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Objectives Data supporting routine infectious diseases (ID) consultation in gram-negative bloodstream infection (GN-BSI) are limited. We evaluated the association between ID consultation and mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario using linked health administrative databases. Methods Hospitalized adult patients with GN-BSI between April 2017 and December 2021 were included. The primary outcome was time to all-cause mortality censored at 30 days, analyzed using a mixed effects Cox proportional hazards model with hospital as a random effect. ID consultation 1–10 days after the first positive blood culture was treated as a time-varying exposure. Results Of 30 159 patients with GN-BSI across 53 hospitals, 11 013 (36.5%) received ID consultation. Median prevalence of ID consultation for patients with GN-BSI across hospitals was 35.0% with wide variability (range 2.7%–76.1%, interquartile range 19.6%–41.1%). In total, 1041 (9.5%) patients who received ID consultation died within 30 days, compared to 1797 (9.4%) patients without ID consultation. In the fully adjusted multivariable model, ID consultation was associated with mortality benefit (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI].77–.88, P <.0001; translating to absolute risk reduction of −3.8% or number needed to treat [NNT] of 27). Exploratory subgroup analyses of the primary outcome showed that ID consultation could have greater benefit in patients with high-risk features (nosocomial infection, polymicrobial or non-Enterobacterales infection, antimicrobial resistance, or non-urinary tract source). Conclusions Early ID consultation was associated with reduced mortality in patients with GN-BSI. If resources permit, routine ID consultation for this patient population should be considered to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus (SA) is a leading cause of bloodstream infection. The liver represents the sentinel immune organ for clearance of bloodstream pathogens and eradication of intracellular SA from liver-resident macrophages (Kupffer cells, KCs) eliminates the likely pathogenic reservoir that contributes to persistent bacteraemia. Objectives We assessed antimicrobial activity at phagolysosome-mimicking pH, intracellular penetration, and SA eradication within KCs in vitro for clinically prescribed antistaphylococcal agents alone or in combination: vancomycin, daptomycin, ceftaroline, ceftobiprole, oritavancin, oxacillin, cefazolin; rifampin and fosfomycin. Methods pH-adjusted broth microdilution assays, intracellular bioaccumulation assays, and intracellular killing assays against clinical bloodstream isolates were performed using a murine KC line with study agents. Results Rifampin and β-lactams exhibited enhanced activity [2- to 16-fold minimum inhibitory concentrations (MIC) decrease] at phagolysosomal pH while vancomycin, oritavancin, daptomycin and fosfomycin demonstrated reduced activity (2- to 32-fold MIC increase in order of least to greatest potency reduction). All agents evaluated had poor to modest intracellular to extracellular concentration ratios (0.024–7.8), with exceptions of rifampin and oritavancin (intracellular to extracellular ratios of 17.4 and 78.2, respectively). Finally, we showed that the first-line treatment for SA bacteraemia (SAB), vancomycin, performed worse than all other tested antibiotics in eradicating intracellular SA at human C max concentration (0.20 log cfu decrease), while oritavancin performed better than all other agents alone (2.05 versus 1.06–1.36 log cfu decrease). Conclusions Our findings raise concerns about the efficacy of commonly prescribed antibiotics against intracellular SA reservoirs and emphasize the need to consider targeting pathogen eradication from the liver to achieve early control of SAB. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the risk factors associated with Elizabethkingia anophelis infection in neonates admitted to a tertiary care neonatal intensive care unit (NICU). A case–control study was undertaken as part of the outbreak investigation for E. anophelis sepsis in a tertiary care NICU in South India. Thirty-eight neonates with E. anophelis bloodstream infection (BSI) between January 2021 and February 2022 were enrolled as cases, and 38 neonates symptomatic with other BSIs, were selected as controls, and risk factors analysed. The 38 cases were relatively stable neonates, likely to be admitted to level 1 and level 2 NICU, unlike the controls, who were sicker and required level 3 NICU care. Only a third of neonates with Elizabethkingia sepsis had traditional risk factors like central lines, need for respiratory support or perinatal risk factors. Multiple logistic regression analysis revealed that neonates with E. anophelis infection were more likely to be stable and on only enteral feeds, cared in level 1 or 2 of the NICU. This observation, combined with isolation of Elizabethkingia meningosepticum from breast pumps earlier, led us to autoclave the feeding vessels and milk containers along with provision of hot water for cleaning breast pumps, and adoption of general infection control measures, after which incident cases declined. Sanger sequencing of 10 representative isolates obtained from the neonates showed 100% sequence identity to E. anophelis. Infection due to E. anophelis affects relatively stable neonates without traditional risk factors for sepsis. Adherence to asepsis routines and housekeeping protocols helps to prevent the spread of infection. [ABSTRACT FROM AUTHOR]

Background Gram-negative bloodstream infections (GNBSIs) more commonly occur in children with comorbidities and are increasingly associated with antimicrobial resistance. There are few large studies of GNBSIs in children that relate the clinical presentation, pathogen characteristics, and outcomes. Methods A 3-year prospective study of GNBSIs in children aged <18 years was conducted in 5 Australian children's hospitals between 2019 and 2021. The clinical characteristics, disease severity, and outcomes were recorded. Causative pathogens underwent antibiotic susceptibility testing and whole genome sequencing. Results There were 931 GNBSI episodes involving 818 children. Median age was 3 years (interquartile range, 0.6–8.5). A total of 576/931 episodes (62%) were community onset, though 661/931 (71%) occurred in children with comorbidities and a central venous catheter was present in 558/931 (60%). Central venous catheter (145/931) and urinary tract (149/931) were the most common sources (16% each). One hundred of 931 (11%) children required intensive care unit admission and a further 11% (105/931) developed GNBSIs in intensive care unit. A total of 659/927 (71%) isolates were Enterobacterales, of which 22% (138/630) were third-generation cephalosporin resistant (3GCR). Extended spectrum beta-lactamase genes were confirmed in 65/138 (47%) 3GCR Enterobacterales. Most common extended spectrum beta-lactamase genes were bla CTX-M-15 (34/94, 36%) and bla SHV-12 (10/94, 11%). There were 48 deaths overall and 30-day in-hospital mortality was 3% (32/931). Infections with 3GCR Enterobacterales were independently associated with higher mortality (adjusted odds ratio, 3.2; 95% confidence interval, 1.6–6.4). Conclusions GNBSIs in children are frequently healthcare associated and affect children younger than age 5 years. Infections with 3GCR Enterobacterales were associated with worse outcomes. These findings will inform optimal management guidelines and help prioritize future antimicrobial clinical trials. [ABSTRACT FROM AUTHOR]

Background Early risk assessment is needed to stratify Staphylococcus aureus infective endocarditis (SA-IE) risk among patients with S. aureus bacteremia (SAB) to guide clinical management. The objective of the current study was to develop a novel risk score that is independent of subjective clinical judgment and can be used early, at the time of blood culture positivity. Methods We conducted a retrospective big data analysis from territory-wide electronic data and included hospitalized patients with SAB between 2009 and 2019. We applied a random forest risk scoring model to select variables from an array of parameters, according to the statistical importance in predicting SA-IE outcome. The data were divided into derivation and validation cohorts. The areas under the curve of the receiver operating characteristic (AUCROCs) were determined. Results We identified 15 741 SAB patients, among them 658 (4.18%) had SA-IE. The AUCROC was 0.74 (95%CI 0.70–0.76), with a negative predictive value of 0.980 (95%CI 0.977–0.983). The four most discriminatory features were age, history of infective endocarditis, valvular heart disease, and community onset. Conclusions We developed a novel risk score with performance comparable with existing scores, which can be used at the time of SAB and prior to subjective clinical judgment. [ABSTRACT FROM AUTHOR]

Antimicrobial susceptibility testing (AST) is a core function of the clinical microbiology laboratory and is critical to the management of patients with bloodstream infections (BSIs) to facilitate optimal antibiotic therapy selection. Recent technological advances have resulted in several rapid methods for determining susceptibility direct from positive blood culture that can provide turnaround times in under 8 h, which is considerably shorter than conventional culture-based methods. As diagnostic results do not directly produce a medical intervention, actionability is a primary determinant of the effect these technologies have on antibiotic use and ultimately patient outcomes. Randomized controlled trials and observational studies consistently show that rapid AST significantly reduces time to results and improves antimicrobial therapy for patients with BSI across various methods, patient populations and organisms. To date, the clinical impact of rapid AST has been demonstrated in some observational studies, but randomized controlled trials have not been sufficiently powered to validate many of these findings. This article reviews various metrics that have been described in the literature to measure the impact of rapid AST on actionability, antibiotic exposure and patient outcomes, as well as highlighting how implementation and workflow processes can affect these metrics. [ABSTRACT FROM AUTHOR]

Background Bloodstream infections are linked to heightened morbidity and mortality rates. The consequences of delayed antibiotic treatment can be detrimental. Effective management of bacteraemia hinges on rapid antimicrobial susceptibility testing. Objectives This retrospective study examined the influence of the VITEK® REVEAL™ Rapid AST system on positive blood culture (PBC) management in a French tertiary hospital. Materials and methods Between November 2021 and March 2022, 79 Gram-negative monomicrobial PBC cases underwent testing with both VITEK®REVEAL™ and VITEK®2 systems. Results The study found that VITEK®REVEAL™ yielded better results than the standard of care, significantly shortening the time to result (7.0 h compared to 9.6 h) as well as the turnaround time (15 h compared to 31.1 h) when applied for all isolates. Conclusions This study implies that the use of VITEK®REVEAL™ enables swift adaptations of antibiotic treatment strategies. By considerably minimizing the turnaround time, healthcare professionals can promptly make necessary adjustments to therapeutic regimens. Notably, these findings underscore the potential of VITEK®REVEAL™ in expediting appropriate antibiotic interventions, even in less ideal conditions. Further studies in varied laboratory contexts are required to validate these encouraging outcomes. [ABSTRACT FROM AUTHOR]

