. These sequence types clustered into two clonal complexes, CC5 and CC8. Notably, two MRSA clones were identified: ST5-CC5-t045-SCCmec_I(1B) and the human-associated endemic clone ST612-CC8-t1257-SCCmec_IVd(2B). Phylogenomic analysis revealed clustering by MLST, indicating strong genetic relationships within clonal complexes. These findings highlight the value of genomic surveillance in guiding targeted interventions to reduce treatment failures and mortality.

Bacterial and fungal superinfections are common in COVID-19, and early diagnosis can enable timely intervention. Serum calprotectin levels increase with bacterial, fungal, and viral infections. This study evaluated serum calprotectin as a diagnostic and prognostic tool for microbial superinfections in COVID-19. Serum samples from adult patients with moderate and severe COVID-19 were collected during hospitalization from 2020 to 2024. Calprotectin levels were measured using an enzyme-linked immunosorbent assay in 63 patients with moderate COVID-19, 60 patients with severe COVID-19, and 34 healthy individuals. Calprotectin serum levels were elevated in patients with moderate COVID-19 compared with controls, and these levels were further increased in the severe cases. Patients with severe COVID-19 and vancomycin-resistant enterococci (VRE) bacteremia had elevated calprotectin levels, but their C-reactive protein and procalcitonin levels were not increased. Fungal superinfections and herpes simplex virus reactivation did not change the calprotectin levels. A calprotectin concentration of 31.29 µg/mL can be used to diagnose VRE bloodstream infection with 60% sensitivity and 96% specificity. These data suggest that serum calprotectin may be a promising biomarker for the early detection of VRE bloodstream infections in patients with COVID-19.

Bloodstream infections (BSIs) can be primary or secondary, with significant associated morbidity and mortality. Primary bloodstream infections (BSIs) are defined as infections where no clear infection source is identified, while secondary BSIs originate from a localized infection site. This study aims to compare patterns, outcomes, and medical costs between primary and secondary BSIs and identify associated factors. Conducted at the University Hospital of Patras, Greece, from May 2016 to May 2018, this single-center retrospective cohort study included 201 patients with confirmed BSIs based on positive blood cultures. Data on patient characteristics, clinical outcomes, hospitalization costs, and laboratory parameters were analyzed using appropriate statistical methods. Primary BSIs occurred in 22.89% (46 patients), while secondary BSIs occurred in 77.11% (155 patients). Primary BSI patients were younger and predominantly nosocomial, whereas secondary BSI was mostly community-acquired. Clinical severity scores (SOFA, APACHE II, SAPS, and qPitt) were significantly higher in primary compared to secondary BSI. The median hospital stay was longer for primary BSI (21 vs. 12 days, p < 0.001). Although not statistically significant, mortality rates were higher in primary BSI (43.24% vs. 26.09%). Total care costs were significantly higher for primary BSI (EUR 4388.3 vs. EUR 2530.25, p = 0.016), driven by longer hospital stays and increased antibiotic costs. This study underscores the distinct clinical and economic challenges of primary versus secondary BSI and emphasizes the need for prompt diagnosis and tailored antimicrobial therapy. Further research should focus on developing specific management guidelines for primary BSI and exploring interventions to reduce BSI burden across healthcare settings.

Knowledge of epidemiology is essential for guiding correct antibiotic prescription, reducing bacteremia-associated mortality, and implementing targeted infection control programs. However, only a few studies have reported on the epidemiology of bloodstream infections (BSIs) in pediatrics. We performed a retrospective analysis of all BSIs (excluding those caused by common skin contaminants) diagnosed from 2006 to 2022 in patients younger than 18 years who were treated at an Italian pediatric tertiary care hospital. Overall, 2395 BSIs were recorded, including 2207 (92.15%) due to bacteria and 188 (7.85%) due to fungi. The incidence rate (BSIs/10,000 hospital discharges, IR) of bacterial BSIs significantly increased during the study period. In particular, BSIs caused by S. aureus (including MRSA), Enterobacterales (including ESBL and AmpC producers), Enterococcus spp., and P. aeruginosa became more common. The frequency of carbapenem-resistant strains was S. pneumoniae. The BSIs were stratified by patient age, and S. aureus was the most frequent cause of BSIs in all age groups, while E. coli was the most frequent in the Enterobacterales family. S. agalactiae was the third most frequent cause of neonatal early-onset BSIs. The prevalence of Enterococcus spp. increased in the subgroups from 8 days to 5 years of age, while P. aeruginosa became more prevalent in children over 5 years of age. S. aureus was also the most frequent isolate in both community- and hospital-onset BSIs, followed by E. coli. The prevalence of multidrug-resistant (MDR) pathogens was very low. It was C. albicans was the most frequently isolated strain, followed by C. parapsilosis. Notably, the IR of fungemia did not change significantly during the study period, in spite of an increase in the absolute number of events. The continuous monitoring of local epidemiology is essential to identify changes in the IRs of pathogens and antibiotic susceptibility and to guide antibiotic treatments, especially in the phase when antibiograms are not yet available.