Objectives To outline the procedural implementation and optimization of rapid diagnostic test (RDT) results for bloodstream infections (BSIs) and to evaluate the combination of RDTs with real-time antimicrobial stewardship team (AST) support plus clinical surveillance platform (CSP) software on time to appropriate therapy in BSIs at a single health system. Methods Blood culture reporting and communication were reported for four time periods: (i) a pre-BCID [BioFire® FilmArray® Blood Culture Identification (BCID) Panel] implementation period that consisted of literature review and blood culture notification procedure revision; (ii) a BCID implementation period that consisted of BCID implementation, real-time results notification via CSP, and creation of a treatment algorithm; (iii) a post-BCID implementation period; and (iv) a BCID2 implementation period. Time to appropriate therapy metrics was reported for the BCID2 time period. Results The mean time from BCID2 result to administration of effective antibiotics was 1.2 h (range 0–7.9 h) and time to optimal therapy was 7.6 h (range 0–113.8 h) during the BCID2 Panel implementation period. When comparing time to optimal antibiotic administration among patients growing ceftriaxone-resistant Enterobacterales, the BCID2 Panel group (mean 2.8 h) was significantly faster than the post-BCID Panel group (17.7 h; P  = 0.0041). Conclusions Challenges exist in communicating results to the appropriate personnel on the healthcare team who have the knowledge to act on these data and prescribe targeted therapy against the pathogen(s) identified. In this report, we outline the procedures for telephonic communication and CSP support that were implemented at our health system to distribute RDT data to individuals capable of assessing results, enabling timely optimization of antimicrobial therapy. [ABSTRACT FROM AUTHOR]

Introduction Bloodstream infections are a significant threat to soldiers wounded in combat and contribute to preventable deaths. Novel and combination therapies that can be delivered on the battlefield or in lower roles of care are urgently needed to address the threat of bloodstream infection among military personnel. In this manuscript, we tested the antibacterial capability of silver ions (Ag+), with long-appreciated antibacterial properties, against ESKAPEE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, and Escherichia coli) pathogens. Materials and Methods We used the GENESYS (RAIN LLC) device to deliver Ag+ to Gram-positive and Gram-negative ESKAPEE organisms grown in broth, human blood, and serum. Following the Ag+ treatment, we quantified the antibacterial effects by quantifying colony-forming units. Results We found that Ag+ was bactericidal against 5 Gram-negative organisms, K pneumoniae, A baumannii, P aeruginosa , E cloacae , and E coli , and bacteriostatic against 2 Gram-positive organisms, E faecium and S aureus. The whole blood and serum inhibited the bactericidal activity of Ag+ against a common agent of bloodstream infection, P aeruginosa. Finally, when Ag+ was added in conjunction with antibiotic in the presence of whole blood, there was no significant effect of Ag+ over antibiotic alone. Conclusions Our results confirmed that Ag+ has broad-spectrum antibacterial properties. However, the therapeutic value of Ag+ may not extend to the treatment of bloodstream infections because of the inhibition of Ag+ activity in blood and serum. [ABSTRACT FROM AUTHOR]

The current manufacturing disruption of BACTEC blood culture bottles has drawn attention to diagnostic stewardship around blood culture utilization. In this perspective, we offer strategies for implementing blood culture stewardship using a graded approach based on a hospital's blood culture bottle supply. These strategies should inform plans to mitigate the impact of the shortage on patient care and reinforce fundamental principles of blood culture stewardship. [ABSTRACT FROM AUTHOR]

Background and Objectives: Candidaemia is a potentially life‐threatening emergency in the intensive care units (ICUs). Surveillance using common protocols in a large network of hospitals would give meaningful estimates of the burden of candidaemia and central line associated candidaemia in low resource settings. We undertook this study to understand the burden and epidemiology of candidaemia in multiple ICUs of India, leveraging the previously established healthcare‐associated infections (HAI) surveillance network. Our aim was also to assess the impact that the pandemic of COVID‐19 had on the rates and associated mortality of candidaemia. Methods: This study included adult patients from 67 Indian ICUs in the AIIMS‐HAI surveillance network that conducted BSI surveillance in COVID‐19 and non‐COVID‐19 ICUs during and before the COVID‐19 pandemic periods. Hospitals identified healthcare‐associated candidaemia and central line associated candidaemia and reported clinical and microbiological data to the network as per established and previously published protocols. Results: A total of 401,601 patient days and 126,051 central line days were reported during the study period. A total of 377 events of candidaemia were recorded. The overall rate of candidaemia in our network was 0.93/1000 patient days. The rate of candidaemia in COVID‐19 ICUs (2.52/1000 patient days) was significantly higher than in non‐COVID‐19 ICUs (1.05/patient days) during the pandemic period. The rate of central line associated candidaemia in COVID‐19 ICUs (4.53/1000 central line days) was also significantly higher than in non‐COVID‐19 ICUs (1.73/1000 central line days) during the pandemic period. Mortality in COVID‐19 ICUs associated with candidaemia (61%) was higher than that in non‐COVID‐19 ICUs (41%). A total of 435 Candida spp. were isolated. C. tropicalis (26.7%) was the most common species. C. auris accounted for 17.5% of all isolates and had a high mortality. Conclusion: Patients in ICUs with COVID‐19 infections have a much higher risk of candidaemia, CLAC and its associated mortality. Network level data helps in understanding the true burden of candidaemia and will help in framing infection control policies for the country. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background When to perform echocardiography to rule out infective endocarditis (IE) in patients with viridans group streptococci (VGS) bloodstream infections (BSIs) is unclear. Objectives We aimed to identify independent risk factors for IE in patients with VGS BSI. Methods This retrospective study conducted at Seoul National University Hospital from January 2013 to December 2022 involved patients with VGS and nutritionally variant streptococcal BSI, excluding single positive blood cultures and polymicrobial BSI cases. Independent risk factors were identified by multivariate logistic regression and sensitivity analyses according to echocardiography results, VGS species or the inclusion of possible IE cases. Results Of 845 VGS BSI cases, 349 were analysed and 86 IE cases were identified (24.6%). In the multivariate analysis, heart valve disease [adjusted odds ratio (aOR), 14.14, 95% CI, 6.14–32.58; P  < 0.001], persistent bacteraemia (aOR, 5.12, 95% CI, 2.03–12.94; P  = 0.001), age (per year, aOR, 0.98; 95% CI, 0.96–1.00; P =  0.015), solid cancer (aOR, 0.26; 95% CI, 0.13–0.53; P <  0.001) and haematologic malignancy (aOR, 0.04; 95% CI, 0.01–0.41; P =  0.006) were independently associated with IE. Sensitivity analyses yielded consistent results; also, infection by a member of the mitis group was independent risk factor for IE (aOR, 6.50; 95% CI, 2.87–14.68; P  < 0.001). Conclusions Younger age, heart valve disease, persistent bacteraemia, absence of underlying malignancy and BSI by a member of the mitis group were independent risk factors for IE in patients with VGS BSI. Echocardiographic evaluation could be prudently considered based on these clinicomicrobiological risk factors. [ABSTRACT FROM AUTHOR]

Background Carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) are a major threat to patients. To date, data on risk factors have been limited, with low internal and external validity. In this multicentre study, risk factors for CRE BSI were determined by comparison with two control groups: patients with carbapenem-susceptible Enterobacterales (CSE) BSI, and patients without Enterobacterales infection (uninfected patients). Methods A multicentre, case-control-control study was nested in a European prospective cohort study on CRE (EURECA). CRE BSI:CSE BSI matching was 1:1, CRE BSI:Uninfected patients matching was 1:3, based on hospital, ward and length of stay. Conditional logistic regression was applied. Results From March 2016 to November 2018, 73 CRE BSIs, 73 CSE BSIs and 219 uninfected patients were included from 18 European hospitals. For CRE versus CSE BSI, previous CRE colonization/infection [incidence rate ratio (IRR) 7.32; 95% CI 1.65–32.38) increased the risk. For CRE versus uninfected controls, independent risk factors included: older age (IRR 1.03; 95% CI 1.01–1.06), patient referral (long-term care facility: IRR 7.19; 95% CI 1.51–34.24; acute care hospital: IRR 5.26; 95% CI 1.61–17.11), previous colonization/infection with other MDR organisms (MDROs) (IRR 9.71; 95% CI 2.33–40.56), haemodialysis (IRR 8.59; 95% CI 1.82–40.53), invasive procedures (IRR 5.66; 95% CI 2.11–15.16), and β-lactam/β-lactamase inhibitor combinations (IRR 3.92; 95% CI 1.68–9.13) or third/fourth generation cephalosporin (IRR 2.75; 95% CI 1.06–7.11) exposure within 3 months before enrolment. Conclusions Evidence of previous CRE colonization/infection was a major risk factor for carbapenem resistance among Enterobacterales BSI. Compared with uninfected patients, evidence of previous MDRO colonization/infection and healthcare exposure were important risk factors for CRE BSI. Targeted screening, infection prevention and antimicrobial stewardship should focus on these high-risk patients. [ABSTRACT FROM AUTHOR]

Early appropriate antimicrobial therapy plays a critical role for patients with Staphylococcus aureus bloodstream infection (SAB). We aim to determine the optimal time-window for appropriate antimicrobial therapy and evaluate the effects of delayed therapy on adverse clinical outcomes (in-hospital mortality, sepsis, and septic shock) in children with SAB by propensity score matching (PSM) analysis. Receiver-operating characteristic was used to determine the cut-off point of the time to appropriate therapy (TTAT), the patients were divided into timely and delayed appropriate antimicrobial therapy (delayed therapy) groups accordingly. The PSM was used to balance the characteristics between the two groups, controlling the effects of potential confounders. Kaplan-Meier methods and Cox proportional hazards regression were applied to the matched groups to analyze the association between delayed therapy and clinical outcomes. Inverse probability of treatment weighting and propensity score covariate adjustment were also performed to investigate the sensitivity of the results under different propensity score-based approaches. In total, 247 patients were included in this study. The optimal cut-off point of TTAT was identified as 6.4 h, with 85.0% sensitivity and 69.2% specificity (AUC 0.803, 95% confidence interval 0.702–0.904). Eighty-seven (35.22%) of the 247 patients who received delayed therapy (TTAT ≥ 6.4 h) had higher in-hospital mortality (19.54% vs 1.88%, p < 0.001), higher incidences of sepsis (44.83% vs 15.00%, p < 0.001) and septic shock (32.18% vs 6.25%, p < 0.001) when compared to timely therapy (TTAT < 6.4 h) patients. After PSM analysis, a total of 134 episodes (67 in each of the two matched groups) were further analyzed. No statistically significant difference was observed in in-hospital mortality between delayed and timely -therapy groups (log-rank test, P = 0.157). Patients with delayed therapy had a higher incidence of sepsis or septic shock than those with timely therapy (log-rank test, P = 0.009; P = 0.018, respectively). Compared to the timely-therapy group, the hazard ratio and 95% confidence interval in delayed-therapy group were 2.512 (1.227–5.144, P = 0.012) for sepsis, 3.109 (1.166–8.290, P = 0.023) for septic shock. Conclusion: Appropriate therapy delayed 6.4 h may increase the incidence of sepsis and septic shock, with similar in-hospital mortality in patients with SAB. What is Known: • Staphylococcus aureus (S. aureus) is a major cause of bloodstream infections in children. Undoubtedly, early antimicrobial application plays a critical role in the treatment of children with Staphylococcus aureus bloodstream infections (SAB). • However, rapid, and aggressive administration of antimicrobials may lead to the overuse of these drugs and the emergence of multidrug-resistant microorganisms. Therefore, it is crucial to determine the optimal time-window for appropriate antimicrobial administration in children with SAB. Unfortunately, the optimal time-window for appropriate antimicrobial administration in children with SAB remains unclear. What is New: • Determining the optimal time-window for appropriate antimicrobial administration in patients with matched data variables is particularly important. The Propensity score matching (PSM) analysis effectively controls for confounding factors to a considerable extent when assessing the impact of treatment, thereby approximating the effects observed in randomized controlled trials. • To our knowledge, this is the first study using PSM method to assess the effects of delayed appropriate antimicrobial therapy on adverse outcomes in children with SAB. In low-risk populations with SAB, a delay of 6.4 h in appropriate therapy might increase the occurrence rate for sepsis and septic shock; however, no correlation has been found between this delay and an increased risk for hospital mortality. [ABSTRACT FROM AUTHOR]

The global burden associated with antimicrobial resistance is of increasing concern. To evaluate risk factors associated with multidrug-resistant (MDR) infection and its clinical impact in a cohort of patients with healthcare-associated bacteraemic urinary tract infections (BUTIs). This was a prospective, multicentre, post-hoc analysis of patients with healthcare-associated-BUTI (ITUBRAS-2). The primary outcome was MDR profile. Secondary outcomes were clinical response (at 48–72 h and at hospital discharge) and length of hospital stay from onset of BUTI. Logistic regression was used to evaluate variables associated with MDR profile and clinical response. Length of hospital stay was evaluated using multivariate median regression. In all, 443 episodes were included, of which 271 (61.17%) were classified as expressing an MDR profile. In univariate analysis, MDR profile was associated with E. coli episodes (odds ratio (OR): 3.13; 95% confidence interval (CI): 2.11–4.69, P < 0.001) and the extensively drug-resistant (XDR) pattern with P. aeruginosa aetiology (7.84; 2.37–25.95; P = 0.001). MDR was independently associated with prior use of fluoroquinolones (adjusted OR: 2.43; 95% CI: 1.25–4.69), cephalosporins (2.14; 1.35–3.41), and imipenem or meropenem (2.08; 1.03–4.20) but not with prior ertapenem. In terms of outcomes, MDR profile was not associated with lower frequency of clinical cure, but was associated with longer hospital stay. MDR profile was independently associated with prior use of fluoroquinolones, cephalosporins, imipenem, and meropenem, but not with prior ertapenem. MDR-BUTI episodes were not associated with worse clinical cure, although they were independently associated with longer duration of hospital stay. [ABSTRACT FROM AUTHOR]

Bloodstream infections (BSIs) caused by Klebsiella pneumoniae (K. pneumoniae) are associated with high morbidity and mortality rates. This study presents a sequence type 25 (ST25) strain of hypermucoid K. pneumoniae A1 isolated from the blood of a patient with liver cirrhosis (LC) who succumbed to severe infections. We performed whole-genome sequencing of K. pneumoniae A1, which revealed virulence factors and antibiotic resistance genes. The strain harbors virulence genes encoding aerobactin, salmochelin, yersiniabactin, enterobactin, and rmpA. Additionally, the strain possessed five drug resistance genes: blaSHV-110, blaSHV-81, fosA6, OqxA, and OqxB. We further constructed a phylogenetic tree using 98 ST25 K. pneumoniae strains downloaded from NCBI together with K. pneumoniae A1. Phylogenetic analysis revealed that our isolated strain was closely related to a highly virulent strain isolated from a neonate in our region, differing by only 123 single nucleotide polymorphisms (SNPs). K. pneumoniae A1 is highly suspected to be Hypervirulent Klebsiella pneumoniae (hvKp). This study provided the first in-depth genomic analysis of ST25 K. pneumoniae in a patient with LC in China, highlighting the urgent need for early identification and diagnosis to combat this emerging threat. [ABSTRACT FROM AUTHOR]

This study aims to investigate the association between antimicrobial resistance genes and virulence factors in ST11 and non-ST11 types of CR-KP in bloodstream infections in the intensive care unit, providing a theoretical basis for infection control and clinical diagnosis and treatment. Methods: From January 2021 to June 2023, samples of Klebsiella pneumoniae from bloodstream infections were collected at our hospital, focusing on those resistant to carbapenems. The resistance genes, housekeeping genes, and virulence genes were identified through PCR and analyzed using the GrapeTree software to perform MLST-based minimum spanning tree typing. Results: Among the 85 CR-KP cases, 61.18% were of the ST11 type, predominantly of the KL64 capsular type; non-ST11 types were mainly ST15, accounting for 25.88%, predominantly of the KL5 capsular type. The carriage rates of virulence genes such as rmpA2, entB, silS, kpn, iucA, peg-344, and terB were significantly higher in the ST11 group than in the non-ST11 group. The primary carbapenemase identified was class A enzyme blaKPC-2, with a higher carriage rate in the ST11 group. Drug susceptibility tests showed that the resistance rates for cefepime, ertapenem, nitrofurantoin, amikacin, and gentamicin were also higher in the ST11 group, consistent with the resistance genotype findings. Conclusion: The study reveals that ST11 type CR-KP in intensive care unit bloodstream infections exhibits stronger resistance and higher virulence compared to non-ST11 types, posing significant challenges to clinical treatment. Thus, strict control over the use of carbapenem antibiotics is essential to prevent the spread of resistant plasmids. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Klebsiella pneumoniae (KP) is the second most prevalent Gram-negative bacterium causing bloodstream infections (BSIs). In recent years, the management of BSIs caused by KP has become increasingly complex due to the emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP). Although numerous studies have explored the risk factors for the development of CRKP-BSIs, the mortality of patients with KP-BSIs, and the molecular epidemiological characteristics of CRKP, the variability in data across different populations, countries, and hospitals has led to inconsistent conclusions. In this single-center retrospective observational study, we utilized logistic regression analyses to identify independent risk factors for CRKP-BSIs and factors associated with mortality in KP-BSI patients. Furthermore, a risk factor-based prediction model was developed. CRKP isolates underwent whole-genome sequencing (WGS), followed by an evaluation of microbiological characteristics, including antimicrobial resistance and virulence genes, as well as epidemiological characteristics and phylogenetic analysis. Results: Our study included a total of 134 patients with KP-BSIs, comprising 50 individuals infected with CRKP and 84 with carbapenem-susceptible Klebsiella pneumoniae (CSKP). The independent risk factors for CRKP-BSIs were identified as gastric catheterization (OR = 9.143; CI = 1.357–61.618; P = 0.023), prior ICU hospitalization (OR = 4.642; CI = 1.312–16.422; P = 0.017), and detection of CRKP in non-blood sites (OR = 8.112; CI = 2.130-30.894; P = 0.002). Multivariate analysis revealed that microbiologic eradication after 6 days (OR = 3.569; CI = 1.119–11.387; P = 0.032), high Pitt bacteremia score (OR = 1.609; CI = 1.226–2.111; P = 0.001), and inappropriate empirical treatment after BSIs (OR = 6.756; CI = 1.922–23.753; P = 0.003) were independent risk factors for the 28-day mortality in KP-BSIs. The prediction model confirmed that microbiologic eradication after 6.5 days and a Pitt bacteremia score of 4.5 or higher were significant predictors of the 28-day mortality. Bioinformatics analysis identified ST11 as the predominant CRKP sequence type, with blaKPC−2 as the most prevalent gene variant. CRKP stains carried multiple plasmid-mediated resistance genes along with some virulence genes. Phylogenetic analysis indicated the presence of nosocomial transmission of ST11 CRKP within the ICU. Conclusions: The analysis of risk factors for developing CRKP-BSIs and the association between KP-BSIs and 28-day mortality, along with the development of a risk factor-based prediction model and the characterization of CRKP strains, enhances clinicians' understanding of the pathogens responsible for BSIs. This understanding may help in the timely administration of antibiotic therapy for patients with suspected KP-BSIs, potentially improving outcomes. [ABSTRACT FROM AUTHOR]