Objectives: This study aimed to evaluate the clinical performance of plasma cellfree DNA (cfDNA) next-generation sequencing (NGS) for pathogen detection in patients with sepsis. Methods: A total of 43 pairs of blood and plasma samples form 33 blood culturepositive patients were used as testing samples in metagenomic NGS (mNGS) and NGS of 16S ribosomal RNA gene amplicons (16S rRNA NGS). The results of routine tests, including microbial culture, complete blood count, and biochemical tests, were collected from electronic medical records. Results: Using blood as an mNGS testing sample, the proportion of host DNA was 99.9%, with only three bacteria and no fungi detected. When using plasma in mNGS, the proportion of host DNA was approximately 97%, with 84 bacteria and two fungi detected. Notably, 16S rRNA NGS detected 15 and 16 bacteria in 43 pairs of blood and plasma samples, respectively. Blood culture detected 49 bacteria (23 gram-negative bacilli and 26 gram-positive cocci) and four fungi, with 14 bacteria considered contaminants by clinical microbiologists. For all blood cultures, plasma cfDNA mNGS detected 78.26% (19/23) gram-negative rods, 17% (2/12) gram-positive cocci, and no fungi. Compared to blood cultures, the sensitivity and specificity of plasma cfDNA mNGS for detecting bacteria and fungi were 62.07% and 57.14%, respectively. Conclusion: Compared to blood, plasma is more suitable for the detection of bloodstream infections using mNGS and is less affected by host DNA. The positive detection rate of plasma cfDNA mNGS for bloodstream infections caused by gram-negative bacteria was higher than that caused by grampositive cocci. [ABSTRACT FROM AUTHOR]

Background: At some point in their lives, many people will require major heart surgery (MHS). Patients are generally older adults with various risk factors for infection. However, the incidence of infection after MHS is poorly known, as reported infection data are frequently biased due to different factors like the surgical procedure, postoperative timing, and infectious syndromes or etiologic agents, among others. In addition, most patient data are retrospectively obtained. Purpose and methods: Data were prospectively collected regarding the incidence of all nosocomial infections produced from the time of surgery to hospital discharge in a cohort of 800 adults consecutively undergoing a MHS procedure. Results: During postoperative hospitalization, 124 of the 800 participants developed one or more infections (15.5%): during their ICU stay in 68 patients (54.8%), during their stay on the general ward post ICU in 50 (40.3%), and during their stay in both wards in 6 (4.8%). The most common infections were pneumonia (related or not to mechanical ventilation), surgical site and bloodstream. As etiological agents, 193 pathogens were isolated: mostly Gram-negative bacilli (54.4%), followed by Gram-positive bacteria (30%), viruses (4.6%) and fungi (1.5%). In our cohort, all-cause mortality was recorded in 33 participants (4.1%) and 9 infection-related deaths (1.1%) were produced. Among subjects who developed infections, overall mortality was 13.7% and in those who did not, this was only 2.3%. Conclusion: Infection following MHS remains frequent and severe. Our data suggest that hospital-acquired infection studies should consider episodes of infection in all populations during their entire hospital stay and not only those related to specific clinical syndromes or acquired while the patient is in intensive care. [ABSTRACT FROM AUTHOR]

(1) Objectives: To assess the impact of optimal joint pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous infusion (CI) piperacillin–tazobactam monotherapy on the microbiological outcome of documented ESBL-producing Enterobacterlaes secondary bloodstream infections (BSIs). (2) Methods: Patients hospitalized in the period January 2022–October 2023, having a documented secondary BSI caused by ESBL-producing Enterobacterales, and being eligible for definitive targeted CI piperacillin–tazobactam monotherapy according to specific pre-defined inclusion criteria (i.e., absence of septic shock at onset; favorable clinical evolution in the first 48 h after starting treatment; low–intermediate risk primary infection source) were prospectively enrolled. A real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program was adopted for optimizing (PK/PD) target attainment of CI piperacillin–tazobactam monotherapy. Steady-state plasma concentrations (Css) of both piperacillin and tazobactam were measured, and the free fractions (f) were calculated based on theoretical protein binding. The joint PK/PD target attainment was considered optimal whenever the piperacillin fCss/MIC ratio was >4 and the tazobactam fCss/target concentration (CT) ratio was >1 (quasi-optimal or suboptimal if only one or neither of the two thresholds were achieved, respectively). Univariate analysis was carried out for assessing variables potentially associated with failure in achieving the optimal joint PK/PD target of piperacillin–tazobactam and microbiological eradication. (3) Results: Overall, 35 patients (median age 79 years; male 51.4%) were prospectively included. Secondary BSIs resulted from urinary tract infections as a primary source in 77.2% of cases. The joint PK/PD target attainment was optimal in as many as 97.1% of patients (34/35). Microbiological eradication occurred in 91.4% of cases (32/35). Attaining the quasi-optimal/suboptimal joint PK/PD target of CI piperacillin–tazobactam showed a trend toward a higher risk of microbiological failure (33.3% vs. 0.0%; p = 0.08) (4) Conclusions: Real-time TDM-guided optimal joint PK/PD target attainment of CI piperacillin–tazobactam monotherapy may represent a valuable and effective carbapenem-sparing strategy when dealing with non-severe ESBL-producing Enterobacterales secondary BSIs. [ABSTRACT FROM AUTHOR]