Background Pseudomonas aeruginosa is a frequent pathogen isolated from bacterial bloodstream infection (BSI) and is associated with high mortality. To survive in the blood, P aeruginosa must resist the bactericidal action of complement (ie, serum killing). Antibodies usually promote serum killing through the classical complement pathway; however, "cloaking antibodies" (cAbs) have been described, which paradoxically protect bacteria from serum killing. The relevance of cAbs in P aeruginosa BSI is unknown. Methods Serum and P aeruginosa were collected from a cohort of 100 patients with BSI. Isolates were tested for sensitivity to healthy control serum (HCS). cAb prevalence was determined in sera. Patient sera were mixed with HCS to determine if killing of the matched isolate was inhibited. Results Overall, 36 patients had elevated titers of cAbs, and 34 isolates were sensitive to HCS killing. Fifteen patients had cAbs and HCS-sensitive isolates; of these patients, 14 had serum that protected their matched bacteria from HCS killing. Patients with cAbs were less likely to be neutropenic or have comorbidities. Conclusions cAbs are prevalent in patients with P aeruginosa BSI and allow survival of otherwise serum-sensitive bacteria in the bloodstream. Generation of cAbs may be a risk factor for the development of BSI. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Temporal trends of routinely obtained parameters may provide valuable information for predicting BSIs, but this association has not yet been established in LVAD patients.This retrospective analysis included data from 347 consecutive recipients of three rotary LVAD types. Study endpoints included the incidence of BSI, the association of temporal trends of routinely obtained blood biomarkers with the development of BSIs, the incidence of BSIs, and survival on LVAD support.During follow‐up, 47.8% (n = 166) of the patients developed BSI. In multivariate analyses, the development of BSI was a significant predictor of mortality (HR 5.78, 95% CI 4.08–8.19, p < 0.0001). In univariate analyses, after adjusting for potential confounders, albumin (SHR 0.94, 95% CI 0.91–0.97, p < 0.00010), creatinine (SHR 1.49, 95% CI 1.03–2.15, p = 0.033), and C‐reactive protein (SHR 1.19, 95% CI 1.08–1.32, p = 0.0007) significantly predicted the development of BSIs during LVAD support. Notably, the strength of the association of parameter changes with the prediction of BSIs demonstrated a time‐dependent correlation in the cases of albumin (p = 0.045) and creatinine (p = 0.003).Bloodstream infections are highly prevalent among LVAD recipients and are independent predictors of mortality. Temporal biomarker trends significantly predict the development of BSIs. These findings suggest opportunities for interventions aiming to reduce the incidence of BSIs. [ABSTRACT FROM AUTHOR]

Timely pathogen identification in bloodstream infections is crucial for patient care. A comparison is made between positive blood culture (BC) pellets from serum separator tubes using a direct identification (DI) method and colonies on agar plates from a short-term incubation (STI) method with a matrix-assisted laser desorption/ionization Biotyper for the evaluation of 354 monomicrobial BCs. Both the DI and STI methods exhibited similar identification rates for different types of bacteria, except for Gram-positive and anaerobic bacteria. The DI method's results aligned closely with the STI method's results for Enterobacterales, glucose-non-fermenting Gram-negative bacilli (GNB), and carbapenem-resistant Enterobacterales. The DI method exhibited high concordance with the conventional method for GNB identification, achieving 88.2 and 87.5% accuracy at the genus and species levels, respectively. Compared with the STI method, the DI method showed a less successful performance for Gram-positive bacterial identification (50.5 vs. 71.3%; p < 0.01). The DI method was useful for anaerobic bacterial identification of slow-growing microorganisms without any need for colony growth, unlike in the STI method (46.7 vs. 13.3%; p = 0.04). However, both methods could not identify yeast in positive BCs. Overall, the DI method provided reliable results for GNB identification, offering many advantages over the STI method by significantly reducing the turnaround time and enabling quicker pathogen identification in positive BCs. [ABSTRACT FROM AUTHOR]

Despite significant improvement in patient blood management, cardiac surgery remains a high hemorrhagic risk procedure. Platelet transfusion is used commonly to treat thrombocytopenia-associated perioperative bleeding. Allogeneic platelet transfusion may induce transfusion-related immunomodulation. However, its association with postoperative healthcare-associated infections is still a matter of debate. The objective was to evaluate the impact of allogeneic platelet transfusion during cardiac surgery on postoperative healthcare-associated infection incidence. Retrospective cohort study. Tertiary referral academic center. Patients undergoing cardiac surgery from 2012 to 2018. None. Intraoperative platelet transfusion was defined as exposure in a causal model. The primary outcome was the incidence of healthcare-associated infections comprised of bloodstream infection, hospital-acquired pneumonia, and surgical-site infection. Among 7,662 included patients, 528 patients (6.8%) were exposed to intraoperative platelet transfusion, and 329 patients (4.3%) developed 454 postoperative infections. Bloodstream infection affected 106 patients (1.4%), hospital-acquired pneumonia affected 174 patients (2.3%), and surgical-site infection affected 148 patients (1.9%). Intraoperative platelet transfusion was associated with an increased risk of bloodstream infection after adjustment by multivariable logistic regression (odds ratio [OR] 2.85; 95% CI 1.40-5.8; p = 0.004; n = 7,662), propensity score matching (OR 3.95; 95% CI 1.57-12.0), p = 0.007; n = 766), and propensity score overlap weighting (OR 3.04; 95% CI 1.51-6.1, p = 0.002; n = 7,762). Surgical-site infection and hospital-acquired pneumonia were not significantly associated with platelet transfusion. These results suggested that intraoperative allogeneic platelet transfusion is a risk factor for bloodstream infection after cardiac surgery. These results supported the development of patient blood management strategies aimed at minimizing perioperative platelet transfusion in cardiac surgery. [ABSTRACT FROM AUTHOR]

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, trimethoprimsulfamethoxazole, 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 redefining the infection control measures are essential to curb the dissemination of these strains. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 <1% and stable over time. Conversely, there was a significant reduction in the incidence of BSIs due to 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 <5% for both Gram-positive (i.e., MRSA and VRE) and Gram-negative (ESBL, AmpC, and carbapenem-resistant) pathogens, and MDR pathogens were almost exclusively detected in hospital-onset BSIs. Fungi accounted for just under 8% of BSIs. 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. [ABSTRACT FROM AUTHOR]

Objectives: Acinetobacter baumannii (A. baumannii) nosocomial infections represent a serious hazard to public health, given high mortality rates and rapid spread of multidrug-resistance. The primary outcome of this study was to evaluate predictors of 14- and 30-d mortality in bloodstream infections (BSIs) due to both carbapenem-resistant and carbapenem-sensitive Acinetobacter. Secondary end points were to identify risk factors for BSIs due to carbapenem-resistant A. baumannii (CRAB) and to develop a predictive model for mortality in CRAB-related BSIs. Methods: Between 2019 and 2023, all consecutive hospitalized adult patients with bacteraemia due to A. baumannii were retrospectively enrolled at a single-centre. Results: One hundred twenty-six episodes of BSI caused by A. baumannii were recorded, 89.7% of which were due to CRAB. Recent burn injuries, older age, previous CRAB colonization, and antibiotics exposure were identified as risk factors for acquiring CRAB BSI. Overall, 14-d mortality was observed in 26.1% of the patients and 30-d mortality in 30.9% of the patients. On multivariate analysis, the Sequential Organ Failure Assessment (SOFA) score was associated with both 14- and 30-d mortality, whereas burn injuries correlated with 30-d survival. Concurrent coronavirus disease (COVID) was associated with mortality, although not reaching statistical figures. No major impact of receiving appropriate treatment was observed. Based on these findings, a multivariable model to predict mortality among patients with CRAB BSI was built and internally validated. Conclusions: A. baumannii BSIs are characterized by poor outcomes and limited therapeutic options. This study aimed to assist physicians in prompt identification of patients who are at greater risk of death, contributing to more informed clinical decision making.

Abstract Background Klebsiella pneumoniae (KP) is the second most prevalent Gram-negative bacterium causing bloodstream infections (BSIs). In recent years, the management of BSIs caused by KP has become increasingly complex due to the emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP). Although numerous studies have explored the risk factors for the development of CRKP-BSIs, the mortality of patients with KP-BSIs, and the molecular epidemiological characteristics of CRKP, the variability in data across different populations, countries, and hospitals has led to inconsistent conclusions. In this single-center retrospective observational study, we utilized logistic regression analyses to identify independent risk factors for CRKP-BSIs and factors associated with mortality in KP-BSI patients. Furthermore, a risk factor-based prediction model was developed. CRKP isolates underwent whole-genome sequencing (WGS), followed by an evaluation of microbiological characteristics, including antimicrobial resistance and virulence genes, as well as epidemiological characteristics and phylogenetic analysis. Results Our study included a total of 134 patients with KP-BSIs, comprising 50 individuals infected with CRKP and 84 with carbapenem-susceptible Klebsiella pneumoniae (CSKP). The independent risk factors for CRKP-BSIs were identified as gastric catheterization (OR = 9.143; CI = 1.357–61.618; P = 0.023), prior ICU hospitalization (OR = 4.642; CI = 1.312–16.422; P = 0.017), and detection of CRKP in non-blood sites (OR = 8.112; CI = 2.130-30.894; P = 0.002). Multivariate analysis revealed that microbiologic eradication after 6 days (OR = 3.569; CI = 1.119–11.387; P = 0.032), high Pitt bacteremia score (OR = 1.609; CI = 1.226–2.111; P = 0.001), and inappropriate empirical treatment after BSIs (OR = 6.756; CI = 1.922–23.753; P = 0.003) were independent risk factors for the 28-day mortality in KP-BSIs. The prediction model confirmed that microbiologic eradication after 6.5 days and a Pitt bacteremia score of 4.5 or higher were significant predictors of the 28-day mortality. Bioinformatics analysis identified ST11 as the predominant CRKP sequence type, with bla KPC−2 as the most prevalent gene variant. CRKP stains carried multiple plasmid-mediated resistance genes along with some virulence genes. Phylogenetic analysis indicated the presence of nosocomial transmission of ST11 CRKP within the ICU. Conclusions The analysis of risk factors for developing CRKP-BSIs and the association between KP-BSIs and 28-day mortality, along with the development of a risk factor-based prediction model and the characterization of CRKP strains, enhances clinicians’ understanding of the pathogens responsible for BSIs. This understanding may help in the timely administration of antibiotic therapy for patients with suspected KP-BSIs, potentially improving outcomes.

Abstract Background Therapeutic plasma exchanges (TPE), which affect the humoral response, are often performed in combination with immunosuppressive drugs. For this reason, TPE may be associated with an increased susceptibility to infections. We aimed to describe blood stream infection (BSI) incidence in ICU patients treated with TPE and to identify associated risk factors. Methods We retrospectively included patients that had received at least one session of TPE in the ICU of one of the 4 participating centers (all in Paris, France) between January 1st 2010 and December 31th 2019. Patients presenting with a BSI during ICU stay were compared to patients without such an infection. Risk factors for BSI were identified by a multivariate logistic regression model. Results Over 10 years in the 4 ICUs, 387 patients were included, with a median of 5 [2–7] TPE sessions per patient. Most frequent indications for TPE were thrombotic microangiopathy (47%), central nervous system inflammatory disorders (11%), hyperviscosity syndrome (11%) and ANCA associated vasculitis (8.5%). Thirty-one patients (8%) presented with a BSI during their ICU stay, a median of 7 [3–11] days after start of TPE. In a multivariate logistic regression model, diabetes (OR 3.32 [1.21–8.32]) and total number of TPE sessions (OR 1.14 [1.08–1.20]) were independent risk factors for BSI. There was no difference between TPE catheter infection related BSI (n = 11 (35%)) and other sources of BSI (n = 20 (65%)) regarding catheter insertion site (p = 0.458) or rate of TPE catheter related deep vein thrombosis (p = 0.601). ICU course was severe in patients presenting with BSI when compared to patients without BSI, with higher need for mechanical ventilation (45% vs 18%, p = 0.001), renal replacement therapy (42% vs 20%, p = 0.011), vasopressors (32% vs 12%, p = 0.004) and a higher mortality (19% vs 5%, p = 0.010). Conclusion Blood stream infections are frequent in patients receiving TPE in the ICU, and are associated with a severe ICU course. Vigilant monitoring is crucial particularly for patients receiving a high number of TPE sessions.

Lei Wang,1 Xinbao Li,2 Yan Li,2 Zhongying Bao,1 Shuhong Duan,1 Jie Zhang1 1Department of Infectious Diseases, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 2Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of ChinaCorrespondence: Lei Wang, Department of Infectious Diseases, Beijing Shijitan Hospital, Capital Medical University, NO. 10, Tie Yi Road, Yang Fang Dian, Haidian District, Beijing, 100038, People’s Republic of China, Tel + 86 10 63926121, Email wanglei2489@bjsjth.cnObjective: In this study we aimed to evaluate the postoperative safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal surface malignancies (PSM), and analyzed the risk factors and pathogen resistance associated with bloodstream infections.Methods: We retrospectively analyzed the incidence of postoperative bloodstream infections in 1500 patients undergoing CRS and HIPEC for PSM. We utilized univariate and multivariate analyses to screen for independent risk factors associated with postoperative bloodstream infections in CRS combined with HIPEC.Results: Among the 1500 cases of individuals undergoing CRS combined with HIPEC, 207 cases (13.8%) experienced bloodstream infections. A total of 233 strains of pathogens were isolated and cultured, consisting of 151 gram-positive cocci, 52 gram-negative bacilli, and 30 fungi. Coagulase-negative staphylococci (SCN) were the gram-positive cocci (54.94%), while Klebsiella pneumoniae subsp. Pneumoniae (7.30%) and Escherichia coli (5.58%) dominated the Gram-negative bacilli. Candida albicans was the predominant fungus. Staphylococci exhibited high sensitivity to tigecycline, linezolid, vancomycin, and quinupristin/dalfopristin. However, K. pneumoniae and E. coli were resistant to imipenem. Furthermore, five parameters were associated with the development of bloodstream infections: age (P = 0.040), surgical history (P = 0.033), prior tumor treatment (P < 0.001), tumor tissue type (P = 0.034), and completeness of cytoreduction (CC) score (P = 0.004). Among these, age (P = 0.013), prior tumor treatment (P = 0.001), tumor tissue type (P = 0.032), and CC score (P = 0.002) emerged as independent risk factors for postoperative bloodstream infections in patients undergoing CRS combined with HIPEC.Conclusion: Postoperative bloodstream infections in patients with PSM undergoing CRS combined with HIPEC are predominantly attributed to SCN, K. pneumoniae subsp. Pneumoniae, and C. albicans. Notably, Enterobacteriaceae exhibited resistance to carbapenem. Independent risk factors for postoperative infections in PSM include age, prior tumor treatment, tumor tissue type, and completeness of cytoreduction score.Keywords: bloodstream infections, cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, pathogens drug resistance, pathogens

Miao-Miao Hua,1 Jia Li,2 Jie Zheng,2 Jing-Jing Wang,2 Chang Liu,2 Yan Zhang,2 Zhi-Feng Zhang,2 Xiao-Li Cao,1,2 Han Shen1,2 1Department of Laboratory Medicine, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, People’s Republic of China; 2Department of Laboratory Medicine, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, Nanjing, People’s Republic of ChinaCorrespondence: Xiao-Li Cao; Han Shen, Email cao-xiao-li@163.com; shenhan10366@sina.comObjective: To investigate the clinical and molecular characteristics of Salmonella spp. causing bloodstream infections (BSIs) in our hospital.Methods: We studied 22 clinical Salmonella isolates from BSIs and 16 from non-BSIs, performing antimicrobial susceptibility testing (AST) and whole genome sequencing (WGS). The analysis included serovars, antibiotic resistance genes (ARGs), virulence factors (VFs), sequence types (STs), plasmid replicons, and genetic relationships. We also assessed pathogenicity of the isolates causing BSIs through growth, biofilm formation, and anti-serum killing assays.Results: WGS analysis identified 13 Salmonella serovars, with four responsible for BSIs. S. Enteritidis was the most prevalent serovar, involved in 19 (50.0%) cases. BSIs were caused by 17S. Enteritidis, two S. Typhimurium, two S. Munster and one S. Diguel. Of the 38 isolates, 27 (71.1%) exhibited high resistance to ampicillin, and 24 (63.2%) to ampicillin/sulbactam. Thirty-six types of ARGs were identified, with blaTEM-1B (n = 25, 65.8%) being the most frequent. Ten plasmid replicons were found; the combination of IncFIB(S)-IncFII(S)-IncX1 was the most common in S. Enteritidis (94.7%). Fifteen STs were identified, among which ST11 was the most prevalent and clonally disseminated, primarily responsible for BSIs. A total of 333 different VFs were detected, 177 of which were common across all strains. No significant differences were observed between the BSI and non-BSI isolates in terms of resistance rates, ARGs, plasmid replicons, and VFs, except for seven VFs. No strong pathogenicity was observed in the BSI-causing isolates.Conclusion: BSIs were predominantly caused by clonally disseminated S. Enteritidis ST11, the majority of which carried multiple ARGs, VFs and plasmid replicons. This study provides the first data on clonally disseminated S. Enteritidis ST11 causing BSIs, highlighting the urgent need for enhanced infection control measures.Keywords: Salmonella enteritidis, bloodstream infections, serovars, antibiotic-resistance genes, virulence factors, sequence type

Abstract 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 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.

Jia Li,1,2 Wenjing Guo,1,2 Jieru Wang,1,2 Xiaomeng Feng,1,2 Qingsong Lin,1,2,&ast; Yizhou Zheng,1,2 Fengkui Zhang,1,2 Yingchang Mi,1,2 Xiaofan Zhu,1,2 Erlie Jiang,1,2 Zhijian Xiao,1,2 Jianxiang Wang,1,2 Sizhou Feng1,2,&ast; 1State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, People’s Republic of China; 2Tianjin Institutes of Health Science, Tianjin, 301600, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sizhou Feng, Hematopoietic Stem Cell Transplantation Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 288 Nanjing Road, Tianjin, 300020, People’s Republic of China, Tel +86-022-23909162, Fax +022-23909047, Email doctor_szhfeng@163.com; szfeng@ihcams.ac.cnObjective: This study aimed to assess the impact of colonization status on the outcomes of Acinetobacter spp. bloodstream infection (BSI) and investigate the homology and within-host evolution between colonizing and bloodstream carbapenem-resistant Acinetobacter spp. (CRA) to inform antibiotic therapeutic decisions.Methods: We analyzed clinical outcomes of 46 hematological patients with Acinetobacter spp. BSI and performed whole-genome sequencing on the remaining CRA isolates.Results: Among the patients, 39.1% (n=18) had prior Acinetobacter spp. colonization. Colonized patients had higher rates of polymicrobial BSI (50.0% vs 21.4%, P=0.044) and CRA BSI (72.2% vs 17.9%, P< 0.001), resulting in elevated inflammatory markers and increased 30-day mortality. Each of the eight pairs of the remaining respiratory colonizing and bloodstream CRA strains belonged to the same genomospecies. Each pair exhibited definitive agreement in at least 21 of the 22 most representative antibiotic susceptibility tests. The minimum spanning tree based on multilocus sequence typing (MLST) and phylogenetic trees based on MLST and single nucleotide polymorphism (SNP) all indicated that each pair shared the same minimum branch. Very few non-synonymous SNPs in genic regions were identified during the transition from respiratory colonization to bloodstream infection, with minimal changes in virulence genes. Homology analysis suggested that CRA BSI originated from colonizing isolates in the respiratory tract.Conclusion: Strict infection control measures are needed to manage Acinetobacter spp. colonisation in hematological patients. Appropriate empirical therapy can be administered for suspected CRA BSI based on the antimicrobial minimum inhibitory concentration of CRA colonising the respiratory tract.Keywords: Acinetobacter, colonization, bloodstream infections, homology, therapy, carbapenem-resistant

Jiayang Li,1,2,&ast; Wenqi Wu,3,&ast; Meilin Wu,4 Zhitao Zhou,4 Jiajie Wang,1 Mingjie Qiu,4 Li Xu,4 Jianan Ren,1,2 Xiuwen Wu1,2 1School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Research Institute of General Surgery, Jinling Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 3School of Medicine, Nanjing University, Nanjing, People’s Republic of China; 4Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiuwen Wu; Jianan Ren, Research Institute of General Surgery, Jinling Hospital, School of Medicine, Southeast University, 305 East Zhongshan Road, Nanjing, 210002, People’s Republic of China, Email wuxiuwen@nju.edu.cn; jiananr@nju.edu.cnPurpose: Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-β-lactamase (NDM) co-producing carbapenem-resistant Klebsiella pneumoniae (KPC-NDM-CRKP) isolates have been increasingly reported worldwide but have not yet been systematically studied. Thus, we have conducted a study to compare the risk factors, molecular characteristics, and mortality involved in clinical bloodstream infections (BSIs) caused by KPC-NDM-CRKP and KPC-CRKP strains.Methods: A retrospective study was conducted on 231 patients with BSIs caused by CRKP at Jinling Hospital in China from January 2020 to December 2022. Antimicrobial susceptibility testing, carbapenemase genes detection and whole-genome sequencing were performed subsequently.Results: Overall, 231 patients were included in this study: 25 patients with KPC-NDM-CRKP BSIs and 206 patients with KPC-CRKP BSIs. Multivariate analysis implicated ICU-acquired BSI, surgery within 30 days, and longer stay of hospitalization prior to CRKP isolation as independent risk factors for KPC-NDM-CRKP BSIs. The 30-day mortality rate of the KPC-NDM-CRKP BSIs group was 56% (14/25) compared with 32.5% (67/206) in the KPC-CRKP BSIs control group (P = 0.02). The ICU-acquired BSIs, APACHE II score at BSI onset, and BSIs caused by KPC-NDM-CRKP were independent predictors for 30-day mortality in patients with CRKP bacteremia. The most prevalent ST in KPC-NDM-CRKP isolates was ST11 (23/25, 92%), followed by ST15 (2/25, 8%).Conclusion: In patients with CRKP BSIs, KPC-NDM-CRKP was associated with an excess of mortality. The likelihood that KPC-NDM-CRKP will become the next “superbug” highlights the significance of epidemiologic surveillance and clinical awareness of this pathogen.Keywords: KPC and NDM co-producing carbapenem-resistant Klebsiella pneumoniae, Bloodstream infections, risk factors, molecular characteristics, mortality

Background: Therapeutic plasma exchanges (TPE), which affect the humoral response, are often performed in combination with immunosuppressive drugs. For this reason, TPE may be associated with an increased susceptibility to infections. We aimed to describe blood stream infection (BSI) incidence in ICU patients treated with TPE and to identify associated risk factors. Methods: We retrospectively included patients that had received at least one session of TPE in the ICU of one of the 4 participating centers (all in Paris, France) between January 1st 2010 and December 31th 2019. Patients presenting with a BSI during ICU stay were compared to patients without such an infection. Risk factors for BSI were identified by a multivariate logistic regression model. Results: Over 10 years in the 4 ICUs, 387 patients were included, with a median of 5 [2–7] TPE sessions per patient. Most frequent indications for TPE were thrombotic microangiopathy (47%), central nervous system inflammatory disorders (11%), hyperviscosity syndrome (11%) and ANCA associated vasculitis (8.5%). Thirty-one patients (8%) presented with a BSI during their ICU stay, a median of 7 [3–11] days after start of TPE. In a multivariate logistic regression model, diabetes (OR 3.32 [1.21–8.32]) and total number of TPE sessions (OR 1.14 [1.08–1.20]) were independent risk factors for BSI. There was no difference between TPE catheter infection related BSI (n = 11 (35%)) and other sources of BSI (n = 20 (65%)) regarding catheter insertion site (p = 0.458) or rate of TPE catheter related deep vein thrombosis (p = 0.601). ICU course was severe in patients presenting with BSI when compared to patients without BSI, with higher need for mechanical ventilation (45% vs 18%, p = 0.001), renal replacement therapy (42% vs 20%, p = 0.011), vasopressors (32% vs 12%, p = 0.004) and a higher mortality (19% vs 5%, p = 0.010). Conclusion: Blood stream infections are frequent in patients receiving TPE in the ICU, and are associated with a severe ICU course. Vigilant monitoring is crucial particularly for patients receiving a high number of TPE sessions. [ABSTRACT FROM AUTHOR]

Introduction: Central Venous Lines (CVL) are an important part of patient care, allowing the administration of intravenous fluids, blood, drugs and parenteral solutions. Their use is a cause of infections due to micro-organisms colonizing the skin at the entry point or the catheter or other point along it or the fluids administered by the Intensive Care Unit (ICU). Central line-associated bloodstream infections (CLABSI's) in children's ICUs are an important factor that negatively affects the course of the disease, causing complications, perhaps irreversible. Aim: The aim of this study was to investigate the interventions for the management of CLABSI's in neonatal and pediatric ICUs. Methodology: Published research articles in the years 2016-2021 in valid scientific journals referring to children with CVL hospitalized in neonatal and pediatric ICUs were studied. A systematic search of the literature was performed in digital scientific databases (Medline, PubMed Scopus, Embase, Cochrane Library) using keywords. The PICOS (Population, Interventions, Controls, Outcome, Study design) procedure was used as a criterion for the inclusion of an article in the present study. The evaluation of the articles of the bibliographic search were evaluated using the PRISMA method. Results: Interventions for the management of CLABSI's included the use of chlorhexidine-soaked pads, implementation of measures to prevent CLABSI's, use of a pre-filled disposable syringe for flushing, implementation of an infection surveillance system, use of new methods/measures for introduction of the catheter, use and management of CVL, use of ethanol lock, use of antibiotic-impregnated catheter and multidimensional approaches. Conclusions: As it was seen from the results of the study, there are several research evidence regarding the effectiveness of nursing interventions to limit CLABSI's in neonatal and children's ICUs. Nevertheless, it seems that prevention measures for CLABSI's and hand hygiene guidelines have a decisive role in limiting CLABSI's in neonatal and pediatric ICUs. [ABSTRACT FROM AUTHOR]

AbstractBackgroundObjectivesMethodsResultsConclusionKlebsiella pneumoniae (KP) accounts for high antimicrobial resistance and mortality rates of bloodstream infections (BSIs).To investigate incidence, antimicrobial resistance and risk factors for mortality of KP BSIs in East China.A retrospective study of patients with KP BSIs was conducted in a tertiary care hospital from 2018 to 2022. Medical records of all hospitalised patients with KP BSIs were reviewed and analysed. The incidence, antimicrobial resistance and mortality of KP BSIs were evaluated. The Kaplan-Meier method was used to plot survival curves and logistic regression was used to analyse risk factors for crude 30-day mortality.A total of 379 inpatients with KP BSIs were enrolled. The incidence of patients with KP BSIs was fluctuating between 4.77 and 9.40 per 100,000 patient-days. The crude 30-day mortality rate of these patients was 26.39%. Of the 379 KPisolates, 197 (51.98%) were carbapenem-resistant (CR) and 252 (66.49%) were multidrug-resistant (MDR). All isolates showed the lowest resistance to tigecycline (13.77%) and polymyxin B (14.61%). Cases with MDR/CR isolates had significantly longer length of hospital stay, higher crude 30-day mortality and medical costs than non-MDR/non-CR isolates. Age, CR phenotype, paracentesis, indwelling central venous catheter (CVC), use of carbapenems, tetracyclines, polymyxins B, and irrational empiric treatment were independently associated with crude 30-day mortality.MDR/CR KP BSIs are associated with increased mortality, healthcare costs and prolonged hospitalisation. Patients with advanced age, CR phenotype, paracentesis, CVC, exposure to some antibiotics, and irrational empirical antibiotic treatment are at higher mortality risk. [ABSTRACT FROM AUTHOR]

Limited experience exists with ceftazidime-avibactam (CAZ-AVI) in treating bacteremia caused by carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CRPA) in hematological patients. We performed a single-center, retrospective, observational study including patients who received CAZ-AVI for bacteremia due to CRE or CRPA between 2018 and 2022. The primary outcome was 30-day survival. We conducted a multivariable analysis to identify predictors of survival. 56 patients were included and 57 (41 CRE and 16 CRPA) strains were isolated. 35 strains produced carbapenemase, including 25 metallo-beta-lactamase (MBL) and 10 serine-beta-lactamase. 48 patients (85.7 %) received combination therapy. All patients with MBL-CRE bacteremia (n = 24) received combination therapy with aztreonam (AZT). The susceptibility rates to CAZ-AVI were only 26.8 % (11/41) in CRE and 80.0 % (8/10) in CRPA. The 30-day survival rates were 85.0 % (34/40) in the CRE group and 81.3 % (13/16) in the CRPA group. In patients with MBL-CRE bacteremia, the 30-day survival was as high as 91.7 % (22/24) due to combination with AZT. Ceftazidime did not influence the activity of aztreonam-avibactam against MBL-CRE in-vitro. Multivariable cox analysis revealed neutropenia >14 days (P = 0.002, HR: 34.483, 95%CI: 3.846–333.333) and a higher Pitt bacteremia score (P = 0.005, HR: 2.074, 95%CI: 1.253–3.436) were risk factors for 30-day survival. CAZ-AVI is highly effective in treating bacteremia due to CRPA and serine-beta-lactamase CRE. The combination of avibactam with AZT is highly effective in treating bacteremia due to AZT-resistant MBL producers. [ABSTRACT FROM AUTHOR]

Studies examining time to positivity (TTP) of blood cultures as a risk factor for death have shown conflicting results. The study objective was to examine the effect of TTP on all-cause-30-day case-fatality among a population-based cohort of patients with bloodstream infections (BSI). A retrospective cohort study including all residents of Queensland, Australia with incident monomicrobial BSI managed in the publicly funded healthcare system from 2000 to 2019 was performed. Clinical, TTP and all-cause 30-day case-fatality information was obtained from state-wide sources. A cohort of 88 314 patients was assembled. The median TTP was 14 hours, with 5th, 25th, 75th, and 95th percentiles of 4, 10, 20, and 53 hours, respectively. The TTP varied significantly by BSI aetiology. The 30-day all-cause case-fatality rate was 2606/17 879 (14.6%), 2834/24 272 (11.7%), 2378/20 359 (11.7%), and 2752/22 431 (12.3%) within the first, second, third, and fourth TTP quartiles, respectively (p < 0.0001). After adjustment for age, sex, onset, comorbidity, and focus of infection, TTP within 10 hours (first quartile) was associated with a significantly increased risk for death (odds ratio 1.43; 95% CI, 1.35–1.50; p < 0.001). After adjustment for confounding variables (odds ratio; 95% CI), TTP within the first quartile for Staphylococcus aureus (1.56; 1.41–1.73), Streptococcus pneumoniae (1.91; 1.49–2.46), β-hemolytic streptococci (1.23; 1.00–1.50), Pseudomonas species (2.23; 1.85–2.69), Escherichia coli (1.37; 1.23–1.53), Enterobacterales (1.38; 1.16–1.63), other Gram-negatives (1.68; 1.36–2.06), and anaerobes (1.58; 1.28–1.94) increased the risk for case-fatality. This population-based analysis provides evidence that TTP is an important determinant of mortality among patients with BSI. [ABSTRACT FROM AUTHOR]

The utility of follow-up blood cultures (FUBCs) in patients with Gram-negative bloodstream infection (GN-BSI) is controversial. Observational studies have suggested significant mortality benefit but may be limited by single-centre designs, immortal time bias, and residual confounding. We examined the impact of FUBCs on mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario, Canada. Adult patients with GN-BSI hospitalized between April 2017 and December 2021 were included. Primary outcome was all-cause mortality within 30 days. FUBC was treated as a time-varying exposure. Secondary outcomes were 90-day mortality, length of stay, and number of days alive and out of hospital at 30 and 90 days. Thirty-four thousand one hundred patients were included; 8807 (25.8%) patients received FUBC, of which 966 (11.0%) were positive. Median proportion of patients receiving FUBC was 18.8% (interquartile range, 10.0–29.7%; range, 0–66.1%) across 101 hospitals; this correlated with positivity and contamination rate. Eight hundred ninety (10.1%) patients in the FUBC group and 2263 (8.9%) patients in the no FUBC group died within 30 days. In the fully adjusted model, there was no association between FUBC and mortality (hazard ratio, 0.97; 95% CI, 0.90–1.04). Patients with FUBC had significantly longer length of stay (median, 11 vs. 7 days; adjusted risk ratio, 1.18; 95% CI, 1.16–1.21) and fewer number of days alive and out of hospital at 30 and 90 days. FUBC collection in patients with GN-BSI varies widely across hospitals and may be associated with prolonged hospitalization without clear survival benefit. Residual confounding may be present given the observational design. Clear benefit should be demonstrated in a randomized trial before widespread adoption of routine FUBC. [Display omitted] [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa bloodstream infections (PA-BSIs) are a serious disease and a therapeutic challenge due to increasing resistance to carbapenems. Our objectives were to describe the prevalence and risk factors associated with carbapenem resistance (CR) and mortality in children with PA-BSI. A retrospective, multi-centre study was carried out, including patients aged <20 years with PA-BSI in four tertiary hospitals in Madrid (Spain) during 2010–2020. Risk factors for CR PA-BSIs and 30-day mortality were evaluated in a multi-variable logistic regression model. In total, 151 patients with PA-BSI were included, with a median age of 29 months (interquartile range: 3.5–87.1). Forty-five (29.8%) cases were CR, 9.9% multi-drug resistant and 6.6% extensively drug resistant. The prevalence of CR remained stable throughout the study period, with 26.7% (12/45) of CR mediated by VIM-type carbapenemase. Patients with BSIs produced by CR-PA were more likely to receive inappropriate empiric treatment (53.3% vs 5.7%, P <0.001) and to have been previously colonized by CR-PA (8.9% vs 0%, P =0.002) than BSIs caused by carbapenem-susceptible P. aeruginosa. CR was associated with carbapenem treatment in the previous month (adjusted odds ratio (aOR) 11.15) and solid organ transplantation (aOR 7.64). The 30-day mortality was 23.2%, which was associated with mechanical ventilation (aOR 4.24), sepsis (aOR 5.72), inappropriate empiric antibiotic therapy (aOR 5.86), and source control as a protective factor (aOR 0.16). This study shows a concerning prevalence of CR in children with PA-BSIs, leading to high mortality. Inappropriate empiric treatment and sepsis were associated with mortality. The high prevalence of CR with an increased risk of inappropriate empiric treatment should be closely monitored. [ABSTRACT FROM AUTHOR]

Staphylococcus argenteus, identified in 2006, represents a challenging case of bacterial taxonomic identification because of its high similarity to Staphylococcus aureus. In this context, neither mass spectrometry (MS) nor 16S gene analysis cannot precisely reveal the difference between the two species. In our study, the sensitivity to antibiotics of S. argenteus isolated from blood culture was tested, and the investigation of the bacterial genome was performed by Multi-Locus Sequence Typing (MLST) and Whole-Genome Next-Generation Sequencing (WG-NGS). The pathogen was identified as ST2250 and presented perfectly matched resistance genes, namely aph(3′)-III, mgrA, and sepA, whereas the virulence gene detected was scn. Two plasmids were found: the pSAS plasmid, belonging to the family of Inc18, and plasmid pN315, belonging to the Rep3 group. The epidemiological distribution and the spread of S. argenteus infection are scarcely documented, particularly when associated with sepsis. Therefore, a correct taxonomy identification, antibiogram, and resistance gene analysis may help in acquiring knowledge about this bacterium and implement its detection and treatment. [ABSTRACT FROM AUTHOR]

This retrospective study aimed to assess and compare guideline adherence and treatment costs in the management of urinary tract infections (UTIs) and bloodstream infections (BSIs) in German tertiary hospitals from January 2019 to December 2020. The study analyzed 586 patient records, with 65% diagnosed with UTIs and 35% with BSIs. Antibiotic treatment was given to 98% of patients, but only 65% received microbiological diagnostics. Bacterial growth was observed in 86% of patients with cultures taken, with Escherichia coli being the leading pathogen. The treatment was intravenous in 63% of cases, with Ceftriaxone as the leading antibiotic agent. The guideline adherence was found to be low, at 33%. Multivariable logistic regression analysis revealed that patients with urogenital risk factors (OR = 1.589; p < 0.001) and increasing age (OR = 1.01; p = 0.007) were significantly more likely to receive guideline-concordant treatment for UTIs and BSIs. Additionally, complicating factors such as diabetes and renal dysfunction were associated with higher adherence rates, underscoring the importance of targeted antibiotic stewardship interventions. [ABSTRACT FROM AUTHOR]

Background: Bloodstream infection (BSI) represent a prevalent complication in haematological malignancies (HMs). Typically, Patients with BSI usually undergo empirical treatment pending pathogen identification. The timely and effective management of BSIs significantly influences patient prognosis. However, pathogen distribution in BSIs exhibits regional variation. In this study, we investigated the clinical characteristics, pathogen spectrum, drug resistance, risk factors of short-term prognosis and long-term prognostic factors of acute myeloid leukemia (AML) patients with BSI at Zhejiang Provincal People's Hospital. Methods: From 2019 to 2021, a total of 56 AML patients with BSI were treated in the Department of Haematology at Zhejiang Province People's Hospital. Data regarding pathogen spectrum and drug resistance were collected for analysis. The patients were stratified into non-survivor cohort and survivor cohort within 30 days after BSI, and the predictors of 30-days mortality were identified through both univariate and multivariate Logistic regression analyses. Furthermore, Kaplan-Meier survival analysis and Cox regression analysis were employed to ascertain the risk factors associated with poor prognosis in AML patients complicated by BSI. Results: A total of 70 strains of pathogenic bacteria were isolated from 56 AML patients with BSI. Gram-negative bacteria constituted the predominant pathogens (71.4%), with Klebsiella pneumoniae being the most prevalent (22.9%). Gram-positive bacteria and fungi accounted for 22.9% and 5.7%, respectively. Univariate and multivariate analyses revealed significant differences in total protein, albumin levels, and the presence of septic shock between the non-survivor cohort and the survior cohort 30 days post-BSI. COX regression analysis showed that agranulocytosis duration exceeding 20 days (HR:3.854; 95% CI: 1.451-10.242) and septic shock (HR:3.788; 95% CI: 1.729-8.299) were independent risk factors for poor prognosis in AML patients complicated by BSI. Notably, the mortality rate within 30 days after Stenotrophomonas maltophilia infection was up to 71.4%. Conclusions: In this study, Gram-negative bacteria, predominantly Klebsiella pneumoniae, constituted the primary pathogens among AML patients with BSIs. Serum albumin levels and the presence of septic shock emerged as independent risk factors for mortality within 30 days among AML patients with BSI. In terms of long-term prognosis, extended agranulocytosis duration exceeding 20 days and septic shock were associated with elevated mortality rates in AML patients with BSI. Additionally, in our centre, Stenotrophomonas maltophilia infection was found to be associated with a poor prognosis. Early intervention for Stenotrophomonas maltophilia infection in our centre could potentially improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Rapid and accurate diagnosis of the causative agents is essential for clinical management of bloodstream infections (BSIs) that might induce sepsis/septic shock. A considerable number of suspected sepsis patients initially enter the health-care system through an emergency department (ED), hence it is vital to establish an early strategy to recognize sepsis and initiate prompt care in ED. This study aimed to evaluate the diagnostic performance and clinical value of droplet digital PCR (ddPCR) assay in suspected sepsis patients in the ED. Methods: This was a prospective single-centered observational study including patients admitted to the ED from 25 October 2022 to 3 June 2023 with suspected BSIs screened by Modified Shapiro Score (MSS) score. The comparison between ddPCRand blood culture (BC)was performed toevaluate the diagnostic performance of ddPCR for BSIs. Meanwhile, correlative analysis between ddPCR and the inflammatory and prognostic-related biomarkers were conducted to explore the relevance. Further, the health economic evaluation of the ddPCR was analyzed. Results: 258 samples from 228 patients, with BC and ddPCR performed simultaneously, were included in this study. We found that ddPCR results were positive in 48.13% (103 of 214) of episodes, with identification of 132 pathogens. In contrast, BC only detected 18 positives, 88.89% of which were identified by ddPCR. When considering culture-proven BSIs, ddPCR shows an overall sensitivity of 88.89% and specificity of 55.61%, the optimal diagnostic power for quantifying BSI through ddPCR is achieved with a copy cutoff of 155.5. We further found that ddPCR exhibited a high accuracy especially in liver abscess patients. Among all the identified virus by ddPCR, EBV has a substantially higher positive rate with a link to immunosuppression. Moreover, the copies of pathogens in ddPCR were positively correlated with various markers of inflammation, coagulation, immunity as well as prognosis. With high sensitivity and specificity, ddPCR facilitates precision antimicrobial stewardship and reduces health care costs. Conclusions: The multiplexed ddPCR delivers precise and quantitative load data on the causal pathogen, offers the ability to monitor the patient's condition and may serve as early warning of sepsis in time-urgent clinical situations as ED. Importance: Early detection and effective administration of antibiotics are essential to improve clinical outcomes for those with life-threatening infection in the emergency department. ddPCR, an emerging tool for rapid and sensitive pathogen identification used as a precise bedside test, has developed to address the current challenges of BSI diagnosis and precise treatment. It characterizes sensitivity, specificity, reproducibility, and absolute quantifications without a standard curve. ddPCR can detect causative pathogens and related resistance genes in patients with suspected BSIs within a span of three hours. In addition, it can identify polymicrobial BSIs and dynamically monitor changes in pathogenic microorganisms in the blood and can be used to evaluate antibiotic efficacy and survival prognosis. Moreover, the copies of pathogens in ddPCR were positively correlated with various markers of inflammation, coagulation, immunity. With high sensitivity and specificity, ddPCR facilitates precision antimicrobial stewardship and reduces health care costs. [ABSTRACT FROM AUTHOR]

Background Clinical trials of treatments for serious infections commonly use the primary endpoint of all-cause mortality. However, many trial participants survive their infection and this endpoint may not truly reflect important benefits and risks of therapy. The win ratio uses a hierarchical composite endpoint that can incorporate and prioritize outcome measures by relative clinical importance. Methods The win ratio methodology was applied post hoc to outcomes observed in the MERINO trial, which compared piperacillin-tazobactam with meropenem. We quantified the win ratio with a primary hierarchical composite endpoint, including all-cause mortality, microbiological relapse, and secondary infection. A win ratio of 1 would correspond to no difference between the 2 antibiotics, while a ratio <1 favors meropenem. Further analyses were performed to calculate the win odds and to introduce a continuous outcome variable in order to reduce ties. Results With the hierarchy of all-cause mortality, microbiological relapse, and secondary infection, the win ratio estimate was 0.40 (95% confidence interval [CI],.22–.71]; P =.002), favoring meropenem over piperacillin-tazobactam. However, 73.4% of the pairs were tied due to the small proportion of events. The win odds, a modification of the win ratio accounting for ties, was 0.79 (95% CI,.68–.92). The addition of length of stay to the primary composite greatly minimized the number of ties (4.6%) with a win ratio estimate of 0.77 (95% CI,.60–.99; P =.04). Conclusions The application of the win ratio methodology to the MERINO trial data illustrates its utility and feasibility for use in antimicrobial trials. [ABSTRACT FROM AUTHOR]

Background Escherichia coli is frequently responsible for bloodstream infections (BSIs). Among digestive BSIs, biliary infections appear to be less severe. Respective roles of host factors, bacterial determinants (phylogroups, virulence, and antibiotic resistance), and portal of entry on outcome are unknown. Methods Clinical characteristics and prognosis of 770 episodes of E coli BSI were analyzed and isolates sequenced (Illumina technology) comparing phylogroups, multilocus sequence type, virulence, and resistance gene content. BSI isolates were compared with 362 commensal E coli from healthy subjects. Results Among 770 episodes, 135 were biliary, 156 nonbiliary digestive, and 479 urinary. Compared to urinary infections, BSIs of digestive origin occurred significantly more in men, comorbid, and immunocompromised patients. Digestive portal of entry was significantly associated with septic shock and death. Among digestive infections, patients with biliary infections were less likely to die (P =.032), despite comparable initial severity. Biliary E coli resembled commensals (phylogroup distribution, sequence type, and few virulence-associated genes) whereas nonbiliary digestive and urinary strains carried many virulence-associated genes. Conclusions Escherichia coli strains responsible for biliary infections exhibit commensal characteristics and are associated with lower mortality rates, despite similar initial severity, than other digestive BSIs. Biliary drainage in addition to antibiotics in the management of biliary infections may explain improved outcome. [ABSTRACT FROM AUTHOR]